Sample records for genetic interactions show
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Bartolomé, E; Menéndez-Buxadera, A; Molina, A; Valera, M
2018-04-01
To obtain a sport horse that excels in the highest levels of competition, breeders must take into account certain genetic and environmental factors that could influence the sport horse's performance, such as the rider-horse interaction (RHI). The main aim of this study was to describe this interaction in a genetic model by modelling it in relation to the horse's age. A total of 31,129 sport results from Spanish Sport Horses were used from a total of 1,101 animals evaluated, and these were grouped in three age levels and had been ridden by 606 different riders. Only riders who had ridden more than one horse (and vice-versa) were considered for the analyses. Five linear models with different random effects were analysed according to the covariates, the homogeneity/heterogeneity of the RHI and the relevant residual random effects. The model of best fit was then selected for the genetic evaluation of the animal. In general, models including the RHI effect (M2, M4 and M5) fitted better than the other models, and the best fit was obtained for M4 (with heterogeneous residual variance). The genetic variance increased constantly with age, whereas heritability showed a response on three intervals. This study revealed the varied evolution of the RHI with age, showing the different "plastic abilities" of this relationship. © 2018 Blackwell Verlag GmbH.
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Han, Lide; Yang, Jian; Zhu, Jun
2007-06-01
A genetic model was proposed for simultaneously analyzing genetic effects of nuclear, cytoplasm, and nuclear-cytoplasmic interaction (NCI) as well as their genotype by environment (GE) interaction for quantitative traits of diploid plants. In the model, the NCI effects were further partitioned into additive and dominance nuclear-cytoplasmic interaction components. Mixed linear model approaches were used for statistical analysis. On the basis of diallel cross designs, Monte Carlo simulations showed that the genetic model was robust for estimating variance components under several situations without specific effects. Random genetic effects were predicted by an adjusted unbiased prediction (AUP) method. Data on four quantitative traits (boll number, lint percentage, fiber length, and micronaire) in Upland cotton (Gossypium hirsutum L.) were analyzed as a worked example to show the effectiveness of the model.
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Directory of Open Access Journals (Sweden)
Rohith Srivas
2013-12-01
Full Text Available Efficient repair of UV-induced DNA damage requires the precise coordination of nucleotide excision repair (NER with numerous other biological processes. To map this crosstalk, we generated a differential genetic interaction map centered on quantitative growth measurements of >45,000 double mutants before and after different doses of UV radiation. Integration of genetic data with physical interaction networks identified a global map of 89 UV-induced functional interactions among 62 protein complexes, including a number of links between the RSC complex and several NER factors. We show that RSC is recruited to both silenced and transcribed loci following UV damage where it facilitates efficient repair by promoting nucleosome remodeling. Finally, a comparison of the response to high versus low levels of UV shows that the degree of genetic rewiring correlates with dose of UV and reveals a network of dose-specific interactions. This study makes available a large resource of UV-induced interactions, and it illustrates a methodology for identifying dose-dependent interactions based on quantitative shifts in genetic networks.
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Predictability of Genetic Interactions from Functional Gene Modules
Directory of Open Access Journals (Sweden)
Jonathan H. Young
2017-02-01
Full Text Available Characterizing genetic interactions is crucial to understanding cellular and organismal response to gene-level perturbations. Such knowledge can inform the selection of candidate disease therapy targets, yet experimentally determining whether genes interact is technically nontrivial and time-consuming. High-fidelity prediction of different classes of genetic interactions in multiple organisms would substantially alleviate this experimental burden. Under the hypothesis that functionally related genes tend to share common genetic interaction partners, we evaluate a computational approach to predict genetic interactions in Homo sapiens, Drosophila melanogaster, and Saccharomyces cerevisiae. By leveraging knowledge of functional relationships between genes, we cross-validate predictions on known genetic interactions and observe high predictive power of multiple classes of genetic interactions in all three organisms. Additionally, our method suggests high-confidence candidate interaction pairs that can be directly experimentally tested. A web application is provided for users to query genes for predicted novel genetic interaction partners. Finally, by subsampling the known yeast genetic interaction network, we found that novel genetic interactions are predictable even when knowledge of currently known interactions is minimal.
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Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
Directory of Open Access Journals (Sweden)
Linda S Kaltenbach
2007-05-01
Full Text Available Huntington's disease (HD is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%-4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to
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Directory of Open Access Journals (Sweden)
Magali Michaut
Full Text Available Genetic interactions help map biological processes and their functional relationships. A genetic interaction is defined as a deviation from the expected phenotype when combining multiple genetic mutations. In Saccharomyces cerevisiae, most genetic interactions are measured under a single phenotype - growth rate in standard laboratory conditions. Recently genetic interactions have been collected under different phenotypic readouts and experimental conditions. How different are these networks and what can we learn from their differences? We conducted a systematic analysis of quantitative genetic interaction networks in yeast performed under different experimental conditions. We find that networks obtained using different phenotypic readouts, in different conditions and from different laboratories overlap less than expected and provide significant unique information. To exploit this information, we develop a novel method to combine individual genetic interaction data sets and show that the resulting network improves gene function prediction performance, demonstrating that individual networks provide complementary information. Our results support the notion that using diverse phenotypic readouts and experimental conditions will substantially increase the amount of gene function information produced by genetic interaction screens.
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Scaling laws and universality for the strength of genetic interactions in yeast
Velenich, Andrea; Dai, Mingjie; Gore, Jeff
2012-02-01
Genetic interactions provide a window to the organization of the thousands of biochemical reactions in living cells. If two mutations affect unrelated cellular functions, the fitness effects of their combination can be easily predicted from the two separate fitness effects. However, because of interactions, for some pairs of mutations their combined fitness effect deviates from the naive prediction. We study genetic interactions in yeast cells by analyzing a publicly available database containing experimental growth rates of 5 million double mutants. We show that the characteristic strength of genetic interactions has a simple power law dependence on the fitness effects of the two interacting mutations and that the probability distribution of genetic interactions is a universal function. We further argue that the strength of genetic interactions depends only on the fitness effects of the interacting mutations and not on their biological origin in terms of single point mutations, entire gene knockouts or even more complicated physiological perturbations. Finally, we discuss the implications of the power law scaling of genetic interactions on the ruggedness of fitness landscapes and the consequent evolutionary dynamics.
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Genetic and environmental interactions
International Nuclear Information System (INIS)
Strong, L.C.
1977-01-01
Cancer may result from a multistage process occurring over a long period of time. Presumably, initial and progressive stages of carcinogenesis may be modified by both genetic and environmental factors. Theoretically, genetic factors may alter susceptibility to the carcinogenic effects of an environmental agent at the initial exposure due to variation in metabolism of the carcinogen or variation in specific target cell response to the active carcinogen, or during the latent phase due to numerous factors that might increase the probability of tumor expression, including growth-promoting factors or immunodeficiency states. Observed genetic and environmental interactions in carcinogenesis include an association between genetically determined inducibility of aryl hydrocarbon hydroxylase and smoking-related cancers, familial susceptibility to certain environmental carcinogens, an association between hereditary disorders of mutagenesis and carcinogenesis, and enhancement of tissue-specific, dominantly inherited tumor predisposition by radiation. Multiple primary tumors occur frequently in genetically predisposed individuals. Specific markers for susceptibility must be sought in order that high-risk individuals be identified and appropriate measures taken for early cancer detection or prevention. Study of the nature of the genetically determined susceptibility and interactions with environmental agents may be revealing in the understanding of carcinogenesis in general
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A map of directional genetic interactions in a metazoan cell.
Fischer, Bernd; Sandmann, Thomas; Horn, Thomas; Billmann, Maximilian; Chaudhary, Varun; Huber, Wolfgang; Boutros, Michael
2015-03-06
Gene-gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene-gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations.
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Comparison of weighting approaches for genetic risk scores in gene-environment interaction studies.
Hüls, Anke; Krämer, Ursula; Carlsten, Christopher; Schikowski, Tamara; Ickstadt, Katja; Schwender, Holger
2017-12-16
Weighted genetic risk scores (GRS), defined as weighted sums of risk alleles of single nucleotide polymorphisms (SNPs), are statistically powerful for detection gene-environment (GxE) interactions. To assign weights, the gold standard is to use external weights from an independent study. However, appropriate external weights are not always available. In such situations and in the presence of predominant marginal genetic effects, we have shown in a previous study that GRS with internal weights from marginal genetic effects ("GRS-marginal-internal") are a powerful and reliable alternative to single SNP approaches or the use of unweighted GRS. However, this approach might not be appropriate for detecting predominant interactions, i.e. interactions showing an effect stronger than the marginal genetic effect. In this paper, we present a weighting approach for such predominant interactions ("GRS-interaction-training") in which parts of the data are used to estimate the weights from the interaction terms and the remaining data are used to determine the GRS. We conducted a simulation study for the detection of GxE interactions in which we evaluated power, type I error and sign-misspecification. We compared this new weighting approach to the GRS-marginal-internal approach and to GRS with external weights. Our simulation study showed that in the absence of external weights and with predominant interaction effects, the highest power was reached with the GRS-interaction-training approach. If marginal genetic effects were predominant, the GRS-marginal-internal approach was more appropriate. Furthermore, the power to detect interactions reached by the GRS-interaction-training approach was only slightly lower than the power achieved by GRS with external weights. The power of the GRS-interaction-training approach was confirmed in a real data application to the Traffic, Asthma and Genetics (TAG) Study (N = 4465 observations). When appropriate external weights are unavailable, we
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Díaz-Mejía, J Javier; Celaj, Albi; Mellor, Joseph C; Coté, Atina; Balint, Attila; Ho, Brandon; Bansal, Pritpal; Shaeri, Fatemeh; Gebbia, Marinella; Weile, Jochen; Verby, Marta; Karkhanina, Anna; Zhang, YiFan; Wong, Cassandra; Rich, Justin; Prendergast, D'Arcy; Gupta, Gaurav; Öztürk, Sedide; Durocher, Daniel; Brown, Grant W; Roth, Frederick P
2018-05-28
Condition-dependent genetic interactions can reveal functional relationships between genes that are not evident under standard culture conditions. State-of-the-art yeast genetic interaction mapping, which relies on robotic manipulation of arrays of double-mutant strains, does not scale readily to multi-condition studies. Here, we describe barcode fusion genetics to map genetic interactions (BFG-GI), by which double-mutant strains generated via en masse "party" mating can also be monitored en masse for growth to detect genetic interactions. By using site-specific recombination to fuse two DNA barcodes, each representing a specific gene deletion, BFG-GI enables multiplexed quantitative tracking of double mutants via next-generation sequencing. We applied BFG-GI to a matrix of DNA repair genes under nine different conditions, including methyl methanesulfonate (MMS), 4-nitroquinoline 1-oxide (4NQO), bleomycin, zeocin, and three other DNA-damaging environments. BFG-GI recapitulated known genetic interactions and yielded new condition-dependent genetic interactions. We validated and further explored a subnetwork of condition-dependent genetic interactions involving MAG1 , SLX4, and genes encoding the Shu complex, and inferred that loss of the Shu complex leads to an increase in the activation of the checkpoint protein kinase Rad53. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.
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Social and genetic interactions drive fitness variation in a free-living dolphin population.
Frère, Celine H; Krützen, Michael; Mann, Janet; Connor, Richard C; Bejder, Lars; Sherwin, William B
2010-11-16
The evolutionary forces that drive fitness variation in species are of considerable interest. Despite this, the relative importance and interactions of genetic and social factors involved in the evolution of fitness traits in wild mammalian populations are largely unknown. To date, a few studies have demonstrated that fitness might be influenced by either social factors or genes in natural populations, but none have explored how the combined effect of social and genetic parameters might interact to influence fitness. Drawing from a long-term study of wild bottlenose dolphins in the eastern gulf of Shark Bay, Western Australia, we present a unique approach to understanding these interactions. Our study shows that female calving success depends on both genetic inheritance and social bonds. Moreover, we demonstrate that interactions between social and genetic factors also influence female fitness. Therefore, our study represents a major methodological advance, and provides critical insights into the interplay of genetic and social parameters of fitness.
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Inferring genetic interactions from comparative fitness data.
Crona, Kristina; Gavryushkin, Alex; Greene, Devin; Beerenwinkel, Niko
2017-12-20
Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax , the fungus Aspergillus niger , and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.
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Tests for genetic interactions in type 1 diabetes
DEFF Research Database (Denmark)
Morahan, Grant; Mehta, Munish; James, Ian
2011-01-01
Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1...... diabetes has not been explained fully and could arise from many factors, including undetected genetic variation and gene interactions....
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Fu, Changhe; Deng, Su; Jin, Guangxu; Wang, Xinxin; Yu, Zu-Guo
2017-09-21
Molecular interaction data at proteomic and genetic levels provide physical and functional insights into a molecular biosystem and are helpful for the construction of pathway structures complementarily. Despite advances in inferring biological pathways using genetic interaction data, there still exists weakness in developed models, such as, activity pathway networks (APN), when integrating the data from proteomic and genetic levels. It is necessary to develop new methods to infer pathway structure by both of interaction data. We utilized probabilistic graphical model to develop a new method that integrates genetic interaction and protein interaction data and infers exquisitely detailed pathway structure. We modeled the pathway network as Bayesian network and applied this model to infer pathways for the coherent subsets of the global genetic interaction profiles, and the available data set of endoplasmic reticulum genes. The protein interaction data were derived from the BioGRID database. Our method can accurately reconstruct known cellular pathway structures, including SWR complex, ER-Associated Degradation (ERAD) pathway, N-Glycan biosynthesis pathway, Elongator complex, Retromer complex, and Urmylation pathway. By comparing N-Glycan biosynthesis pathway and Urmylation pathway identified from our approach with that from APN, we found that our method is able to overcome its weakness (certain edges are inexplicable). According to underlying protein interaction network, we defined a simple scoring function that only adopts genetic interaction information to avoid the balance difficulty in the APN. Using the effective stochastic simulation algorithm, the performance of our proposed method is significantly high. We developed a new method based on Bayesian network to infer detailed pathway structures from interaction data at proteomic and genetic levels. The results indicate that the developed method performs better in predicting signaling pathways than previously
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A genetic ensemble approach for gene-gene interaction identification
Directory of Open Access Journals (Sweden)
Ho Joshua WK
2010-10-01
Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of
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Genetic and genomic interactions of animals with different ploidy levels.
Bogart, J P; Bi, K
2013-01-01
Polyploid animals have independently evolved from diploids in diverse taxa across the tree of life. We review a few polyploid animal species or biotypes where recently developed molecular and cytogenetic methods have significantly improved our understanding of their genetics, reproduction and evolution. Mitochondrial sequences that target the maternal ancestor of a polyploid show that polyploids may have single (e.g. unisexual salamanders in the genus Ambystoma) or multiple (e.g. parthenogenetic polyploid lizards in the genus Aspidoscelis) origins. Microsatellites are nuclear markers that can be used to analyze genetic recombinations, reproductive modes (e.g. Ambystoma) and recombination events (e.g. polyploid frogs such as Pelophylax esculentus). Hom(e)ologous chromosomes and rare intergenomic exchanges in allopolyploids have been distinguished by applying genome-specific fluorescent probes to chromosome spreads. Polyploids arise, and are maintained, through perturbations of the 'normal' meiotic program that would include pre-meiotic chromosome replication and genomic integrity of homologs. When possible, asexual, unisexual and bisexual polyploid species or biotypes interact with diploid relatives, and genes are passed from diploid to polyploid gene pools, which increase genetic diversity and ultimately evolutionary flexibility in the polyploid. When diploid relatives do not exist, polyploids can interact with another polyploid (e.g. species of African Clawed Frogs in the genus Xenopus). Some polyploid fish (e.g. salmonids) and frogs (Xenopus) represent independent lineages whose ancestors experienced whole genome duplication events. Some tetraploid frogs (P. esculentus) and fish (Squaliusalburnoides) may be in the process of becoming independent species, but diploid and triploid forms of these 'species' continue to genetically interact with the comparatively few tetraploid populations. Genetic and genomic interaction between polyploids and diploids is a complex
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Detecting Genetic Interactions for Quantitative Traits Using m-Spacing Entropy Measure
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Jaeyong Yee
2015-01-01
Full Text Available A number of statistical methods for detecting gene-gene interactions have been developed in genetic association studies with binary traits. However, many phenotype measures are intrinsically quantitative and categorizing continuous traits may not always be straightforward and meaningful. Association of gene-gene interactions with an observed distribution of such phenotypes needs to be investigated directly without categorization. Information gain based on entropy measure has previously been successful in identifying genetic associations with binary traits. We extend the usefulness of this information gain by proposing a nonparametric evaluation method of conditional entropy of a quantitative phenotype associated with a given genotype. Hence, the information gain can be obtained for any phenotype distribution. Because any functional form, such as Gaussian, is not assumed for the entire distribution of a trait or a given genotype, this method is expected to be robust enough to be applied to any phenotypic association data. Here, we show its use to successfully identify the main effect, as well as the genetic interactions, associated with a quantitative trait.
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Environmental and genetic interactions in human cancer
International Nuclear Information System (INIS)
Paterson, M.C.
Humans, depending upon their genetic make-up, differ in their susceptibility to the cancer-causing effects of extrinsic agents. Clinical and laboratory studies on the hereditary disorder, ataxia telangiectasia (AT) show that persons afflicted with this are cancer-prone and unusually sensitive to conventional radiotherapy. Their skin cells, when cultured, are hypersensitive to killing by ionizing radiation, being defective in the enzymatic repair of radiation-induced damange to the genetic material, deoxyribonucleic acid (DNA). This molecular finding implicates DNA damage and its imperfect repair as an early step in the induction of human cancer by radiation and other carcinogens. The parents of AT patients are clincally normal but their cultured cells are often moderately radiosensitive. The increased radiosensitivity of cultured cells offers a means of identifying a presumed cancer-prone subpopulation that should avoid undue exposure to certain carcinogens. The radioresponse of cells from patients with other cancer-associated genetic disorders and persons suspected of being genetically predisposed to radiation-induced cancer has also been measured. Increased cell killing by γ-rays appears in the complex genetic disease, tuberous sclerosis. Cells from cancer-stricken members of a leukemia-prone family are also radiosensitive, as are cells from one patient with radiation-associated breast cancer. These radiobiological data, taken together, strongly suggest that genetic factors can interact with extrinsic agents and thereby play a greater causative role in the development of common cancers in man than previously thought. (L.L.)
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Functional genetics of intraspecific ecological interactions in Arabidopsis thaliana
Wolf, Jason B.; Mutic, Joshua J.; Kover, Paula X.
2011-01-01
Studying the genetic basis of traits involved in ecological interactions is a fundamental part of elucidating the connections between evolutionary and ecological processes. Such knowledge allows one to link genetic models of trait evolution with ecological models describing interactions within and between species. Previous work has shown that connections between genetic and ecological processes in Arabidopsis thaliana may be mediated by the fact that quantitative trait loci (QTL) with ‘direct...
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A global genetic interaction network maps a wiring diagram of cellular function.
Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D; Pelechano, Vicent; Styles, Erin B; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F; Li, Sheena C; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; San Luis, Bryan-Joseph; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M; Moore, Claire L; Rosebrock, Adam P; Caudy, Amy A; Myers, Chad L; Andrews, Brenda; Boone, Charles
2016-09-23
We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. Copyright © 2016, American Association for the Advancement of Science.
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Directory of Open Access Journals (Sweden)
J Matthew Mahoney
2015-01-01
Full Text Available Systemic sclerosis (SSc is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected
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Jasper, James R.; Habicht, Christopher; Moffitt, Steve; Brenner, Rich; Marsh, Jennifer; Lewis, Bert; Creelman Fox, Elisabeth; Grauvogel, Zac; Rogers Olive, Serena D.; Grant, W. Stewart
2013-01-01
The extent to which stray, hatchery-reared salmon affect wild populations is much debated. Although experiments show that artificial breeding and culture influence the genetics of hatchery salmon, little is known about the interaction between hatchery and wild salmon in a natural setting. Here, we estimated historical and contemporary genetic population structures of chum salmon (Oncorhynchus keta) in Prince William Sound (PWS), Alaska, with 135 single nucleotide polymorphism (SNP) markers. H...
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Sardana, Richa; White, Joshua P; Johnson, Arlen W
2013-06-01
Bud23 is responsible for the conserved methylation of G1575 of 18S rRNA, in the P-site of the small subunit of the ribosome. bud23Δ mutants have severely reduced small subunit levels and show a general failure in cleavage at site A2 during rRNA processing. Site A2 is the primary cleavage site for separating the precursors of 18S and 25S rRNAs. Here, we have taken a genetic approach to identify the functional environment of BUD23. We found mutations in UTP2 and UTP14, encoding components of the SSU processome, as spontaneous suppressors of a bud23Δ mutant. The suppressors improved growth and subunit balance and restored cleavage at site A2. In a directed screen of 50 ribosomal trans-acting factors, we identified strong positive and negative genetic interactions with components of the SSU processome and strong negative interactions with components of RNase MRP. RNase MRP is responsible for cleavage at site A3 in pre-rRNA, an alternative cleavage site for separating the precursor rRNAs. The strong negative genetic interaction between RNase MRP mutants and bud23Δ is likely due to the combined defects in cleavage at A2 and A3. Our results suggest that Bud23 plays a role at the time of A2 cleavage, earlier than previously thought. The genetic interaction with the SSU processome suggests that Bud23 could be involved in triggering disassembly of the SSU processome, or of particular subcomplexes of the processome.
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Social evolution and genetic interactions in the short and long term.
Van Cleve, Jeremy
2015-08-01
The evolution of social traits remains one of the most fascinating and feisty topics in evolutionary biology even after half a century of theoretical research. W.D. Hamilton shaped much of the field initially with his 1964 papers that laid out the foundation for understanding the effect of genetic relatedness on the evolution of social behavior. Early theoretical investigations revealed two critical assumptions required for Hamilton's rule to hold in dynamical models: weak selection and additive genetic interactions. However, only recently have analytical approaches from population genetics and evolutionary game theory developed sufficiently so that social evolution can be studied under the joint action of selection, mutation, and genetic drift. We review how these approaches suggest two timescales for evolution under weak mutation: (i) a short-term timescale where evolution occurs between a finite set of alleles, and (ii) a long-term timescale where a continuum of alleles are possible and populations evolve continuously from one monomorphic trait to another. We show how Hamilton's rule emerges from the short-term analysis under additivity and how non-additive genetic interactions can be accounted for more generally. This short-term approach reproduces, synthesizes, and generalizes many previous results including the one-third law from evolutionary game theory and risk dominance from economic game theory. Using the long-term approach, we illustrate how trait evolution can be described with a diffusion equation that is a stochastic analogue of the canonical equation of adaptive dynamics. Peaks in the stationary distribution of the diffusion capture classic notions of convergence stability from evolutionary game theory and generally depend on the additive genetic interactions inherent in Hamilton's rule. Surprisingly, the peaks of the long-term stationary distribution can predict the effects of simple kinds of non-additive interactions. Additionally, the peaks
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Coffee, Genetic Variants, and Parkinson's Disease: Gene–Environment Interactions
Yamada-Fowler, Naomi; Söderkvist, Peter
2015-01-01
Studies of gene–environment interactions may help us to understand the disease mechanisms of common and complex diseases such as Parkinson's disease (PD). Sporadic PD, the common form of PD, is thought to be a multifactorial disorder caused by combinations of multiple genetic factors and environmental or life-style exposures. Since one of the most extensively studied life-style factors in PD is coffee/caffeine intake, here, the studies of genetic polymorphisms with life-style interactions of ...
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Social interactions predict genetic diversification: an experimental manipulation in shorebirds.
Cunningham, Charles; Parra, Jorge E; Coals, Lucy; Beltrán, Marcela; Zefania, Sama; Székely, Tamás
2018-01-01
Mating strategy and social behavior influence gene flow and hence affect levels of genetic differentiation and potentially speciation. Previous genetic analyses of closely related plovers Charadrius spp. found strikingly different population genetic structure in Madagascar: Kittlitz's plovers are spatially homogenous whereas white-fronted plovers have well segregated and geographically distinct populations. Here, we test the hypotheses that Kittlitz's plovers are spatially interconnected and have extensive social interactions that facilitate gene flow, whereas white-fronted plovers are spatially discrete and have limited social interactions. By experimentally removing mates from breeding pairs and observing the movements of mate-searching plovers in both species, we compare the spatial behavior of Kittlitz's and white-fronted plovers within a breeding season. The behavior of experimental birds was largely consistent with expectations: Kittlitz's plovers travelled further, sought new mates in larger areas, and interacted with more individuals than white-fronted plovers, however there was no difference in breeding dispersal. These results suggest that mating strategies, through spatial behavior and social interactions, are predictors of gene flow and thus genetic differentiation and speciation. Our study highlights the importance of using social behavior to understand gene flow. However, further work is needed to investigate the relative importance of social structure, as well as intra- and inter-season dispersal, in influencing the genetic structures of populations.
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Functional genetics of intraspecific ecological interactions in Arabidopsis thaliana.
Wolf, Jason B; Mutic, Joshua J; Kover, Paula X
2011-05-12
Studying the genetic basis of traits involved in ecological interactions is a fundamental part of elucidating the connections between evolutionary and ecological processes. Such knowledge allows one to link genetic models of trait evolution with ecological models describing interactions within and between species. Previous work has shown that connections between genetic and ecological processes in Arabidopsis thaliana may be mediated by the fact that quantitative trait loci (QTL) with 'direct' effects on traits of individuals also have pleiotropic 'indirect' effects on traits expressed in neighbouring plants. Here, we further explore these connections by examining functional relationships between traits affected directly and indirectly by the same QTL. We develop a novel approach using structural equation models (SEMs) to determine whether observed pleiotropic effects result from traits directly affected by the QTL in focal individuals causing the changes in the neighbours' phenotypes. This hypothesis was assessed using SEMs to test whether focal plant phenotypes appear to mediate the connection between the focal plants' genotypes and the phenotypes of their neighbours, or alternatively, whether the connection between the focal plants' genotypes and the neighbours' phenotypes is mediated by unmeasured traits. We implement this analysis using a QTL of major effect that maps to the well-characterized flowering locus, FRIGIDA. The SEMs support the hypothesis that the pleiotropic indirect effects of this locus arise from size and developmental timing-related traits in focal plants affecting the expression of developmental traits in their neighbours. Our findings provide empirical insights into the genetics and nature of intraspecific ecological interactions. Our technique holds promise in directing future work into the genetic basis and functional relationship of traits mediating and responding to ecological interactions.
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Schuck, Nicolas W; Petok, Jessica R; Meeter, Martijn; Schjeide, Brit-Maren M; Schröder, Julia; Bertram, Lars; Gluck, Mark A; Li, Shu-Chen
2018-01-01
Probabilistic category learning involves complex interactions between the hippocampus and striatum that may depend on whether acquisition occurs via feedback or observation. Little is known about how healthy aging affects these processes. We tested whether age-related behavioral differences in probabilistic category learning from feedback or observation depend on a genetic factor known to influence individual differences in hippocampal function, the KIBRA gene (single nucleotide polymorphism rs17070145). Results showed comparable age-related performance impairments in observational as well as feedback-based learning. Moreover, genetic analyses indicated an age-related interactive effect of KIBRA on learning: among older adults, the beneficial T-allele was positively associated with learning from feedback, but negatively with learning from observation. In younger adults, no effects of KIBRA were found. Our results add behavioral genetic evidence to emerging data showing age-related differences in how neural resources relate to memory functions, namely that hippocampal and striatal contributions to probabilistic category learning may vary with age. Our findings highlight the effects genetic factors can have on differential age-related decline of different memory functions. Copyright © 2017 Elsevier Inc. All rights reserved.
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Genetic Allee effects and their interaction with ecological Allee effects.
Wittmann, Meike J; Stuis, Hanna; Metzler, Dirk
2018-01-01
It is now widely accepted that genetic processes such as inbreeding depression and loss of genetic variation can increase the extinction risk of small populations. However, it is generally unclear whether extinction risk from genetic causes gradually increases with decreasing population size or whether there is a sharp transition around a specific threshold population size. In the ecological literature, such threshold phenomena are called 'strong Allee effects' and they can arise for example from mate limitation in small populations. In this study, we aim to (i) develop a meaningful notion of a 'strong genetic Allee effect', (ii) explore whether and under what conditions such an effect can arise from inbreeding depression due to recessive deleterious mutations, and (iii) quantify the interaction of potential genetic Allee effects with the well-known mate-finding Allee effect. We define a strong genetic Allee effect as a genetic process that causes a population's survival probability to be a sigmoid function of its initial size. The inflection point of this function defines the critical population size. To characterize survival-probability curves, we develop and analyse simple stochastic models for the ecology and genetics of small populations. Our results indicate that inbreeding depression can indeed cause a strong genetic Allee effect, but only if individuals carry sufficiently many deleterious mutations (lethal equivalents). Populations suffering from a genetic Allee effect often first grow, then decline as inbreeding depression sets in and then potentially recover as deleterious mutations are purged. Critical population sizes of ecological and genetic Allee effects appear to be often additive, but even superadditive interactions are possible. Many published estimates for the number of lethal equivalents in birds and mammals fall in the parameter range where strong genetic Allee effects are expected. Unfortunately, extinction risk due to genetic Allee effects
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Directory of Open Access Journals (Sweden)
Brett A McKinney
2009-03-01
Full Text Available Evidence from human genetic studies of several disorders suggests that interactions between alleles at multiple genes play an important role in influencing phenotypic expression. Analytical methods for identifying Mendelian disease genes are not appropriate when applied to common multigenic diseases, because such methods investigate association with the phenotype only one genetic locus at a time. New strategies are needed that can capture the spectrum of genetic effects, from Mendelian to multifactorial epistasis. Random Forests (RF and Relief-F are two powerful machine-learning methods that have been studied as filters for genetic case-control data due to their ability to account for the context of alleles at multiple genes when scoring the relevance of individual genetic variants to the phenotype. However, when variants interact strongly, the independence assumption of RF in the tree node-splitting criterion leads to diminished importance scores for relevant variants. Relief-F, on the other hand, was designed to detect strong interactions but is sensitive to large backgrounds of variants that are irrelevant to classification of the phenotype, which is an acute problem in genome-wide association studies. To overcome the weaknesses of these data mining approaches, we develop Evaporative Cooling (EC feature selection, a flexible machine learning method that can integrate multiple importance scores while removing irrelevant genetic variants. To characterize detailed interactions, we construct a genetic-association interaction network (GAIN, whose edges quantify the synergy between variants with respect to the phenotype. We use simulation analysis to show that EC is able to identify a wide range of interaction effects in genetic association data. We apply the EC filter to a smallpox vaccine cohort study of single nucleotide polymorphisms (SNPs and infer a GAIN for a collection of SNPs associated with adverse events. Our results suggest an important
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Genetics of simple and complex host-parasite interactions
International Nuclear Information System (INIS)
Sidhu, G.S.; Webster, J.M.
1977-01-01
In nature a host plant can be viewed as a miniature replica of an ecological system where true and incidental parasites share the same habitat. Consequently, they influence each other's presence directly by interspecific interaction, and indirectly by inducing changes in the host's physiology and so form disease complexes. Since all physiological phenomena have their counterpart in the respective genetic systems of interacting organisms, valuable genetic information can be derived from the analysis of complex parasitic systems. Disease complexes may be classified according to the nature of interaction between various parasites on the same host. One parasite may nullify the host's resistance to another (e.g. Tomato - Meloidogyne incognita + Fusarium oxysporum lycopersici system). Conversely, a parasite may invoke resistance in the host against another parasite (e.g. Tomato - Fusarium oxysporum lycopersici + Verticillium albo atrum system). From the study of simple parasitic systems we know that resistance versus susceptibility against a single parasite is normally monogenically controlled. However, when more than one parasite interacts to invoke or nullify each other's responses on the same host plant, the genetic results suggest epistatic ratios. Nevertheless, epistatic ratios have been obtained also from simple parasitic systems owing to gene interaction. The epistatic ratios obtained from complex and simple parasitic systems are contrasted and compared. It is suggested that epistatic ratios obtained from simple parasitic systems may, in fact, be artifacts resulting from complex parasitic associations that often occur in nature. Polygenic inheritance and the longevity of a cultivar is also discussed briefly in relation to complex parasitic associations. Induced mutations can play a significant role in the study of complex parasitic associations, and thus can be very useful in controlling plant diseases
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Fashion sketch design by interactive genetic algorithms
Mok, P. Y.; Wang, X. X.; Xu, J.; Kwok, Y. L.
2012-11-01
Computer aided design is vitally important for the modern industry, particularly for the creative industry. Fashion industry faced intensive challenges to shorten the product development process. In this paper, a methodology is proposed for sketch design based on interactive genetic algorithms. The sketch design system consists of a sketch design model, a database and a multi-stage sketch design engine. First, a sketch design model is developed based on the knowledge of fashion design to describe fashion product characteristics by using parameters. Second, a database is built based on the proposed sketch design model to define general style elements. Third, a multi-stage sketch design engine is used to construct the design. Moreover, an interactive genetic algorithm (IGA) is used to accelerate the sketch design process. The experimental results have demonstrated that the proposed method is effective in helping laypersons achieve satisfied fashion design sketches.
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Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models.
Moran, Paula; Stokes, Jennifer; Marr, Julia; Bock, Gavin; Desbonnet, Lieve; Waddington, John; O'Tuathaigh, Colm
2016-01-01
The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.
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Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models
Marr, Julia; Bock, Gavin; Desbonnet, Lieve; Waddington, John
2016-01-01
The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia. PMID:27725886
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Detecting high-order interactions of single nucleotide polymorphisms using genetic programming.
Nunkesser, Robin; Bernholt, Thorsten; Schwender, Holger; Ickstadt, Katja; Wegener, Ingo
2007-12-15
Not individual single nucleotide polymorphisms (SNPs), but high-order interactions of SNPs are assumed to be responsible for complex diseases such as cancer. Therefore, one of the major goals of genetic association studies concerned with such genotype data is the identification of these high-order interactions. This search is additionally impeded by the fact that these interactions often are only explanatory for a relatively small subgroup of patients. Most of the feature selection methods proposed in the literature, unfortunately, fail at this task, since they can either only identify individual variables or interactions of a low order, or try to find rules that are explanatory for a high percentage of the observations. In this article, we present a procedure based on genetic programming and multi-valued logic that enables the identification of high-order interactions of categorical variables such as SNPs. This method called GPAS cannot only be used for feature selection, but can also be employed for discrimination. In an application to the genotype data from the GENICA study, an association study concerned with sporadic breast cancer, GPAS is able to identify high-order interactions of SNPs leading to a considerably increased breast cancer risk for different subsets of patients that are not found by other feature selection methods. As an application to a subset of the HapMap data shows, GPAS is not restricted to association studies comprising several 10 SNPs, but can also be employed to analyze whole-genome data. Software can be downloaded from http://ls2-www.cs.uni-dortmund.de/~nunkesser/#Software
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Added value measures in education show genetic as well as environmental influence.
Haworth, Claire M A; Asbury, Kathryn; Dale, Philip S; Plomin, Robert
2011-02-02
Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%). The pervasiveness of genetic influence in how and how much children learn is compatible with an active view of learning in which children create their own educational experiences in part on the basis of their genetic propensities.
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Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models
Directory of Open Access Journals (Sweden)
Paula Moran
2016-01-01
Full Text Available The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.
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DEFF Research Database (Denmark)
Tan, Qihua; De Benedictis, G; Yashin, Annatoli
2001-01-01
New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic and demographicinf......New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic...
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Dolphin shows and interaction programs: benefits for conservation education?
Miller, L J; Zeigler-Hill, V; Mellen, J; Koeppel, J; Greer, T; Kuczaj, S
2013-01-01
Dolphin shows and dolphin interaction programs are two types of education programs within zoological institutions used to educate visitors about dolphins and the marine environment. The current study examined the short- and long-term effects of these programs on visitors' conservation-related knowledge, attitude, and behavior. Participants of both dolphin shows and interaction programs demonstrated a significant short-term increase in knowledge, attitudes, and behavioral intentions. Three months following the experience, participants of both dolphin shows and interaction programs retained the knowledge learned during their experience and reported engaging in more conservation-related behaviors. Additionally, the number of dolphin shows attended in the past was a significant predictor of recent conservation-related behavior suggesting that repetition of these types of experiences may be important in inspiring people to conservation action. These results suggest that both dolphin shows and dolphin interaction programs can be an important part of a conservation education program for visitors of zoological facilities. © 2012 Wiley Periodicals, Inc.
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Hanseniaspora uvarum from winemaking environments show spatial and temporal genetic clustering
Directory of Open Access Journals (Sweden)
Warren eAlbertin
2016-01-01
Full Text Available Hanseniaspora uvarum is one of the most abundant yeast species found on grapes and in grape must, at least before the onset of alcoholic fermentation which is usually performed by Saccharomyces species. The aim of this study was to characterise the genetic and phenotypic variability within the H. uvarum species. One hundred and fifteen strains isolated from winemaking environments in different geographical origins were analysed using 11 microsatellite markers and a subset of 47 strains were analysed by AFLP. H. uvarum isolates clustered mainly on the basis of their geographical localisation as revealed by microsatellites. In addition, a strong clustering based on year of isolation was evidenced, indicating that the genetic diversity of Hanseniaspora uvarum isolates was related to both spatial and temporal variations. Conversely, clustering analysis based on AFLP data provided a different picture with groups showing no particular characteristics, but provided higher strain discrimination. This result indicated that AFLP approaches are inadequate to establish the genetic relationship between individuals, but allowed good strain discrimination. At the phenotypic level, several extracellular enzymatic activities of enological relevance (pectinase, chitinase, protease, β-glucosidase were measured but showed low diversity. The impact of environmental factors of enological interest (temperature, anaerobia and copper addition on growth was also assessed and showed poor variation. Altogether, this work provided both new analytical tool (microsatellites and new insights into the genetic and phenotypic diversity of H. uvarum, a yeast species that has previously been identified as a potential candidate for co-inoculation in grape must, but whose intraspecific variability had never been fully assessed.
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Genetic interaction network of the Saccharomyces cerevisiae type 1 phosphatase Glc7
Directory of Open Access Journals (Sweden)
Neszt Michael
2008-07-01
Full Text Available Abstract Background Protein kinases and phosphatases regulate protein phosphorylation, a critical means of modulating protein function, stability and localization. The identification of functional networks for protein phosphatases has been slow due to their redundant nature and the lack of large-scale analyses. We hypothesized that a genome-scale analysis of genetic interactions using the Synthetic Genetic Array could reveal protein phosphatase functional networks. We apply this approach to the conserved type 1 protein phosphatase Glc7, which regulates numerous cellular processes in budding yeast. Results We created a novel glc7 catalytic mutant (glc7-E101Q. Phenotypic analysis indicates that this novel allele exhibits slow growth and defects in glucose metabolism but normal cell cycle progression and chromosome segregation. This suggests that glc7-E101Q is a hypomorphic glc7 mutant. Synthetic Genetic Array analysis of glc7-E101Q revealed a broad network of 245 synthetic sick/lethal interactions reflecting that many processes are required when Glc7 function is compromised such as histone modification, chromosome segregation and cytokinesis, nutrient sensing and DNA damage. In addition, mitochondrial activity and inheritance and lipid metabolism were identified as new processes involved in buffering Glc7 function. An interaction network among 95 genes genetically interacting with GLC7 was constructed by integration of genetic and physical interaction data. The obtained network has a modular architecture, and the interconnection among the modules reflects the cooperation of the processes buffering Glc7 function. Conclusion We found 245 genes required for the normal growth of the glc7-E101Q mutant. Functional grouping of these genes and analysis of their physical and genetic interaction patterns bring new information on Glc7-regulated processes.
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Busby, Posy E; Lamit, Louis J; Keith, Arthur R; Newcombe, George; Gehring, Catherine A; Whitham, Thomas G; Dirzo, Rodolfo
2015-07-01
Plant resistance to pathogens or insect herbivores is common, but its potential for indirectly influencing plant-associated communities is poorly known. Here, we test whether pathogens' indirect effects on arthropod communities and herbivory depend on plant resistance to pathogens and/or herbivores, and address the overarching interacting foundation species hypothesis that genetics-based interactions among a few highly interactive species can structure a much larger community. In a manipulative field experiment using replicated genotypes of two Populus species and their interspecific hybrids, we found that genetic variation in plant resistance to both pathogens and insect herbivores modulated the strength of pathogens' indirect effects on arthropod communities and insect herbivory. First, due in part to the pathogens' differential impacts on leaf biomass among the two Populus species and the hybrids, the pathogen most strongly impacted arthropod community composition, richness, and abundance on the pathogen-susceptible tree species. Second, we found similar patterns comparing pathogen-susceptible and pathogen-resistant genotypes within species. Third, within a plant species, pathogens caused a fivefold greater reduction in herbivory on insect-herbivore-susceptible plant genotypes than on herbivore-resistant genotypes, demonstrating that the pathogen-herbivore interaction is genotype dependent. We conclude that interactions among plants, pathogens, and herbivores can structure multitrophic communities, supporting the interacting foundation species hypothesis. Because these interactions are genetically based, evolutionary changes in genetic resistance could result in ecological changes in associated communities, which may in turn feed back to affect plant fitness.
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Genome complexity, robustness and genetic interactions in digital organisms
Lenski, Richard E.; Ofria, Charles; Collier, Travis C.; Adami, Christoph
1999-08-01
Digital organisms are computer programs that self-replicate, mutate and adapt by natural selection. They offer an opportunity to test generalizations about living systems that may extend beyond the organic life that biologists usually study. Here we have generated two classes of digital organism: simple programs selected solely for rapid replication, and complex programs selected to perform mathematical operations that accelerate replication through a set of defined `metabolic' rewards. To examine the differences in their genetic architecture, we introduced millions of single and multiple mutations into each organism and measured the effects on the organism's fitness. The complex organisms are more robust than the simple ones with respect to the average effects of single mutations. Interactions among mutations are common and usually yield higher fitness than predicted from the component mutations assuming multiplicative effects; such interactions are especially important in the complex organisms. Frequent interactions among mutations have also been seen in bacteria, fungi and fruitflies. Our findings support the view that interactions are a general feature of genetic systems.
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CRISPR genetic screens to discover host-virus interactions.
McDougall, William M; Perreira, Jill M; Reynolds, Erin C; Brass, Abraham L
2018-04-01
Viruses impose an immense burden on human health. With the goal of treating and preventing viral infections, researchers have carried out genetic screens to improve our understanding of viral dependencies and identify potential anti-viral strategies. The emergence of CRISPR genetic screening tools has facilitated this effort by enabling host-virus screens to be undertaken in a more versatile and fidelitous manner than previously possible. Here we review the growing number of CRISPR screens which continue to increase our understanding of host-virus interactions. Copyright © 2018 Elsevier B.V. All rights reserved.
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Esposito, Gianluca; Truzzi, Anna; Setoh, Peipei; Putnick, Diane L.; Shinohara, Kazuyuki; Bornstein, Marc H.
2018-01-01
Parental bonding and oxytocin receptor (OXTR) gene genotype each influences social abilities in adulthood. Here, we hypothesized an interaction between the two – environmental experience (parental bonding history) and genetic factors (OXTR gene genotype) – in shaping adults’ social sensitivity (physiological response to distress). We assessed heart rate and peripheral temperature (tip of the nose) in 42 male adults during presentation of distress vocalizations (distress cries belonging to female human infants and adults as well as bonobo). The two physiological responses index, respectively, state of arousal and readiness to action. Participants’ parental bonding in childhood was assessed through the self-report Parental Bonding Instrument. To assess participants’ genetic predispositions, buccal mucosa cell samples were collected, and region rs2254298 of the oxytocin receptor gene was analyzed: previous OXTR gene findings point to associations between the G allele and better sociality (protective factor) and the A allele and poorer sociality (risk factor). We found a gene * environment interaction for susceptibility to social distress: Participants with a genetic risk factor (A carriers) with a history of high paternal overprotection showed higher heart rate increase than those without this risk factor (G/G genotype) to social distress. Also, a significant effect of the interaction between paternal care and genotype on nose temperature changes was found. This susceptibility appears to represent an indirect pathway through which genes and experiences interact to shape mature social sensitivity in males. PMID:27343933
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Kobayashi, Tetsuya
2016-01-01
Many plant-parasite interactions that include major plant resistance genes have subsequently been shown to exhibit features of gene-for-gene interactions between plant Resistance genes and parasite Avirulence genes. The brown planthopper (BPH) Nilaparvata lugens is an important pest of rice (Oryza sativa). Historically, major Resistance genes have played an important role in agriculture. As is common in gene-for-gene interactions, evolution of BPH virulence compromises the effectiveness of singly-deployed resistance genes. It is therefore surprising that laboratory studies of BPH have supported the conclusion that virulence is conferred by changes in many genes rather than a change in a single gene, as is proposed by the gene-for-gene model. Here we review the behaviour, physiology and genetics of the BPH in the context of host plant resistance. A problem for genetic understanding has been the use of various insect populations that differ in frequencies of virulent genotypes. We show that the previously proposed polygenic inheritance of BPH virulence can be explained by the heterogeneity of parental populations. Genetic mapping of Avirulence genes indicates that virulence is a monogenic trait. These evolving concepts, which have brought the gene-for-gene model back into the picture, are accelerating our understanding of rice-BPH interactions at the molecular level. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Braberg, Hannes; Moehle, Erica A.; Shales, Michael; Guthrie, Christine; Krogan, Nevan J.
2014-01-01
We have achieved a residue-level resolution of genetic interaction mapping – a technique that measures how the function of one gene is affected by the alteration of a second gene – by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post-translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to date, systematic high-throughput genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure-function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine. PMID:24842270
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Pooled-matrix protein interaction screens using Barcode Fusion Genetics.
Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C; Weile, Jochen; Jacob, Yves; Verby, Marta; Ozturk, Sedide B; Li, Siyang; Cote, Atina G; Mosca, Roberto; Knapp, Jennifer J; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Sahni, Nidhi; Yi, Song; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F; Wong, Cassandra; Musa, Louai; Snider, Jamie; Liu, Yi-Chun; Yu, Haiyuan; Braun, Pascal; Stagljar, Igor; Hao, Tong; Calderwood, Michael A; Pelletier, Laurence; Aloy, Patrick; Hill, David E; Vidal, Marc; Roth, Frederick P
2016-04-22
High-throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome-scale interaction mapping. Here, we report Barcode Fusion Genetics-Yeast Two-Hybrid (BFG-Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG-Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein-pair barcodes that can be quantified via next-generation sequencing. We applied BFG-Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG-Y2H increases the efficiency of protein matrix screening, with quality that is on par with state-of-the-art Y2H methods. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.
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Sameith, Katrin; Amini, Saman; Groot Koerkamp, Marian J A; van Leenen, Dik; Brok, Mariel; Brabers, Nathalie; Lijnzaad, Philip; van Hooff, Sander R; Benschop, Joris J; Lenstra, Tineke L; Apweiler, Eva; van Wageningen, Sake; Snel, Berend; Holstege, Frank C P; Kemmeren, Patrick
2015-12-23
Genetic interactions, or non-additive effects between genes, play a crucial role in many cellular processes and disease. Which mechanisms underlie these genetic interactions has hardly been characterized. Understanding the molecular basis of genetic interactions is crucial in deciphering pathway organization and understanding the relationship between genotype, phenotype and disease. To investigate the nature of genetic interactions between gene-specific transcription factors (GSTFs) in Saccharomyces cerevisiae, we systematically analyzed 72 GSTF pairs by gene expression profiling double and single deletion mutants. These pairs were selected through previously published growth-based genetic interactions as well as through similarity in DNA binding properties. The result is a high-resolution atlas of gene expression-based genetic interactions that provides systems-level insight into GSTF epistasis. The atlas confirms known genetic interactions and exposes new ones. Importantly, the data can be used to investigate mechanisms that underlie individual genetic interactions. Two molecular mechanisms are proposed, "buffering by induced dependency" and "alleviation by derepression". These mechanisms indicate how negative genetic interactions can occur between seemingly unrelated parallel pathways and how positive genetic interactions can indirectly expose parallel rather than same-pathway relationships. The focus on GSTFs is important for understanding the transcription regulatory network of yeast as it uncovers details behind many redundancy relationships, some of which are completely new. In addition, the study provides general insight into the complex nature of epistasis and proposes mechanistic models for genetic interactions, the majority of which do not fall into easily recognizable within- or between-pathway relationships.
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Roux, F; Bergelson, J
2016-01-01
In the context of global change, predicting the responses of plant communities in an ever-changing biotic environment calls for a multipronged approach at the interface of evolutionary genetics and community ecology. However, our understanding of the genetic basis of natural variation involved in mediating biotic interactions, and associated adaptive dynamics of focal plants in their natural communities, is still in its infancy. Here, we review the genetic and molecular bases of natural variation in the response to biotic interactions (viruses, bacteria, fungi, oomycetes, herbivores, and plants) in the model plant Arabidopsis thaliana as well as the adaptive value of these bases. Among the 60 identified genes are a number that encode nucleotide-binding site leucine-rich repeat (NBS-LRR)-type proteins, consistent with early examples of plant defense genes. However, recent studies have revealed an extensive diversity in the molecular mechanisms of defense. Many types of genetic variants associate with phenotypic variation in biotic interactions, even among the genes of large effect that tend to be identified. In general, we found that (i) balancing selection rather than directional selection explains the observed patterns of genetic diversity within A. thaliana and (ii) the cost/benefit tradeoffs of adaptive alleles can be strongly dependent on both genomic and environmental contexts. Finally, because A. thaliana rarely interacts with only one biotic partner in nature, we highlight the benefit of exploring diffuse biotic interactions rather than tightly associated host-enemy pairs. This challenge would help to improve our understanding of coevolutionary quantitative genetics within the context of realistic community complexity. © 2016 Elsevier Inc. All rights reserved.
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Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill
2011-01-01
Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…
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Variation in the peacock's train shows a genetic component.
Petrie, Marion; Cotgreave, Peter; Pike, Thomas W
2009-01-01
Female peafowl (Pavo cristatus) show a strong mating preference for males with elaborate trains. This, however, poses something of a paradox because intense directional selection should erode genetic variation in the males' trains, so that females will no longer benefit by discriminating among males on the basis of these traits. This situation is known as the 'lek paradox', and leads to the theoretical expectation of low heritability in the peacock's train. We used two independent breeding experiments, involving a total of 42 sires and 86 of their male offspring, to estimate the narrow sense heritabilities of male ornaments and other morphometric traits. Contrary to expectation, we found significant levels of heritability in a trait known to be used by females during mate choice (train length), while no significant heritabilities were evident for other, non-fitness related morphological traits (tarsus length, body weight or spur length). This study adds to the building body of evidence that high levels of additive genetic variance can exist in secondary sexual traits under directional selection, but further emphasizes the main problem of what maintains this variation.
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Drury, Crawford; Schopmeyer, Stephanie; Goergen, Elizabeth; Bartels, Erich; Nedimyer, Ken; Johnson, Meaghan; Maxwell, Kerry; Galvan, Victor; Manfrino, Carrie; Lirman, Diego
2017-08-01
Threatened Caribbean coral communities can benefit from high-resolution genetic data used to inform management and conservation action. We use Genotyping by Sequencing (GBS) to investigate genetic patterns in the threatened coral, Acropora cervicornis , across the Florida Reef Tract (FRT) and the western Caribbean. Results show extensive population structure at regional scales and resolve previously unknown structure within the FRT. Different regions also exhibit up to threefold differences in genetic diversity (He), suggesting targeted management based on the goals and resources of each population is needed. Patterns of genetic diversity have a strong spatial component, and our results show Broward and the Lower Keys are among the most diverse populations in Florida. The genetic diversity of Caribbean staghorn coral is concentrated within populations and within individual reefs (AMOVA), highlighting the complex mosaic of population structure. This variance structure is similar over regional and local scales, which suggests that in situ nurseries are adequately capturing natural patterns of diversity, representing a resource that can replicate the average diversity of wild assemblages, serving to increase intraspecific diversity and potentially leading to improved biodiversity and ecosystem function. Results presented here can be translated into specific goals for the recovery of A. cervicornis , including active focus on low diversity areas, protection of high diversity and connectivity, and practical thresholds for responsible restoration.
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Genetic connections between dressage and show jumping in Dutch Warmblood horses
DEFF Research Database (Denmark)
Rovere, G; Madsen, Per; Ducro, B J
2012-01-01
During the last decades a process of specialization has occurred into show jumping (JH) and dressage (DH) in the Dutch Warmblood studbook (KWPN). As a consequence, the genetic base might become stratified. The objective of this study was to estimate the connectedness between JH and DH...
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Genetic connections between dressage and show jumping in Dutch Warmblood horses
DEFF Research Database (Denmark)
Rovere, G; Madsen, Per; Ducro, B J
2012-01-01
During the last decades a process of specialization has occurred into show jumping (JH) and dressage (DH) in the Dutch Warmblood studbook (KWPN). As a consequence, the genetic base might become stratified. The objective of this study was to estimate the connectedness between JH and DH subpopulati...
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Institute of Scientific and Technical Information of China (English)
无
2007-01-01
Soybean seed products contain isoflavones (genistein, daidzein, and glycitein) that display biological effects when ingested by humans and animals. These effects are species, dose and age dependent. Therefore, the content and quality of isoflavones in soybeans is a key factor to the biological effect. Our objective was to identify the genetic effects that underlie the isoflavone content in soybean seeds. A genetic model for quantitative traits of seeds in diploid plants was applied to estimate the genetic main effects and genotype × environment (GE) interaction effects for the isoflavone content (IC) of soybean seeds by using two years experimental data with an incomplete diallel mating design of six parents. Results showed that the IC of soybean seeds was simultaneously controlled by the genetic effects of maternal,embryo, and cytoplasm, of which maternal genetic effects were most important, followed by embryo and cytoplasmic genetic effects. The main effects of different genetic systems on IC trait were more important than environment interaction effects. The strong dominance effects on isoflavone from residual was made easily by environment conditions. Therefore,the improvement of the IC of soybean seeds would be more efficient when selection is based on maternal plants than that on the single seed. Maternal heritability (65.73%) was most important for IC, followed by embryo heritability (25.87%) and cytoplasmic heritability (8.39%). Based on predicated genetic effects, Yudou 29 and Zheng 90007 were better than other parents for increasing IC in the progeny and improving the quality of soybean. The significant effects of maternal and embryo dominance effects in variance show that the embryo heterosis and maternal heterosis are existent and uninfluenced by environment interaction effects.
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Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny
2014-01-01
Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812
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Lekman, Magnus; Hössjer, Ola; Andrews, Peter; Källberg, Henrik; Uvehag, Daniel; Charney, Dennis; Manji, Husseini; Rush, John A; McMahon, Francis J; Moore, Jason H; Kockum, Ingrid
2014-01-01
Genetic contributions to major depressive disorder (MDD) are thought to result from multiple genes interacting with each other. Different procedures have been proposed to detect such interactions. Which approach is best for explaining the risk of developing disease is unclear. This study sought to elucidate the genetic interaction landscape in candidate genes for MDD by conducting a SNP-SNP interaction analysis using an exhaustive search through 3,704 SNP-markers in 1,732 cases and 1,783 controls provided from the GAIN MDD study. We used three different methods to detect interactions, two logistic regressions models (multiplicative and additive) and one data mining and machine learning (MDR) approach. Although none of the interaction survived correction for multiple comparisons, the results provide important information for future genetic interaction studies in complex disorders. Among the 0.5% most significant observations, none had been reported previously for risk to MDD. Within this group of interactions, less than 0.03% would have been detectable based on main effect approach or an a priori algorithm. We evaluated correlations among the three different models and conclude that all three algorithms detected the same interactions to a low degree. Although the top interactions had a surprisingly large effect size for MDD (e.g. additive dominant model Puncorrected = 9.10E-9 with attributable proportion (AP) value = 0.58 and multiplicative recessive model with Puncorrected = 6.95E-5 with odds ratio (OR estimated from β3) value = 4.99) the area under the curve (AUC) estimates were low (< 0.54). Moreover, the population attributable fraction (PAF) estimates were also low (< 0.15). We conclude that the top interactions on their own did not explain much of the genetic variance of MDD. The different statistical interaction methods we used in the present study did not identify the same pairs of interacting markers. Genetic interaction studies may uncover previously
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Directory of Open Access Journals (Sweden)
Dowling Damian K
2011-07-01
Full Text Available Abstract Background Biologists studying adaptation under sexual selection have spent considerable effort assessing the relative importance of two groups of models, which hinge on the idea that females gain indirect benefits via mate discrimination. These are the good genes and genetic compatibility models. Quantitative genetic studies have advanced our understanding of these models by enabling assessment of whether the genetic architectures underlying focal phenotypes are congruent with either model. In this context, good genes models require underlying additive genetic variance, while compatibility models require non-additive variance. Currently, we know very little about how the expression of genotypes comprised of distinct parental haplotypes, or how levels and types of genetic variance underlying key phenotypes, change across environments. Such knowledge is important, however, because genotype-environment interactions can have major implications on the potential for evolutionary responses to selection. Results We used a full diallel breeding design to screen for complex genotype-environment interactions, and genetic architectures underlying key morphological traits, across two thermal environments (the lab standard 27°C, and the cooler 23°C in the Australian field cricket, Teleogryllus oceanicus. In males, complex three-way interactions between sire and dam parental haplotypes and the rearing environment accounted for up to 23 per cent of the scaled phenotypic variance in the traits we measured (body mass, pronotum width and testes mass, and each trait harboured significant additive genetic variance in the standard temperature (27°C only. In females, these three-way interactions were less important, with interactions between the paternal haplotype and rearing environment accounting for about ten per cent of the phenotypic variance (in body mass, pronotum width and ovary mass. Of the female traits measured, only ovary mass for crickets
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Family Conflict Interacts with Genetic Liability in Predicting Childhood and Adolescent Depression
Rice, Frances; Harold, Gordon T.; Shelton, Katherine H.; Thapar, Anita
2006-01-01
Objective: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms…
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Genetic connections between dressage and show-jumping horses in Dutch Warmblood horses
DEFF Research Database (Denmark)
Rovere, Gabriel; Madsen, Per; Norberg, Elise
2014-01-01
During the last decades, the breeding practice within the Dutch Warmblood studbook (KWPN) has resulted in an increasing specialisation of horses into show-jumping (JH) and dressage (DH). The objective of this study was to describe the effect of the specialisation on the connectedness between...... and within subpopulations were analysed in three periods of time to describe changes in genetic connectedness between subpopulations. A decline in GS (0.97–0.45), GC0.5 (0.69–0.13) and r (0.018–0.014) in the recent years was observed. Both subpopulations have a common genetic pool; however...
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Roetker, Nicholas S; Page, C David; Yonker, James A; Chang, Vicky; Roan, Carol L; Herd, Pamela; Hauser, Taissa S; Hauser, Robert M; Atwood, Craig S
2013-10-01
We examined depression within a multidimensional framework consisting of genetic, environmental, and sociobehavioral factors and, using machine learning algorithms, explored interactions among these factors that might better explain the etiology of depressive symptoms. We measured current depressive symptoms using the Center for Epidemiologic Studies Depression Scale (n = 6378 participants in the Wisconsin Longitudinal Study). Genetic factors were 78 single nucleotide polymorphisms (SNPs); environmental factors-13 stressful life events (SLEs), plus a composite proportion of SLEs index; and sociobehavioral factors-18 personality, intelligence, and other health or behavioral measures. We performed traditional SNP associations via logistic regression likelihood ratio testing and explored interactions with support vector machines and Bayesian networks. After correction for multiple testing, we found no significant single genotypic associations with depressive symptoms. Machine learning algorithms showed no evidence of interactions. Naïve Bayes produced the best models in both subsets and included only environmental and sociobehavioral factors. We found no single or interactive associations with genetic factors and depressive symptoms. Various environmental and sociobehavioral factors were more predictive of depressive symptoms, yet their impacts were independent of one another. A genome-wide analysis of genetic alterations using machine learning methodologies will provide a framework for identifying genetic-environmental-sociobehavioral interactions in depressive symptoms.
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A Simple Interactive Introduction to Teaching Genetic Engineering
Child, Paula
2013-01-01
In the UK, at key stage 4, students aged 14-15 studying GCSE Core Science or Unit 1 of the GCSE Biology course are required to be able to describe the process of genetic engineering to produce bacteria that can produce insulin. The simple interactive introduction described in this article allows students to consider the problem, devise a model and…
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Genetic Interactions of STAT3 and Anticancer Drug Development
International Nuclear Information System (INIS)
Fang, Bingliang
2014-01-01
Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors
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Directory of Open Access Journals (Sweden)
Bart A Ellenbroek
2016-09-01
Full Text Available There is ample evidence that prenatal exposure to valproate (or valproic acid, VPA enhances the risk of developing Autism Spectrum Disorders (ASD. In line with this, a single injection of VPA induces a multitude of ASD-like symptoms in animals such as rats and mice. However, there is equally strong evidence that genetic factors contribute significantly to the risk of ASD and indeed, like most other psychiatric disorders, ASD is now generally thought to results from an interaction between genetic and environmental factors. Given that VPA significantly impacts on the serotonergic system, and serotonin has strong biochemical and genetic links to ASD, we aimed to investigate the interaction between genetic reduction in the serotonin transporter and prenatal valproate administration. More specifically, we exposed both wildtype (SERT+/+ rats and rats heterozygous for the serotonin transporter deletion (SERT+/- to a single injection of 400 mg/kg VPA at gestational day (GD 12. The offspring, in adulthood, was assessed in four different tests: Elevated Plus Maze and Novelty Suppressed Feeding as measures for anxiety and prepulse inhibition (PPI and latent inhibition as measures for cognition and information processing. The results show that prenatal VPA significantly increased anxiety in both paradigm, reduced PPI and reduced conditioning in the latent inhibition paradigm. However, we failed to find a significant gene – environment interaction. We propose that this may be related to the timing of the VPA injection and suggest that whereas GD12 might be optimal for affecting normal rat, rats with a genetically compromised serotonergic system may be more sensitive to VPA at earlier time points during gestation. Overall our data are the first to investigate gene * environmental interactions in a genetic rat model for ASD suggest that timing may be of crucial importance to the long-term outcome.
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Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina
2015-03-01
The authors sought to clarify the relationship between IQ and subsequent risk for schizophrenia. IQ was assessed at ages 18-20 in 1,204,983 Swedish males born between 1951 and 1975. Schizophrenia was assessed by hospital diagnosis through 2010. Cox proportional hazards models were used to investigate future risk for schizophrenia in individuals as a function of their IQ score, and then stratified models using pairs of relatives were used to adjust for familial cluster. Finally, regression models were used to examine the interaction between IQ and genetic liability on risk for schizophrenia. IQ had a monotonic relationship with schizophrenia risk across the IQ range, with a mean increase in risk of 3.8% per 1-point decrease in IQ; this association was stronger in the lower than the higher IQ range. Co-relative control analyses showed a similar association between IQ and schizophrenia in the general population and in cousin, half-sibling, and full-sibling pairs. A robust interaction was seen between genetic liability to schizophrenia and IQ in predicting schizophrenia risk. Genetic susceptibility for schizophrenia had a much stronger impact on risk of illness for those with low than high intelligence. The IQ-genetic liability interaction arose largely from IQ differences between close relatives. IQ assessed in late adolescence is a robust risk factor for subsequent onset of schizophrenia. This association is not the result of a declining IQ associated with insidious onset. In this large, representative sample, we found no evidence for a link between genius and schizophrenia. Co-relative control analyses showed that the association between lower IQ and schizophrenia is not the result of shared familial risk factors and may be causal. The strongest effect was seen with IQ differences within families. High intelligence substantially attenuates the impact of genetic liability on the risk for schizophrenia.
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Interactions between Genetic and Ecological Effects on the Evolution of Life Cycles.
Rescan, Marie; Lenormand, Thomas; Roze, Denis
2016-01-01
Sexual reproduction leads to an alternation between haploid and diploid phases, whose relative length varies widely across taxa. Previous genetical models showed that diploid or haploid life cycles may be favored, depending on dominance interactions and on effective recombination rates. By contrast, niche differentiation between haploids and diploids may favor biphasic life cycles, in which development occurs in both phases. In this article, we explore the interplay between genetical and ecological factors, assuming that deleterious mutations affect the competitivity of individuals within their ecological niche and allowing different effects of mutations in haploids and diploids (including antagonistic selection). We show that selection on a modifier gene affecting the relative length of both phases can be decomposed into a direct selection term favoring the phase with the highest mean fitness (due to either ecological differences or differential effects of mutations) and an indirect selection term favoring the phase in which selection is more efficient. When deleterious alleles occur at many loci and in the presence of ecological differentiation between haploids and diploids, evolutionary branching often occurs and leads to the stable coexistence of alleles coding for haploid and diploid cycles, while temporal variations in niche sizes may stabilize biphasic cycles.
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Exploitation of genetic interaction network topology for the prediction of epistatic behavior
Alanis Lobato, Gregorio
2013-10-01
Genetic interaction (GI) detection impacts the understanding of human disease and the ability to design personalized treatment. The mapping of every GI in most organisms is far from complete due to the combinatorial amount of gene deletions and knockdowns required. Computational techniques to predict new interactions based only on network topology have been developed in network science but never applied to GI networks.We show that topological prediction of GIs is possible with high precision and propose a graph dissimilarity index that is able to provide robust prediction in both dense and sparse networks.Computational prediction of GIs is a strong tool to aid high-throughput GI determination. The dissimilarity index we propose in this article is able to attain precise predictions that reduce the universe of candidate GIs to test in the lab. © 2013 Elsevier Inc.
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Exploitation of genetic interaction network topology for the prediction of epistatic behavior
Alanis Lobato, Gregorio; Cannistraci, Carlo; Ravasi, Timothy
2013-01-01
Genetic interaction (GI) detection impacts the understanding of human disease and the ability to design personalized treatment. The mapping of every GI in most organisms is far from complete due to the combinatorial amount of gene deletions and knockdowns required. Computational techniques to predict new interactions based only on network topology have been developed in network science but never applied to GI networks.We show that topological prediction of GIs is possible with high precision and propose a graph dissimilarity index that is able to provide robust prediction in both dense and sparse networks.Computational prediction of GIs is a strong tool to aid high-throughput GI determination. The dissimilarity index we propose in this article is able to attain precise predictions that reduce the universe of candidate GIs to test in the lab. © 2013 Elsevier Inc.
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Kazma, Rémi; Bonaïti-Pellié, Catherine; Norris, Jill,; Génin, Emmanuelle
2010-01-01
International audience; Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for ...
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Interactive genetic counseling role-play: a novel educational strategy for family physicians.
Blaine, Sean M; Carroll, June C; Rideout, Andrea L; Glendon, Gord; Meschino, Wendy; Shuman, Cheryl; Telner, Deanna; Van Iderstine, Natasha; Permaul, Joanne
2008-04-01
Family physicians (FPs) are increasingly involved in delivering genetic services. Familiarization with aspects of genetic counseling may enable FPs to help patients make informed choices. Exploration of interactive role-play as a means to raise FPs' awareness of the process and content of genetic counseling. FPs attending two large Canadian family medicine conferences in 2005 were eligible -- 93 participated. FPs discussed a case during a one-on-one session with a genetic counselor. Evaluation involved pre and post intervention questionnaires FPs' baseline genetic knowledge was self-rated as uniformly poor. Baseline confidence was highest in eliciting family history and providing psychosocial support and lowest in discussing risks/benefits of genetic testing and counseling process. Post-intervention, 80% of FPs had better appreciation of family history and 97% indicated this was an effective learning experience. Role-play with FPs is effective in raising awareness of the process and content of genetic counseling and may be applied to other health disciplines.
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The genetics of music accomplishment: evidence for gene-environment correlation and interaction.
Hambrick, David Z; Tucker-Drob, Elliot M
2015-02-01
Theories of skilled performance that emphasize training history, such as K. Anders Ericsson and colleagues' deliberate-practice theory, have received a great deal of recent attention in both the scientific literature and the popular press. Twin studies, however, have demonstrated evidence for moderate-to-strong genetic influences on skilled performance. Focusing on musical accomplishment in a sample of over 800 pairs of twins, we found evidence for gene-environment correlation, in the form of a genetic effect on music practice. However, only about one quarter of the genetic effect on music accomplishment was explained by this genetic effect on music practice, suggesting that genetically influenced factors other than practice contribute to individual differences in music accomplishment. We also found evidence for gene-environment interaction, such that genetic effects on music accomplishment were most pronounced among those engaging in music practice, suggesting that genetic potentials for skilled performance are most fully expressed and fostered by practice.
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Human-directed social behaviour in dogs shows significant heritability.
Persson, M E; Roth, L S V; Johnsson, M; Wright, D; Jensen, P
2015-04-01
Through domestication and co-evolution with humans, dogs have developed abilities to attract human attention, e.g. in a manner of seeking assistance when faced with a problem solving task. The aims of this study were to investigate within breed variation in human-directed contact seeking in dogs and to estimate its genetic basis. To do this, 498 research beagles, bred and kept under standardized conditions, were tested in an unsolvable problem task. Contact seeking behaviours recorded included both eye contact and physical interactions. Behavioural data was summarized through a principal component analysis, resulting in four components: test interactions, social interactions, eye contact and physical contact. Females scored significantly higher on social interactions and physical contact and age had an effect on eye contact scores. Narrow sense heritabilities (h(2) ) of the two largest components were estimated at 0.32 and 0.23 but were not significant for the last two components. These results show that within the studied dog population, behavioural variation in human-directed social behaviours was sex dependent and that the utilization of eye contact seeking increased with age and experience. Hence, heritability estimates indicate a significant genetic contribution to the variation found in human-directed social interactions, suggesting that social skills in dogs have a genetic basis, but can also be shaped and enhanced through individual experiences. This research gives the opportunity to further investigate the genetics behind dogs' social skills, which could also play a significant part into research on human social disorders such as autism. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
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Expression Profiling of Human Genetic and Protein Interaction Networks in Type 1 Diabetes
DEFF Research Database (Denmark)
Brunak, Søren; Bergholdt, R; Brorsson, C
2009-01-01
Proteins contributing to a complex disease are often members of the same functional pathways. Elucidation of such pathways may provide increased knowledge about functional mechanisms underlying disease. By combining genetic interactions in Type 1 Diabetes (T1D) with protein interaction data we have...
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Characterizing Male–Female Interactions Using Natural Genetic Variation in Drosophila melanogaster
Reinhart, Michael; Carney, Tara; Clark, Andrew G.
2015-01-01
Drosophila melanogaster females commonly mate with multiple males establishing the opportunity for pre- and postcopulatory sexual selection. Traits impacting sexual selection can be affected by a complex interplay of the genotypes of the competing males, the genotype of the female, and compatibilities between the males and females. We scored males from 96 2nd and 94 3rd chromosome substitution lines for traits affecting reproductive success when mated with females from 3 different genetic backgrounds. The traits included male-induced female refractoriness, male remating ability, the proportion of offspring sired under competitive conditions and male-induced female fecundity. We observed significant effects of male line, female genetic background, and strong male by female interactions. Some males appeared to be “generalists” and performed consistently across the different females; other males appeared to be “specialists” and performed very well with a particular female and poorly with others. “Specialist” males did not, however, prefer to court those females with whom they had the highest reproductive fitness. Using 143 polymorphisms in male reproductive genes, we mapped several genes that had consistent effects across the different females including a derived, high fitness allele in Acp26Aa that may be the target of adaptive evolution. We also identified a polymorphism upstream of PebII that may interact with the female genetic background to affect male-induced refractoriness to remating. These results suggest that natural variation in PebII might contribute to the observed male–female interactions. PMID:25425680
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Identification of genetic components involved in Lotus-endophyte interactions
DEFF Research Database (Denmark)
Zgadzaj, Rafal Lukasz
of growth hormones or nitrogen fixation. However, the genes involved in plant-endophyte interactions and bacterial accomodation within plant tissues are not known. In order to shed some light on such processes, an approach “one host-one endophyte” was chosen. The focus on a single plant species and a single......Endophytes are microorganisms capable of colonising plant tissues without inducing host defense responses. They have a large impact on plants, since they can modulate plant responses to pathogens, herbivores and environmental stress. They can also induce plant growth promotion through synthesis...... bacterial strain aimed at obtaining a reliable and easy to handle system for plant-microsymbiont interaction research. Two different methods were tested for their usefulness in identification of genetic components involved in plant-endophyte interactions. The first method was based on measuring growth...
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Kim, Yong-Ku; Ham, Byung-Joo; Han, Kyu-Man
2018-03-10
The etiology of depression is characterized by the interplay of genetic and environmental factors and brain structural alteration. Childhood adversity is a major contributing factor in the development of depression. Interactions between childhood adversity and candidate genes for depression could affect brain morphology via the modulation of neurotrophic factors, serotonergic neurotransmission, or the hypothalamus-pituitary-adrenal (HPA) axis, and this pathway may explain the subsequent onset of depression. Childhood adversity is associated with structural changes in the hippocampus, amygdala, anterior cingulate cortex (ACC), and prefrontal cortex (PFC), as well as white matter tracts such as the corpus callosum, cingulum, and uncinate fasciculus. Childhood adversity showed an interaction with the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism, serotonin transporter-linked promoter region (5-HTTLPR), and FK506 binding protein 51 (FKBP5) gene rs1360780 in brain morphologic changes in patients with depression and in a non-clinical population. Individuals with the Met allele of BDNF Val66Met and a history of childhood adversity had reduced volume in the hippocampus and its subfields, amygdala, and PFC and thinner rostral ACC in a study of depressed patients and healthy controls. The S allele of 5-HTTLPR combined with exposure to childhood adversity or a poorer parenting environment was associated with a smaller hippocampal volume and subsequent onset of depression. The FKBP5 gene rs160780 had a significant interaction with childhood adversity in the white matter integrity of brain regions involved in emotion processing. This review identified that imaging genetic studies on childhood adversity may deepen our understanding on the neurobiological background of depression by scrutinizing complicated pathways of genetic factors, early psychosocial environments, and the accompanying morphologic changes in emotion-processing neural circuitry. Copyright
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The genetics of childhood obesity and interaction with dietary macronutrients.
Garver, William S; Newman, Sara B; Gonzales-Pacheco, Diana M; Castillo, Joseph J; Jelinek, David; Heidenreich, Randall A; Orlando, Robert A
2013-05-01
The genes contributing to childhood obesity are categorized into three different types based on distinct genetic and phenotypic characteristics. These types of childhood obesity are represented by rare monogenic forms of syndromic or non-syndromic childhood obesity, and common polygenic childhood obesity. In some cases, genetic susceptibility to these forms of childhood obesity may result from different variations of the same gene. Although the prevalence for rare monogenic forms of childhood obesity has not increased in recent times, the prevalence of common childhood obesity has increased in the United States and developing countries throughout the world during the past few decades. A number of recent genome-wide association studies and mouse model studies have established the identification of susceptibility genes contributing to common childhood obesity. Accumulating evidence suggests that this type of childhood obesity represents a complex metabolic disease resulting from an interaction with environmental factors, including dietary macronutrients. The objective of this article is to provide a review on the origins, mechanisms, and health consequences of obesity susceptibility genes and interaction with dietary macronutrients that predispose to childhood obesity. It is proposed that increased knowledge of these obesity susceptibility genes and interaction with dietary macronutrients will provide valuable insight for individual, family, and community preventative lifestyle intervention, and eventually targeted nutritional and medicinal therapies.
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Usaj, Matej; Tan, Yizhao; Wang, Wen; VanderSluis, Benjamin; Zou, Albert; Myers, Chad L; Costanzo, Michael; Andrews, Brenda; Boone, Charles
2017-05-05
Providing access to quantitative genomic data is key to ensure large-scale data validation and promote new discoveries. TheCellMap.org serves as a central repository for storing and analyzing quantitative genetic interaction data produced by genome-scale Synthetic Genetic Array (SGA) experiments with the budding yeast Saccharomyces cerevisiae In particular, TheCellMap.org allows users to easily access, visualize, explore, and functionally annotate genetic interactions, or to extract and reorganize subnetworks, using data-driven network layouts in an intuitive and interactive manner. Copyright © 2017 Usaj et al.
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Fejerman, Laura; Stern, Mariana C; John, Esther M; Torres-Mejía, Gabriela; Hines, Lisa M; Wolff, Roger K; Baumgartner, Kathy B; Giuliano, Anna R; Ziv, Elad; Pérez-Stable, Eliseo J; Slattery, Martha L
2015-11-01
Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014]. The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. ©2015 American Association for Cancer Research.
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Directory of Open Access Journals (Sweden)
Han Kyungsook
2010-06-01
Full Text Available Abstract Background Genetic interaction profiles are highly informative and helpful for understanding the functional linkages between genes, and therefore have been extensively exploited for annotating gene functions and dissecting specific pathway structures. However, our understanding is rather limited to the relationship between double concurrent perturbation and various higher level phenotypic changes, e.g. those in cells, tissues or organs. Modifier screens, such as synthetic genetic arrays (SGA can help us to understand the phenotype caused by combined gene mutations. Unfortunately, exhaustive tests on all possible combined mutations in any genome are vulnerable to combinatorial explosion and are infeasible either technically or financially. Therefore, an accurate computational approach to predict genetic interaction is highly desirable, and such methods have the potential of alleviating the bottleneck on experiment design. Results In this work, we introduce a computational systems biology approach for the accurate prediction of pairwise synthetic genetic interactions (SGI. First, a high-coverage and high-precision functional gene network (FGN is constructed by integrating protein-protein interaction (PPI, protein complex and gene expression data; then, a graph-based semi-supervised learning (SSL classifier is utilized to identify SGI, where the topological properties of protein pairs in weighted FGN is used as input features of the classifier. We compare the proposed SSL method with the state-of-the-art supervised classifier, the support vector machines (SVM, on a benchmark dataset in S. cerevisiae to validate our method's ability to distinguish synthetic genetic interactions from non-interaction gene pairs. Experimental results show that the proposed method can accurately predict genetic interactions in S. cerevisiae (with a sensitivity of 92% and specificity of 91%. Noticeably, the SSL method is more efficient than SVM, especially for
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Su, Shih-Heng; Krysan, Patrick J
2016-12-01
Mitogen-activated protein kinase cascades are conserved in all eukaryotes. In Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal abnormal phenotypes for a majority of these genes. One strategy for uncovering gene function when single-mutant lines do not produce an informative phenotype is to perform a systematic genetic interaction screen whereby double-mutants are created from a large library of single-mutant lines. Here we describe a new collection of 275 double-mutant lines derived from a library of single-mutants targeting genes related to MAP kinase signaling. To facilitate this study, we developed a high-throughput double-mutant generating pipeline using a system for growing Arabidopsis seedlings in 96-well plates. A quantitative root growth assay was used to screen for evidence of genetic interactions in this double-mutant collection. Our screen revealed four genetic interactions, all of which caused synthetic enhancement of the root growth defects observed in a MAP kinase 4 (MPK4) single-mutant line. Seeds for this double-mutant collection are publicly available through the Arabidopsis Biological Resource Center. Scientists interested in diverse biological processes can now screen this double-mutant collection under a wide range of growth conditions in order to search for additional genetic interactions that may provide new insights into MAP kinase signaling. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.
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Neufeld, Stanley J; Wang, Fan; Cobb, John
2014-11-01
The growth and development of the vertebrate limb relies on homeobox genes of the Hox and Shox families, with their independent mutation often giving dose-dependent effects. Here we investigate whether Shox2 and Hox genes function together during mouse limb development by modulating their relative dosage and examining the limb for nonadditive effects on growth. Using double mRNA fluorescence in situ hybridization (FISH) in single embryos, we first show that Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 expression restricted to the proximal limb along with Hoxd9 and Hoxa11 expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D cluster deletions, we then show that their coordinated proximal limb expression is critical to generate normally proportioned limb segments. These epistatic interactions tune limb length, where Shox2 underexpression enhances, and Shox2 overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or Hox genes leads to a similar reduction in Runx2 expression in the developing humerus, suggesting their concerted action drives cartilage maturation during normal development. While we furthermore provide evidence that Hox gene function influences Shox2 expression, this regulation is limited in extent and is unlikely on its own to be a major explanation for their genetic interaction. Given the similar effect of human SHOX mutations on regional limb growth, Shox and Hox genes may generally function as genetic interaction partners during the growth and development of the proximal vertebrate limb. Copyright © 2014 by the Genetics Society of America.
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International Nuclear Information System (INIS)
Zhou, H.K.; Hayat, Y.; Fang, L.J.; Guo, R.F.; He, J.M.; Xu, H.M.
2010-01-01
A diallel cross experiment of 4 rice (Oryza sativa L.) female and 6 male varieties was conducted to study the genetic effects and their interaction with salt-stress condition of 7 agronomic traits in normal and salt-stressed planting conditions. The panicle length (PL), effective number of panicles per plant (ENP), plumped number of grains per panicles (PNG), total number of grains per panicles (TNG), 1000-grain weight (W), seed setting ratio (SSR) and grain weight per plant (PGW), were investigated. A genetic model including additive effect, dominance effect and their interaction effects with environment (ADE) was employed for analysis of data. It was observed that significant (p<0.05) additive effects, dominance effects, additive X environment interaction effects and dominance X environment interaction effects exist for most of the agronomic traits of rice. In addition, significant (p<0.05) narrow sense heritabilities of ENP, PNG, TNG, W and PGW were found, indicating that the genetic performance of these traits are greatly affected by salt stress condition. A significant (p<0.05) negative correlations in the additive effects and additive X environment interaction effects detected between ENP and PNG suggesting that selection on increasing of ENP can reduce PNG. In addition, there exist a highly significant (p<0.01) positive dominance correlation among the dominance effects of the ENP, PNG and TNG, which shows that it is possible to breed salt-tolerant rice variety by coordinating large panicle and multi-panicle in utilization of heterosis. (author)
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Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.
Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich
2014-01-01
The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.
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Lipscomb, Shannon T.; Laurent, Heidemarie; Neiderhiser, Jenae M.; Shaw, Daniel S.; Natsuaki, Misaki N.; Reiss, David; Leve, Leslie D.
2014-01-01
The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental…
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Kazma, Rémi; Bonaïti-Pellié, Catherine; Norris, Jill M; Génin, Emmanuelle
2010-01-01
Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for genetic factors. A test comparing the recurrence risks in sibs according to the exposure of indexes is proposed and its power is studied for varying values of model parameters. The Exposed versus Unexposed Recurrence Analysis (EURECA) is valuable for common diseases with moderate familial aggregation, only when the role of exposure has been clearly outlined. Interestingly, accounting for a sibling correlation for the exposure increases the power of EURECA. An application on a sample ascertained through one index affected with type 2 diabetes is presented where gene-environment interactions involving obesity and physical inactivity are investigated. Association of obesity with type 2 diabetes is clearly evidenced and a potential interaction involving this factor is suggested in Hispanics (P=0.045), whereas a clear gene-environment interaction is evidenced involving physical inactivity only in non-Hispanic whites (P=0.028). The proposed method might be of particular interest before genetic studies to help determine the environmental risk factors that will need to be accounted for to increase the power to detect genetic risk factors and to select the most appropriate samples to genotype.
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Gene interactions and genetics for yield and its attributes in grass pea
Indian Academy of Sciences (India)
[Parihar A. K., Dixit G. P. and Singh D. 2016 Gene interactions and genetics for yield and its attributes .... Biological yield. Seed yield factors. Plant height. Primary branches plant pod ..... indicates that these traits are under the control of several.
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Alleles versus genotypes: Genetic interactions and the dynamics of selection in sexual populations
Neher, Richard
2010-03-01
Physical interactions between amino-acids are essential for protein structure and activity, while protein-protein interactions and regulatory interactions are central to cellular function. As a consequence of these interactions, the combined effect of two mutations can differ from the sum of the individual effects of the mutations. This phenomenon of genetic interaction is known as epistasis. However, the importance of epistasis and its effects on evolutionary dynamics are poorly understood, especially in sexual populations where recombination breaks up existing combinations of alleles to produce new ones. Here, we present a computational model of selection dynamics involving many epistatic loci in a recombining population. We demonstrate that a large number of polymorphic interacting loci can, despite frequent recombination, exhibit cooperative behavior that locks alleles into favorable genotypes leading to a population consisting of a set of competing clones. As the recombination rate exceeds a certain critical value this ``genotype selection'' phase disappears in an abrupt transition giving way to ``allele selection'' - the phase where different loci are only weakly correlated as expected in sexually reproducing populations. Clustering of interacting sets of genes on a chromosome leads to the emergence of an intermediate regime, where localized blocks of cooperating alleles lock into genetic modules. Large populations attain highest fitness at a recombination rate just below critical, suggesting that natural selection might tune recombination rates to balance the beneficial aspect of exploration of genotype space with the breaking up of synergistic allele combinations.
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Glucose levels and genetic variants across transcriptional pathways: interaction effects with BMI
Povel, C.M.; Feskens, E.J.M.; Imholz, S.; Blaak, E.E.; Boer, J.M.A.; Dollé, M.E.T.
2010-01-01
Objective: Much of the genetic variation in glucose levels remains to be discovered. Especially, research on gene–environment interactions is scarce. Overweight is one of the main risk factors for hyperglycemia. As transcriptional regulation is important for both weight maintenance and glucose
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Pain, Oliver; Dudbridge, Frank; Cardno, Alastair G; Freeman, Daniel; Lu, Yi; Lundstrom, Sebastian; Lichtenstein, Paul; Ronald, Angelica
2018-03-31
This study aimed to test for overlap in genetic influences between psychotic-like experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic-like experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl. siblings = 6,297-10,098). A mega-genome-wide association study (mega-GWAS) for each psychotic-like experience domain was performed. Single nucleotide polymorphism (SNP)-heritability of each psychotic-like experience domain was estimated using genomic-relatedness-based restricted maximum-likelihood (GREML) and linkage disequilibrium- (LD-) score regression. Genetic overlap between specific psychotic-like experience domains and schizophrenia, bipolar disorder, and major depression was assessed using polygenic risk score (PRS) and LD-score regression. GREML returned SNP-heritability estimates of 3-9% for psychotic-like experience trait domains, with higher estimates for less skewed traits (Anhedonia, Cognitive Disorganization) than for more skewed traits (Paranoia and Hallucinations, Parent-rated Negative Symptoms). Mega-GWAS analysis identified one genome-wide significant association for Anhedonia within IDO2 but which did not replicate in an independent sample. PRS analysis revealed that the schizophrenia PRS significantly predicted all adolescent psychotic-like experience trait domains (Paranoia and Hallucinations only in non-zero scorers). The major depression PRS significantly predicted Anhedonia and Parent-rated Negative Symptoms in adolescence. Psychotic-like experiences during adolescence in the community show additive genetic effects and partly share genetic influences with clinically-recognized psychiatric disorders, specifically schizophrenia and
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Directory of Open Access Journals (Sweden)
Jian Gong
2016-10-01
Full Text Available Genome-wide association studies (GWAS have identified many genetic susceptibility loci for colorectal cancer (CRC. However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO. Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10-8; permuted p-value 3.51x10-8 region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1×10-4 and TT genotypes (OR,0.62 [95% CI, 0.51-0.75]; P = 1.3×10-6 but not associated among those with the CC genotype (p = 0.059. No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.
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Directory of Open Access Journals (Sweden)
James R Jasper
Full Text Available The extent to which stray, hatchery-reared salmon affect wild populations is much debated. Although experiments show that artificial breeding and culture influence the genetics of hatchery salmon, little is known about the interaction between hatchery and wild salmon in a natural setting. Here, we estimated historical and contemporary genetic population structures of chum salmon (Oncorhynchus keta in Prince William Sound (PWS, Alaska, with 135 single nucleotide polymorphism (SNP markers. Historical population structure was inferred from the analysis of DNA from fish scales, which had been archived since the late 1960's for several populations in PWS. Parallel analyses with microsatellites and a test based on Hardy-Weinberg proportions showed that about 50% of the fish-scale DNA was cross-contaminated with DNA from other fish. These samples were removed from the analysis. We used a novel application of the classical source-sink model to compare SNP allele frequencies in these archived fish-scales (1964-1982 with frequencies in contemporary samples (2008-2010 and found a temporal shift toward hatchery allele frequencies in some wild populations. Other populations showed markedly less introgression, despite moderate amounts of hatchery straying. The extent of introgression may reflect similarities in spawning time and life-history traits between hatchery and wild fish, or the degree that hybrids return to a natal spawning area. The source-sink model is a powerful means of detecting low levels of introgression over several generations.
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Trichoderma-plant-pathogen interactions: advances in genetics of biological control.
Mukherjee, Mala; Mukherjee, Prasun K; Horwitz, Benjamin A; Zachow, Christin; Berg, Gabriele; Zeilinger, Susanne
2012-12-01
Trichoderma spp. are widely used in agriculture as biofungicides. Induction of plant defense and mycoparasitism (killing of one fungus by another) are considered to be the most important mechanisms of Trichoderma-mediated biological control. Understanding these mechanisms at the molecular level would help in developing strains with superior biocontrol properties. In this article, we review our current understanding of the genetics of interactions of Trichoderma with plants and plant pathogens.
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Genetic interactions underlying hybrid male sterility in the Drosophila bipectinata species complex.
Mishra, Paras Kumar; Singh, Bashisth Narayan
2006-06-01
Understanding genetic mechanisms underlying hybrid male sterility is one of the most challenging problems in evolutionary biology especially speciation. By using the interspecific hybridization method roles of Y chromosome, Major Hybrid Sterility (MHS) genes and cytoplasm in sterility of hybrid males have been investigated in a promising group, the Drosophila bipectinata species complex that consists of four closely related species: D. pseudoananassae, D. bipectinata, D. parabipectinata and D. malerkotliana. The interspecific introgression analyses show that neither cytoplasm nor MHS genes are involved but X-Y interactions may be playing major role in hybrid male sterility between D. pseudoananassae and the other three species. The results of interspecific introgression analyses also show considerable decrease in the number of males in the backcross offspring and all males have atrophied testes. There is a significant positive correlation between sex - ratio distortion and severity of sterility in backcross males. These findings provide evidence that D. pseudoananassae is remotely related with other three species of the D. bipectinata species complex.
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Ussar, Siegfried; Griffin, Nicholas W; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I; Kahn, C Ronald
2015-09-01
Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Jessica A Hill
Full Text Available Clinical genetic testing is becoming an integral part of medical care for inherited disorders. While genetic testing and counseling are readily available in high-income countries, in low- and middle-income countries like Kenya genetic testing is limited and genetic counseling is virtually non-existent. Genetic testing is likely to become widespread in Kenya within the next decade, yet there has not been a concomitant increase in genetic counseling resources. To address this gap, we designed an interactive workshop for clinicians in Kenya focused on the genetics of the childhood eye cancer retinoblastoma. The objectives were to increase retinoblastoma genetics knowledge, build genetic counseling skills and increase confidence in those skills.The workshop was conducted at the 2013 Kenyan National Retinoblastoma Strategy meeting. It included a retinoblastoma genetics presentation, small group discussion of case studies and genetic counseling role-play. Knowledge was assessed by standardized test, and genetic counseling skills and confidence by questionnaire.Knowledge increased significantly post-workshop, driven by increased knowledge of retinoblastoma causative genetics. One-year post-workshop, participant knowledge had returned to baseline, indicating that knowledge retention requires more frequent reinforcement. Participants reported feeling more confident discussing genetics with patients, and had integrated more genetic counseling into patient interactions.A comprehensive retinoblastoma genetics workshop can increase the knowledge and skills necessary for effective retinoblastoma genetic counseling.
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Hill, Jessica A; Lee, Su Yeon; Njambi, Lucy; Corson, Timothy W; Dimaras, Helen
2015-01-01
Clinical genetic testing is becoming an integral part of medical care for inherited disorders. While genetic testing and counseling are readily available in high-income countries, in low- and middle-income countries like Kenya genetic testing is limited and genetic counseling is virtually non-existent. Genetic testing is likely to become widespread in Kenya within the next decade, yet there has not been a concomitant increase in genetic counseling resources. To address this gap, we designed an interactive workshop for clinicians in Kenya focused on the genetics of the childhood eye cancer retinoblastoma. The objectives were to increase retinoblastoma genetics knowledge, build genetic counseling skills and increase confidence in those skills. The workshop was conducted at the 2013 Kenyan National Retinoblastoma Strategy meeting. It included a retinoblastoma genetics presentation, small group discussion of case studies and genetic counseling role-play. Knowledge was assessed by standardized test, and genetic counseling skills and confidence by questionnaire. Knowledge increased significantly post-workshop, driven by increased knowledge of retinoblastoma causative genetics. One-year post-workshop, participant knowledge had returned to baseline, indicating that knowledge retention requires more frequent reinforcement. Participants reported feeling more confident discussing genetics with patients, and had integrated more genetic counseling into patient interactions. A comprehensive retinoblastoma genetics workshop can increase the knowledge and skills necessary for effective retinoblastoma genetic counseling.
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Babbar-Sebens, M.; Minsker, B. S.
2006-12-01
that met the DM's preference criteria, therefore allowing the expert to select among several strong candidate designs depending on her/his LTM budget, c) two of the methodologies - Case-Based Micro Interactive Genetic Algorithm (CBMIGA) and Interactive Genetic Algorithm with Mixed Initiative Interaction (IGAMII) - were also able to assist in controlling human fatigue and adapt to the DM's learning process.
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Mandelli, Laura; Toscano, Elena; Porcelli, Stefano; Fabbri, Chiara; Serretti, Alessandro
2016-03-01
In this study we evaluated the role of a candidate gene for major psychosis, Sialyltransferase (ST8SIA2), in the risk to develop a schizophrenia spectrum disorders, taking into account exposure to stressful life events (SLEs). Eight polymorphisms (SNPs) were tested in 94 Schizophreniainpatients and 176 healthy controls. Schizophrenia patients were also evaluated for SLEs in different life periods. None of the SNPs showed association with schizophrenia. Nevertheless, when crossing genetic variants with childhood SLEs, we could observe trends of interaction with age of onset. Though several limitations, our results support a protective role of ST8SIA2 in individuals exposed to moderate childhood stress.
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Bralten, Janita; Franke, Barbara; Waldman, Irwin; Rommelse, Nanda; Hartman, Catharina; Asherson, Philip; Banaschewski, Tobias; Ebstein, Richard P; Gill, Michael; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A; Oosterlaan, Jaap; Sonuga-Barke, Edmund; Steinhausen, Hans-Christoph; Faraone, Stephen V; Buitelaar, Jan K; Arias-Vásquez, Alejandro
2013-11-01
Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD. The pathway was described as a predefined gene selection based on a well-established database or literature data. Common genetic variants in pathways involved in dopamine/norepinephrine and serotonin neurotransmission and genes involved in neuritic outgrowth were investigated in cases from the International Multicentre ADHD Genetics (IMAGE) study. Multivariable analysis was performed to combine the effects of single genetic variants within the pathway genes. Phenotypes were DSM-IV symptom counts for inattention and hyperactivity/impulsivity (n = 871) and symptom severity measured with the Conners Parent (n = 930) and Teacher (n = 916) Rating Scales. Summing genetic effects of common genetic variants within the pathways showed a significant association with hyperactive/impulsive symptoms ((p)empirical = .007) but not with inattentive symptoms ((p)empirical = .73). Analysis of parent-rated Conners hyperactive/impulsive symptom scores validated this result ((p)empirical = .0018). Teacher-rated Conners scores were not associated. Post hoc analyses showed a significant contribution of all pathways to the hyperactive/impulsive symptom domain (dopamine/norepinephrine, (p)empirical = .0004; serotonin, (p)empirical = .0149; neuritic outgrowth, (p)empirical = .0452). The present analysis shows an association between common variants in 3 genetic pathways and the hyperactive/impulsive component of ADHD. This study demonstrates that pathway-based association analyses, using quantitative measurements of ADHD symptom domains, can increase the power of genetic analyses to
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Lipscomb, Shannon T; Laurent, Heidemarie; Neiderhiser, Jenae M; Shaw, Daniel S; Natsuaki, Misaki N; Reiss, David; Leve, Leslie D
2014-01-01
The current study examined interactions among genetic influences and children's early environments on the development of externalizing behaviors from 18 months to 6 years of age. Participants included 233 families linked through adoption (birth parents and adoptive families). Genetic influences were assessed by birth parent temperamental regulation. Early environments included both family (overreactive parenting) and out-of-home factors (center-based Early Care and Education; ECE). Overreactive parenting predicted more child externalizing behaviors. Attending center-based ECE was associated with increasing externalizing behaviors only for children with genetic liability for dysregulation. Additionally, children who were at risk for externalizing behaviors due to both genetic variability and exposure to center-based ECE were more sensitive to the effects of overreactive parenting on externalizing behavior than other children.
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Newcomb, Polly A.; Campbell, Peter T.; Baron, John A.; Berndt, Sonja I.; Bezieau, Stephane; Brenner, Hermann; Casey, Graham; Chan, Andrew T.; Chang-Claude, Jenny; Du, Mengmeng; Figueiredo, Jane C.; Gallinger, Steven; Giovannucci, Edward L.; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jeon, Jihyoun; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Lin, Yi; Lindor, Noralane M.; Nishihara, Reiko; Ogino, Shuji; Potter, John D.; Rudolph, Anja; Schoen, Robert E.; Seminara, Daniela; Slattery, Martha L.; Thibodeau, Stephen N.; Thornquist, Mark; Toth, Reka; Wallace, Robert; White, Emily; Jiao, Shuo; Lemire, Mathieu; Hsu, Li; Peters, Ulrike
2016-01-01
Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk. PMID:27723779
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Directory of Open Access Journals (Sweden)
Weronica eEk
2012-03-01
Full Text Available Most biological traits are regulated by a complex interplay between genetic and environmental factors. By intercrossing divergent lines, it is possible to identify individual and interacting QTL involved in the genetic architecture of these traits. When the loci have been mapped, alternative strategies are needed for fine-mapping and studying the individual and interactive effects of the QTL in detail. We have previously identified, replicated and fine-mapped a four-locus QTL network that determines nearly half of the eight-fold difference in body-weight at 56 days of age between two divergently selected chicken lines. Here, we describe, to our knowledge, the first generation of a three-locus QTL introgression line in chickens to further study the effect of three of the interacting loci in this network on metabolic phenotypes. Recurrent marker assisted backcrossing was used to simultaneously transfer QTL alleles from the low-weight selected line into the high-weight selected line. Three generations of backcrossing and one generation of intercrossing resulted in an introgression line where all three introgressed QTL and several unlinked and linked control-loci were segregating at nearly expected allele frequencies. We show that marker-based sexing is an efficient method for sexing breeding populations and how intensive selection can be applied using artificial insemination to generate large half-sib families. Based on our empirical observations, we provide recommendations for future introgression-line breeding experiments. In the future, use of this confirmed introgression line will facilitate detailed studies of the effects of genetic interactions on complex traits.
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SLiM 2: Flexible, Interactive Forward Genetic Simulations.
Haller, Benjamin C; Messer, Philipp W
2017-01-01
Modern population genomic datasets hold immense promise for revealing the evolutionary processes operating in natural populations, but a crucial prerequisite for this goal is the ability to model realistic evolutionary scenarios and predict their expected patterns in genomic data. To that end, we present SLiM 2: an evolutionary simulation framework that combines a powerful, fast engine for forward population genetic simulations with the capability of modeling a wide variety of complex evolutionary scenarios. SLiM achieves this flexibility through scriptability, which provides control over most aspects of the simulated evolutionary scenarios with a simple R-like scripting language called Eidos. An example SLiM simulation is presented to illustrate the power of this approach. SLiM 2 also includes a graphical user interface for simulation construction, interactive runtime control, and dynamic visualization of simulation output, facilitating easy and fast model development with quick prototyping and visual debugging. We conclude with a performance comparison between SLiM and two other popular forward genetic simulation packages. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Environmental confounding in gene-environment interaction studies.
Vanderweele, Tyler J; Ko, Yi-An; Mukherjee, Bhramar
2013-07-01
We show that, in the presence of uncontrolled environmental confounding, joint tests for the presence of a main genetic effect and gene-environment interaction will be biased if the genetic and environmental factors are correlated, even if there is no effect of either the genetic factor or the environmental factor on the disease. When environmental confounding is ignored, such tests will in fact reject the joint null of no genetic effect with a probability that tends to 1 as the sample size increases. This problem with the joint test vanishes under gene-environment independence, but it still persists if estimating the gene-environment interaction parameter itself is of interest. Uncontrolled environmental confounding will bias estimates of gene-environment interaction parameters even under gene-environment independence, but it will not do so if the unmeasured confounding variable itself does not interact with the genetic factor. Under gene-environment independence, if the interaction parameter without controlling for the environmental confounder is nonzero, then there is gene-environment interaction either between the genetic factor and the environmental factor of interest or between the genetic factor and the unmeasured environmental confounder. We evaluate several recently proposed joint tests in a simulation study and discuss the implications of these results for the conduct of gene-environment interaction studies.
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Directory of Open Access Journals (Sweden)
Ewelina Pośpiech
2015-01-01
Full Text Available The current data are still inconclusive in terms of a genetic component involved in the susceptibility to renal cell carcinoma. Our aim was to evaluate 40 selected candidate polymorphisms for potential association with clear cell renal cell carcinoma (ccRCC based on independent group of 167 patients and 200 healthy controls. The obtained data were searched for independent effects of particular polymorphisms as well as haplotypes and genetic interactions. Association testing implied position rs4765623 in the SCARB1 gene (OR=1.688, 95% CI: 1.104–2.582, P=0.016 and a haplotype in VDR comprising positions rs739837, rs731236, rs7975232, and rs1544410 (P=0.012 to be the risk factors in the studied population. The study detected several epistatic effects contributing to the genetic susceptibility to ccRCC. Variation in GNAS1 was implicated in a strong synergistic interaction with BIRC5. This effect was part of a model suggested by multifactor dimensionality reduction method including also a synergy between GNAS1 and SCARB1 (P=0.036. Significance of GNAS1-SCARB1 interaction was further confirmed by logistic regression (P=0.041, which also indicated involvement of SCARB1 in additional interaction with EPAS1 (P=0.008 as well as revealing interactions between GNAS1 and EPAS1 (P=0.016, GNAS1 and MC1R (P=0.031, GNAS1 and VDR (P=0.032, and MC1R and VDR (P=0.035.
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Brown, Simon David; Jarosinska, Olga Dorota; Lorenz, Alexander
2018-03-17
Hop1 is a component of the meiosis-specific chromosome axis and belongs to the evolutionarily conserved family of HORMA domain proteins. Hop1 and its orthologs in higher eukaryotes are a major factor in promoting double-strand DNA break formation and inter-homolog recombination. In budding yeast and mammals, they are also involved in a meiotic checkpoint kinase cascade monitoring the completion of double-strand DNA break repair. We used the fission yeast, Schizosaccharomyces pombe, which lacks a canonical synaptonemal complex to test whether Hop1 has a role beyond supporting the generation of double-strand DNA breaks and facilitating inter-homolog recombination events. We determined how mutants of homologous recombination factors genetically interact with hop1, studied the role(s) of the HORMA domain of Hop1, and characterized a bio-informatically predicted interactor of Hop1, Aho1 (SPAC688.03c). Our observations indicate that in fission yeast, Hop1 does require its HORMA domain to support wild-type levels of meiotic recombination and localization to meiotic chromatin. Furthermore, we show that hop1∆ only weakly interacts genetically with mutants of homologous recombination factors, and in fission yeast likely has no major role beyond break formation and promoting inter-homolog events. We speculate that after the evolutionary loss of the synaptonemal complex, Hop1 likely has become less important for modulating recombination outcome during meiosis in fission yeast, and that this led to a concurrent rewiring of genetic pathways controlling meiotic recombination.
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Pereyra, Silvana; Bertoni, Bernardo; Sapiro, Rossana
2016-07-01
Preterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental-genetic influence on PTB. The study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations. We conducted a case-control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother-offspring dyads who delivered at preterm (gestational ageenvironmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB). We detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB. Interactions between maternal and fetal genomes may influence the timing of birth. By incorporating environmental data, we revealed genetic associations with PTB, a finding not found when we analyzed genetic data alone. Our results stress the importance of studying the effect of
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Genetic and environmental factors interact to influence anxiety.
Gross, Cornelius; Hen, René
2004-01-01
Both genetic and environmental factors influence normal anxiety traits as well as anxiety disorders. In addition it is becoming increasingly clear that these factors interact to produce specific anxiety-related behaviors. For example, in humans and in monkeys mutations in the gene encoding for the serotonin transporter result in increased anxiety in adult life when combined with a stressful environment during development. Another recent example comes from twin studies suggesting that a small hippocampus can be a predisposing condition that renders individuals susceptible to post traumatic stress disorder. Such examples illustrate how specific mutations leading to abnormal brain development may increase vulnerability to environmental insults which may in turn lead to specific anxiety disorders.
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An interaction map of circulating metabolites, immune gene networks, and their genetic regulation.
Nath, Artika P; Ritchie, Scott C; Byars, Sean G; Fearnley, Liam G; Havulinna, Aki S; Joensuu, Anni; Kangas, Antti J; Soininen, Pasi; Wennerström, Annika; Milani, Lili; Metspalu, Andres; Männistö, Satu; Würtz, Peter; Kettunen, Johannes; Raitoharju, Emma; Kähönen, Mika; Juonala, Markus; Palotie, Aarno; Ala-Korpela, Mika; Ripatti, Samuli; Lehtimäki, Terho; Abraham, Gad; Raitakari, Olli; Salomaa, Veikko; Perola, Markus; Inouye, Michael
2017-08-01
Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts (total N = 2168), including a subset of individuals with matched multi-omic data at 7-year follow-up. We identify topologically replicable gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules show complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) reveal five modules with mQTLs that have both cis and trans effects. The strongest mQTL is in ARHGEF3 (rs1354034) and affects a module enriched for platelet function, independent of platelet counts. Modules of mast cell/basophil and neutrophil function show temporally stable metabolite associations over 7-year follow-up, providing evidence that these modules and their constituent gene products may play central roles in metabolic inflammation. Furthermore, the strongest mQTL in ARHGEF3 also displays clear temporal stability, supporting widespread trans effects at this locus. This study provides a detailed map of natural variation at the blood immunometabolic interface and its genetic basis, and may facilitate subsequent studies to explain inter-individual variation in cardiometabolic disease.
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Zhao, Wei; Ware, Erin B; He, Zihuai; Kardia, Sharon L R; Faul, Jessica D; Smith, Jennifer A
2017-09-29
Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index)-associated genetic loci identified through large-scale genome-wide association studies (GWAS) only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms) modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS). In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs) within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS). Childhood socioeconomic status (parental education) was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488) by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA) ( p = 0.07).
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Directory of Open Access Journals (Sweden)
Wei Zhao
2017-09-01
Full Text Available Obesity, which develops over time, is one of the leading causes of chronic diseases such as cardiovascular disease. However, hundreds of BMI (body mass index-associated genetic loci identified through large-scale genome-wide association studies (GWAS only explain about 2.7% of BMI variation. Most common human traits are believed to be influenced by both genetic and environmental factors. Past studies suggest a variety of environmental features that are associated with obesity, including socioeconomic status and psychosocial factors. This study combines both gene/regions and environmental factors to explore whether social/psychosocial factors (childhood and adult socioeconomic status, social support, anger, chronic burden, stressful life events, and depressive symptoms modify the effect of sets of genetic variants on BMI in European American and African American participants in the Health and Retirement Study (HRS. In order to incorporate longitudinal phenotype data collected in the HRS and investigate entire sets of single nucleotide polymorphisms (SNPs within gene/region simultaneously, we applied a novel set-based test for gene-environment interaction in longitudinal studies (LGEWIS. Childhood socioeconomic status (parental education was found to modify the genetic effect in the gene/region around SNP rs9540493 on BMI in European Americans in the HRS. The most significant SNP (rs9540488 by childhood socioeconomic status interaction within the rs9540493 gene/region was suggestively replicated in the Multi-Ethnic Study of Atherosclerosis (MESA (p = 0.07.
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DEFF Research Database (Denmark)
Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W
2013-01-01
Background Epistasis has been historically used to describe the phenomenon that the effect of a given gene on a phenotype can be dependent on one or more other genes, and is an essential element for understanding the association between genetic and phenotypic variations. Quantifying epistasis......-way epistasis. Methods Such a measure is based on information gain, and is able to separate all lower order effects from pure three-way epistasis. Results Our method was verified on synthetic data and applied to real data from a candidate-gene study of tuberculosis in a West African population....... In the tuberculosis data, we found a statistically significant pure three-way epistatic interaction effect that was stronger than any lower-order associations. Conclusion Our study provides a methodological basis for detecting and characterizing high-order gene-gene interactions in genetic association studies....
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Genetic variation in foundation species governs the dynamics of trophic interactions
Valencia-Cuevas, Leticia; Mussali-Galante, Patricia; Cano-Santana, Zenón; Pujade-Villar, Juli; Equihua-Martínez, Armando
2018-01-01
Abstract Various studies have demonstrated that the foundation species genetic diversity can have direct effects that extend beyond the individual or population level, affecting the dependent communities. Additionally, these effects may be indirectly extended to higher trophic levels throughout the entire community. Quercus castanea is an oak species with characteristics of foundation species beyond presenting a wide geographical distribution and being a dominant element of Mexican temperate forests. In this study, we analyzed the influence of population (He) and individual (HL) genetic diversity of Q. castanea on its canopy endophagous insect community and associated parasitoids. Specifically, we studied the composition, richness (S) and density of leaf-mining moths (Lepidoptera: Tischeridae, Citheraniidae), gall-forming wasps (Hymenoptera: Cynipidae), and canopy parasitoids of Q. castanea. We sampled 120 trees belonging to six populations (20/site) through the previously recognized gradient of genetic diversity. In total, 22 endophagous insect species belonging to three orders (Hymenoptera, Lepidoptera, and Diptera) and 20 parasitoid species belonging to 13 families were identified. In general, we observed that the individual genetic diversity of the host plant (HL) has a significant positive effect on the S and density of the canopy endophagous insect communities. In contrast, He has a significant negative effect on the S of endophagous insects. Additionally, indirect effects of HL were observed, affecting the S and density of parasitoid insects. Our results suggest that genetic variation in foundation species can be one of the most important factors governing the dynamics of tritrophic interactions that involve oaks, herbivores, and parasitoids. PMID:29492034
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Genes, Culture and Conservatism-A Psychometric-Genetic Approach.
Schwabe, Inga; Jonker, Wilfried; van den Berg, Stéphanie M
2016-07-01
The Wilson-Patterson conservatism scale was psychometrically evaluated using homogeneity analysis and item response theory models. Results showed that this scale actually measures two different aspects in people: on the one hand people vary in their agreement with either conservative or liberal catch-phrases and on the other hand people vary in their use of the "?" response category of the scale. A 9-item subscale was constructed, consisting of items that seemed to measure liberalism, and this subscale was subsequently used in a biometric analysis including genotype-environment interaction, correcting for non-homogeneous measurement error. Biometric results showed significant genetic and shared environmental influences, and significant genotype-environment interaction effects, suggesting that individuals with a genetic predisposition for conservatism show more non-shared variance but less shared variance than individuals with a genetic predisposition for liberalism.
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Engineering genetic circuit interactions within and between synthetic minimal cells
Adamala, Katarzyna P.; Martin-Alarcon, Daniel A.; Guthrie-Honea, Katriona R.; Boyden, Edward S.
2017-05-01
Genetic circuits and reaction cascades are of great importance for synthetic biology, biochemistry and bioengineering. An open question is how to maximize the modularity of their design to enable the integration of different reaction networks and to optimize their scalability and flexibility. One option is encapsulation within liposomes, which enables chemical reactions to proceed in well-isolated environments. Here we adapt liposome encapsulation to enable the modular, controlled compartmentalization of genetic circuits and cascades. We demonstrate that it is possible to engineer genetic circuit-containing synthetic minimal cells (synells) to contain multiple-part genetic cascades, and that these cascades can be controlled by external signals as well as inter-liposomal communication without crosstalk. We also show that liposomes that contain different cascades can be fused in a controlled way so that the products of incompatible reactions can be brought together. Synells thus enable a more modular creation of synthetic biology cascades, an essential step towards their ultimate programmability.
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Genetic interactions between neurofibromin and endothelin receptor B in mice.
Directory of Open Access Journals (Sweden)
Mugdha Deo
Full Text Available When mutations in two different genes produce the same mutant phenotype, it suggests that the encoded proteins either interact with each other, or act in parallel to fulfill a similar purpose. Haploinsufficiency of Neurofibromin and over-expression of Endothelin 3 both cause increased numbers of melanocytes to populate the dermis during mouse development, and thus we are interested in how these two signaling pathways might intersect. Neurofibromin is mutated in the human genetic disease, neurofibromatosis type 1, which is characterized by the development of Schwann cell based tumors and skin hyper-pigmentation. Neurofibromin is a GTPase activating protein, while the Endothelin 3 ligand activates Endothelin receptor B, a G protein coupled receptor. In order to study the genetic interactions between endothelin and neurofibromin, we defined the deletion breakpoints of the classical Ednrb piebald lethal allele (Ednrb(s-l and crossed these mice to mice with a loss-of-function mutation in neurofibromin, Dark skin 9 (Dsk9. We found that Neurofibromin haploinsufficiency requires Endothelin receptor B to darken the tail dermis. In contrast, Neurofibromin haploinsufficiency increases the area of the coat that is pigmented in Endothelin receptor B null mice. We also found an oncogenic mutation in the G protein alpha subunit, GNAQ, which couples to Endothelin receptor B, in a uveal melanoma from a patient with neurofibromatosis type 1. Thus, this data suggests that there is a complex relationship between Neurofibromin and Endothelin receptor B.
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Role of the XRCC1 - APE1 interaction in the maintenance of genetic stability
International Nuclear Information System (INIS)
Sossou-Becker, M.
2005-09-01
This thesis is divided in four chapters: the first one concerns the genetic instability, the second one is devoted to the DNA repair, the third one is related to the XRCC1 and the chapter four concerns APE1. Then, are defined the objectives and the results. This work fits into the studies of repair mechanisms. The physical and functional characterisation of the interaction between XRCC1 and APE1 allowed to understand its involvement in the prevention of the genetic instability at the origin of cancer. (N.C.)
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Identifying Interacting Genetic Variations by Fish-Swarm Logic Regression
Yang, Aiyuan; Yan, Chunxia; Zhu, Feng; Zhao, Zhongmeng; Cao, Zhi
2013-01-01
Understanding associations between genotypes and complex traits is a fundamental problem in human genetics. A major open problem in mapping phenotypes is that of identifying a set of interacting genetic variants, which might contribute to complex traits. Logic regression (LR) is a powerful multivariant association tool. Several LR-based approaches have been successfully applied to different datasets. However, these approaches are not adequate with regard to accuracy and efficiency. In this paper, we propose a new LR-based approach, called fish-swarm logic regression (FSLR), which improves the logic regression process by incorporating swarm optimization. In our approach, a school of fish agents are conducted in parallel. Each fish agent holds a regression model, while the school searches for better models through various preset behaviors. A swarm algorithm improves the accuracy and the efficiency by speeding up the convergence and preventing it from dropping into local optimums. We apply our approach on a real screening dataset and a series of simulation scenarios. Compared to three existing LR-based approaches, our approach outperforms them by having lower type I and type II error rates, being able to identify more preset causal sites, and performing at faster speeds. PMID:23984382
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Identifying Interacting Genetic Variations by Fish-Swarm Logic Regression
Directory of Open Access Journals (Sweden)
Xuanping Zhang
2013-01-01
Full Text Available Understanding associations between genotypes and complex traits is a fundamental problem in human genetics. A major open problem in mapping phenotypes is that of identifying a set of interacting genetic variants, which might contribute to complex traits. Logic regression (LR is a powerful multivariant association tool. Several LR-based approaches have been successfully applied to different datasets. However, these approaches are not adequate with regard to accuracy and efficiency. In this paper, we propose a new LR-based approach, called fish-swarm logic regression (FSLR, which improves the logic regression process by incorporating swarm optimization. In our approach, a school of fish agents are conducted in parallel. Each fish agent holds a regression model, while the school searches for better models through various preset behaviors. A swarm algorithm improves the accuracy and the efficiency by speeding up the convergence and preventing it from dropping into local optimums. We apply our approach on a real screening dataset and a series of simulation scenarios. Compared to three existing LR-based approaches, our approach outperforms them by having lower type I and type II error rates, being able to identify more preset causal sites, and performing at faster speeds.
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Class II HLA interactions modulate genetic risk for multiple sclerosis
Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil
2016-01-01
Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388
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DEFF Research Database (Denmark)
Bilde, T.; Friberg, U.; Maklakov, A.A.
2008-01-01
variance in F1 productivity, but lower genetic variance in egg-to-adult survival, which was strongly influenced by maternal and paternal effects. Conclusion Our results show that, in order to gain a relevant understanding of the genetic architecture of fitness, measures of offspring fitness should...... is the genetic interaction between parental genomes, as indicated by large amounts of non-additive genetic variance (dominance and/or epistasis) for F1 productivity. We discuss the processes that may maintain additive and non-additive genetic variance for fitness and how these relate to indirect selection...
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Geronikolou, Styliani A; Pavlopoulou, Athanasia; Cokkinos, Dennis; Chrousos, George
2017-01-01
Obesity is a chronic disease of increasing prevalence reaching epidemic proportions. Genetic defects as well as epigenetic effects contribute to the obesity phenotype. Investigating gene (e.g. MC4R defects)-environment (behavior, infectious agents, stress) interactions is a relative new field of great research interest. In this study, we have made an effort to create an interactome (henceforth referred to as "obesidome"), where extrinsic stressors response, intrinsic predisposition, immunity response to inflammation and autonomous nervous system implications are integrated. These pathways are presented in one interactome network for the first time. In our study, obesity-related genes/gene products were found to form a complex interactions network.
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Mann, Frank D; Patterson, Megan W; Grotzinger, Andrew D; Kretsch, Natalie; Tackett, Jennifer L; Tucker-Drob, Elliot M; Harden, K Paige
2016-07-01
Both sensation seeking and affiliation with deviant peer groups are risk factors for delinquency in adolescence. In this study, we use a sample of adolescent twins (n = 549), 13 to 20 years old (M age = 15.8 years), in order to test the interactive effects of peer deviance and sensation seeking on delinquency in a genetically informative design. Consistent with a socialization effect, affiliation with deviant peers was associated with higher delinquency even after controlling for selection effects using a co-twin-control comparison. At the same time, there was evidence for person-environment correlation; adolescents with genetic dispositions toward higher sensation seeking were more likely to report having deviant peer groups. Genetic influences on sensation seeking substantially overlapped with genetic influences on adolescent delinquency. Finally, the environmentally mediated effect of peer deviance on adolescent delinquency was moderated by individual differences in sensation seeking. Adolescents reporting high levels of sensation seeking were more susceptible to deviant peers, a Person × Environment interaction. These results are consistent with both selection and socialization processes in adolescent peer relationships, and they highlight the role of sensation seeking as an intermediary phenotype for genetic risk for delinquency. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
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Shinohara, Mitsuru; Sato, Naoyuki; Shimamura, Munehisa; Kurinami, Hitomi; Hamasaki, Toshimitsu; Chatterjee, Amarnath; Rakugi, Hiromi; Morishita, Ryuichi
2014-01-01
The benefits of statins, commonly prescribed for hypercholesterolemia, in treating Alzheimer's disease (AD) have not yet been fully established. A recent randomized clinical trial did not show any therapeutic effects of two statins on cognitive function in AD. Interestingly, however, the results of the Rotterdam study, one of the largest prospective cohort studies, showed reduced risk of AD in statin users. Based on the current understanding of statin actions and AD pathogenesis, it is still worth exploring whether statins can prevent AD when administered decades before the onset of AD or from midlife. This review discusses the possible beneficial effects of statins, drawn from previous clinical observations, pathogenic mechanisms, which include β-amyloid (Aβ) and tau metabolism, genetic and non-genetic risk factors (apolipoprotein E, cholesterol, sex, hypertension, and diabetes), and other clinical features (vascular dysfunction and oxidative and inflammatory stress) of AD. These findings suggest that administration of statins in midlife might prevent AD in late life by modifying genetic and non-genetic risk factors for AD. It should be clarified whether statins inhibit Aβ accumulation, tau pathological features, and brain atrophy in humans. To answer this question, a randomized controlled study using amyloid positron emission tomography (PET), tau-PET, and magnetic resonance imaging would be useful. This clinical evaluation could help us to overcome this devastating disease.
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Hruby, Adela; McKeown, Nicola M.; Song, Yiqing; Djoussé, Luc
2013-01-01
Nutritional genomics has exploded in the last decade, yielding insights—both nutrigenomic and nutrigenetic—into the physiology of dietary interactions and our genes. Among these are insights into the regulation of magnesium transport and homeostasis and mechanisms underlying magnesium’s role in insulin and glucose handling. Recent observational evidence has attempted to examine some promising research avenues on interaction between genetics and dietary magnesium in relation to diabetes and diabetes risk factors. This brief review summarizes the recent evidence on dietary magnesium’s role in diabetes and related traits in the presence of underlying genetic risk, and discusses future potential research directions. PMID:24322525
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Directory of Open Access Journals (Sweden)
Wang Kai
2011-05-01
Full Text Available Abstract Background Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs have multiple cores, whereas Graphics Processing Units (GPUs also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits. Findings Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1 the interaction of SNPs within it in parallel, and 2 the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run. Conclusions GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from http://www.cceb.upenn.edu/~mli/software/GENIE/.
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Langenberg, C.; Sharp, S.; Forouhi, N.G.; Feskens, E.J.M.
2011-01-01
Aims/Hypothesis: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for
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Directory of Open Access Journals (Sweden)
Pablo Perez-Martinez
Full Text Available Glucokinase Regulatory Protein (GCKR plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS risk.To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP and n-3 PUFA in MetS subjects.Homeostasis model assessment of insulin resistance (HOMA-IR, HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019, C-peptide (P = 0.004, HOMA-IR (P = 0.008 and CRP (P = 0.032 as compared with subjects carrying the minor T-allele (Leu446. In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.ClinicalTrials.gov NCT00429195.
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Institute of Scientific and Technical Information of China (English)
Roger B. Sher
2017-01-01
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that results in the progres-sive death of motor neurons, leading to paralysis and eventual death. There is presently no cure for ALS, and only two drugs are available, neither of which provide significant extension of life. The wide variation in onset and progression of the disease, both in sporadic and even in strongly penetrant monogenic famil-ial forms of ALS, indicate that in addition to background genetic variation impacting the disease process, environmental exposures are likely contributors. Epidemiological evidence worldwide implicates exposures to bacterial toxins, heavy metals, pesticides, and trauma as probable environmental factors. Here, we review current advances in gene-environment interactions in ALS animal models. We report our recent discov-eries in a zebrafish model of ALS in relation to exposure to the cyanobacterial toxin BMAA, and discuss several results from mouse models that show interactions with exposure to mercury and statin drugs, both leading to acceleration of the disease process. The increasing research into this combinatorial gene-environ-ment process is just starting, but shows early promise to uncover the underlying biochemical pathways that instigate the initial motor neuron defects and lead to their rapidly progressive dysfunction.
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Genetic Variability of Show Jumping Attributes in Young Horses Commencing Competing
Directory of Open Access Journals (Sweden)
Tomasz Próchniak
2015-08-01
Full Text Available The aim of the study was to select traits that may constitute a prospective criterion for breeding value prediction of young horses. The results of 1,232 starts of 894 four-, five-, six-, and seven-year-old horses, obtained during jumping championships for young horses which had not been evaluated in, alternative to championships, training centres were analyed. Nine traits were chosen of those recorded: ranking in the championship, elimination (y/n, conformation, rating of style on day one, two, and three, and penalty points on day one, two, and three of a championship. (Covariance components were estimated via the Gibbs sampling procedure and adequate (covariance component ratios were calculated. Statistical classifications were trait dependent but all fitted random additive genetic and permanent environment effects. It was found that such characteristics as penalty points and jumping style are potential indicators of jumping ability, and the genetic variability of the traits was within the range of 14% to 27%. Given the low genetic correlations between the conformation and other results achieved on the parkour, the relevance of assessment of conformation in four-years-old horses has been questioned.
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Gottlieb, S.; Ruvkun, G.
1994-01-01
Under conditions of high population density and low food, Caenorhabditis elegans forms an alternative third larval stage, called the dauer stage, which is resistant to desiccation and harsh environments. Genetic analysis of some dauer constitutive (Daf-c) and dauer defective (Daf-d) mutants has revealed a complex pathway that is likely to function in particular neurons and/or responding tissues. Here we analyze the genetic interactions between three genes which comprise a branch of the dauer ...
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Gorton, Amanda J; Heath, Katy D; Pilet-Nayel, Marie-Laure; Baranger, Alain; Stinchcombe, John R
2012-11-01
Mutualisms are known to be genetically variable, where the genotypes differ in the fitness benefits they gain from the interaction. To date, little is known about the loci that underlie such genetic variation in fitness or whether the loci influencing fitness are partner specific, and depend on the genotype of the interaction partner. In the legume-rhizobium mutualism, one set of potential candidate genes that may influence the fitness benefits of the symbiosis are the plant genes involved in the initiation of the signaling pathway between the two partners. Here we performed quantitative trait loci (QTL) mapping in Medicago truncatula in two different rhizobium strain treatments to locate regions of the genome influencing plant traits, assess whether such regions are dependent on the genotype of the rhizobial mutualist (QTL × rhizobium strain), and evaluate the contribution of sequence variation at known symbiosis signaling genes. Two of the symbiotic signaling genes, NFP and DMI3, colocalized with two QTL affecting average fruit weight and leaf number, suggesting that natural variation in nodulation genes may potentially influence plant fitness. In both rhizobium strain treatments, there were QTL that influenced multiple traits, indicative of either tight linkage between loci or pleiotropy, including one QTL with opposing effects on growth and reproduction. There was no evidence for QTL × rhizobium strain or genotype × genotype interactions, suggesting either that such interactions are due to small-effect loci or that more genotype-genotype combinations need to be tested in future mapping studies.
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Goudie, Catherine; Coltin, Hallie; Witkowski, Leora; Mourad, Stephanie; Malkin, David; Foulkes, William D
2017-08-01
Identifying cancer predisposition syndromes in children with tumors is crucial, yet few clinical guidelines exist to identify children at high risk of having germline mutations. The McGill Interactive Pediatric OncoGenetic Guidelines project aims to create a validated pediatric guideline in the form of a smartphone/tablet application using algorithms to process clinical data and help determine whether to refer a child for genetic assessment. This paper discusses the initial stages of the project, focusing on its overall structure, the methodology underpinning the algorithms, and the upcoming algorithm validation process. © 2017 Wiley Periodicals, Inc.
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DEFF Research Database (Denmark)
Alemu, Setegn Worku; Berg, Peer; Janss, Luc
2016-01-01
interactions in group-housed mink. Furthermore, we investigated whether systematic non-genetic interactions between kin or individuals of the same sex influence the estimates of genetic parameters. As a second objective, we clarify the relationship between estimates of the traditional IGE model and a family...
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St Pourcain, B; Robinson, E B; Anttila, V; Sullivan, B B; Maller, J; Golding, J; Skuse, D; Ring, S; Evans, D M; Zammit, S; Fisher, S E; Neale, B M; Anney, R J L; Ripke, S; Hollegaard, M V; Werge, T; Ronald, A; Grove, J; Hougaard, D M; Børglum, A D; Mortensen, P B; Daly, M J; Davey Smith, G
2018-02-01
Difficulties in social communication are part of the phenotypic overlap between autism spectrum disorders (ASD) and schizophrenia. Both conditions follow, however, distinct developmental patterns. Symptoms of ASD typically occur during early childhood, whereas most symptoms characteristic of schizophrenia do not appear before early adulthood. We investigated whether overlap in common genetic influences between these clinical conditions and impairments in social communication depends on the developmental stage of the assessed trait. Social communication difficulties were measured in typically-developing youth (Avon Longitudinal Study of Parents and Children, N⩽5553, longitudinal assessments at 8, 11, 14 and 17 years) using the Social Communication Disorder Checklist. Data on clinical ASD (PGC-ASD: 5305 cases, 5305 pseudo-controls; iPSYCH-ASD: 7783 cases, 11 359 controls) and schizophrenia (PGC-SCZ2: 34 241 cases, 45 604 controls, 1235 trios) were either obtained through the Psychiatric Genomics Consortium (PGC) or the Danish iPSYCH project. Overlap in genetic influences between ASD and social communication difficulties during development decreased with age, both in the PGC-ASD and the iPSYCH-ASD sample. Genetic overlap between schizophrenia and social communication difficulties, by contrast, persisted across age, as observed within two independent PGC-SCZ2 subsamples, and showed an increase in magnitude for traits assessed during later adolescence. ASD- and schizophrenia-related polygenic effects were unrelated to each other and changes in trait-disorder links reflect the heterogeneity of genetic factors influencing social communication difficulties during childhood versus later adolescence. Thus, both clinical ASD and schizophrenia share some genetic influences with impairments in social communication, but reveal distinct developmental profiles in their genetic links, consistent with the onset of clinical symptoms.
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Directory of Open Access Journals (Sweden)
D. Pagliari
2015-01-01
Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.
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Stergiadis, S; Bieber, A; Franceschin, E; Isensee, A; Eyre, M D; Maurer, V; Chatzidimitriou, E; Cozzi, G; Bapst, B; Stewart, G; Gordon, A; Butler, G
2015-05-15
This study investigated the effect of, and interactions between, contrasting crossbreed genetics (US Brown Swiss [BS] × Improved Braunvieh [BV] × Original Braunvieh [OB]) and feeding regimes (especially grazing intake and pasture type) on milk fatty acid (FA) profiles. Concentrations of total polyunsaturated FAs, total omega-3 FAs and trans palmitoleic, vaccenic, α-linolenic, eicosapentaenoic and docosapentaenoic acids were higher in cows with a low proportion of BS genetics. Highest concentrations of the nutritionally desirable FAs, trans palmitoleic, vaccenic and eicosapentaenoic acids were found for cows with a low proportion of BS genetics (0-24% and/or 25-49%) on high grazing intake (75-100% of dry matter intake) diets. Multivariate analysis indicated that the proportion of OB genetics is a positive driver for nutritionally desirable monounsaturated and polyunsaturated FAs while BS genetics proportion was positive driver for total and undesirable individual saturated FAs. Significant genetics × feeding regime interactions were also detected for a range of FAs. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Genetic interactions between planar cell polarity genes cause diverse neural tube defects in mice
Directory of Open Access Journals (Sweden)
Jennifer N. Murdoch
2014-10-01
Full Text Available Neural tube defects (NTDs are among the commonest and most severe forms of developmental defect, characterized by disruption of the early embryonic events of central nervous system formation. NTDs have long been known to exhibit a strong genetic dependence, yet the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure is disrupted in mice homozygous for mutations in planar cell polarity (PCP pathway genes, providing a strong link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes in humans with NTDs, although the range of phenotypes is greater than in the mouse mutants. In addition, the sequence variants detected in affected humans are heterozygous, and can often be detected in unaffected individuals. It has been suggested that interactions between multiple heterozygous gene mutations cause the NTDs in humans. To determine the phenotypes produced in double heterozygotes, we bred mice with all three pairwise combinations of Vangl2Lp, ScribCrc and Celsr1Crsh mutations, the most intensively studied PCP mutants. The majority of double-mutant embryos had open NTDs, with the range of phenotypes including anencephaly and spina bifida, therefore reflecting the defects observed in humans. Strikingly, even on a uniform genetic background, variability in the penetrance and severity of the mutant phenotypes was observed between the different double-heterozygote combinations. Phenotypically, Celsr1Crsh;Vangl2Lp;ScribCrc triply heterozygous mutants were no more severe than doubly heterozygous or singly homozygous mutants. We propose that some of the variation between double-mutant phenotypes could be attributed to the nature of the protein disruption in each allele: whereas ScribCrc is a null mutant and produces no Scrib protein, Celsr1Crsh and Vangl2Lp homozygotes both express mutant proteins, consistent with dominant effects. The variable outcomes of these genetic
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Genetic transformation of Neisseria gonorrhoeae shows a strand preference
Duffin, Paul M.; Seifert, H. Steven
2012-01-01
Natural transformation is the main means of horizontal genetic exchange in the obligate human pathogen Neisseria gonorrhoeae. Neisseria spp. have been shown to preferentially take up and transform their own DNA by recognizing a non-palindromic 10 or 12 nucleotide DNA uptake sequence (DUS10 or DUS12). We investigated the ability of the DUS12 to enhance single-stranded DNA (ssDNA) transformation. Given the non-palindromic nature of the DUS12, we tested whether both strands of the DUS equally en...
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Directory of Open Access Journals (Sweden)
Suresh Gopalan
2007-10-01
Full Text Available Viruses constitute a major class of pathogens that infect a variety of hosts. Understanding the intricacies of signaling during host-virus interactions should aid in designing disease prevention strategies and in understanding mechanistic aspects of host and pathogen signaling machinery.An Arabidopsis mutant, B149, impaired in susceptibility to Tobacco etch virus (TEV, a positive strand RNA virus of picoRNA family, was identified using a high-throughput genetic screen and a counterselection scheme. The defects include initiation of infection foci, rate of cell-to-cell movement and long distance movement.The defect in infectivity is conferred by a recessive locus. Molecular genetic analysis and complementation analysis with three alleles of a previously published mutant lsp1 (loss of susceptibility to potyviruses indicate a genetic interaction conferring haploinsufficiency between the B149 locus and certain alleles of lsp1 resulting in impaired host susceptibility. The pattern of restriction of TEV foci on leaves at or near the boundaries of certain cell types and leaf boundaries suggest dysregulation of a multidirectional non-cell autonomous regulatory mechanism. Understanding the nature of this multidirectional signal and the molecular genetic mechanism conferring it should potentially reveal a novel arsenal in the cellular machinery.
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Pool, John E.
2015-01-01
North American populations of Drosophila melanogaster derive from both European and African source populations, but despite their importance for genetic research, patterns of ancestry along their genomes are largely undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome, which may have implications for reference alignment, association mapping, and population genomic studies in Drosophila. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Combining my estimate of admixture timing with historical records, I provide the first estimate of natural generation time for this species (approximately 15 generations per year). Ancestry levels were found to vary strikingly across the genome, with less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes (e.g., circadian rhythm). An important role for natural selection during the admixture process was further supported by evidence that many unlinked pairs of loci showed a deficiency of Africa–Europe allele combinations between them. Numerous epistatic fitness interactions may therefore exist between African and European genotypes, leading to ongoing selection against incompatible variants. By focusing on hubs in this network of fitness interactions, I identified a set of interacting loci that include genes with roles in sensation and neuropeptide/hormone reception. These findings suggest that admixed D. melanogaster samples could become an important study system for the genetics of early-stage isolation between populations. PMID:26354524
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Caenorhabditis elegans ABCRNAi transporters interact genetically with rde-2 and mut-7.
Sundaram, Prema; Han, Wang; Cohen, Nancy; Echalier, Benjamin; Albin, John; Timmons, Lisa
2008-02-01
RNA interference (RNAi) mechanisms are conserved and consist of an interrelated network of activities that not only respond to exogenous dsRNA, but also perform endogenous functions required in the fine tuning of gene expression and in maintaining genome integrity. Not surprisingly, RNAi functions have widespread influences on cellular function and organismal development. Previously, we observed a reduced capacity to mount an RNAi response in nine Caenorhabditis elegans mutants that are defective in ABC transporter genes (ABC(RNAi) mutants). Here, we report an exhaustive study of mutants, collectively defective in 49 different ABC transporter genes, that allowed for the categorization of one additional transporter into the ABC(RNAi) gene class. Genetic complementation tests reveal functions for ABC(RNAi) transporters in the mut-7/rde-2 branch of the RNAi pathway. These second-site noncomplementation interactions suggest that ABC(RNAi) proteins and MUT-7/RDE-2 function together in parallel pathways and/or as multiprotein complexes. Like mut-7 and rde-2, some ABC(RNAi) mutants display transposon silencing defects. Finally, our analyses reveal a genetic interaction network of ABC(RNAi) gene function with respect to this part of the RNAi pathway. From our results, we speculate that the coordinated activities of ABC(RNAi) transporters, through their effects on endogenous RNAi-related mechanisms, ultimately affect chromosome function and integrity.
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Barnes, J C; Jacobs, Bruce A
2013-01-01
Despite mounds of evidence to suggest that neighborhood structural factors predict violent behavior, almost no attention has been given to how these influences work synergistically (i.e., interact) with an individual's genetic propensity toward violent behavior. Indeed, two streams of research have, heretofore, flowed independently of one another. On one hand, criminologists have underscored the importance of neighborhood context in the etiology of violence. On the other hand, behavioral geneticists have argued that individual-level genetic propensities are important for understanding violence. The current study seeks to integrate these two compatible frameworks by exploring gene-environment interactions (GxE). Two GxEs were examined and supported by the data (i.e., the National Longitudinal Study of Adolescent Health). Using a scale of genetic risk based on three dopamine genes, the analysis revealed that genetic risk had a greater influence on violent behavior when the individual was also exposed to neighborhood disadvantage or when the individual was exposed to higher violent crime rates. The relevance of these findings for criminological theorizing was considered.
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Kim, Jihye; Kraft, Peter; Hagan, Kaitlin A; Harrington, Laura B; Lindstroem, Sara; Kabrhel, Christopher
2018-06-01
Venous thromboembolism (VTE) is highly heritable. Physical activity, physical inactivity and body mass index (BMI) are also risk factors, but evidence of interaction between genetic and environmental risk factors is limited. Data on 2,134 VTE cases and 3,890 matched controls were obtained from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS). We calculated a weighted genetic risk score (wGRS) using 16 single nucleotide polymorphisms associated with VTE risk in published genome-wide association studies (GWAS). Data on three risk factors, physical activity (metabolic equivalent [MET] hours per week), physical inactivity (sitting hours per week) and BMI, were obtained from biennial questionnaires. VTE cases were incident since cohort inception; controls were matched to cases on age, cohort, and genotype array. Using conditional logistic regression, we assessed joint effects and interaction effects on both additive and multiplicative scales. We also ran models using continuous wGRS stratified by risk-factor categories. We observed a supra-additive interaction between wGRS and BMI. Having both high wGRS and high BMI was associated with a 3.4-fold greater risk of VTE (relative excess risk due to interaction = 0.69, p = 0.046). However, we did not find evidence for a multiplicative interaction with BMI. No interactions were observed for physical activity or inactivity. We found a synergetic effect between a genetic risk score and high BMI on the risk of VTE. Intervention efforts lowering BMI to decrease VTE risk may have particularly large beneficial effects among individuals with high genetic risk. © 2018 WILEY PERIODICALS, INC.
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Genetic by environment interaction for post weaning growth traits in tropical cattle
Navès, Michel; Menendez Buxadera, Alberto; Farant, Alain; Mandonnet, Nathalie
2006-01-01
Genetic by environment interactions for post weaning traits were studied in a local breed of cattle, well adapted to tropical conditions. After weaning, 444 beef calves of both sexes were separated within two management systems, either in intensive fattening or at pasture. The traits analysed included weights at standard age, of 365 days (W12), 455 days (W15) and 545 days (W18), and post weaning growth rates from weaning until 15 months (PWG15) or 18 months (PWG18). (Co)varianc...
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Vlasblom, James; Gagarinova, Alla; Phanse, Sadhna; Graham, Chris; Yousif, Fouad; Ding, Huiming; Xiong, Xuejian; Nazarians-Armavil, Anaies; Alamgir, Md; Ali, Mehrab; Pogoutse, Oxana; Pe'er, Asaf; Arnold, Roland; Michaut, Magali; Parkinson, John; Golshani, Ashkan; Whitfield, Chris; Wodak, Shoshana J.; Moreno-Hagelsieb, Gabriel; Greenblatt, Jack F.; Emili, Andrew
2011-01-01
As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium) and prototrophic (minimal medium) culture conditions. The differential patterns of genetic interactions detected among >235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens) and an important target. PMID:22125496
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Directory of Open Access Journals (Sweden)
Mohan Babu
2011-11-01
Full Text Available As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium and prototrophic (minimal medium culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens and an important target.
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Directory of Open Access Journals (Sweden)
Thomas W Winkler
2015-10-01
Full Text Available Genome-wide association studies (GWAS have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI, a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE, sex-specific effects (G x SEX or age-specific effects that differed between men and women (G x AGE x SEX. For BMI, we identified 15 loci (11 previously established for main effects, four novel that showed significant (FDR<5% age-specific effects, of which 11 had larger effects in younger (<50y than in older adults (≥50y. No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
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Directory of Open Access Journals (Sweden)
Gilberto Bento
2017-02-01
Full Text Available Negative frequency-dependent selection (NFDS is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR- locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into
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Bento, Gilberto; Routtu, Jarkko; Fields, Peter D; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter
2017-02-01
Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis.
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Islam, Mohammed M; Smith, Derek K; Niu, Wenze; Fang, Sanhua; Iqbal, Nida; Sun, Guoqiang; Shi, Yanhong; Zhang, Chun-Li
2015-11-10
The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming.
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Directory of Open Access Journals (Sweden)
Ye Ping
2005-12-01
Full Text Available Abstract Background Synthetic lethality experiments identify pairs of genes with complementary function. More direct functional associations (for example greater probability of membership in a single protein complex may be inferred between genes that share synthetic lethal interaction partners than genes that are directly synthetic lethal. Probabilistic algorithms that identify gene modules based on motif discovery are highly appropriate for the analysis of synthetic lethal genetic interaction data and have great potential in integrative analysis of heterogeneous datasets. Results We have developed Genetic Interaction Motif Finding (GIMF, an algorithm for unsupervised motif discovery from synthetic lethal interaction data. Interaction motifs are characterized by position weight matrices and optimized through expectation maximization. Given a seed gene, GIMF performs a nonlinear transform on the input genetic interaction data and automatically assigns genes to the motif or non-motif category. We demonstrate the capacity to extract known and novel pathways for Saccharomyces cerevisiae (budding yeast. Annotations suggested for several uncharacterized genes are supported by recent experimental evidence. GIMF is efficient in computation, requires no training and automatically down-weights promiscuous genes with high degrees. Conclusion GIMF effectively identifies pathways from synthetic lethality data with several unique features. It is mostly suitable for building gene modules around seed genes. Optimal choice of one single model parameter allows construction of gene networks with different levels of confidence. The impact of hub genes the generic probabilistic framework of GIMF may be used to group other types of biological entities such as proteins based on stochastic motifs. Analysis of the strongest motifs discovered by the algorithm indicates that synthetic lethal interactions are depleted between genes within a motif, suggesting that synthetic
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International Nuclear Information System (INIS)
Finch, W.I.; Granger, H.C.; Lupe, R.; McCammon, R.B.
1980-01-01
Current methods of evaluating favourability for undiscovered uranium resources are unduly subjective, quite possibly inconsistent and, as a consequence, of questionable reliability. This research is aimed at reducing the subjectivity and increasing the reliability by designing an improved method that depends largely on geological data and their statistical frequency of occurrence. This progress report outlines a genetic approach to modelling the geological factors that controlled uranium mineralization in order to evaluate the favourability for the occurrence of undiscovered uranium deposits of the type modelled. A genetic model is constructed from all the factors that describe the processes, in chronological sequence, that formed uranium deposits thought to have a common origin. The field and laboratory evidence for the processes constitute a geologic-occurrence base that parallels the chronological sequence of events. The genetic model and the geologic-occurrence base are portrayed as two columns of an interactive matrix called the ''genetic-geologic model''. For each column, eight chronological stages are used to describe the overall formation of the uranium deposits. These stages consist of (1) precursor processes; (2) host-rock formation; (3) preparation of host-rock; (4) uranium-source development; (5) transport of uranium; (6) primary uranium deposition; (7) post-deposition modification; and (8) preservation. To apply the genetic-geological model to evaluate favourability, a question is posed that determines the presence or absence of each attribute listed under the geologic-occurrence base. By building a logic circuit of the attributes according to either their essential or non-essential nature, the resultant match between a well-documented control area and the test area may be determined. The degree of match is a measure of favourability for uranium occurrence as hypothesized in the genetic model
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Okoye, Namdi N. S.
2009-01-01
The study tried to examine the interaction between two independent variables of selective attention and cognitive development on Achievement in Genetics at the Secondary School level. In looking at the problem of this study three null hypotheses were generated for testing at 0.05 level of significance. Factorial Analysis of Variance design with…
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Directory of Open Access Journals (Sweden)
Elif eTunc-Ozcan
2014-08-01
Full Text Available Fetal alcohol spectrum disorder (FASD presents a collection of symptoms representing physiological and behavioral phenotypes caused by maternal alcohol consumption. Symptom severity is modified by genetic differences in fetal susceptibility and resistance as well as maternal genetic factors such as maternal alcohol sensitivity. Animal models demonstrate that both maternal and paternal genetics contribute to the variation in the fetus’ vulnerability to alcohol exposure. Maternal and paternal genetics define the variations in these phenotypes even without the effect of alcohol in utero, as most of these traits are polygenic, non-Mendelian, in their inheritance. In addition, the epigenetic alterations that instigate the alcohol induced neurodevelopmental deficits can interact with the polygenic inheritance of respective traits. Here, based on specific examples, we present the hypothesis that the principles of non-Mendelian inheritance, or ‘exceptions’ to Mendelian genetics, can be the driving force behind the severity of the prenatal alcohol-exposed individual’s symptomology. One such exception is when maternal alleles lead to an altered intrauterine hormonal environment and, therefore, produce variations in the long-term consequences on the development of the alcohol-exposed fetus. Another exception is when epigenetic regulation of allele-specific gene expression generates disequilibrium between the maternal versus paternal genetic contributions, and thereby, modifies the effect of prenatal alcohol exposure on the fetus. We propose that these situations in which one parent has an exaggerated influence over the offspring’s vulnerability to prenatal alcohol are major contributing mechanisms responsible for the variations in the symptomology of FASD in the exposed generation and beyond.
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Aalfs, Cora M.; Oort, Frans J.; de Haes, Hanneke C. J. M.; Leschot, Nico J.; Smets, Ellen M. A.
2006-01-01
OBJECTIVE: To investigate the influence of a pregnancy and other counselee characteristics on several aspects of counselor-counselee interaction during the initial clinical genetic consultation. METHODS: The consultations, of a group of pregnant women (n = 82) and of a control group of non-pregnant
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Pool, John E
2015-12-01
North American populations of Drosophila melanogaster derive from both European and African source populations, but despite their importance for genetic research, patterns of ancestry along their genomes are largely undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome, which may have implications for reference alignment, association mapping, and population genomic studies in Drosophila. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Combining my estimate of admixture timing with historical records, I provide the first estimate of natural generation time for this species (approximately 15 generations per year). Ancestry levels were found to vary strikingly across the genome, with less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes (e.g., circadian rhythm). An important role for natural selection during the admixture process was further supported by evidence that many unlinked pairs of loci showed a deficiency of Africa-Europe allele combinations between them. Numerous epistatic fitness interactions may therefore exist between African and European genotypes, leading to ongoing selection against incompatible variants. By focusing on hubs in this network of fitness interactions, I identified a set of interacting loci that include genes with roles in sensation and neuropeptide/hormone reception. These findings suggest that admixed D. melanogaster samples could become an important study system for the genetics of early-stage isolation between populations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
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International Nuclear Information System (INIS)
Meza, Mercedes; Gandolfi, A. Jay; Klimecki, Walter T.
2007-01-01
The complexity of arsenic toxicology has confounded the identification of specific pathways of disease causation. One focal point of arsenic research is aimed at fully characterizing arsenic biotransformation in humans, a process that appears to be quite variable, producing a mixture of several arsenic species with greatly differing toxic potencies. In an effort to characterize genetic determinants of variability in arsenic biotransformation, a genetic association study of 135 subjects in western Sonora, Mexico was performed by testing 23 polymorphic sites in three arsenic biotransformation candidate genes. One gene, arsenic 3 methyltransferase (AS3MT), was strongly associated with the ratio of urinary dimethylarsinic acid to monomethylarsonic acid (D/M) in children (7-11 years) but not in adults (18-79 years). Subsequent analyses revealed that the high D/M values associated with variant AS3MT alleles were primarily due to lower levels of monomethylarsonic acid as percent of total urinary arsenic (%MMA5). In light of several reports of arsenic-induced disease being associated with relatively high %MMA5 levels, these findings raise the possibility that variant AS3MT individuals may suffer less risk from arsenic exposure than non-variant individuals. These analyses also provide evidence that, in this population, regardless of AS3MT variant status, children tend to have lower %MMA5 values than adults, suggesting that the global developmental regulation of arsenic biotransformation may interact with genetic variants in metabolic genes to result in novel genetic effects such as those in this report
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Directory of Open Access Journals (Sweden)
Carlo Renieri
2011-10-01
Full Text Available Two coat phenotypes exist in Alpaca, Huacaya and Suri. The two coats show different fleece structure, textile characteristics and prices on the market. Although present scientific knowledge suggests a simple genetic model of inheritance, there is a tendency to manage and consider the two phenotypes as two different breeds. A 13 microsatellite panel was used in this study to assess genetic distance between Suri and Huacaya alpacas in a sample of non-related animals from two phenotypically pure flocks at the Illpa-Puno experimental station in Quimsachata, Peru. The animals are part of a germplasm established approximately 20 years ago and have been bred separately according to their coat type since then. Genetic variability parameters were also calculated. The data were statistically analyzed using the software Genalex 6.3, Phylip 3.69 and Fstat 2.9.3.2. The sample was tested for Hardy-Weinberg equilibrium (HWE and after strict Bonferroni correction only one locus (LCA37 showed deviation from equilibrium (Ploci associations showed significant disequilibrium. Observed heterozygosis (Ho= 0.766; SE=0.044, expected heterozygosis (He=0.769; SE=0.033, number of alleles (Na=9.667, SE=0.772 and Fixation index (F=0.004; SE=0.036 are comparable to data from previous studies. Measures of genetic distance were 0.06 for Nei’s and 0.03 for Cavalli-Sforza’s. The analysis of molecular variance reported no existing variance between populations. Considering the origin of the animals, their post domestication evolution and the reproductive practices in place, the results do not show genetic differentiation between the two populations for the studied loci.
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Directory of Open Access Journals (Sweden)
Harlid Sophia
2012-06-01
Full Text Available Abstract Background Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs and height, body mass index (BMI and hormone replacement therapy (HRT. Methods We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case–control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model. Results One SNP (rs851987 in ESR1 tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007 and rs13281615 (on 8q24 tended to confer risk only in non users of HRT (p-for interaction = 0.03. There were no significant interactions after correction for multiple testing. Conclusions We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.
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Mapping Haplotype-haplotype Interactions with Adaptive LASSO
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Li Ming
2010-08-01
Full Text Available Abstract Background The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity. Results In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L1-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L1-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA neonates data set, and significant interactions between different genomes are detected. Conclusions As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be
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Ussar, Siegfried; Griffin, Nicholas W.; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I.; Kahn, C. Ronald
2015-01-01
Obesity, diabetes and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly-used inbred strains of mice – obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ, from Jackson Laboratory and obesity-prone, but diabetes resistant 129S6/SvEvTac from Taconic - plus three derivative lines generated by breeding these strains in a new, common environm...
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Harper, Kathryn M; Hiramoto, Takeshi; Tanigaki, Kenji; Kang, Gina; Suzuki, Go; Trimble, William; Hiroi, Noboru
2012-08-01
Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception-and their genetic underpinnings-are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene.
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Koo, Ching Lee; Liew, Mei Jing; Mohamad, Mohd Saberi; Salleh, Abdul Hakim Mohamed
2013-01-01
Recently, the greatest statistical computational challenge in genetic epidemiology is to identify and characterize the genes that interact with other genes and environment factors that bring the effect on complex multifactorial disease. These gene-gene interactions are also denoted as epitasis in which this phenomenon cannot be solved by traditional statistical method due to the high dimensionality of the data and the occurrence of multiple polymorphism. Hence, there are several machine learning methods to solve such problems by identifying such susceptibility gene which are neural networks (NNs), support vector machine (SVM), and random forests (RFs) in such common and multifactorial disease. This paper gives an overview on machine learning methods, describing the methodology of each machine learning methods and its application in detecting gene-gene and gene-environment interactions. Lastly, this paper discussed each machine learning method and presents the strengths and weaknesses of each machine learning method in detecting gene-gene interactions in complex human disease.
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A Review for Detecting Gene-Gene Interactions Using Machine Learning Methods in Genetic Epidemiology
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Ching Lee Koo
2013-01-01
Full Text Available Recently, the greatest statistical computational challenge in genetic epidemiology is to identify and characterize the genes that interact with other genes and environment factors that bring the effect on complex multifactorial disease. These gene-gene interactions are also denoted as epitasis in which this phenomenon cannot be solved by traditional statistical method due to the high dimensionality of the data and the occurrence of multiple polymorphism. Hence, there are several machine learning methods to solve such problems by identifying such susceptibility gene which are neural networks (NNs, support vector machine (SVM, and random forests (RFs in such common and multifactorial disease. This paper gives an overview on machine learning methods, describing the methodology of each machine learning methods and its application in detecting gene-gene and gene-environment interactions. Lastly, this paper discussed each machine learning method and presents the strengths and weaknesses of each machine learning method in detecting gene-gene interactions in complex human disease.
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Zhang, Qingrun; Long, Quan; Ott, Jurg
2014-06-01
Identifying gene-gene interaction is a hot topic in genome wide association studies. Two fundamental challenges are: (1) how to smartly identify combinations of variants that may be associated with the trait from astronomical number of all possible combinations; and (2) how to test epistatic interaction when all potential combinations are available. We developed AprioriGWAS, which brings two innovations. (1) Based on Apriori, a successful method in field of Frequent Itemset Mining (FIM) in which a pattern growth strategy is leveraged to effectively and accurately reduce search space, AprioriGWAS can efficiently identify genetically associated genotype patterns. (2) To test the hypotheses of epistasis, we adopt a new conditional permutation procedure to obtain reliable statistical inference of Pearson's chi-square test for the [Formula: see text] contingency table generated by associated variants. By applying AprioriGWAS to age-related macular degeneration (AMD) data, we found that: (1) angiopoietin 1 (ANGPT1) and four retinal genes interact with Complement Factor H (CFH). (2) GO term "glycosaminoglycan biosynthetic process" was enriched in AMD interacting genes. The epistatic interactions newly found by AprioriGWAS on AMD data are likely true interactions, since genes interacting with CFH are retinal genes, and GO term enrichment also verified that interaction between glycosaminoglycans (GAGs) and CFH plays an important role in disease pathology of AMD. By applying AprioriGWAS on Bipolar disorder in WTCCC data, we found variants without marginal effect show significant interactions. For example, multiple-SNP genotype patterns inside gene GABRB2 and GRIA1 (AMPA subunit 1 receptor gene). AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system. The GABRB2 mediates the fastest inhibitory synaptic transmission in the central nervous system. GRIA1 and GABRB2 are relevant to mental disorders supported by multiple
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Maternal-Zygotic Epistasis and the Evolution of Genetic Diseases
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Nicholas K. Priest
2010-01-01
Full Text Available Many birth defects and genetic diseases are expressed in individuals that do not carry the disease causing alleles. Genetic diseases observed in offspring can be caused by gene expression in mothers and by interactions between gene expression in mothers and offspring. It is not clear whether the underlying pattern of gene expression (maternal versus offspring affects the incidence of genetic disease. Here we develop a 2-locus population genetic model with epistatic interactions between a maternal gene and a zygotic gene to address this question. We show that maternal effect genes that affect disease susceptibility in offspring persist longer and at higher frequencies in a population than offspring genes with the same effects. We find that specific forms of maternal-zygotic epistasis can maintain disease causing alleles at high frequencies over a range of plausible values. Our findings suggest that the strength and form of epistasis and the underlying pattern of gene expression may greatly influence the prevalence of human genetic diseases.
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Background: Leukocyte telomere length (LTL) attrition has been associated with age-related diseases. Telomerase RNA Component (TERC) genetic variants have been associated with LTL; whereas fatty acids (FAs) can interact with genetic factors and influence in aging. We explore whether variability at t...
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Exploring Genetic Suppression Interactions on a Global Scale
van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C.; Yamaguchi, Takafumi N.; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire
2016-01-01
Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insig...
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Mapping determinants of gene expression plasticity by genetical genomics in C. elegans.
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Yang Li
2006-12-01
Full Text Available Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 degrees C and 24 degrees C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii and N2 (Bristol. No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 degrees C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity.
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Energy Technology Data Exchange (ETDEWEB)
McInerney, Joseph D.
2003-03-31
"Genetics and Major Psychiatric Disorders: A Program for Genetic Counselors" provides an introduction to psychiatric genetics, with a focus on the genetics of common complex disease, for genetics professionals. The program is available as a CD-ROM and an online educational resource. The on-line version requires a direct internet connection. Each educational module begins with an interactive case study that raises significant issues addressed in each module. In addition, case studies provided throughout the educational materials support teaching of major concepts. Incorporated throughout the content are expert video clips, video clips from individuals affected by psychiatric illness, and optional "learn more" materials that offer greater depth about a particular topic. The structure of the CD-ROM permits self-navigation, but we have suggested a sequence that allows materials to build upon each other. At any point in the materials, users may pause and look up terms in the glossary or review the DSM-IV criteria for selected psychiatric disorders. A detailed site map is available for those who choose to self navigate through the content.
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Directory of Open Access Journals (Sweden)
Heather A Lawson
2011-09-01
Full Text Available Context-dependent genetic effects, including genotype-by-environment and genotype-by-sex interactions, are a potential mechanism by which genetic variation of complex traits is maintained in populations. Pleiotropic genetic effects are also thought to play an important role in evolution, reflecting functional and developmental relationships among traits. We examine context-dependent genetic effects at pleiotropic loci associated with normal variation in multiple metabolic syndrome (MetS components (obesity, dyslipidemia, and diabetes-related traits. MetS prevalence is increasing in Western societies and, while environmental in origin, presents substantial variation in individual response. We identify 23 pleiotropic MetS quantitative trait loci (QTL in an F(16 advanced intercross between the LG/J and SM/J inbred mouse strains (Wustl:LG,SM-G16; n = 1002. Half of each family was fed a high-fat diet and half fed a low-fat diet; and additive, dominance, and parent-of-origin imprinting genotypic effects were examined in animals partitioned into sex, diet, and sex-by-diet cohorts. We examine the context-dependency of the underlying additive, dominance, and imprinting genetic effects of the traits associated with these pleiotropic QTL. Further, we examine sequence polymorphisms (SNPs between LG/J and SM/J as well as differential expression of positional candidate genes in these regions. We show that genetic associations are different in different sex, diet, and sex-by-diet settings. We also show that over- or underdominance and ecological cross-over interactions for single phenotypes may not be common, however multidimensional synthetic phenotypes at loci with pleiotropic effects can produce situations that favor the maintenance of genetic variation in populations. Our findings have important implications for evolution and the notion of personalized medicine.
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Byrne, Enda M; Raheja, Uttam; Stephens, Sarah H.; Heath, Andrew C; Madden, Pamela AF; Vaswani, Dipika; Nijjar, Gagan V.; Ryan, Kathleen A.; Youssufi, Hassaan; Gehrman, Philip R; Shuldiner, Alan R; Martin, Nicholas G; Montgomery, Grant W; Wray, Naomi R; Nelson, Elliot C; Mitchell, Braxton D; Postolache, Teodor T
2015-01-01
Objective To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. Methods A meta-analysis of genome-wide association studies (GWAS) conducted in Australian and Amish populations in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered. The total sample size was 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ) were calculated to test for overlap in risk between psychiatric disorders and seasonality. Results The most significant association was with rs11825064 (p = 1.7 × 10−6, β = 0.64, S.E = 0.13), an intergenic SNP found on chromosome 11. The evidence for overlap in risk factors was strongest for SCZ and seasonality, with the SCZ genetic profile scores explaining 3% of the variance in log-transformed GSS. BD genetic profile scores were also significantly associated with seasonality, although at much weaker levels, and no evidence for overlap in risk was detected between MDD and seasonality. Conclusions Common SNPs of very large effect likely do not exist for seasonality in the populations examined. As expected, there was overlapping genetic risk factors for BD (but not MDD) with seasonality. Unexpectedly, the risk for SCZ and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations, and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and SCZ PMID:25562672
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Cardoso, F F; Tempelman, R J
2012-07-01
The objectives of this work were to assess alternative linear reaction norm (RN) models for genetic evaluation of Angus cattle in Brazil. That is, we investigated the interaction between genotypes and continuous descriptors of the environmental variation to examine evidence of genotype by environment interaction (G×E) in post-weaning BW gain (PWG) and to compare the environmental sensitivity of national and imported Angus sires. Data were collected by the Brazilian Angus Improvement Program from 1974 to 2005 and consisted of 63,098 records and a pedigree file with 95,896 animals. Six models were implemented using Bayesian inference and compared using the Deviance Information Criterion (DIC). The simplest model was M(1), a traditional animal model, which showed the largest DIC and hence the poorest fit when compared with the 4 alternative RN specifications accounting for G×E. In M(2), a 2-step procedure was implemented using the contemporary group posterior means of M(1) as the environmental gradient, ranging from -92.6 to +265.5 kg. Moreover, the benefits of jointly estimating all parameters in a 1-step approach were demonstrated by M(3). Additionally, we extended M(3) to allow for residual heteroskedasticity using an exponential function (M(4)) and the best fitting (smallest DIC) environmental classification model (M(5)) specification. Finally, M(6) added just heteroskedastic residual variance to M(1). Heritabilities were less at harsh environments and increased with the improvement of production conditions for all RN models. Rank correlations among genetic merit predictions obtained by M(1) and by the best fitting RN models M(3) (homoskedastic) and M(5) (heteroskedastic) at different environmental levels ranged from 0.79 and 0.81, suggesting biological importance of G×E in Brazilian Angus PWG. These results suggest that selection progress could be optimized by adopting environment-specific genetic merit predictions. The PWG environmental sensitivity of
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Meidtner, Karina; Podmore, Clara; Kröger, Janine; van der Schouw, Yvonne T; Bendinelli, Benedetta; Agnoli, Claudia; Arriola, Larraitz; Barricarte, Aurelio; Boeing, Heiner; Cross, Amanda J.; Dow, Courtney; Ekblom, Kim; Fagherazzi, Guy; Franks, Paul W.; Gunter, Marc J.; Huerta, José María; Jakszyn, Paula; Jenab, Mazda; Katzke, Verena A.; Key, Timothy J.; Khaw, Kay Tee; Kühn, Tilman; Kyrø, Cecilie; Mancini, Francesca Romana; Melander, Olle; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, José Ramón; Rodriguez-Barranco, Miguel; Sacerdote, Carlotta; Sluijs, Ivonne; Stepien, Magdalena; Tjonneland, Anne; Tumino, Rosario; Forouhi, Nita G.; Sharp, Stephen J.; Langenberg, Claudia; Schulze, Matthias B.; Riboli, Elio; Wareham, Nicholas J.
2018-01-01
© 2017 by the American Diabetes Association. OBJECTIVE Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic
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van der Meij, Leander; Almela, Mercedes; Buunk, Abraham P.; Fawcett, Tim W.; Salvador, Alicia
2012-01-01
Testosterone (T) is thought to play a key role in male–male competition and courtship in many vertebrates, but its precise effects are unclear. We explored whether courtship behaviour in humans is modulated and preceded by changes in T. Pairs of healthy male students first competed in a non-physical contest in which their T levels became elevated. Each participant then had a short, informal interaction with either an unfamiliar man or woman. The sex of the stimulus person did not affect the participants' behaviour overall. However, in interactions with women, those men who had experienced a greater T increase during the contest subsequently showed more interest in the woman, engaged in more self-presentation, smiled more and made more eye contact. No such effects were seen in interactions with other men. This is the first study to provide direct evidence that elevating T during male–male competition is followed by increased affiliative behaviour towards women. PMID:21632627
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Burgess, Kelly R; Carmany, Erin P; Trepanier, Angela M
2016-02-01
Growing demand for and limited geographic access to genetic counseling services is increasing the need for alternative service delivery models (SDM) like telephone genetic counseling (TGC). Little research has been done on genetic counselors' perspectives of the practice of TGC. We created an anonymous online survey to assess whether telephone genetic counselors believed the tasks identified in the ABGC (American Board of Genetic Counseling) Practice Analysis were performed similarly or differently in TGC compared to in person genetic counseling (IPGC). If there were differences noted, we sought to determine the nature of the differences and if additional training might be needed to address them. Eighty eight genetic counselors with experience in TGC completed some or all of the survey. Respondents identified differences in 13 (14.8%) of the 88 tasks studied. The tasks identified as most different in TGC were: "establishing rapport through verbal and nonverbal interactions" (60.2%; 50/83 respondents identified the task as different), "recognizing factors affecting the counseling interaction" (47.8%; 32/67), "assessing client/family emotions, support, etc." (40.1%; 27/66) and "educating clients about basic genetic concepts" (35.6%; 26/73). A slight majority (53.8%; 35/65) felt additional training was needed to communicate information without visual aids and more effectively perform psychosocial assessments. In summary, although a majority of genetic counseling tasks are performed similarly between TGC and IPGC, TGC counselors recognize that specific training in the TGC model may be needed to address the key differences.
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Exploring genetic suppression interactions on a global scale.
van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C; Yamaguchi, Takafumi N; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire E; Cao, Jessica; Cote, Atina; Gebbia, Marinella; Horecka, Gene; Horecka, Ira; Kuzmin, Elena; Legro, Nicole; Liang, Wendy; van Lieshout, Natascha; McNee, Margaret; San Luis, Bryan-Joseph; Shaeri, Fatemeh; Shuteriqi, Ermira; Sun, Song; Yang, Lu; Youn, Ji-Young; Yuen, Michael; Costanzo, Michael; Gingras, Anne-Claude; Aloy, Patrick; Oostenbrink, Chris; Murray, Andrew; Graham, Todd R; Myers, Chad L; Andrews, Brenda J; Roth, Frederick P; Boone, Charles
2016-11-04
Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations,in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population. These findings allow us to formulate and quantify general mechanisms of genetic suppression. Copyright © 2016, American Association for the Advancement of Science.
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Implications of recurrent disturbance for genetic diversity.
Davies, Ian D; Cary, Geoffrey J; Landguth, Erin L; Lindenmayer, David B; Banks, Sam C
2016-02-01
Exploring interactions between ecological disturbance, species' abundances and community composition provides critical insights for ecological dynamics. While disturbance is also potentially an important driver of landscape genetic patterns, the mechanisms by which these patterns may arise by selective and neutral processes are not well-understood. We used simulation to evaluate the relative importance of disturbance regime components, and their interaction with demographic and dispersal processes, on the distribution of genetic diversity across landscapes. We investigated genetic impacts of variation in key components of disturbance regimes and spatial patterns that are likely to respond to climate change and land management, including disturbance size, frequency, and severity. The influence of disturbance was mediated by dispersal distance and, to a limited extent, by birth rate. Nevertheless, all three disturbance regime components strongly influenced spatial and temporal patterns of genetic diversity within subpopulations, and were associated with changes in genetic structure. Furthermore, disturbance-induced changes in temporal population dynamics and the spatial distribution of populations across the landscape resulted in disrupted isolation by distance patterns among populations. Our results show that forecast changes in disturbance regimes have the potential to cause major changes to the distribution of genetic diversity within and among populations. We highlight likely scenarios under which future changes to disturbance size, severity, or frequency will have the strongest impacts on population genetic patterns. In addition, our results have implications for the inference of biological processes from genetic data, because the effects of dispersal on genetic patterns were strongly mediated by disturbance regimes.
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Islam, Mohammed M.; Smith, Derek K.; Niu, Wenze; Fang, Sanhua; Iqbal, Nida; Sun, Guoqiang; Shi, Yanhong; Zhang, Chun-Li
2015-01-01
Summary The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming. PMID:26607952
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Directory of Open Access Journals (Sweden)
Mohammed M. Islam
2015-11-01
Full Text Available The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming.
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Josephson, Matthew P; Aliani, Rana; Norris, Megan L; Ochs, Matthew E; Gujar, Mahekta; Lundquist, Erik A
2017-02-01
During nervous system development, neurons and their progenitors migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tumor suppressor in humans. Mutations in NF2 lead to neurofibromatosis type II, characterized by benign tumors of glial tissues. Here we demonstrate that in C. elegans, nfm-1 is required for the ability of Q cells and their descendants to extend protrusions and to migrate, but is not required for direction of migration. Using a combination of mosaic analysis and cell-specific expression, we show that NFM-1 is required nonautonomously, possibly in muscles, to promote Q lineage migrations. We also show a genetic interaction between nfm-1 and the C. elegans Slit homolog slt-1, which encodes a conserved secreted guidance cue. Our results suggest that NFM-1 might be involved in the generation of an extracellular cue that promotes Q neuroblast protrusion and migration that acts with or in parallel to SLT-1 In vertebrates, NF2 and Slit2 interact in axon pathfinding, suggesting a conserved interaction of NF2 and Slit2 in regulating migratory events. Copyright © 2017 by the Genetics Society of America.
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Directory of Open Access Journals (Sweden)
Tariq Waseem Chohan
2014-09-01
Full Text Available Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1 and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET and wild-type (WT mice using [3H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV and the dentate gyrus (DG of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex.
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Greenlandic Inuit show genetic signatures of diet and climate adaptation
DEFF Research Database (Denmark)
Fumagalli, Matteo; Moltke, Ida; Grarup, Niels
2015-01-01
The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes......, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs....
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Gene-Environment Interactions in Severe Mental Illness
Directory of Open Access Journals (Sweden)
Rudolf eUher
2014-05-01
Full Text Available Severe mental illness is a broad category that includes schizophrenia, bipolar disorder and severe depression. Both genetic disposition and environmental exposures play important roles in the development of severe mental illness. Multiple lines of evidence suggest that the roles of genetic and environmental depend on each other. Gene-environment interactions may underlie the paradox of strong environmental factors for highly heritable disorders, the low estimates of shared environmental influences in twin studies of severe mental illness and the heritability gap between twin and molecular heritability estimates. Sons and daughters of parents with severe mental illness are more vulnerable to the effects of prenatal and postnatal environmental exposures, suggesting that the expression of genetic liability depends on environment. In the last decade, gene-environment interactions involving specific molecular variants in candidate genes have been identified. Replicated findings include an interaction between a polymorphism in the AKT1 gene and cannabis use in the development of psychosis and an interaction between the length polymorphism of the serotonin transporter gene and childhood maltreatment in the development of persistent depressive disorder. Bipolar disorder has been underinvestigated, with only a single study showing an interaction between a functional polymorphism in BDNF and stressful life events triggering bipolar depressive episodes. The first systematic search for gene-environment interactions has found that a polymorphism in CTNNA3 may sensitise the developing brain to the pathogenic effect of cytomegalovirus in utero, leading to schizophrenia in adulthood. Strategies for genome-wide investigations will likely include coordination between epidemiological and genetic research efforts, systematic assessment of multiple environmental factors in large samples, and prioritization of genetic variants.
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Directory of Open Access Journals (Sweden)
Russell Bell
2009-03-01
Full Text Available We have mapped a protein interaction network of human homologs of proteins that modify longevity in invertebrate species. This network is derived from a proteome-scale human protein interaction Core Network generated through unbiased high-throughput yeast two-hybrid searches. The longevity network is composed of 175 human homologs of proteins known to confer increased longevity through loss of function in yeast, nematode, or fly, and 2,163 additional human proteins that interact with these homologs. Overall, the network consists of 3,271 binary interactions among 2,338 unique proteins. A comparison of the average node degree of the human longevity homologs with random sets of proteins in the Core Network indicates that human homologs of longevity proteins are highly connected hubs with a mean node degree of 18.8 partners. Shortest path length analysis shows that proteins in this network are significantly more connected than would be expected by chance. To examine the relationship of this network to human aging phenotypes, we compared the genes encoding longevity network proteins to genes known to be changed transcriptionally during aging in human muscle. In the case of both the longevity protein homologs and their interactors, we observed enrichments for differentially expressed genes in the network. To determine whether homologs of human longevity interacting proteins can modulate life span in invertebrates, homologs of 18 human FRAP1 interacting proteins showing significant changes in human aging muscle were tested for effects on nematode life span using RNAi. Of 18 genes tested, 33% extended life span when knocked-down in Caenorhabditis elegans. These observations indicate that a broad class of longevity genes identified in invertebrate models of aging have relevance to human aging. They also indicate that the longevity protein interaction network presented here is enriched for novel conserved longevity proteins.
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[Genetics and epigenetics in autism].
Nakayama, Atsuo; Masaki, Shiego; Aoki, Eiko
2006-11-01
Autism is a behaviorally defined syndrome characterized by impaired social interaction and communication, and restricted, stereotyped interests and behaviors. Several lines of evidence support the contention that genetic factors are a large component to autism etiology. However, in spite of vigorous genetic studies, no single causative or susceptibility gene common in autism has been identified. Thus multiple susceptibility genes in interaction are considered to account for the disorder. Furthermore, environmental risk factors can accelerate the autism development of. Recent advances in understanding the epigenetic regulation may shed light on the interaction among multiple genetic factors and environmental factors.
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Genetic compatibility determines endophyte-grass combinations.
Directory of Open Access Journals (Sweden)
Kari Saikkonen
Full Text Available Even highly mutually beneficial microbial-plant interactions, such as mycorrhizal- and rhizobial-plant exchanges, involve selfishness, cheating and power-struggles between the partners, which depending on prevailing selective pressures, lead to a continuum of interactions from antagonistic to mutualistic. Using manipulated grass-endophyte combinations in a five year common garden experiment, we show that grass genotypes and genetic mismatches constrain genetic combinations between the vertically (via host seeds transmitted endophytes and the out-crossing host, thereby reducing infections in established grass populations. Infections were lost in both grass tillers and seedlings in F(1 and F(2 generations, respectively. Experimental plants were collected as seeds from two different environments, i.e., meadows and nearby riverbanks. Endophyte-related benefits to the host included an increased number of inflorescences, but only in meadow plants and not until the last growing season of the experiment. Our results illustrate the importance of genetic host specificity and trans-generational maternal effects on the genetic structure of a host population, which act as destabilizing forces in endophyte-grass symbioses. We propose that (1 genetic mismatches may act as a buffering mechanism against highly competitive endophyte-grass genotype combinations threatening the biodiversity of grassland communities and (2 these mismatches should be acknowledged, particularly in breeding programmes aimed at harnessing systemic and heritable endophytes to improve the agriculturally valuable characteristics of cultivars.
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Journal of Genetics | Indian Academy of Sciences
Indian Academy of Sciences (India)
PprA, a pleiotropic protein for radioresistance, works through DNA gyrase and shows cellular dynamics during postirradiation recovery in Deinococcus radiodurans .... Gene interactions and genetics of blast resistance and yield attributes in rice (Oryza ... Molecular mapping of a stripe rust resistance gene in wheat line C51.
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Slutske, Wendy S; Deutsch, Arielle R; Piasecki, Thomas M
2018-05-07
Genetic influences on alcohol involvement are likely to vary as a function of the 'alcohol environment,' given that exposure to alcohol is a necessary precondition for genetic risk to be expressed. However, few gene-environment interaction studies of alcohol involvement have focused on characteristics of the community-level alcohol environment. The goal of this study was to examine whether living in a community with more alcohol outlets would facilitate the expression of the genetic propensity to drink in a genetically-informed national survey of United States young adults. The participants were 2434 18-26-year-old twin, full-, and half-sibling pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Participants completed in-home interviews in which alcohol use was assessed. Alcohol outlet densities were extracted from state-level liquor license databases aggregated at the census tract level to derive the density of outlets. There was evidence that the estimates of genetic and environmental influences on alcohol use varied as a function of the density of alcohol outlets in the community. For example, the heritability of the frequency of alcohol use for those residing in a neighborhood with ten or more outlets was 74% (95% confidence limits = 55-94%), compared with 16% (95% confidence limits = 0-34%) for those in a neighborhood with zero outlets. This moderating effect of alcohol outlet density was not explained by the state of residence, population density, or neighborhood sociodemographic characteristics. The results suggest that living in a neighborhood with many alcohol outlets may be especially high-risk for those individuals who are genetically predisposed to frequently drink.
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T. Tanaka (Toshiko); J.S. Ngwa; F.J.A. van Rooij (Frank); M.C. Zillikens (Carola); M.K. Wojczynski (Mary ); A.C. Frazier-Wood (Alexis); D.K. Houston (Denise); S. Kanoni (Stavroula); R.N. Lemaitre (Rozenn ); J. Luan; V. Mikkilä (Vera); F. Renström (Frida); E. Sonestedt (Emily); J.H. Zhao (Jing Hua); A.Y. Chu (Audrey); L. Qi (Lu); D.I. Chasman (Daniel); M.C. De Oliveira Otto (Marcia); E.J. Dhurandhar (Emily); M.F. Feitosa (Mary Furlan); I. Johansson (Ingegerd); K-T. Khaw (Kay-Tee); K. Lohman (Kurt); A. Manichaikul (Ani); N.M. McKeown (Nicola ); D. Mozaffarian (Dariush); A.B. Singleton (Andrew); K. Stirrups (Kathy); J. Viikari (Jorma); Z. Ye (Zheng); S. Bandinelli (Stefania); I.E. Barroso (Inês); P. Deloukas (Panagiotis); N.G. Forouhi (Nita); A. Hofman (Albert); Y. Liu (YongMei); L.-P. Lyytikäinen (Leo-Pekka); K.E. North (Kari); M. Dimitriou (Maria); G. Hallmans (Göran); M. Kähönen (Mika); C. Langenberg (Claudia); J.M. Ordovas (Jose); A.G. Uitterlinden (André); F.B. Hu (Frank); I.-P. Kalafati (Ioanna-Panagiota); O. Raitakari (Olli); O.H. Franco (Oscar); A. Johnson (Anthony); V. Emilsson (Valur); J.A. Schrack (Jennifer); R.D. Semba; D.S. Siscovick (David); D.K. Arnett (Donna); I.B. Borecki (Ingrid); P.W. Franks (Paul); S.B. Kritchevsky (Stephen); R.J.F. Loos (Ruth); M. Orho-Melander (Marju); J.I. Rotter (Jerome); N.J. Wareham (Nick); J.C.M. Witteman (Jacqueline); L. Ferrucci (Luigi); G.V. Dedoussis (George); L.A. Cupples (Adrienne); J.A. Nettleton (Jennifer )
2013-01-01
textabstractBackground: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants. Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake.
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Mapping genetic factors controlling potato - cyst nematode interactions
Rouppe van der Voort, J.N.A.M.
1998-01-01
The thesis describes strategies for genetic mapping of the genomes of the potato cyst nematode and potato. Mapping in cyst nematodes was achieved by AFLP genotyping of single cysts and subsequent segregation analysis in a family of sibling populations. The genetic map of Globodera
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In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.
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Coevolutionary genetic variation in the legume-rhizobium transcriptome.
Heath, Katy D; Burke, Patricia V; Stinchcombe, John R
2012-10-01
Coevolutionary change requires reciprocal selection between interacting species, where the partner genotypes that are favoured in one species depend on the genetic composition of the interacting species. Coevolutionary genetic variation is manifested as genotype × genotype (G × G) interactions for fitness in interspecific interactions. Although quantitative genetic approaches have revealed abundant evidence for G × G interactions in symbioses, the molecular basis of this variation remains unclear. Here we study the molecular basis of G × G interactions in a model legume-rhizobium mutualism using gene expression microarrays. We find that, like quantitative traits such as fitness, variation in the symbiotic transcriptome may be partitioned into additive and interactive genetic components. Our results suggest that plant genetic variation had the largest influence on nodule gene expression and that plant genotype and the plant genotype × rhizobium genotype interaction determine global shifts in rhizobium gene expression that in turn feedback to influence plant fitness benefits. Moreover, the transcriptomic variation we uncover implicates regulatory changes in both species as drivers of symbiotic gene expression variation. Our study is the first to partition genetic variation in a symbiotic transcriptome and illuminates potential molecular routes of coevolutionary change. © 2012 Blackwell Publishing Ltd.
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Singh, Akanksha; Braun, Julia; Decker, Emilia; Hans, Sarah; Wagner, Agnes; Weisser, Wolfgang W; Zytynska, Sharon E
2014-10-21
Interactions between aboveground and belowground terrestrial communities are often mediated by plants, with soil organisms interacting via the roots and aboveground organisms via the shoots and leaves. Many studies now show that plant genetics can drive changes in the structure of both above and belowground communities; however, the role of plant genetic variation in mediating aboveground-belowground interactions is still unclear. We used an earthworm-plant-aphid model system with two aphid species (Aphis fabae and Acyrthosiphon pisum) to test the effect of host-plant (Vicia faba) genetic variation on the indirect interaction between the belowground earthworms (Eisenia veneta) on the aboveground aphid populations. Our data shows that host-plant variety mediated an indirect ecological effect of earthworms on generalist black bean aphids (A. fabae), with earthworms increasing aphid growth rate in three plant varieties but decreasing it in another variety. We found no effect of earthworms on the second aphid species, the pea aphid (A. pisum), and no effect of competition between the aphid species. Plant biomass was increased when earthworms were present, and decreased when A. pisum was feeding on the plant (mediated by plant variety). Although A. fabae aphids were influenced by the plants and worms, they did not, in turn, alter plant biomass. Previous work has shown inconsistent effects of earthworms on aphids, but we suggest these differences could be explained by plant genetic variation and variation among aphid species. This study demonstrates that the outcome of belowground-aboveground interactions can be mediated by genetic variation in the host-plant, but depends on the identity of the species involved.
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Evolving hard problems: Generating human genetics datasets with a complex etiology
Directory of Open Access Journals (Sweden)
Himmelstein Daniel S
2011-07-01
Full Text Available Abstract Background A goal of human genetics is to discover genetic factors that influence individuals' susceptibility to common diseases. Most common diseases are thought to result from the joint failure of two or more interacting components instead of single component failures. This greatly complicates both the task of selecting informative genetic variants and the task of modeling interactions between them. We and others have previously developed algorithms to detect and model the relationships between these genetic factors and disease. Previously these methods have been evaluated with datasets simulated according to pre-defined genetic models. Results Here we develop and evaluate a model free evolution strategy to generate datasets which display a complex relationship between individual genotype and disease susceptibility. We show that this model free approach is capable of generating a diverse array of datasets with distinct gene-disease relationships for an arbitrary interaction order and sample size. We specifically generate eight-hundred Pareto fronts; one for each independent run of our algorithm. In each run the predictiveness of single genetic variation and pairs of genetic variants have been minimized, while the predictiveness of third, fourth, or fifth-order combinations is maximized. Two hundred runs of the algorithm are further dedicated to creating datasets with predictive four or five order interactions and minimized lower-level effects. Conclusions This method and the resulting datasets will allow the capabilities of novel methods to be tested without pre-specified genetic models. This allows researchers to evaluate which methods will succeed on human genetics problems where the model is not known in advance. We further make freely available to the community the entire Pareto-optimal front of datasets from each run so that novel methods may be rigorously evaluated. These 76,600 datasets are available from http://discovery.dartmouth.edu/model_free_data/.
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Environmental and genetic factors affecting faecal worm egg counts ...
African Journals Online (AJOL)
Environmental and genetic factors affecting faecal worm egg counts in Merinos divergently selected for reproduction. ... The fixed effect of birth year x sex interaction was significant, with rams showing higher mean values for FWEC than ewes ...
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Genetic variants influencing phenotypic variance heterogeneity.
Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa
2018-03-01
Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.
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Directory of Open Access Journals (Sweden)
Angelo Scuteri
2007-07-01
Full Text Available The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x10(-7, hip circumference (p = 3.4 x 10(-8, and weight (p = 9.1 x 10(-7. In Sardinia, homozygotes for the rare "G" allele of this SNP (minor allele frequency = 0.46 were 1.3 BMI units heavier than homozygotes for the common "A" allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6. Homozygotes for the rare "A" allele of this SNP (minor allele frequency = 0.12 were 1.8 BMI units heavier than homozygotes for the common "G" allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496 and in Hispanic Americans (N = 839, we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001, weight (p = 0.001, and hip circumference (p = 0.0005. We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A" allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G" allele. In summary, we have completed a whole genome-association scan for
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Xu, Meiyu; Li, Lina; Ohtsu, Hiroshi; Pittenger, Christopher
2015-05-19
Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene histidine decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d-amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48h after it had been paired with a shock. During the 30min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Analysis of conditional genetic effects and variance components in developmental genetics.
Zhu, J
1995-12-01
A genetic model with additive-dominance effects and genotype x environment interactions is presented for quantitative traits with time-dependent measures. The genetic model for phenotypic means at time t conditional on phenotypic means measured at previous time (t-1) is defined. Statistical methods are proposed for analyzing conditional genetic effects and conditional genetic variance components. Conditional variances can be estimated by minimum norm quadratic unbiased estimation (MINQUE) method. An adjusted unbiased prediction (AUP) procedure is suggested for predicting conditional genetic effects. A worked example from cotton fruiting data is given for comparison of unconditional and conditional genetic variances and additive effects.
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Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis.
Diego, Vincent P; de Chaves, Raquel Nichele; Blangero, John; de Souza, Michele Caroline; Santos, Daniel; Gomes, Thayse Natacha; dos Santos, Fernanda Karina; Garganta, Rui; Katzmarzyk, Peter T; Maia, José A R
2015-08-01
The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families. The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF). Sex-specific effects were assessed by genotype-by-sex interaction (GSI) models and sex-specific heritabilities. GSI effects and heterogeneity were tested in the residual environmental variance. SPSS 17 and SOLAR v. 4.1 were used in all computations. The genetic component for PA and SB domains varied from low to moderate (11% to 46%), when analyzing both genders combined. We found GSI effects for vigorous PA (p = 0.02) and time spent watching television (WT) (p < 0.001) that showed significantly higher additive genetic variance estimates in males. The heterogeneity in the residual environmental variance was significant for moderate PA (p = 0.02), vigorous PA (p = 0.006) and total PA (p = 0.001). Sex-specific heritability estimates were significantly higher in males only for WT, with a male-to-female difference in heritability of 42.5 (95% confidence interval: 6.4, 70.4). Low to moderate genetic effects on PA and SB traits were found. Results from the GSI model show that there are sex-specific effects in two phenotypes, VPA and WT with a stronger genetic influence in males.
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Directory of Open Access Journals (Sweden)
Sucheston Lara
2010-09-01
Full Text Available Abstract Background Multifactorial diseases such as cancer and cardiovascular diseases are caused by the complex interplay between genes and environment. The detection of these interactions remains challenging due to computational limitations. Information theoretic approaches use computationally efficient directed search strategies and thus provide a feasible solution to this problem. However, the power of information theoretic methods for interaction analysis has not been systematically evaluated. In this work, we compare power and Type I error of an information-theoretic approach to existing interaction analysis methods. Methods The k-way interaction information (KWII metric for identifying variable combinations involved in gene-gene interactions (GGI was assessed using several simulated data sets under models of genetic heterogeneity driven by susceptibility increasing loci with varying allele frequency, penetrance values and heritability. The power and proportion of false positives of the KWII was compared to multifactor dimensionality reduction (MDR, restricted partitioning method (RPM and logistic regression. Results The power of the KWII was considerably greater than MDR on all six simulation models examined. For a given disease prevalence at high values of heritability, the power of both RPM and KWII was greater than 95%. For models with low heritability and/or genetic heterogeneity, the power of the KWII was consistently greater than RPM; the improvements in power for the KWII over RPM ranged from 4.7% to 14.2% at for α = 0.001 in the three models at the lowest heritability values examined. KWII performed similar to logistic regression. Conclusions Information theoretic models are flexible and have excellent power to detect GGI under a variety of conditions that characterize complex diseases.
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Duneau, David; Luijckx, Pepijn; Ben-Ami, Frida; Laforsch, Christian; Ebert, Dieter
2011-02-22
Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key force behind coevolutionary cycles. We discuss how different
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Directory of Open Access Journals (Sweden)
Laforsch Christian
2011-02-01
Full Text Available Abstract Background Infection processes consist of a sequence of steps, each critical for the interaction between host and parasite. Studies of host-parasite interactions rarely take into account the fact that different steps might be influenced by different factors and might, therefore, make different contributions to shaping coevolution. We designed a new method using the Daphnia magna - Pasteuria ramosa system, one of the rare examples where coevolution has been documented, in order to resolve the steps of the infection and analyse the factors that influence each of them. Results Using the transparent Daphnia hosts and fluorescently-labelled spores of the bacterium P. ramosa, we identified a sequence of infection steps: encounter between parasite and host; activation of parasite dormant spores; attachment of spores to the host; and parasite proliferation inside the host. The chances of encounter had been shown to depend on host genotype and environment. We tested the role of genetic and environmental factors in the newly described activation and attachment steps. Hosts of different genotypes, gender and species were all able to activate endospores of all parasite clones tested in different environments; suggesting that the activation cue is phylogenetically conserved. We next established that parasite attachment occurs onto the host oesophagus independently of host species, gender and environmental conditions. In contrast to spore activation, attachment depended strongly on the combination of host and parasite genotypes. Conclusions Our results show that different steps are influenced by different factors. Host-type-independent spore activation suggests that this step can be ruled out as a major factor in Daphnia-Pasteuria coevolution. On the other hand, we show that the attachment step is crucial for the pronounced genetic specificities of this system. We suggest that this one step can explain host population structure and could be a key
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Directory of Open Access Journals (Sweden)
Hua Dong
2015-12-01
Full Text Available Interaction between HBV and host genome integrations in hepatocellular carcinoma (HCC development is a complex process and the mechanism is still unclear. Here we described in details the quality controls and data mining of aCGH and transcriptome sequencing data on 50 HCC samples from the Chinese patients, published by Dong et al. (2015 (GEO#: GSE65486. In additional to the HBV-MLL4 integration discovered, we also investigated the genetic aberrations of HBV and host genes as well as their genetic interactions. We reported human genome copy number changes and frequent transcriptome variations (e.g. TP53, CTNNB1 mutation, especially MLL family mutations in this cohort of the patients. For HBV genotype C, we identified a novel linkage disequilibrium region covering HBV replication regulatory elements, including basal core promoter, DR1, epsilon and poly-A regions, which is associated with HBV core antigen over-expression and almost exclusive to HBV-MLL4 integration.
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MacNeil, M D; Cardoso, F F; Hay, E
2017-09-01
It has long been recognized that genotype × environment interaction potentially influences genetic evaluation of beef cattle. However, this recognition has largely been ignored in systems for national cattle evaluation. The objective of this investigation was to determine if direct and maternal genetic effects on preweaning gain would be reranked depending on an environmental gradient as determined by year effects. Data used were from the 76-yr selection experiment with the Line 1 Hereford cattle raised at Miles City, MT. The data comprised recorded phenotypes from 7,566 animals and an additional 1,862 ancestral records included in the pedigree. The presence of genotype × environment interaction was examined using reaction norms wherein year effects on preweaning gain were hypothesized to linearly influence the EBV. Estimates of heritability for direct and maternal effects, given the average environment, were 10 ± 2 and 26 ± 3%, respectively. In an environment that is characterized by the 5th (95th) percentile of the distribution of year effects, the corresponding estimates of heritability were 18 ± 3 (22 ± 3%) and 30 ± 3% (30 ± 3%), respectively. Rank correlations of direct and maternal EBV appropriate to the 5th and 95th percentiles of the year effects were 0.67 and 0.92, respectively. In the average environment, the genetic trends were 255 ± 1 g/yr for direct effects and 557 ± 3 g/yr for maternal effects. In the fifth percentile environment, the corresponding estimates of genetic trend were 271 ± 1 and 540 ± 3 g/yr, respectively, and in the 95th percentile environment, they were 236 ± 1 and 578 ± 3 g/yr, respectively. Linear genetic trends in environmental sensitivity were observed for both the direct (-8.06 × 10 ± 0.49 × 10) and maternal (8.72 × 10 ± 0.43 × 10) effects. Therefore, changing systems of national cattle evaluation to more fully account for potential genotype × environment interaction would improve the assessment of breeding
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Wang, Tiange; Heianza, Yoriko; Sun, Dianjianyi; Huang, Tao; Ma, Wenjie; Rimm, Eric B; Manson, JoAnn E; Hu, Frank B; Willett, Walter C
2018-01-01
Abstract Objective To investigate whether improving adherence to healthy dietary patterns interacts with the genetic predisposition to obesity in relation to long term changes in body mass index and body weight. Design Prospective cohort study. Setting Health professionals in the United States. Participants 8828 women from the Nurses’ Health Study and 5218 men from the Health Professionals Follow-up Study. Exposure Genetic predisposition score was calculated on the basis of 77 variants associated with body mass index. Dietary patterns were assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH), and Alternate Mediterranean Diet (AMED). Main outcome measures Five repeated measurements of four year changes in body mass index and body weight over follow-up (1986 to 2006). Results During a 20 year follow-up, genetic association with change in body mass index was significantly attenuated with increasing adherence to the AHEI-2010 in the Nurses’ Health Study (P=0.001 for interaction) and Health Professionals Follow-up Study (P=0.005 for interaction). In the combined cohorts, four year changes in body mass index per 10 risk allele increment were 0.07 (SE 0.02) among participants with decreased AHEI-2010 score and −0.01 (0.02) among those with increased AHEI-2010 score, corresponding to 0.16 (0.05) kg versus −0.02 (0.05) kg weight change every four years (Pdietary patterns could attenuate the genetic association with weight gain. Moreover, the beneficial effect of improved diet quality on weight management was particularly pronounced in people at high genetic risk for obesity. PMID:29321156
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Carnaval, Ana Carolina; Bates, John M
2007-12-01
The glacial refugia paradigm has been broadly applied to patterns of species dynamics and population diversification. However, recent geological studies have demonstrated striking Pleistocene climate changes in currently semiarid northeastern Brazil at time intervals much more frequent than the climatic oscillations associated with glacial and interglacial periods. These geomorphic data documented recurrent pulses of wet regimes in the past 210,000 years that correlate with climate anomalies affecting multiple continents. While analyzing DNA sequences of two mitochondrial genes (cytochrome b and NADH-dehydrogenase subunit 2) and one nuclear marker (cellular-myelocytomatosis proto-oncogene) in the forest-associated frogs Proceratophrys boiei and Ischnocnema gr. ramagii, we found evidence of biological responses consistent with these pluvial maxima events. Sampled areas included old, naturally isolated forest enclaves within the semiarid Caatinga, as well as recent man-made fragments of humid coastal Atlantic forest. Results show that mtDNA lineages in enclave populations are monophyletic or nearly so, whereas nonenclave populations are polyphyletic and more diverse. The studied taxa show evidence of demographic expansions at times that match phases of pluvial maxima inferred from geological data. Divergence times between several populations fall within comparatively drier intervals suggested by geomorphology. Mitochondrial and nuclear data show local populations to be genetically structured, with some high levels of differentiation that suggest the need of further taxonomic work.
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Genetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilities.
Lobo, Daniela S S; Kennedy, James L
2009-09-01
To summarize and discuss findings from genetic studies conducted on pathological gambling (PG). Searches were conducted on PubMed and PsychInfo databases using the keywords: 'gambling and genes', 'gambling and family' and 'gambling and genetics', yielding 18 original research articles investigating the genetics of PG. Twin studies using the Vietnam Era Twin Registry have found that: (i) the heritability of PG is estimated to be 50-60%; (ii) PG and subclinical PG are a continuum of the same disorder; (iii) PG shares genetic vulnerability factors with antisocial behaviours, alcohol dependence and major depressive disorder; (iv) genetic factors underlie the association between exposure to traumatic life-events and PG. Molecular genetic investigations on PG are at an early stage and published studies have reported associations with genes involved in the brain's reward and impulse control systems. Despite the paucity of studies in this area, published studies have provided considerable evidence of the influence of genetic factors on PG and its complex interaction with other psychiatric disorders and environmental factors. The next step would be to investigate the association and interaction of these variables in larger molecular genetic studies with subphenotypes that underlie PG. Results from family and genetic investigations corroborate further the importance of understanding the biological underpinnings of PG in the development of more specific treatment and prevention strategies.
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International Nuclear Information System (INIS)
Grosovsky, A.J.; Nelson, S.L.; Smith, L.E.
1995-01-01
Clonal karyotypic analysis was performed using G-banding on four groups of clones derived from TK6 human lymphoblasts: 25 HPRT - total gene deletion mutants induced by exposure to 2 Gy of x-rays; 8 spontaneous HPRT - total gene deletion mutants; 25 clones irradiated with 2 Gy, not selected with 6-thioguanine. Ten to twenty metaphases were examined for each clone. Extensive karyotypic heterogeneity was observed among x-ray induced HPRT - mutants involving translocations, deletions, duplications and aneuploidy; recovery of chromosomal aberrations and karyotypic heterogeneity was greater than the additive effects of clones treated with x-irradiation or 6-thioguanine alone. This synergistic interaction between x-irradiation and 6-thioguanine was observed despite a 7 day phenotypic expression interval between exposure to the two agents. Thus, x-irradiated TK6 cells appear to be persistently hypersensitive to the induction of genetic instability. Several mutants appeared to exhibit evidence of clonal evolution since aberrant chromosomes observed in one metaphase, were found to be further modified in other metaphases. In order to determine if genetic instability, identified by clonal karyotypic heterogeneity, affected specific locus mutation rates, we utilized the heterozygous thymidine kinase (tk) locus as a genetic marker. Four x-ray induced HPRT - mutants with extensive karyotypic heterogeneity, exhibited mutation rates at tk ranging from 5 to 8 fold higher than the parental TK6 cells. Further analysis, using fractionated low dose radiation exposure, is currently in progress
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Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice
Directory of Open Access Journals (Sweden)
Qingtao Liu
2016-11-01
Full Text Available H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06 virus was highly pathogenic for mice, with a 50% mouse lethal dose of 102.83 50% egg infectious dose, whereas the A/duck/Nanjing/01/1999 (NJ01 virus was low pathogenic for mice, with a 50% mouse lethal dose of >106.81 50% egg infectious dose. Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only twelve different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.
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Guo, Guang; Tong, Yuying; Cai, Tianji
2010-01-01
In this study, we set out to investigate whether introducing molecular genetic measures into an analysis of sexual partner variety will yield novel sociological insights. The data source is the white male DNA sample in the National Longitudinal Study of Adolescent Health. Our empirical analysis has produced a robust protective effect of the 9R/9R genotype relative to the Any10R genotype in the dopamine transporter gene (DAT1). The gene-environment interaction analysis demonstrates that the protective effect of 9R/9R tends to be lost in schools in which higher proportions of students start having sex early or among those with relatively low levels of cognitive ability. Our genetics-informed sociological analysis suggests that the “one size” of a single social theory may not fit all. Explaining a human trait or behavior may require a theory that accommodates the complex interplay between social contextual and individual influences and genetic predispositions. PMID:19569400
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Clucas, Gemma V; Younger, Jane L; Kao, Damian; Rogers, Alex D; Handley, Jonathan; Miller, Gary D; Jouventin, Pierre; Nolan, Paul; Gharbi, Karim; Miller, Karen J; Hart, Tom
2016-10-13
Seabirds are important components of marine ecosystems, both as predators and as indicators of ecological change, being conspicuous and sensitive to changes in prey abundance. To determine whether fluctuations in population sizes are localised or indicative of large-scale ecosystem change, we must first understand population structure and dispersal. King penguins are long-lived seabirds that occupy a niche across the sub-Antarctic zone close to the Polar Front. Colonies have very different histories of exploitation, population recovery, and expansion. We investigated the genetic population structure and patterns of colonisation of king penguins across their current range using a dataset of 5154 unlinked, high-coverage single nucleotide polymorphisms generated via restriction site associated DNA sequencing (RADSeq). Despite breeding at a small number of discrete, geographically separate sites, we find only very slight genetic differentiation among colonies separated by thousands of kilometers of open-ocean, suggesting migration among islands and archipelagos may be common. Our results show that the South Georgia population is slightly differentiated from all other colonies and suggest that the recently founded Falkland Island colony is likely to have been established by migrants from the distant Crozet Islands rather than nearby colonies on South Georgia, possibly as a result of density-dependent processes. The observed subtle differentiation among king penguin colonies must be considered in future conservation planning and monitoring of the species, and demographic models that attempt to forecast extinction risk in response to large-scale climate change must take into account migration. It is possible that migration could buffer king penguins against some of the impacts of climate change where colonies appear panmictic, although it is unlikely to protect them completely given the widespread physical changes projected for their Southern Ocean foraging grounds
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Genetic basis of hybrid male sterility among three closely related species of Drosophila.
Mishra, Paras Kumar; Singh, B N
2005-05-01
The genetic basis of hybrid male sterility among three closely related species, Drosophila bipectinata, D. parabipectinata and D. malerkotliana has been investigated by using backcross analysis methods. The role of Y chromosome, major hybrid sterility (MHS) genes (genetic factors) and cytoplasm (non-genetic factor) have been studied in the hybrids of these three species. In the species pair, bipectinata--parabipectinata, Y chromosome introgression of parabipectinata in the genomic background of bipectinata and the reciprocal Y chromosome introgression were unsuccessful as all males in second backcross generation were sterile. Neither MHS genes nor cytoplasm was found important for sterility. This suggests the involvement of X-Y, X-autosomes or polygenic interactions in hybrid male sterility. In bipectinata--malerkotliana and parabipectinata--malerkotliana species pairs, Y chromosome substitution in reciprocal crosses did not affect male fertility. Backcross analyses also show no involvement of MHS genes or cytoplasm in hybrid male sterility in these two species pairs. Therefore, X- autosome interaction or polygenic interaction is supposed to be involved in hybrid male sterility in these two species pairs. These findings also provide evidence that even in closely related species, genetic interactions underlying hybrid male sterility may vary.
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Wang, Tiange; Heianza, Yoriko; Sun, Dianjianyi; Huang, Tao; Ma, Wenjie; Rimm, Eric B; Manson, JoAnn E; Hu, Frank B; Willett, Walter C; Qi, Lu
2018-01-10
To investigate whether improving adherence to healthy dietary patterns interacts with the genetic predisposition to obesity in relation to long term changes in body mass index and body weight. Prospective cohort study. Health professionals in the United States. 8828 women from the Nurses' Health Study and 5218 men from the Health Professionals Follow-up Study. Genetic predisposition score was calculated on the basis of 77 variants associated with body mass index. Dietary patterns were assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), Dietary Approach to Stop Hypertension (DASH), and Alternate Mediterranean Diet (AMED). Five repeated measurements of four year changes in body mass index and body weight over follow-up (1986 to 2006). During a 20 year follow-up, genetic association with change in body mass index was significantly attenuated with increasing adherence to the AHEI-2010 in the Nurses' Health Study (P=0.001 for interaction) and Health Professionals Follow-up Study (P=0.005 for interaction). In the combined cohorts, four year changes in body mass index per 10 risk allele increment were 0.07 (SE 0.02) among participants with decreased AHEI-2010 score and -0.01 (0.02) among those with increased AHEI-2010 score, corresponding to 0.16 (0.05) kg versus -0.02 (0.05) kg weight change every four years (Pdietary patterns could attenuate the genetic association with weight gain. Moreover, the beneficial effect of improved diet quality on weight management was particularly pronounced in people at high genetic risk for obesity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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DEFF Research Database (Denmark)
Liebenberg, Nico; Brink, Christiaan; Brand, Linda
2008-01-01
Background: The N-methyl-D-aspartate (NMDA)/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway has been implicated in the neurobiology of depression. Recently we suggested a possible complex interaction between the cholinergic and NO-cGMP pathways in the antidepressant-like response....... Conclusions: Using a genetic animal model of depression, we have confirmed the antidepressant-like property of sildenafil following “unmasking” by concomitant block of muscarinic receptors. These findings hint at a novel interaction between the cGMP and cholinergic systems in depression, and suggest...
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[Analytic methods for seed models with genotype x environment interactions].
Zhu, J
1996-01-01
Genetic models with genotype effect (G) and genotype x environment interaction effect (GE) are proposed for analyzing generation means of seed quantitative traits in crops. The total genetic effect (G) is partitioned into seed direct genetic effect (G0), cytoplasm genetic of effect (C), and maternal plant genetic effect (Gm). Seed direct genetic effect (G0) can be further partitioned into direct additive (A) and direct dominance (D) genetic components. Maternal genetic effect (Gm) can also be partitioned into maternal additive (Am) and maternal dominance (Dm) genetic components. The total genotype x environment interaction effect (GE) can also be partitioned into direct genetic by environment interaction effect (G0E), cytoplasm genetic by environment interaction effect (CE), and maternal genetic by environment interaction effect (GmE). G0E can be partitioned into direct additive by environment interaction (AE) and direct dominance by environment interaction (DE) genetic components. GmE can also be partitioned into maternal additive by environment interaction (AmE) and maternal dominance by environment interaction (DmE) genetic components. Partitions of genetic components are listed for parent, F1, F2 and backcrosses. A set of parents, their reciprocal F1 and F2 seeds is applicable for efficient analysis of seed quantitative traits. MINQUE(0/1) method can be used for estimating variance and covariance components. Unbiased estimation for covariance components between two traits can also be obtained by the MINQUE(0/1) method. Random genetic effects in seed models are predictable by the Adjusted Unbiased Prediction (AUP) approach with MINQUE(0/1) method. The jackknife procedure is suggested for estimation of sampling variances of estimated variance and covariance components and of predicted genetic effects, which can be further used in a t-test for parameter. Unbiasedness and efficiency for estimating variance components and predicting genetic effects are tested by
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Jung, Su Yon; Ho, Gloria; Rohan, Thomas; Strickler, Howard; Bea, Jennifer; Papp, Jeanette; Sobel, Eric; Zhang, Zuo-Feng; Crandall, Carolyn
2017-07-01
Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related pathways are incompletely understood. We used 75 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, and data from 1003 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying via obesity and lifestyle modifiers, we assessed the role of IGF-I/IR traits (fasting IGF-I, IGF-binding protein 3, insulin, glucose, and homeostatic model assessment-insulin resistance) in breast cancer risk as a mediator or influencing factor. Seven SNPs in IGF-I and INS genes were associated with breast cancer risk. These associations differed between non-obese/active and obese/inactive women and between exogenous E non-users and users. The mediation effects of IGF-I/IR traits on the relationship between these SNPs and cancer differed between strata, but only roughly 35% of the cancer risk due to the SNPs was mediated by traits. Similarly, carriers of 20 SNPs in PIK3R1, AKT1/2, and MAPK1 genes (signaling pathways-genetic variants) had different associations with breast cancer between strata, and the proportion of the SNP-cancer relationship explained by traits varied 45-50% between the strata. Our findings suggest that IGF-I/IR genetic variants interact with obesity and lifestyle factors, altering cancer risk partially through pathways other than IGF-I/IR traits. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce breast cancer risk.
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Indirect Genetic Effects for group-housed animals
DEFF Research Database (Denmark)
Alemu, Setegn Worku
This thesis investigated social interactions in group-housed animals. The main findings of this thesis: 1) Statistical methods to estimate indirect genetic effects when interactions differ between kin vs. non-kin were developed. 2) Indirect genetic effects contribute a substantial amount...... of heritable variation for bite mark traits in group-housed min. 3) Indirect genetic effects estimation needs to take into account systematic interactions due to sex or kin for bite mark trait in group-housed min. 4) Genomic selection can be used to increase the response to selection for survival time in Brown...
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Lo Bianco, L; Blasi, G; Taurisano, P; Di Giorgio, A; Ferrante, F; Ursini, G; Fazio, L; Gelao, B; Romano, R; Papazacharias, A; Caforio, G; Sinibaldi, L; Popolizio, T; Bellantuono, C; Bertolino, A
2013-02-01
Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.
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Directory of Open Access Journals (Sweden)
Estruch Francisco
2012-09-01
Full Text Available Abstract Background The various steps of mRNP biogenesis (transcription, processing and export are interconnected. It has been shown that the transcription machinery plays a pivotal role in mRNP assembly, since several mRNA export factors are recruited during transcription and physically interact with components of the transcription machinery. Although the shuttling DEAD-box protein Dbp5p is concentrated on the cytoplasmic fibrils of the NPC, previous studies demonstrated that it interacts physically and genetically with factors involved in transcription initiation. Results We investigated the effect of mutations affecting various components of the transcription initiation apparatus on the phenotypes of mRNA export mutant strains. Our results show that growth and mRNA export defects of dbp5 and mex67 mutant strains can be suppressed by mutation of specific transcription initiation components, but suppression was not observed for mutants acting in the very first steps of the pre-initiation complex (PIC formation. Conclusions Our results indicate that mere reduction in the amount of mRNP produced is not sufficient to suppress the defects caused by a defective mRNA export factor. Suppression occurs only with mutants affecting events within a narrow window of the mRNP biogenesis process. We propose that reducing the speed with which transcription converts from initiation and promoter clearance to elongation may have a positive effect on mRNP formation by permitting more effective recruitment of partially-functional mRNP proteins to the nascent mRNP.
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Results of studies investigating relationships between lifestyle factors and elevated plasma homocysteine (Hcy), an independent risk factor for cardiovascular disease, are conflicting. The objective of this study was to investigate genetic and lifestyle factors and their interactions on plasma Hcy c...
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Stergiadis, S.; Bieber, A.; Franeschin, E.; Isensee, A.; Eyre, M.D.; Maurer, V.; Chatzidimitriou, E.; Cozzi, G.; Bapst, B.; Stewart, G.; Gordon, A.; Butler, G.
2015-01-01
This study investigated the effect of, and interactions between, contrasting crossbreed genetics (US Brown Swiss [BS] x Improved Braunvieh [BV] x Original Braunvieh [OB]) and feeding regimes (especially grazing intake and pasture type) on milk fatty acid (FA) profiles. Concentrations of total polyunsaturated FAs, total omega-3 FAs and trans palmitoleic, vaccenic, a-linolenic, eicosapentaenoic and docosapentaenoic acids were higher in cows with a low proportion of BS genetics. Highest concentr...
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The cellular robustness by genetic redundancy in budding yeast.
Directory of Open Access Journals (Sweden)
Jingjing Li
2010-11-01
Full Text Available The frequent dispensability of duplicated genes in budding yeast is heralded as a hallmark of genetic robustness contributed by genetic redundancy. However, theoretical predictions suggest such backup by redundancy is evolutionarily unstable, and the extent of genetic robustness contributed from redundancy remains controversial. It is anticipated that, to achieve mutual buffering, the duplicated paralogs must at least share some functional overlap. However, counter-intuitively, several recent studies reported little functional redundancy between these buffering duplicates. The large yeast genetic interactions released recently allowed us to address these issues on a genome-wide scale. We herein characterized the synthetic genetic interactions for ∼500 pairs of yeast duplicated genes originated from either whole-genome duplication (WGD or small-scale duplication (SSD events. We established that functional redundancy between duplicates is a pre-requisite and thus is highly predictive of their backup capacity. This observation was particularly pronounced with the use of a newly introduced metric in scoring functional overlap between paralogs on the basis of gene ontology annotations. Even though mutual buffering was observed to be prevalent among duplicated genes, we showed that the observed backup capacity is largely an evolutionarily transient state. The loss of backup capacity generally follows a neutral mode, with the buffering strength decreasing in proportion to divergence time, and the vast majority of the paralogs have already lost their backup capacity. These observations validated previous theoretic predictions about instability of genetic redundancy. However, departing from the general neutral mode, intriguingly, our analysis revealed the presence of natural selection in stabilizing functional overlap between SSD pairs. These selected pairs, both WGD and SSD, tend to have decelerated functional evolution, have higher propensities of co
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DEFF Research Database (Denmark)
2014-01-01
The anti-reenactment 'Show-Bix &' consists of 5 dias projectors, a dial phone, quintophonic sound, and interactive elements. A responsive interface will enable the Dias projectors to show copies of original dias slides from the Show-Bix piece ”March på Stedet”, 265 images in total. The copies are...
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Genetics of productive peduncles on main stem and branches in mungbean (vigna radiata (L.) wilczek)
International Nuclear Information System (INIS)
Khattak, G.S.
2010-01-01
Components of genetic variation for productive peduncles on main stem and branches in mungbean were estimated using triple test cross procedure. Treatments used for estimation of genetic variation for both traits exhibited highly significant differences which indicate the existence of considerable genetic variation among inbred lines, testers and developed recombinants. Epistatic effect showed significant role in the inheritance of both traits. Productive peduncles on main stem exhibited almost equal values for both i type, and j + l type non-allelic interaction whereas i type interactions value was more compared to j + l type interactions in productive peduncles on branches. This indicated that additive x additive type non-allelic interaction plays an important role in the inheritance of productive peduncles on branches. The complex inheritance of both traits can be exploited for improvement by delay in selection until the material is advanced through bulk procedure. (author)
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Rębała, Krzysztof; Veselinović, Igor; Siváková, Daniela; Patskun, Erika; Kravchenko, Sergey; Szczerkowska, Zofia
2014-01-01
Studies on Y-chromosomal markers revealed significant genetic differentiation between Southern and Northern (Western and Eastern) Slavic populations. The northern Serbian region of Vojvodina is inhabited by Southern Slavic Serbian majority and, inter alia, Western Slavic (Slovak) and Eastern Slavic (Ruthenian) minorities. In the study, 15 autosomal STR markers were analysed in unrelated Slovaks, Ruthenians and Serbs from northern Serbia and western Slovakia. Additionally, Slovak males from Serbia were genotyped for 17 Y-chromosomal STR loci. The results were compared to data available for other Slavic populations. Genetic distances for autosomal markers revealed homogeneity between Serbs from northern Serbia and Slovaks from western Slovakia and distinctiveness of Serbian Slovaks and Ruthenians. Y-STR variation showed a clear genetic departure of the Slovaks and Ruthenians inhabiting Vojvodina from their Serbian neighbours and genetic similarity to the Northern Slavic populations of Slovakia and Ukraine. Admixture estimates revealed negligible Serbian paternal ancestry in both Northern Slavic minorities of Vojvodina, providing evidence for their genetic isolation from the Serbian majority population. No reduction of genetic diversity at autosomal and Y-chromosomal markers was found, excluding genetic drift as a reason for differences observed at autosomal STRs. Analysis of molecular variance detected significant population stratification of autosomal and Y-chromosomal microsatellites in the three Slavic populations of northern Serbia, indicating necessity for separate databases used for estimations of frequencies of autosomal and Y-chromosomal STR profiles in forensic casework. Our results demonstrate that regarding Y-STR haplotypes, Serbian Slovaks and Ruthenians fit in the Eastern European metapopulation defined in the Y chromosome haplotype reference database. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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Construction and application of a protein and genetic interaction network (yeast interactome).
Stuart, Gregory R; Copeland, William C; Strand, Micheline K
2009-04-01
Cytoscape is a bioinformatic data analysis and visualization platform that is well-suited to the analysis of gene expression data. To facilitate the analysis of yeast microarray data using Cytoscape, we constructed an interaction network (interactome) using the curated interaction data available from the Saccharomyces Genome Database (www.yeastgenome.org) and the database of yeast transcription factors at YEASTRACT (www.yeastract.com). These data were formatted and imported into Cytoscape using semi-automated methods, including Linux-based scripts, that simplified the process while minimizing the introduction of processing errors. The methods described for the construction of this yeast interactome are generally applicable to the construction of any interactome. Using Cytoscape, we illustrate the use of this interactome through the analysis of expression data from a recent yeast diauxic shift experiment. We also report and briefly describe the complex associations among transcription factors that result in the regulation of thousands of genes through coordinated changes in expression of dozens of transcription factors. These cells are thus able to sensitively regulate cellular metabolism in response to changes in genetic or environmental conditions through relatively small changes in the expression of large numbers of genes, affecting the entire yeast metabolome.
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Gene interaction at seed-awning loci in the genetic background of wild rice.
Ikemoto, Mai; Otsuka, Mitsuharu; Thanh, Pham Thien; Phan, Phuong Dang Thai; Ishikawa, Ryo; Ishii, Takashige
2017-09-12
Seed awning is one of the important traits for successful propagation in wild rice. During the domestication of rice by ancient humans, plants with awnless seeds may have been selected because long awns hindered collection and handling activities. To investigate domestication of awnless rice, QTL analysis for seed awning was first carried out using backcross recombinant inbred lines between Oryza sativa Nipponbare (recurrent parent) and O. rufipogon W630 (donor parent). Two strong QTLs were detected in the same regions as known major seed-awning loci, An-1 and RAE2. Subsequent causal mutation surveying and fine mapping confirmed that O. rufipogon W630 has functional alleles at both loci. The gene effects and interactions at these loci were examined using two backcross populations with reciprocal genetic backgrounds of O. sativa Nipponbare and O. rufipogon W630. As awn length in wild rice varied among seeds even in the same plant, awn length was measured based on spikelet position. In the genetic background of cultivated rice, the wild alleles at An-1 and RAE2 had awning effects, and plants having both wild homozygous alleles produced awns whose length was about 70% of those of the wild parent. On the other hand, in the genetic background of wild rice, the substitution of cultivated alleles at An-1 and RAE2 contributed little to awn length reduction. These results indicate that the domestication process of awnless seeds was complicated because many genes are involved in awn formation in wild rice.
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Bertolino, Alessandro; Fazio, Leonardo; Di Giorgio, Annabella; Blasi, Giuseppe; Romano, Raffaella; Taurisano, Paolo; Caforio, Grazia; Sinibaldi, Lorenzo; Ursini, Gianluca; Popolizio, Teresa; Tirotta, Emanuele; Papp, Audrey; Dallapiccola, Bruno; Borrelli, Emiliana; Sadee, Wolfgang
2009-01-28
Dopamine modulation of neuronal activity during memory tasks identifies a nonlinear inverted-U shaped function. Both the dopamine transporter (DAT) and dopamine D(2) receptors (encoded by DRD(2)) critically regulate dopamine signaling in the striatum and in prefrontal cortex during memory. Moreover, in vitro studies have demonstrated that DAT and D(2) proteins reciprocally regulate each other presynaptically. Therefore, we have evaluated the genetic interaction between a DRD(2) polymorphism (rs1076560) causing reduced presynaptic D(2) receptor expression and the DAT 3'-VNTR variant (affecting DAT expression) in a large sample of healthy subjects undergoing blood oxygenation level-dependent (BOLD)-functional magnetic resonance imaging (MRI) during memory tasks and structural MRI. Results indicated a significant DRD(2)/DAT interaction in prefrontal cortex and striatum BOLD activity during both working memory and encoding of recognition memory. The differential effect on BOLD activity of the DAT variant was mostly manifest in the context of the DRD(2) allele associated with lower presynaptic expression. Similar results were also evident for gray matter volume in caudate. These interactions describe a nonlinear relationship between compound genotypes and brain activity or gray matter volume. Complementary data from striatal protein extracts from wild-type and D(2) knock-out animals (D2R(-/-)) indicate that DAT and D(2) proteins interact in vivo. Together, our results demonstrate that the interaction between genetic variants in DRD(2) and DAT critically modulates the nonlinear relationship between dopamine and neuronal activity during memory processing.
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DEFF Research Database (Denmark)
Bukh, Jens Drachmann; Bock, Camilla; Vinberg, Maj
2009-01-01
Genetic polymorphisms seem to influence the response on antidepressant treatment and moderate the impact of stress on depression. The present study aimed to assess, whether allelic variants and stressful life events interact on the clinical outcome of depression. In a sample of 290 systematically...... recruited patients diagnosed with a single depressive episode according to ICD-10, we assessed the outcome of antidepressant treatment and the presence of stressful life events in a 6-month period preceding onset of depression by means of structured interviews. Further, we genotyped nine polymorphisms...... dependent on stressful life events experienced by the individual prior to onset of depression....
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Directory of Open Access Journals (Sweden)
Maklakov AA
2008-10-01
Full Text Available Abstract Background Quantifying the amount of standing genetic variation in fitness represents an empirical challenge. Unfortunately, the shortage of detailed studies of the genetic architecture of fitness has hampered progress in several domains of evolutionary biology. One such area is the study of sexual selection. In particular, the evolution of adaptive female choice by indirect genetic benefits relies on the presence of genetic variation for fitness. Female choice by genetic benefits fall broadly into good genes (additive models and compatibility (non-additive models where the strength of selection is dictated by the genetic architecture of fitness. To characterize the genetic architecture of fitness, we employed a quantitative genetic design (the diallel cross in a population of the seed beetle Callosobruchus maculatus, which is known to exhibit post-copulatory female choice. From reciprocal crosses of inbred lines, we assayed egg production, egg-to-adult survival, and lifetime offspring production of the outbred F1 daughters (F1 productivity. Results We used the bio model to estimate six components of genetic and environmental variance in fitness. We found sizeable additive and non-additive genetic variance in F1 productivity, but lower genetic variance in egg-to-adult survival, which was strongly influenced by maternal and paternal effects. Conclusion Our results show that, in order to gain a relevant understanding of the genetic architecture of fitness, measures of offspring fitness should be inclusive and should include quantifications of offspring reproductive success. We note that our estimate of additive genetic variance in F1 productivity (CVA = 14% is sufficient to generate indirect selection on female choice. However, our results also show that the major determinant of offspring fitness is the genetic interaction between parental genomes, as indicated by large amounts of non-additive genetic variance (dominance and/or epistasis
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International Nuclear Information System (INIS)
Robinson, A.
1984-01-01
In recent years, practitioners of medicine have become increasingly aware of the importance of genetics in the understanding of physical and mental health and in the management of disease. The last decades have witnessed unprecedented developments in genetics that have increased our understanding of the basic processes of heredity enormously. New techniques and understanding have provided insights directly applicable to medicine. The fundamental fact of heredity may be considered the ability of living organisms to produce offspring that resemble their parents more than others. One of the basic characteristics of the human condition is the uniqueness and diversity of all individuals. This results from their genetic individuality (with the exception of identical twins) and the interaction of the genetic constitution (the genome) with the environment, which is generally unique to the individual as well. In short, the interaction of genes with the environment is what confers biologic uniqueness to all humans
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Jones, F A; Comita, L S
2008-12-07
Tropical trees may show positive density dependence in fruit set and maturation due to pollen limitation in low-density populations. However, pollen from closely related individuals in the local neighbourhood might reduce fruit set or increase fruit abortion in self-incompatible tree species. We investigated the role of neighbourhood density and genetic relatedness on individual fruit set and abortion in the neotropical tree Jacaranda copaia in a large forest plot in central Panama. Using nested neighbourhood models, we found a strong positive effect of increased conspecific density on fruit set and maturation. However, high neighbourhood genetic relatedness interacted with density to reduce total fruit set and increase the proportion of aborted fruit. Our results imply a fitness advantage for individuals growing in high densities as measured by fruit set, but realized fruit set is lowered by increased neighbourhood relatedness. We hypothesize that the mechanism involved is increased visitation by density-dependent invertebrate pollinators in high-density populations, which increases pollen quantity and carry-over and increases fruit set and maturation, coupled with self-incompatibility at early and late stages due to biparental inbreeding that lowers fruit set and increases fruit abortion. Implications for the reproductive ecology and conservation of tropical tree communities in continuous and fragmented habitats are discussed.
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DEFF Research Database (Denmark)
Guo, Li; Brügger, Kim; Liu, Chao
2011-01-01
The genomes of two Sulfolobus islandicus strains obtained from Icelandic solfataras were sequenced and analyzed. Strain REY15A is a host for a versatile genetic toolbox. It exhibits a genome of minimal size, is stable genetically, and is easy to grow and manipulate. Strain HVE10/4 shows a broad h...
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Gordon, Natalie; Greene, Edie
2018-01-01
Research has shown that the low-activity MAOA genotype in conjunction with a history of childhood maltreatment increases the likelihood of violent behaviors. This genetic-environment (G × E) interaction has been introduced as mitigation during the sentencing phase of capital trials, yet there is scant data on its effectiveness. This study addressed that issue. In a factorial design that varied mitigating evidence offered by the defense [environmental (i.e., childhood maltreatment), genetic, G × E, or none] and the likelihood of the defendant's future dangerousness (low or high), 600 mock jurors read sentencing phase evidence in a capital murder trial, rendered individual verdicts, and half deliberated as members of a jury to decide a sentence of death or life imprisonment. The G × E evidence had little mitigating effect on sentencing preferences: participants who received the G × E evidence were no less likely to sentence the defendant to death than those who received evidence of childhood maltreatment or a control group that received neither genetic nor maltreatment evidence. Participants with evidence of a G × E interaction were more likely to sentence the defendant to death when there was a high risk of future dangerousness than when there was a low risk. Sentencing preferences were more lenient after deliberation than before. We discuss limitations and future directions. Copyright © 2017 John Wiley & Sons, Ltd.
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Host genetic variation impacts microbiome composition across human body sites.
Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G
2015-09-15
The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.
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Genetics and epigenetics of obesity
Herrera, Blanca M.; Keildson, Sarah; Lindgren, Cecilia M.
2011-01-01
Obesity results from interactions between environmental and genetic factors. Despite a relatively high heritability of common, non-syndromic obesity (40?70%), the search for genetic variants contributing to susceptibility has been a challenging task. Genome wide association (GWA) studies have dramatically changed the pace of detection of common genetic susceptibility variants. To date, more than 40 genetic variants have been associated with obesity and fat distribution. However, since these v...
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Hauser, Kurt F.; Knapp, Pamela E.
2014-01-01
Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome (neuroAIDS) and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individua...
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Genetic divergence of tomato subsamples
Directory of Open Access Journals (Sweden)
André Pugnal Mattedi
2014-02-01
Full Text Available Understanding the genetic variability of a species is crucial for the progress of a genetic breeding program and requires characterization and evaluation of germplasm. This study aimed to characterize and evaluate 101 tomato subsamples of the Salad group (fresh market and two commercial controls, one of the Salad group (cv. Fanny and another of the Santa Cruz group (cv. Santa Clara. Four experiments were conducted in a randomized block design with three replications and five plants per plot. The joint analysis of variance was performed and characteristics with significant complex interaction between control and experiment were excluded. Subsequently, the multicollinearity diagnostic test was carried out and characteristics that contributed to severe multicollinearity were excluded. The relative importance of each characteristics for genetic divergence was calculated by the Singh's method (Singh, 1981, and the less important ones were excluded according to Garcia (1998. Results showed large genetic divergence among the subsamples for morphological, agronomic and organoleptic characteristics, indicating potential for genetic improvement. The characteristics total soluble solids, mean number of good fruits per plant, endocarp thickness, mean mass of marketable fruit per plant, total acidity, mean number of unmarketable fruit per plant, internode diameter, internode length, main stem thickness and leaf width contributed little to the genetic divergence between the subsamples and may be excluded in future studies.
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Interactions between genetic background, insulin resistance and β-cell function.
Kahn, S E; Suvag, S; Wright, L A; Utzschneider, K M
2012-10-01
An interaction between genes and the environment is a critical component underlying the pathogenesis of the hyperglycaemia of type 2 diabetes. The development of more sophisticated techniques for studying gene variants and for analysing genetic data has led to the discovery of some 40 genes associated with type 2 diabetes. Most of these genes are related to changes in β-cell function, with a few associated with decreased insulin sensitivity and obesity. Interestingly, using quantitative traits based on continuous measures rather than dichotomous ones, it has become evident that not all genes associated with changes in fasting or post-prandial glucose are also associated with a diagnosis of type 2 diabetes. Identification of these gene variants has provided novel insights into the physiology and pathophysiology of the β-cell, including the identification of molecules involved in β-cell function that were not previously recognized as playing a role in this critical cell. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.
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[Analysis of genetic models and gene effects on main agronomy characters in rapeseed].
Li, J; Qiu, J; Tang, Z; Shen, L
1992-01-01
According to four different genetic models, the genetic patterns of 8 agronomy traits were analysed by using the data of 24 generations which included positive and negative cross of 81008 x Tower, both of the varieties are of good quality. The results showed that none of 8 characters could fit in with additive-dominance models. Epistasis was found in all of these characters, and it has significant effect on generation means. Seed weight/plant and some other main yield characters are controlled by duplicate interaction genes. The interaction between triple genes or multiple genes needs to be utilized in yield heterosis.
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Rubber particle proteins, HbREF and HbSRPP, show different interactions with model membranes.
Berthelot, Karine; Lecomte, Sophie; Estevez, Yannick; Zhendre, Vanessa; Henry, Sarah; Thévenot, Julie; Dufourc, Erick J; Alves, Isabel D; Peruch, Frédéric
2014-01-01
The biomembrane surrounding rubber particles from the hevea latex is well known for its content of numerous allergen proteins. HbREF (Hevb1) and HbSRPP (Hevb3) are major components, linked on rubber particles, and they have been shown to be involved in rubber synthesis or quality (mass regulation), but their exact function is still to be determined. In this study we highlighted the different modes of interactions of both recombinant proteins with various membrane models (lipid monolayers, liposomes or supported bilayers, and multilamellar vesicles) to mimic the latex particle membrane. We combined various biophysical methods (polarization-modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS)/ellipsometry, attenuated-total reflectance Fourier-transform infrared (ATR-FTIR), solid-state nuclear magnetic resonance (NMR), plasmon waveguide resonance (PWR), fluorescence spectroscopy) to elucidate their interactions. Small rubber particle protein (SRPP) shows less affinity than rubber elongation factor (REF) for the membranes but displays a kind of "covering" effect on the lipid headgroups without disturbing the membrane integrity. Its structure is conserved in the presence of lipids. Contrarily, REF demonstrates higher membrane affinity with changes in its aggregation properties, the amyloid nature of REF, which we previously reported, is not favored in the presence of lipids. REF binds and inserts into membranes. The membrane integrity is highly perturbed, and we suspect that REF is even able to remove lipids from the membrane leading to the formation of mixed micelles. These two homologous proteins show affinity to all membrane models tested but neatly differ in their interacting features. This could imply differential roles on the surface of rubber particles. © 2013.
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2013-01-01
Advances in research in the past few years on the ornamental plant torenia (Torenia spps.) have made it notable as a model plant on the frontier of genetic engineering aimed at studying ornamental characteristics and pest control in horticultural ecosystems. The remarkable advantage of torenia over other ornamental plant species is the availability of an easy and high-efficiency transformation system for it. Unfortunately, most of the current torenia research is still not very widespread, because this species has not become prominent as an alternative to other successful model plants such as Arabidopsis, snapdragon and petunia. However, nowadays, a more global view using not only a few selected models but also several additional species are required for creating innovative ornamental traits and studying horticultural ecosystems. We therefore introduce and discuss recent research on torenia, the family Scrophulariaceae, for secondary metabolite bioengineering, in which global insights into horticulture, agriculture and ecology have been advanced. Floral traits, in torenia particularly floral color, have been extensively studied by manipulating the flavonoid biosynthetic pathways in flower organs. Plant aroma, including volatile terpenoids, has also been genetically modulated in order to understand the complicated nature of multi-trophic interactions that affect the behavior of predators and pollinators in the ecosystem. Torenia would accordingly be of great use for investigating both the variation in ornamental plants and the infochemical-mediated interactions with arthropods. PMID:23803155
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Blackett, Piers R; Sanghera, Dharambir K
2013-01-01
This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes, and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus, it follows that the genetics of dyslipidemia, obesity, and nonalcoholic fatty liver disease are central in triggering progression of the syndrome to overt expression of disease traits and have become a key focus of interest for early detection and for designing prevention and treatments. To support the "birds' eye view" approach, we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacologic targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.
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DEFF Research Database (Denmark)
Corwin, Jason A; Subedy, Anushriya; Eshbaugh, Robert
2016-01-01
and genetic diversity for virulence-associated phenotypes in a generalist plant pathogen, we grew a population of 15 isolates of Botrytis cinerea from throughout the world, under a variety of in vitro and in planta conditions. Under in planta conditions, phenotypic differences between the isolates were......The modern evolutionary synthesis suggests that both environmental variation and genetic diversity are critical determinants of pathogen success. However, the relative contribution of these two sources of variation is not routinely measured. To estimate the relative contribution of plasticity...... determined by the combination of genotypic variation within the pathogen and environmental variation. In contrast, phenotypic differences between the isolates under in vitro conditions were predominantly determined by genetic variation in the pathogen. Using a correlation network approach, we link...
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Chung, Sun Ju; Armasu, Sebastian M; Anderson, Kari J; Biernacka, Joanna M; Lesnick, Timothy G; Rider, David N; Cunningham, Julie M; Ahlskog, J Eric; Frigerio, Roberta; Maraganore, Demetrius M
2013-06-01
Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. Five pairwise interactions had uncorrected P-values coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Hafeez-ur-Rahman
2006-01-01
Full Text Available Heat tolerance is measured at tissue level by cellular membrane thermostability (CMT and at the whole plant level by the heat tolerance index (HTI. Eight upland cotton cultivars and 15 crosses were used to determine the type and extent of genetic variability associated with the expression of these traits between and within environments. Heat stress and non-stress conditions were used as the CMT environments and years for HTI. The wide variation in heterotic expression and combining ability effects observed for CMT and HTI suggest multigenic inheritance of these traits. Significant genetic variability across environments was evident but the traits were not highly heritable because of substantial environmental interaction. The available genetic variability included both additive and non-additive components, but the proportion of additive genetic variability was high for HTI. The parental cultivars CRIS-19 and CIM-448 were good donor parents for high CMT under heat-stressed conditions, and MNH-552 and N-Karishma under non-stressed conditions. Cultivar FH-634 was a good donor parent for HTI. The results show two types of general combining ability (GCA inheritance among high CMT parents: positive GCA inheritance expressed by CRIS-19 in the presence of heat stress and MNH-552 and N-Karishma in the absence of heat stress; and negative GCA inheritance expressed by FH-900 in the presence of heat stress. It was also evident that genes controlling high CMT in cultivar CRIS-19 were different from those present in the MNH-552, N-Karishma and FH-900 cultivars. Similarly, among high HTI parents, FH-634 showed positive and CIM-443 negative GCA inheritance. No significant relationship due to genetic causes existed between tissue and whole plant heat tolerance, diminishing the likelihood of simultaneous improvement and selection of the two traits.
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Genetic mouse models of brain ageing and Alzheimer's disease.
Bilkei-Gorzo, Andras
2014-05-01
Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.
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Dietary management and genetic predisposition
DEFF Research Database (Denmark)
Jensen, Hanne Holbæk; Larsen, Lesli Hingstrup
2013-01-01
variation, and epigenetics might identify additional genetic contributions to obesity, and the use of omics data with integration of nutrigenetics and nutrigenomics will identify genetic subgroups who will benefit from specific dietary advice to optimize health and prevent disease. Keywords: Diet . Mutation...... epidemically worldwide, the investigation of genetic predisposition might help to prevent and treat obesity. Predisposition to obesity includes syndromes, such as Prader-Willi Syndrome (PWS), severe early-onset obesity, such as mutations in the melanocortin 4 receptor (MC4R), and common forms of obesity......, such as genetic variation in the fat mass and obesity associated gene (FTO). Several studies have explored gene-diet interactions in obesity, weight loss, and regain, but there is a lack of consistency in the identified interactions. This inconsistency is most probably due to a low-moderate effect size...
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Weight Stigma Reduction and Genetic Determinism.
Hilbert, Anja
2016-01-01
One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of-and responsibility for-obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention's gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity.
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Weight Stigma Reduction and Genetic Determinism.
Directory of Open Access Journals (Sweden)
Anja Hilbert
Full Text Available One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of-and responsibility for-obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1 develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2 evaluate this intervention in the general population (N = 128 and determine mechanisms of change. The results showed (1 decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2 decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention's gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity.
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The information value of non-genetic inheritance in plants and animals.
Directory of Open Access Journals (Sweden)
Sinead English
Full Text Available Parents influence the development of their offspring in many ways beyond the transmission of DNA. This includes transfer of epigenetic states, nutrients, antibodies and hormones, and behavioural interactions after birth. While the evolutionary consequences of such non-genetic inheritance are increasingly well understood, less is known about how inheritance mechanisms evolve. Here, we present a simple but versatile model to explore the adaptive evolution of non-genetic inheritance. Our model is based on a switch mechanism that produces alternative phenotypes in response to different inputs, including genes and non-genetic factors transmitted from parents and the environment experienced during development. This framework shows how genetic and non-genetic inheritance mechanisms and environmental conditions can act as cues by carrying correlational information about future selective conditions. Differential use of these cues is manifested as different degrees of genetic, parental or environmental morph determination. We use this framework to evaluate the conditions favouring non-genetic inheritance, as opposed to genetic determination of phenotype or within-generation plasticity, by applying it to two putative examples of adaptive non-genetic inheritance: maternal effects on seed germination in plants and transgenerational phase shift in desert locusts. Our simulation models show how the adaptive value of non-genetic inheritance depends on its mechanism, the pace of environmental change, and life history characteristics.
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Directory of Open Access Journals (Sweden)
Mohan Babu
2014-02-01
Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.
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Kim, Sun; Chatr-aryamontri, Andrew; Chang, Christie S.; Oughtred, Rose; Rust, Jennifer; Wilbur, W. John; Comeau, Donald C.; Dolinski, Kara; Tyers, Mike
2017-01-01
A great deal of information on the molecular genetics and biochemistry of model organisms has been reported in the scientific literature. However, this data is typically described in free text form and is not readily amenable to computational analyses. To this end, the BioGRID database systematically curates the biomedical literature for genetic and protein interaction data. This data is provided in a standardized computationally tractable format and includes structured annotation of experimental evidence. BioGRID curation necessarily involves substantial human effort by expert curators who must read each publication to extract the relevant information. Computational text-mining methods offer the potential to augment and accelerate manual curation. To facilitate the development of practical text-mining strategies, a new challenge was organized in BioCreative V for the BioC task, the collaborative Biocurator Assistant Task. This was a non-competitive, cooperative task in which the participants worked together to build BioC-compatible modules into an integrated pipeline to assist BioGRID curators. As an integral part of this task, a test collection of full text articles was developed that contained both biological entity annotations (gene/protein and organism/species) and molecular interaction annotations (protein–protein and genetic interactions (PPIs and GIs)). This collection, which we call the BioC-BioGRID corpus, was annotated by four BioGRID curators over three rounds of annotation and contains 120 full text articles curated in a dataset representing two major model organisms, namely budding yeast and human. The BioC-BioGRID corpus contains annotations for 6409 mentions of genes and their Entrez Gene IDs, 186 mentions of organism names and their NCBI Taxonomy IDs, 1867 mentions of PPIs and 701 annotations of PPI experimental evidence statements, 856 mentions of GIs and 399 annotations of GI evidence statements. The purpose, characteristics and possible future
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Genetic effects of ionising radiation
International Nuclear Information System (INIS)
Saunders, P.
1981-01-01
The mutagenic effects of ionising radiation on germ cells with resulting genetic abnormalities in subsequent generations, are considered. Having examined a simple model to explain the interaction of ionising radiation with genetic material and discussed its limitations, the methods whereby mutations are transmitted are discussed. Methods of estimating genetic risks and the results of such studies are examined. (U.K.)
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Genetic interactions matter more in less-optimal environments: a focused review
Directory of Open Access Journals (Sweden)
Dustin A. Landers
2014-08-01
Full Text Available An increase in the distribution of data points indicates the presence of genetic or environmental modifiers. Mapping of the genetic control of the spread of points, the uniformity, allows us to allocate genetic difference in point distribution to adjacent, cis effects or to independently segregating, trans genetic effects. Our genetic architecture-mapping experiment elucidated the ‘environmental context specificity’ of modifiers, the number and effect size of positive and negative alleles important for uniformity in single and combined stress, and the extent of additivity in estimated allele effects in combined stress environments. We found no alleles for low uniformity in combined stress treatments in the maize mapping population we examined.The major advances in this research area since early 2011 have been in improved methods for modeling of distributions and means and detection of important loci. Double hierarchical general linear models and, more recently, a likelihood ratio formulation have been developed to better model and estimate the genetic and environmental effects in populations. These new methods have been applied to real data sets by the method authors and we now encourage additional development of the software and wider application of the methods. We also propose that simulations of genetic regulatory network models to examine differences in uniformity and systematic exploration of models using shared simulations across communities of researchers would be constructive avenues for developing further insight into the genetic mechanisms of variation control.
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The Genetic Architecture of Type 1 Diabetes
Directory of Open Access Journals (Sweden)
Samuel T Jerram
2017-08-01
Full Text Available Type 1 diabetes (T1D is classically characterised by the clinical need for insulin, the presence of disease-associated serum autoantibodies, and an onset in childhood. The disease, as with other autoimmune diseases, is due to the interaction of genetic and non-genetic effects, which induce a destructive process damaging insulin-secreting cells. In this review, we focus on the nature of this interaction, and how our understanding of that gene–environment interaction has changed our understanding of the nature of the disease. We discuss the early onset of the disease, the development of distinct immunogenotypes, and the declining heritability with increasing age at diagnosis. Whilst Human Leukocyte Antigens (HLA have a major role in causing T1D, we note that some of these HLA genes have a protective role, especially in children, whilst other non-HLA genes are also important. In adult-onset T1D, the disease is often not insulin-dependent at diagnosis, and has a dissimilar immunogenotype with reduced genetic predisposition. Finally, we discuss the putative nature of the non-genetic factors and how they might interact with genetic susceptibility, including preliminary studies of the epigenome associated with T1D.
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Blackett, Piers R; Sanghera, Dharambir K
2012-01-01
This review provides a translational and unifying summary of metabolic syndrome genetics and highlights evidence that genetic studies are starting to unravel and untangle origins of the complex and challenging cluster of disease phenotypes. The associated genes effectively express in the brain, liver, kidney, arterial endothelium, adipocytes, myocytes and β cells. Progression of syndrome traits has been associated with ectopic lipid accumulation in the arterial wall, visceral adipocytes, myocytes, and liver. Thus it follows that the genetics of dyslipidemia, obesity, and non-alcoholic fatty liver (NAFLD) disease are central in triggering progression of the syndrome to overt expression of disease traits, and have become a key focus of interest for early detection and for designing prevention and treatments. To support the “birds’ eye view” approach we provide a road-map depicting commonality and interrelationships between the traits and their genetic and environmental determinants based on known risk factors, metabolic pathways, pharmacological targets, treatment responses, gene networks, pleiotropy, and association with circadian rhythm. Although only a small portion of the known heritability is accounted for and there is insufficient support for clinical application of gene-based prediction models, there is direction and encouraging progress in a rapidly moving field that is beginning to show clinical relevance. PMID:23351585
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Hulle, Van, Dirk
2015-01-01
Abstract: Genetics of translation may suggest a unidirectional link between two fields of research (genetic criticism applied to translation), but there are many ways in which translation and genetic criticism interact. This article's research hypothesis is that an exchange of ideas between translation studies and genetic criticism can be mutually beneficial in more than one way. The main function of this exchange is to enhance a form of textual awareness, and to realize this enhanced textual...
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DEFF Research Database (Denmark)
Sandvik, Kjetil; Laursen, Ditte
2014-01-01
User interaction with radio and television programmes is not a new thing. However, with new cross-media production concepts such as X Factor and Voice, this is changing dramatically. The second-screen logic of these productions encourages viewers, along with TV’s traditional one-way communication...... mode, to communicate on interactive (dialogue-enabling) devices such as laptops, smartphones and tablets. Using the TV show Voice as our example, this article shows how the technological and situational set-up of the production invites viewers to engage in new ways of interaction and communication...
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Directory of Open Access Journals (Sweden)
Robert Alexandre
2011-09-01
Full Text Available Abstract Background While the ultimate causes of most species extinctions are environmental, environmental constraints have various secondary consequences on evolutionary and ecological processes. The roles of demographic, genetic mechanisms and their interactions in limiting the viabilities of species or populations have stirred much debate and remain difficult to evaluate in the absence of demography-genetics conceptual and technical framework. Here, I computed projected times to metapopulation extinction using (1 a model focusing on the effects of species properties, habitat quality, quantity and temporal variability on the time to demographic extinction; (2 a genetic model focusing on the dynamics of the drift and inbreeding loads under the same species and habitat constraints; (3 a demo-genetic model accounting for demographic-genetic processes and feedbacks. Results Results indicate that a given population may have a high demographic, but low genetic viability or vice versa; and whether genetic or demographic aspects will be the most limiting to overall viability depends on the constraints faced by the species (e.g., reduction of habitat quantity or quality. As a consequence, depending on metapopulation or species characteristics, incorporating genetic considerations to demographically-based viability assessments may either moderately or severely reduce the persistence time. On the other hand, purely genetically-based estimates of species viability may either underestimate (by neglecting demo-genetic interactions or overestimate (by neglecting the demographic resilience true viability. Conclusion Unbiased assessments of the viabilities of species may only be obtained by identifying and considering the most limiting processes (i.e., demography or genetics, or, preferentially, by integrating them.
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A global interaction network maps a wiring diagram of cellular function
Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles
2017-01-01
We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008
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Okoye, Nnamdi S.; Okecha, Rita Ebele
2008-01-01
The study examined the interaction of logical reasoning ability (cognitive development) and socio-economic status on achievement in genetics amongst secondary school students in Nigeria. Factorial Analysis of variance design with one dependent variable and two independent variables at two levels together with the t-test was used in the analysis of…
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Abdullah, N; Abdul Murad, N A; Mohd Haniff, E A; Syafruddin, S E; Attia, J; Oldmeadow, C; Kamaruddin, M A; Abd Jalal, N; Ismail, N; Ishak, M; Jamal, R; Scott, R J; Holliday, E G
2017-08-01
Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene-environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene-environment interactions that may explain additional risk variation. This was a case-control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project. The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R 2 and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants. The models including environmental risk factors only had pseudo R 2 values of 16.5-28.3% and AUC of 0.75-0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10 -4 -4.83 × 10 -12 ) and increased the pseudo R 2 by about 1-2% and AUC by 1-3%. None of the gene-environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 variation in Malaysian population groups. If gene-environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for
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Are Genetics and Environment Substitutes or Complements in Affecting Entrepreneurial Choice?
DEFF Research Database (Denmark)
Zunino, Diego
Recent twin and adoption studies have shown that genes matter for entrepreneurial choice. This related study addresses how a genetic predisposition to entrepreneurship interacts with the (entrepreneurship friendliness of the) environment, using a dataset of Italian twins. In particular, we study ...... a role, and that a favorable environment to entrepreneurship selects those with higher predisposition rather than simply increasing the rate of self-employment....... whether the genetic effect is different across genders, based on the stylized fact that barriers to entrepreneurship entry are stronger for females than for males. Using regression analysis, the study confirms earlier findings showing substantial genetic effects. More interestingly, the study finds...
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A VR Based Interactive Genetic Algorithm Framework For Design of Support Schemes to Deep Excavations
International Nuclear Information System (INIS)
Wei, Riyu; Wu, Heng
2002-01-01
An interactive genetic algorithm (IGA) framework for the design of support schemes to deep excavations is proposed in this paper, in which virtual reality (VR) is used as an aid to the evaluation of design schemes that is performed interactively. The fitness of a scheme individual is evaluated by two steps. Firstly a fitness value is automatically assigned to a scheme individual according to the the estimated construction cost of the individual. And the human evaluation is introduced to modify the fitness value by taking into account other factors, such as the feasibility factor. The design scheme is composed of four basic categories, i. e., cantilever walls, reinforced soil walls, tieback systems and bracing systems, each of which is encoded by a binary string. To assist human evaluation, 3D models of design schemes are created and visualized in a virtual reality environment, providing designers with a reality sense of various schemes
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Zeroing in on the Genetics of Intelligence
Directory of Open Access Journals (Sweden)
Ruben C. Arslan
2015-04-01
Full Text Available Despite the high heritability of intelligence in the normal range, molecular genetic studies have so far yielded many null findings. However, large samples and self-imposed stringent standards have prevented false positives and gradually narrowed down where effects can still be expected. Rare variants and mutations of large effect do not appear to play a main role beyond intellectual disability. Common variants can account for about half the heritability of intelligence and show promise that collaborative efforts will identify more causal genetic variants. Gene–gene interactions may explain some of the remainder, but are only starting to be tapped. Evolutionarily, stabilizing selection and selective (near-neutrality are consistent with the facts known so far.
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Santana, M L; Pereira, R J; Bignardi, A B; Filho, A E Vercesi; Menéndez-Buxadera, A; El Faro, L
2015-12-01
In an attempt to determine the possible detrimental effects of continuous selection for milk yield on the genetic tolerance of Zebu cattle to heat stress, genetic parameters and trends of the response to heat stress for 86,950 test-day (TD) milk yield records from 14,670 first lactations of purebred dairy Gir cows were estimated. A random regression model with regression on days in milk (DIM) and temperature-humidity index (THI) values was applied to the data. The most detrimental effect of THI on milk yield was observed in the stage of lactation with higher milk production, DIM 61 to 120 (-0.099kg/d per THI). Although modest variations were observed for the THI scale, a reduction in additive genetic variance as well as in permanent environmental and residual variance was observed with increasing THI values. The heritability estimates showed a slight increase with increasing THI values for any DIM. The correlations between additive genetic effects across the THI scale showed that, for most of the THI values, genotype by environment interactions due to heat stress were less important for the ranking of bulls. However, for extreme THI values, this type of genotype by environment interaction may lead to an important error in selection. As a result of the selection for milk yield practiced in the dairy Gir population for 3 decades, the genetic trend of cumulative milk yield was significantly positive for production in both high (51.81kg/yr) and low THI values (78.48kg/yr). However, the difference between the breeding values of animals at high and low THI may be considered alarming (355kg in 2011). The genetic trends observed for the regression coefficients related to general production level (intercept of the reaction norm) and specific ability to respond to heat stress (slope of the reaction norm) indicate that the dairy Gir population is heading toward a higher production level at the expense of lower tolerance to heat stress. These trends reflect the genetic
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Advance in the studies about Musa spp.-Mycosphaerella fijiensis Morelet interaction
Directory of Open Access Journals (Sweden)
Milady Francisca Mendoza-Rodríguez
2014-07-01
Full Text Available Black leaf streak disease caused by Mycosphaerella fijiensis Morelet [anamorfo: Pseudocercospora fijiensis (Morelet Deighton], is considered the most destructive and costly foliar disease of bananas and plantain around the world. Taking into account the chemical compounds injure, the increase of fungi resistance to some fungicides besides of, the genetic complexity of Musa spp. resistance to M. fijiensis and the troubles which are present with the genetic improvement of cultivars due to sterility and triploidi, it is necessary to find sustainable alternatives for the management of the disease. To reach this goal the pathogen knowledge and the physiological, genetic and mainly the molecular bases which govern plants interactions to find candidate gene related with the resistance, for the utilization in genetic engineering could be a promissory choice. In this complex scenario biochemical and histological analysis together with the use of different molecular techniques, result of a great contribution to the knowledge of Musa spp.-M. fijiensis pathosystem. At the present work is showed a review of the scientific literature plant-pathogen interaction. Key words: Biochemical analysis, Molecular techniques, Musa spp., Mycosphaerella fijiensis, Plant-pathogen interaction
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Brinker, T.; Raymond, B.; Bijma, P.; Vereijken, A.; Ellen, E.D.
2017-01-01
Mortality of laying hens due to cannibalism is a major problem in the egg-laying industry. Survival depends on two genetic effects: the direct genetic effect of the individual itself (DGE) and the indirect genetic effects of its group mates (IGE). For hens housed in sire-family groups, DGE and
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Genetic architecture of resistance in Daphnia hosts against two species of host-specific parasites.
Routtu, J; Ebert, D
2015-02-01
Understanding the genetic architecture of host resistance is key for understanding the evolution of host-parasite interactions. Evolutionary models often assume simple genetics based on few loci and strong epistasis. It is unknown, however, whether these assumptions apply to natural populations. Using a quantitative trait loci (QTL) approach, we explore the genetic architecture of resistance in the crustacean Daphnia magna to two of its natural parasites: the horizontally transmitted bacterium Pasteuria ramosa and the horizontally and vertically transmitted microsporidium Hamiltosporidium tvaerminnensis. These two systems have become models for studies on the evolution of host-parasite interactions. In the QTL panel used here, Daphnia's resistance to P. ramosa is controlled by a single major QTL (which explains 50% of the observed variation). Resistance to H. tvaerminnensis horizontal infections shows a signature of a quantitative trait based in multiple loci with weak epistatic interactions (together explaining 38% variation). Resistance to H. tvaerminnensis vertical infections, however, shows only one QTL (explaining 13.5% variance) that colocalizes with one of the QTLs for horizontal infections. QTLs for resistance to Pasteuria and Hamiltosporidium do not colocalize. We conclude that the genetics of resistance in D. magna are drastically different for these two parasites. Furthermore, we infer that based on these and earlier results, the mechanisms of coevolution differ strongly for the two host-parasite systems. Only the Pasteuria-Daphnia system is expected to follow the negative frequency-dependent selection (Red Queen) model. How coevolution works in the Hamiltosporidium-Daphnia system remains unclear.
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Parasites and deleterious mutations: interactions influencing the evolutionary maintenance of sex.
Park, A W; Jokela, J; Michalakis, Y
2010-05-01
The restrictive assumptions associated with purely genetic and purely ecological mechanisms suggest that neither of the two forces, in isolation, can offer a general explanation for the evolutionary maintenance of sex. Consequently, attention has turned to pluralistic models (i.e. models that apply both ecological and genetic mechanisms). Existing research has shown that combining mutation accumulation and parasitism allows restrictive assumptions about genetic and parasite parameter values to be relaxed while still predicting the maintenance of sex. However, several empirical studies have shown that deleterious mutations and parasitism can reduce fitness to a greater extent than would be expected if the two acted independently. We show how interactions between these genetic and ecological forces can completely reverse predictions about the evolution of reproductive modes. Moreover, we demonstrate that synergistic interactions between infection and deleterious mutations can render sex evolutionarily stable even when there is antagonistic epistasis among deleterious mutations, thereby widening the conditions for the evolutionary maintenance of sex.
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Multi-location wheat stripe rust QTL analysis: genetic background and epistatic interactions.
Vazquez, M Dolores; Zemetra, Robert; Peterson, C James; Chen, Xianming M; Heesacker, Adam; Mundt, Christopher C
2015-07-01
Epistasis and genetic background were important influences on expression of stripe rust resistance in two wheat RIL populations, one with resistance conditioned by two major genes and the other conditioned by several minor QTL. Stripe rust is a foliar disease of wheat (Triticum aestivum L.) caused by the air-borne fungus Puccinia striiformis f. sp. tritici and is present in most regions around the world where commercial wheat is grown. Breeding for durable resistance to stripe rust continues to be a priority, but also is a challenge due to the complexity of interactions among resistance genes and to the wide diversity and continuous evolution of the pathogen races. The goal of this study was to detect chromosomal regions for resistance to stripe rust in two winter wheat populations, 'Tubbs'/'NSA-98-0995' (T/N) and 'Einstein'/'Tubbs' (E/T), evaluated across seven environments and mapped with diversity array technology and simple sequence repeat markers covering polymorphic regions of ≈1480 and 1117 cM, respectively. Analysis of variance for phenotypic data revealed significant (P located in chromosomes 2AS and 6AL, with epistatic interaction between them, were responsible for the main phenotypic response. For the T/N population, eight QTL were identified, with those in chromosomes 2AL and 2BL accounting for the largest percentage of the phenotypic variance.
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Van Assche, Evelien; Moons, Tim; Cinar, Ozan; Viechtbauer, Wolfgang; Oldehinkel, Albertine J.; Van Leeuwen, Karla; Verschueren, Karine; Colpin, Hilde; Lambrechts, Diether; Van den Noortgate, Wim; Goossens, Luc; Claes, Stephan; van Winkel, Ruud
2017-01-01
BACKGROUND: Most gene-environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric
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Directory of Open Access Journals (Sweden)
Ronald de Vlaming
2017-01-01
Full Text Available Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called 'missing heritability'. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP calculator (available at www.devlaming.eu which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from the MetaGAP calculator with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51-62% in the number of genome-wide significant loci and a relative loss in polygenic score R2 of 36-38%. Hence, cross-study heterogeneity contributes to the missing heritability.
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Directory of Open Access Journals (Sweden)
Su Yon Jung
Full Text Available Genetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E, influencing postmenopausal colorectal cancer (CRC risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs in genes related to insulin-like growth factor-I (IGF-I/ insulin resistance (IR traits and signaling pathways, using data from 704 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment-insulin resistance on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related genetic variants had different associations with CRC risk between strata, and the proportion of the SNP-cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.
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Detecting mutually exclusive interactions in protein-protein interaction maps.
Sánchez Claros, Carmen
2012-06-08
Comprehensive protein interaction maps can complement genetic and biochemical experiments and allow the formulation of new hypotheses to be tested in the system of interest. The computational analysis of the maps may help to focus on interesting cases and thereby to appropriately prioritize the validation experiments. We show here that, by automatically comparing and analyzing structurally similar regions of proteins of known structure interacting with a common partner, it is possible to identify mutually exclusive interactions present in the maps with a sensitivity of 70% and a specificity higher than 85% and that, in about three fourth of the correctly identified complexes, we also correctly recognize at least one residue (five on average) belonging to the interaction interface. Given the present and continuously increasing number of proteins of known structure, the requirement of the knowledge of the structure of the interacting proteins does not substantially impact on the coverage of our strategy that can be estimated to be around 25%. We also introduce here the Estrella server that embodies this strategy, is designed for users interested in validating specific hypotheses about the functional role of a protein-protein interaction and it also allows access to pre-computed data for seven organisms.
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Detecting mutually exclusive interactions in protein-protein interaction maps.
Sá nchez Claros, Carmen; Tramontano, Anna
2012-01-01
Comprehensive protein interaction maps can complement genetic and biochemical experiments and allow the formulation of new hypotheses to be tested in the system of interest. The computational analysis of the maps may help to focus on interesting cases and thereby to appropriately prioritize the validation experiments. We show here that, by automatically comparing and analyzing structurally similar regions of proteins of known structure interacting with a common partner, it is possible to identify mutually exclusive interactions present in the maps with a sensitivity of 70% and a specificity higher than 85% and that, in about three fourth of the correctly identified complexes, we also correctly recognize at least one residue (five on average) belonging to the interaction interface. Given the present and continuously increasing number of proteins of known structure, the requirement of the knowledge of the structure of the interacting proteins does not substantially impact on the coverage of our strategy that can be estimated to be around 25%. We also introduce here the Estrella server that embodies this strategy, is designed for users interested in validating specific hypotheses about the functional role of a protein-protein interaction and it also allows access to pre-computed data for seven organisms.
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Looping Genomes: Diagnostic Change and the Genetic Makeup of the Autism Population.
Navon, Daniel; Eyal, Gil
2016-03-01
This article builds on Hacking's framework of "dynamic nominalism" to show how knowledge about biological etiology can interact with the "kinds of people" delineated by diagnostic categories in ways that "loop" or modify both over time. The authors use historical materials to show how "geneticization" played a crucial role in binding together autism as a biosocial community and how evidence from genetics research later made an important contribution to the diagnostic expansion of autism. In the second part of the article, the authors draw on quantitative and qualitative analyses of autism rates over time in several rare conditions that are delineated strictly according to genomic mutations in order to demonstrate that these changes in diagnostic practice helped to both increase autism's prevalence and create its enormous genetic heterogeneity. Thus, a looping process that began with geneticization and involved the social effects of genetics research itself transformed the autism population and its genetic makeup.
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Genetic counselors’ implicit racial attitudes and their relationship to communication
Schaa, Kendra L; Roter, Debra L; Biesecker, Barbara B; Cooper, Lisa A; Erby, Lori H
2015-01-01
Objective Implicit racial attitudes are thought to shape interpersonal interactions and may contribute to health care disparities. This study explored the relationship between genetic counselors’ implicit racial attitudes and their communication during simulated genetic counseling sessions. Methods A nationally representative sample of genetic counselors completed a web-based survey that included the Race Implicit Association Test (IAT). A subset of these counselors (n=67) had participated in an earlier study in which they were video recorded counseling Black, Hispanic and non-Hispanic White simulated clients (SC) about their prenatal or cancer risks. The counselors’ IAT scores were related to their session communication through robust regression modeling. Results Genetic counselors showed a moderate to strong pro-White bias on the Race IAT (M=0.41, SD=0.35). Counselors with stronger pro-White bias were rated as displaying lower levels of positive affect (pcommunication (pcommunication in minority client sessions and may contribute to racial disparities in processes of care related to genetic services. PMID:25622081
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The genetic basis of natural variation in mushroom body size in Drosophila melanogaster.
Zwarts, Liesbeth; Vanden Broeck, Lies; Cappuyns, Elisa; Ayroles, Julien F; Magwire, Michael M; Vulsteke, Veerle; Clements, Jason; Mackay, Trudy F C; Callaerts, Patrick
2015-12-11
Genetic variation in brain size may provide the basis for the evolution of the brain and complex behaviours. The genetic substrate and the selective pressures acting on brain size are poorly understood. Here we use the Drosophila Genetic Reference Panel to map polymorphic variants affecting natural variation in mushroom body morphology. We identify 139 genes and 39 transcription factors and confirm effects on development and adult plasticity. We show correlations between morphology and aggression, sleep and lifespan. We propose that natural variation in adult brain size is controlled by interaction of the environment with gene networks controlling development and plasticity.
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Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae
Reguly, Teresa; Breitkreutz, Ashton; Boucher, Lorrie; Breitkreutz, Bobby-Joe; Hon, Gary C; Myers, Chad L; Parsons, Ainslie; Friesen, Helena; Oughtred, Rose; Tong, Amy; Stark, Chris; Ho, Yuen; Botstein, David; Andrews, Brenda; Boone, Charles; Troyanskya, Olga G; Ideker, Trey; Dolinski, Kara; Batada, Nizar N; Tyers, Mike
2006-01-01
Background The study of complex biological networks and prediction of gene function has been enabled by high-throughput (HTP) methods for detection of genetic and protein interactions. Sparse coverage in HTP datasets may, however, distort network properties and confound predictions. Although a vast number of well substantiated interactions are recorded in the scientific literature, these data have not yet been distilled into networks that enable system-level inference. Results We describe here a comprehensive database of genetic and protein interactions, and associated experimental evidence, for the budding yeast Saccharomyces cerevisiae, as manually curated from over 31,793 abstracts and online publications. This literature-curated (LC) dataset contains 33,311 interactions, on the order of all extant HTP datasets combined. Surprisingly, HTP protein-interaction datasets currently achieve only around 14% coverage of the interactions in the literature. The LC network nevertheless shares attributes with HTP networks, including scale-free connectivity and correlations between interactions, abundance, localization, and expression. We find that essential genes or proteins are enriched for interactions with other essential genes or proteins, suggesting that the global network may be functionally unified. This interconnectivity is supported by a substantial overlap of protein and genetic interactions in the LC dataset. We show that the LC dataset considerably improves the predictive power of network-analysis approaches. The full LC dataset is available at the BioGRID () and SGD () databases. Conclusion Comprehensive datasets of biological interactions derived from the primary literature provide critical benchmarks for HTP methods, augment functional prediction, and reveal system-level attributes of biological networks. PMID:16762047
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Genetic Risk for Alcoholic Chronic Pancreatitis
Directory of Open Access Journals (Sweden)
Flair José Carrilho
2011-06-01
Full Text Available In recent years many studies have examined the genetic predisposition to pancreatic diseases. Pancreatic disease of an alcoholic etiology was determined to be a multi-factorial disease, where environmental factors interact with the genetic profile of the individual. In this review we discuss the main results from studies examining the frequency of genetic mutations in alcoholic chronic pancreatitis.
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Directory of Open Access Journals (Sweden)
Peri E Bolton
Full Text Available Assessment of genetic diversity and connectivity between regions can inform conservation managers about risk of inbreeding, potential for adaptation and where population boundaries lie. The Gouldian finch (Erythrura gouldiae is a threatened species in northern Australia, occupying the savannah woodlands of the biogeographically complex monsoon tropics. We present the most comprehensive population genetic analysis of diversity and structure the Gouldian finch using 16 microsatellite markers, mitochondrial control region and 3,389 SNPs from genotyping-by-sequencing. Mitochondrial diversity is compared across three related, co-distributed finches with different conservation threat-statuses. There was no evidence of genetic differentiation across the western part of the range in any of the molecular markers, and haplotype diversity but not richness was lower than a common co-distributed species. Individuals within the panmictic population in the west may be highly dispersive within this wide area, and we urge caution when interpreting anecdotal observations of changes to the distribution and/or flock sizes of Gouldian finch populations as evidence of overall changes to the population size of this species.
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Wang, Yishu; Zhao, Hongyu; Deng, Minghua; Fang, Huaying; Yang, Dejie
2017-08-24
Epistatic miniarrary profile (EMAP) studies have enabled the mapping of large-scale genetic interaction networks and generated large amounts of data in model organisms. It provides an incredible set of molecular tools and advanced technologies that should be efficiently understanding the relationship between the genotypes and phenotypes of individuals. However, the network information gained from EMAP cannot be fully exploited using the traditional statistical network models. Because the genetic network is always heterogeneous, for example, the network structure features for one subset of nodes are different from those of the left nodes. Exponentialfamily random graph models (ERGMs) are a family of statistical models, which provide a principled and flexible way to describe the structural features (e.g. the density, centrality and assortativity) of an observed network. However, the single ERGM is not enough to capture this heterogeneity of networks. In this paper, we consider a mixture ERGM (MixtureEGRM) networks, which model a network with several communities, where each community is described by a single EGRM.
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Islamaj Dogan, Rezarta; Kim, Sun; Chatr-Aryamontri, Andrew; Chang, Christie S; Oughtred, Rose; Rust, Jennifer; Wilbur, W John; Comeau, Donald C; Dolinski, Kara; Tyers, Mike
2017-01-01
A great deal of information on the molecular genetics and biochemistry of model organisms has been reported in the scientific literature. However, this data is typically described in free text form and is not readily amenable to computational analyses. To this end, the BioGRID database systematically curates the biomedical literature for genetic and protein interaction data. This data is provided in a standardized computationally tractable format and includes structured annotation of experimental evidence. BioGRID curation necessarily involves substantial human effort by expert curators who must read each publication to extract the relevant information. Computational text-mining methods offer the potential to augment and accelerate manual curation. To facilitate the development of practical text-mining strategies, a new challenge was organized in BioCreative V for the BioC task, the collaborative Biocurator Assistant Task. This was a non-competitive, cooperative task in which the participants worked together to build BioC-compatible modules into an integrated pipeline to assist BioGRID curators. As an integral part of this task, a test collection of full text articles was developed that contained both biological entity annotations (gene/protein and organism/species) and molecular interaction annotations (protein-protein and genetic interactions (PPIs and GIs)). This collection, which we call the BioC-BioGRID corpus, was annotated by four BioGRID curators over three rounds of annotation and contains 120 full text articles curated in a dataset representing two major model organisms, namely budding yeast and human. The BioC-BioGRID corpus contains annotations for 6409 mentions of genes and their Entrez Gene IDs, 186 mentions of organism names and their NCBI Taxonomy IDs, 1867 mentions of PPIs and 701 annotations of PPI experimental evidence statements, 856 mentions of GIs and 399 annotations of GI evidence statements. The purpose, characteristics and possible future
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Directory of Open Access Journals (Sweden)
Moldovan Laura
2010-10-01
Full Text Available Abstract Background Computer-based teaching (CBT is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II. Aim To develop interactive teaching software functioning as a virtual clinic for the management of MPS II. Implementation and Results The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca, was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available. Conclusions The
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Al-Jasmi, Fatma; Moldovan, Laura; Clarke, Joe T R
2010-10-25
Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II). To develop interactive teaching software functioning as a virtual clinic for the management of MPS II. The Hunter disease eClinic, a self-training, user-friendly educational software program, available at the Lysosomal Storage Research Group (http://www.lysosomalstorageresearch.ca), was developed using the Adobe Flash multimedia platform. It was designed to function both to provide a realistic, interactive virtual clinic and instantaneous access to supporting literature on Hunter disease. The Hunter disease eClinic consists of an eBook and an eClinic. The eClinic is the interactive virtual clinic component of the software. Within an environment resembling a real clinic, the trainee is instructed to perform a medical history, to examine the patient, and to order appropriate investigation. The program provides clinical data derived from the management of actual patients with Hunter disease. The eBook provides instantaneous, electronic access to a vast collection of reference information to provide detailed background clinical and basic science, including relevant biochemistry, physiology, and genetics. In the eClinic, the trainee is presented with quizzes designed to provide immediate feedback on both trainee effectiveness and efficiency. User feedback on the merits of the program was collected at several seminars and formal clinical rounds at several medical centres, primarily in Canada. In addition, online usage statistics were documented for a 2-year period. Feedback was consistently positive and confirmed the practical benefit of the program. The online English-language version is accessed daily by users from all over the world; a Japanese translation of the program is also available. The Hunter disease eClinic employs a CBT model providing the trainee with realistic
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Radiation induced mutants in elite genetic background for the augmentation of genetic diversity
International Nuclear Information System (INIS)
Kumar, V.; Bhagwat, S.G.
2011-01-01
Rice (Oryza sativa L.), an important food crop for India, shows large genetic diversity. However, despite the large genetic resource, high genetic similarity is reported in cultivated varieties indicating genetic erosion. Radiation induced mutations provide genetic variability in elite background. In the present study, twenty gamma ray induced mutants of rice variety WL112 (carrying sd-1 semi-dwarfing gene) were analysed for genetic diversity using microsatellite markers. The high range of genetic diversity among mutants indicated that the mutants possess potential for enhancing variability in rice. Cluster analysis showed presence of five clusters having small sub-clusters. Earliness, semi-dwarf stature or resistance to blast disease observed among the mutants showed that these will be useful in breeding programmes. (author)
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Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.
Directory of Open Access Journals (Sweden)
J M Vonk
Full Text Available Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma.We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1 the overall interaction effect and 2 the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study, including 12,475 subjects.First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02. Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4. The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03.Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.
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Hauser, Kurt F; Knapp, Pamela E
2014-01-01
Considerable insight has been gained into the comorbid, interactive effects of HIV and drug abuse in the brain using experimental models. This review, which considers opiates, methamphetamine, and cocaine, emphasizes the importance of host genetics and glial plasticity in driving the pathogenic neuron remodeling underlying neuro-acquired immunodeficiency syndrome and drug abuse comorbidity. Clinical findings are less concordant than experimental work, and the response of individuals to HIV and to drug abuse can vary tremendously. Host-genetic variability is important in determining viral tropism, neuropathogenesis, drug responses, and addictive behavior. However, genetic differences alone cannot account for individual variability in the brain "connectome." Environment and experience are critical determinants in the evolution of synaptic circuitry throughout life. Neurons and glia both exercise control over determinants of synaptic plasticity that are disrupted by HIV and drug abuse. Perivascular macrophages, microglia, and to a lesser extent astroglia can harbor the infection. Uninfected bystanders, especially astroglia, propagate and amplify inflammatory signals. Drug abuse by itself derails neuronal and glial function, and the outcome of chronic exposure is maladaptive plasticity. The negative consequences of coexposure to HIV and drug abuse are determined by numerous factors including genetics, sex, age, and multidrug exposure. Glia and some neurons are generated throughout life, and their progenitors appear to be targets of HIV and opiates/psychostimulants. The chronic nature of HIV and drug abuse appears to result in sustained alterations in the maturation and fate of neural progenitors, which may affect the balance of glial populations within multiple brain regions. © 2014 Elsevier Inc. All rights reserved.
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Genetic and hormonal control of hepatic steatosis in female and male mice.
Norheim, Frode; Hui, Simon T; Kulahcioglu, Emre; Mehrabian, Margarete; Cantor, Rita M; Pan, Calvin; Parks, Brian W; Lusis, Aldons J
2017-01-01
The etiology of nonalcoholic fatty liver disease is complex and influenced by factors such as obesity, insulin resistance, hyperlipidemia, and sex. We now report a study on sex difference in hepatic steatosis in the context of genetic variation using a population of inbred strains of mice. While male mice generally exhibited higher concentration of hepatic TG levels on a high-fat high-sucrose diet, sex differences showed extensive interaction with genetic variation. Differences in percentage body fat were the best predictor of hepatic steatosis among the strains and explained about 30% of the variation in both sexes. The difference in percent gonadal fat and HDL explained 9.6% and 6.7% of the difference in hepatic TGs between the sexes, respectively. Genome-wide association mapping of hepatic TG revealed some striking differences in genetic control of hepatic steatosis between females and males. Gonadectomy increased the hepatic TG to body fat percentage ratio among male, but not female, mice. Our data suggest that the difference between the sexes in hepatic TG can be partly explained by differences in body fat distribution, plasma HDL, and genetic regulation. Future studies are required to understand the molecular interactions between sex, genetics, and the environment. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
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Mediation and modification of genetic susceptibility to obesity by eating behaviors.
de Lauzon-Guillain, Blandine; Clifton, Emma Ad; Day, Felix R; Clément, Karine; Brage, Soren; Forouhi, Nita G; Griffin, Simon J; Koudou, Yves Akoli; Pelloux, Véronique; Wareham, Nicholas J; Charles, Marie-Aline; Heude, Barbara; Ong, Ken K
2017-10-01
Background: Many genetic variants show highly robust associations with body mass index (BMI). However, the mechanisms through which genetic susceptibility to obesity operates are not well understood. Potentially modifiable mechanisms, including eating behaviors, are of particular interest to public health. Objective: Here we explore whether eating behaviors mediate or modify genetic susceptibility to obesity. Design: Genetic risk scores for BMI (BMI-GRSs) were calculated for 3515 and 2154 adults in the Fenland and EDEN (Etude des déterminants pré et postnatals de la santé et du développement de l'enfant) population-based cohort studies, respectively. The eating behaviors-emotional eating, uncontrolled eating, and cognitive restraint-were measured through the use of a validated questionnaire. The mediating effect of each eating behavior on the association between the BMI-GRS and measured BMI was assessed by using the Sobel test. In addition, we tested for interactions between each eating behavior and the BMI-GRS on BMI. Results: The association between the BMI-GRS and BMI was mediated by both emotional eating (EDEN: P- Sobel = 0.01; Fenland: P- Sobel = 0.02) and uncontrolled eating (EDEN: P- Sobel = 0.04; Fenland: P -Sobel = 0.0006) in both sexes combined. Cognitive restraint did not mediate this association ( P -Sobel > 0.10), except among EDEN women ( P -Sobel = 0.0009). Cognitive restraint modified the relation between the BMI-GRS and BMI among men (EDEN: P -interaction = 0.0001; Fenland: P -interaction = 0.04) and Fenland women ( P -interaction = 0.0004). By tertiles of cognitive restraint, the association between the BMI-GRS and BMI was strongest in the lowest tertile of cognitive restraint, and weakest in the highest tertile. Conclusions: Genetic susceptibility to obesity was partially mediated by the "appetitive" eating behavior traits (uncontrolled and emotional eating) and, in 3 of the 4 population groups studied, was modified by cognitive restraint
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Morgante, Fabio; Huang, Wen; Maltecca, Christian; Mackay, Trudy F C
2018-06-01
Predicting complex phenotypes from genomic data is a fundamental aim of animal and plant breeding, where we wish to predict genetic merits of selection candidates; and of human genetics, where we wish to predict disease risk. While genomic prediction models work well with populations of related individuals and high linkage disequilibrium (LD) (e.g., livestock), comparable models perform poorly for populations of unrelated individuals and low LD (e.g., humans). We hypothesized that low prediction accuracies in the latter situation may occur when the genetics architecture of the trait departs from the infinitesimal and additive architecture assumed by most prediction models. We used simulated data for 10,000 lines based on sequence data from a population of unrelated, inbred Drosophila melanogaster lines to evaluate this hypothesis. We show that, even in very simplified scenarios meant as a stress test of the commonly used Genomic Best Linear Unbiased Predictor (G-BLUP) method, using all common variants yields low prediction accuracy regardless of the trait genetic architecture. However, prediction accuracy increases when predictions are informed by the genetic architecture inferred from mapping the top variants affecting main effects and interactions in the training data, provided there is sufficient power for mapping. When the true genetic architecture is largely or partially due to epistatic interactions, the additive model may not perform well, while models that account explicitly for interactions generally increase prediction accuracy. Our results indicate that accounting for genetic architecture can improve prediction accuracy for quantitative traits.
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Geographically structured genetic variation in the Medicago lupulina-Ensifer mutualism.
Harrison, Tia L; Wood, Corlett W; Heath, Katy D; Stinchcombe, John R
2017-07-01
Gene flow between genetically differentiated populations can maintain variation in species interactions, especially when population structure is congruent between interacting species. However, large-scale empirical comparisons of the population structure of interacting species are rare, particularly in positive interspecific interactions (mutualisms). One agriculturally and ecologically important mutualism is the partnership between legume plants and rhizobia. Through characterizing and comparing the population genomic structure of the legume Medicago lupulina and two rhizobial species (Ensifer medicae and E. meliloti), we explored the spatial scale of population differentiation between interacting partners in their introduced range in North America. We found high proportions of E. meliloti in southeastern populations and high proportions of E. medicae in northwestern populations. Medicago lupulina and the Ensifer genus showed similar patterns of spatial genetic structure (isolation by distance). However, we detected no evidence of isolation by distance or population structure within either species of bacteria. Genome-wide nucleotide diversity within each of the two Ensifer species was low, suggesting limited introduction of strains, founder events, or severe bottlenecks. Our results suggest that there is potential for geographically structured coevolution between M. lupulina and the Ensifer genus, but not between M. lupulina and either Ensifer species. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.
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A genome-wide survey of transgenerational genetic effects in autism.
Directory of Open Access Journals (Sweden)
Kathryn M Tsang
Full Text Available Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction. We used simple models of single locus parent-child interaction and identified suggestive results (P<10(-4 that cannot be explained by main effects, but no genome-wide significant signals. Some of these maternal and maternal-child associations were in or adjacent to autism candidate genes including: PCDH9, FOXP1, GABRB3, NRXN1, RELN, MACROD2, FHIT, RORA, CNTN4, CNTNAP2, FAM135B, LAMA1, NFIA, NLGN4X, RAPGEF4, and SDK1. We attempted validation of potential autism association under maternal-specific models using maternal-paternal comparison in family-based GWAS datasets. Our results suggest that further study of parental genetic effects and parent-child interaction in autism is warranted.
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Wise regulates bone deposition through genetic interactions with Lrp5.
Ellies, Debra L; Economou, Androulla; Viviano, Beth; Rey, Jean-Philippe; Paine-Saunders, Stephenie; Krumlauf, Robb; Saunders, Scott
2014-01-01
In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development.
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Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90.
Geiler-Samerotte, Kerry A; Zhu, Yuan O; Goulet, Benjamin E; Hall, David W; Siegal, Mark L
2016-10-01
The protein-folding chaperone Hsp90 has been proposed to buffer the phenotypic effects of mutations. The potential for Hsp90 and other putative buffers to increase robustness to mutation has had major impact on disease models, quantitative genetics, and evolutionary theory. But Hsp90 sometimes contradicts expectations for a buffer by potentiating rapid phenotypic changes that would otherwise not occur. Here, we quantify Hsp90's ability to buffer or potentiate (i.e., diminish or enhance) the effects of genetic variation on single-cell morphological features in budding yeast. We corroborate reports that Hsp90 tends to buffer the effects of standing genetic variation in natural populations. However, we demonstrate that Hsp90 tends to have the opposite effect on genetic variation that has experienced reduced selection pressure. Specifically, Hsp90 tends to enhance, rather than diminish, the effects of spontaneous mutations and recombinations. This result implies that Hsp90 does not make phenotypes more robust to the effects of genetic perturbation. Instead, natural selection preferentially allows buffered alleles to persist and thereby creates the false impression that Hsp90 confers greater robustness.
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Hernández Velázquez, J D; Barroso-Flores, J; Gama Goicochea, A
2016-11-23
Two of the most commonly encountered friction-reducing agents used in plastic sheet production are the amides known as erucamide and behenamide, which despite being almost identical chemically, lead to markedly different values of the friction coefficient. To understand the origin of this contrasting behavior, in this work we model brushes made of these two types of linear-chain molecules using quantum mechanical numerical simulations under the density functional theory at the B97D/6-31G(d,p) level of theory. Four chains of erucamide and behenamide were linked to a 2 × 10 zigzag graphene sheet and optimized both in vacuum and in continuous solvent using the SMD implicit solvation model. We find that erucamide chains tend to remain closer together through π-π stacking interactions arising from the double bonds located at C13-C14, a feature behenamide lacks, and thus a more spread configuration is obtained with the latter. It is argued that this arrangement of the erucamide chains is responsible for the lower friction coefficient of erucamide brushes, compared with behenamide brushes, which is a macroscopic consequence of cooperative quantum mechanical interactions. While only quantum level interactions are modeled here, we show that behenamide chains are more spread out in the brush than erucamide chains as a consequence of those interactions. The spread-out configuration allows more solvent particles to penetrate the brush, leading in turn to more friction, in agreement with macroscopic measurements and mesoscale simulations of the friction coefficient reported in the literature.
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Reyes-Gibby, Cielito C; Yuan, Christine; Wang, Jian; Yeung, Sai-Ching J; Shete, Sanjay
2015-06-05
Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders. Addictive behaviors have a bidirectional relationship with pain. We hypothesize that the associations between alcohol, smoking, and opioid addiction observed in cancer patients have a genetic basis. Therefore, using bioinformatics tools, we explored the underlying genetic basis and identified new candidate genes and common biological pathways for smoking, alcohol, and opioid addiction. Literature search showed 56 genes associated with alcohol, smoking and opioid addiction. Using Core Analysis function in Ingenuity Pathway Analysis software, we found that ERK1/2 was strongly interconnected across all three addiction networks. Genes involved in immune signaling pathways were shown across all three networks. Connect function from IPA My Pathway toolbox showed that DRD2 is the gene common to both the list of genetic variations associated with all three addiction phenotypes and the components of the brain neuronal signaling network involved in substance addiction. The top canonical pathways associated with the 56 genes were: 1) calcium signaling, 2) GPCR signaling, 3) cAMP-mediated signaling, 4) GABA receptor signaling, and 5) G-alpha i signaling. Cancer patients are often prescribed opioids for cancer pain thus increasing their risk for opioid abuse and addiction. Our findings provide candidate genes and biological pathways underlying addiction phenotypes, which may be future targets for treatment of addiction. Further study of the variations of the candidate genes could allow physicians to make more informed decisions when treating cancer pain with opioid analgesics.
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Anholt, Robert R H; Mackay, Trudy F C
2012-01-01
Aggression mediates competition for food, mating partners, and habitats and, among social animals, establishes stable dominance hierarchies. In humans, abnormal aggression is a hallmark of neuropsychiatric disorders and can be elicited by environmental factors acting on an underlying genetic susceptibility. Identifying the genetic architecture that predisposes to aggressive behavior in people is challenging because of difficulties in quantifying the phenotype, genetic heterogeneity, and uncontrolled environmental conditions. Studies on mice have identified single-gene mutations that result in hyperaggression, contingent on genetic background. These studies can be complemented by systems genetics approaches in Drosophila melanogaster, in which mutational analyses together with genome-wide transcript analyses, artificial selection studies, and genome-wide analysis of epistasis have revealed that a large segment of the genome contributes to the manifestation of aggressive behavior with widespread epistatic interactions. Comparative genomic analyses based on the principle of evolutionary conservation are needed to enable a complete dissection of the neurogenetic underpinnings of this universal fitness trait.
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Leo, Sarah S T; Gonzalez, Andrew; Millien, Virginie
2016-05-01
Zoonotic disease transmission systems involve sets of species interacting with each other and their environment. This complexity impedes development of disease monitoring and control programs that require reliable identification of spatial and biotic variables and mechanisms facilitating disease emergence. To overcome this difficulty, we propose a framework that simultaneously examines all species involved in disease emergence by integrating concepts and methods from population genetics, landscape ecology, and spatial statistics. Multi-taxa integrated landscape genetics (MTILG) can reveal how interspecific interactions and landscape variables influence disease emergence patterns. We test the potential of our MTILG-based framework by modelling the emergence of a disease system across multiple species dispersal, interspecific interaction, and landscape scenarios. Our simulations showed that both interspecific-dependent dispersal patterns and landscape characteristics significantly influenced disease spread. Using our framework, we were able to detect statistically similar inter-population genetic differences and highly correlated spatial genetic patterns that imply species-dependent dispersal. Additionally, species that were assigned coupled-dispersal patterns were affected to the same degree by similar landscape variables. This study underlines the importance of an integrated approach to investigating emergence of disease systems. MTILG is a robust approach for such studies and can identify potential avenues for targeted disease management strategies.
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Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon
2018-01-19
Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; p trend colorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer.
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Axelsson, E Petter; Iason, Glenn R; Julkunen-Tiitto, Riitta; Whitham, Thomas G
2015-01-01
A central issue in the field of community genetics is the expectation that trait variation among genotypes play a defining role in structuring associated species and in forming community phenotypes. Quantifying the existence of such community phenotypes in two common garden environments also has important consequences for our understanding of gene-by-environment interactions at the community level. The existence of community phenotypes has not been evaluated in the crowns of boreal forest trees. In this study we address the influence of tree genetics on needle chemistry and genetic x environment interactions on two gall-inducing adelgid aphids (Adelges spp. and Sacchiphantes spp.) that share the same elongating bud/shoot niche. We examine the hypothesis that the canopies of different genotypes of Norway spruce (Picea abies L.) support different community phenotypes. Three patterns emerged. First, the two gallers show clear differences in their response to host genetics and environment. Whereas genetics significantly affected the abundance of Adelges spp. galls, Sacchiphantes spp. was predominately affected by the environment suggesting that the genetic influence is stronger in Adelges spp. Second, the among family variation in genetically controlled resistance was large, i.e. fullsib families differed as much as 10 fold in susceptibility towards Adelges spp. (0.57 to 6.2 galls/branch). Also, the distribution of chemical profiles was continuous, showing both overlap as well as examples of significant differences among fullsib families. Third, despite the predicted effects of host chemistry on galls, principal component analyses using 31 different phenolic substances showed only limited association with galls and a similarity test showed that trees with similar phenolic chemical characteristics, did not host more similar communities of gallers. Nonetheless, the large genetic variation in trait expression and clear differences in how community members respond to host
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Directory of Open Access Journals (Sweden)
E Petter Axelsson
Full Text Available A central issue in the field of community genetics is the expectation that trait variation among genotypes play a defining role in structuring associated species and in forming community phenotypes. Quantifying the existence of such community phenotypes in two common garden environments also has important consequences for our understanding of gene-by-environment interactions at the community level. The existence of community phenotypes has not been evaluated in the crowns of boreal forest trees. In this study we address the influence of tree genetics on needle chemistry and genetic x environment interactions on two gall-inducing adelgid aphids (Adelges spp. and Sacchiphantes spp. that share the same elongating bud/shoot niche. We examine the hypothesis that the canopies of different genotypes of Norway spruce (Picea abies L. support different community phenotypes. Three patterns emerged. First, the two gallers show clear differences in their response to host genetics and environment. Whereas genetics significantly affected the abundance of Adelges spp. galls, Sacchiphantes spp. was predominately affected by the environment suggesting that the genetic influence is stronger in Adelges spp. Second, the among family variation in genetically controlled resistance was large, i.e. fullsib families differed as much as 10 fold in susceptibility towards Adelges spp. (0.57 to 6.2 galls/branch. Also, the distribution of chemical profiles was continuous, showing both overlap as well as examples of significant differences among fullsib families. Third, despite the predicted effects of host chemistry on galls, principal component analyses using 31 different phenolic substances showed only limited association with galls and a similarity test showed that trees with similar phenolic chemical characteristics, did not host more similar communities of gallers. Nonetheless, the large genetic variation in trait expression and clear differences in how community members
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Journal of Genetics | Indian Academy of Sciences
Indian Academy of Sciences (India)
Genetic interaction and mapping studies on the leaflet development (lld) mutant in Pisum ... Genetic features of thyroid hormone receptors ... DREB1/CBF transcription factors: their structure, function and role in abiotic stress tolerance in plants.
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He, Xiaoqing; Jin, Yi; Ye, Meixia; Chen, Nan; Zhu, Jing; Wang, Jingqi; Jiang, Libo; Wu, Rongling
2017-01-01
How a species responds to such a biotic environment in the community, ultimately leading to its evolution, has been a topic of intense interest to ecological evolutionary biologists. Until recently, limited knowledge was available regarding the genotypic changes that underlie phenotypic changes. Our study implemented GWAS (Genome-Wide Association Studies) to illustrate the genetic architecture of ecological interactions that take place in microbial populations. By choosing 45 such interspecific pairs of Escherichia coli and Staphylococcus aureus strains that were all genotyped throughout the entire genome, we employed Q-ROADTRIPS to analyze the association between single SNPs and microbial abundance measured at each time point for bacterial populations reared in monoculture and co-culture, respectively. We identified a large number of SNPs and indels across the genomes (35.69 G clean data of E. coli and 50.41 G of S. aureus ). We reported 66 and 111 SNPs that were associated with interaction in E. coli and S. aureus , respectively. 23 out of 66 polymorphic changes resulted in amino acid alterations.12 significant genes, such as murE, treA, argS , and relA , which were also identified in previous evolutionary studies. In S. aureus , 111 SNPs detected in coding sequences could be divided into 35 non-synonymous and 76 synonymous SNPs. Our study illustrated the potential of genome-wide association methods for studying rapidly evolving traits in bacteria. Genetic association study methods will facilitate the identification of genetic elements likely to cause phenotypes of interest and provide targets for further laboratory investigation.
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Liorzou, Mathilde; Pernet, Alix; Li, Shubin; Chastellier, Annie; Thouroude, Tatiana; Michel, Gilles; Malécot, Valéry; Gaillard, Sylvain; Briée, Céline; Foucher, Fabrice; Oghina-Pavie, Cristiana; Clotault, Jérémy; Grapin, Agnès
2016-08-01
Hybridization with introduced genetic resources is commonly practiced in ornamental plant breeding to introgress desired traits. The 19th century was a golden age for rose breeding in France. The objective here was to study the evolution of rose genetic diversity over this period, which included the introduction of Asian genotypes into Europe. A large sample of 1228 garden roses encompassing the conserved diversity cultivated during the 18th and 19th centuries was genotyped with 32 microsatellite primer pairs. Its genetic diversity and structure were clarified. Wide diversity structured in 16 genetic groups was observed. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background was observed in cultivated European hybrids during the 19th century. Frequent crosses with Asian roses throughout the 19th century and/or selection for Asiatic traits may have induced this shift. In addition, the consistency of the results with respect to a horticultural classification is discussed. Some horticultural groups, defined according to phenotype and/or knowledge of their pedigree, seem to be genetically more consistent than others, highlighting the difficulty of classifying cultivated plants. Therefore, the horticultural classification is probably more appropriate for commercial purposes rather than genetic relatedness, especially to define preservation and breeding strategies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.
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Gene-Lifestyle Interactions in Obesity.
van Vliet-Ostaptchouk, Jana V; Snieder, Harold; Lagou, Vasiliki
2012-01-01
Obesity is a complex multifaceted disease resulting from interactions between genetics and lifestyle. The proportion of phenotypic variance ascribed to genetic variance is 0.4 to 0.7 for obesity and recent years have seen considerable success in identifying disease-susceptibility variants. Although with the advent of genome-wide association studies the list of genetic variants predisposing to obesity has significantly increased the identified variants only explain a fraction of disease heritability. Studies of gene-environment interactions can provide more insight into the biological mechanisms involved in obesity despite the challenges associated with such designs. Epigenetic changes that affect gene function without DNA sequence modifications may be a key factor explaining interindividual differences in obesity, with both genetic and environmental factors influencing the epigenome. Disentangling the relative contributions of genetic, environmental and epigenetic marks to the establishment of obesity is a major challenge given the complex interplay between these determinants.
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The genetic links between the big five personality traits and general interest domains.
Kandler, Christian; Bleidorn, Wiebke; Riemann, Rainer; Angleitner, Alois; Spinath, Frank M
2011-12-01
This is the first genetically informative study in which multiple informants were used to quantify the genetic and environmental sources of individual differences in general interests as well as the phenotypic and genetic links between general interests and Big Five personality traits. Self-reports and two peer ratings from 844 individuals, including 225 monozygotic and 113 dizygotic complete twin pairs, were collected. Multiple-rater scores (composites) revealed that the averaged levels of genetic and environmental effects on seven broad interest domains were similar to those on personality traits. Multivariate analyses showed that about 35% of the genetic and 9% of the environmental variance in interests were explained by personality domains, in particular by Openness. The findings suggest that interests cannot easily be considered as a byproduct of the interactions between personality genotypes and the environmental influences but rather as an internal regulation of behavior with an own genetic basis.
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Rodriguez-Fontenla, Cristina; Gonzalez, Antonio
2015-01-01
Osteoarthritis (OA) is a complex disease caused by the interaction of multiple genetic and environmental factors. This review focuses on the studies that have contributed to the discovery of genetic susceptibility factors in OA. The most relevant associations discovered until now are discussed in detail: GDF-5, 7q22 locus, MCF2L, DOT1L, NCOA3 and also some important findings from the arcOGEN study. Moreover, the different approaches that can be used to minimize the specific problems of the study of OA genetics are discussed. These include the study of microsatellites, phenotype standardization and other methods such as meta-analysis of GWAS and gene-based analysis. It is expected that these new approaches contribute to finding new susceptibility genetic factors for OA. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
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The genetics of indirect ecological effects - plant parasites and aphid herbivores
Directory of Open Access Journals (Sweden)
Jennifer K Rowntree
2014-04-01
Full Text Available When parasitic plants and aphid herbivores share a host, both direct and indirect ecological effects (IEEs can influence evolutionary processes. We used a hemiparasitic plant (Rhinanthus minor, a grass host (Hordeum vulgare and a cereal aphid (Sitobion avenae to investigate the genetics of IEEs between the aphid and the parasitic plant, and looked to see how these might affect or be influenced by the genetic diversity of the host plants. Survival of R. minor depended on the parasite’s population of origin, the genotypes of the aphids sharing the host and the genetic diversity in the host plant community. Hence the indirect effects of the aphids on the parasitic plants depended on the genetic environment of the system. Here, we show that genetic variation can be important in determining the outcome of IEEs. Therefore, IEEs have the potential to influence evolutionary processes and the continuity of species interactions over time.
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Genetics of nonsyndromic obesity.
Lee, Yung Seng
2013-12-01
Common obesity is widely regarded as a complex, multifactorial trait influenced by the 'obesogenic' environment, sedentary behavior, and genetic susceptibility contributed by common and rare genetic variants. This review describes the recent advances in understanding the role of genetics in obesity. New susceptibility loci and genetic variants are being uncovered, but the collective effect is relatively small and could not explain most of the BMI heritability. Yet-to-be identified common and rare variants, epistasis, and heritable epigenetic changes may account for part of the 'missing heritability'. Evidence is emerging about the role of epigenetics in determining obesity susceptibility, mediating developmental plasticity, which confers obesity risk from early life experiences. Genetic prediction scores derived from selected genetic variants, and also differential DNA methylation levels and methylation scores, have been shown to correlate with measures of obesity and response to weight loss intervention. Genetic variants, which confer susceptibility to obesity-related morbidities like nonalcoholic fatty liver disease, were also discovered recently. We can expect discovery of more rare genetic variants with the advent of whole exome and genome sequencing, and also greater understanding of epigenetic mechanisms by which environment influences genetic expression and which mediate the gene-environment interaction.
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[Genetics factors in pathogenesis and clinical genetics of binge eating disorder].
Kibitov, А О; Мazo, G E
2016-01-01
Genetic studies have shown that binge eating disorder (ВЕD) aggregates in families, heritability was estimated as about 60% and additive genetic influences on BED up to 50%. Using a genetic approach has proved useful for verifying the diagnostic categories of BED using DSM-IV criteria and supporting the validity of considering this pathology as a separate nosological category. The results confirmed the genetic and pathogenic originality of BED as a separate psychopathological phenomenon, but not a subtype of obesity. It seems fruitful to considerate BED as a disease with hereditary predisposition with significant genetic influence and a complex psychopathological syndrome, including not only eating disorders, but also depressive and addictive component. A possible mechanism of pathogenesis of BED may be the interaction of the neuroendocrine and neurotransmitters systems including the active involvement of the reward system in response to a variety of chronic stress influences with the important modulatory role of specific personality traits. The high level of genetic influence on the certain clinical manifestations of BED confirms the ability to identify the subphenotypes of BED on genetic basis involving clinical criteria. It can not only contribute to further genetic studies, taking into account more homogeneous samples, but also help in finding differentiated therapeutic approaches.
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Genetic effects of ionising radiation
International Nuclear Information System (INIS)
Saunders, P.A.H.
1991-12-01
Ionizing radiation effects on the gem cells, which can result in genetic abnormalities, are described. The basic mechanisms of radiation interactions with chromosomes, or specifically DNA, which can result in radiation induced mutation are discussed. Methods of estimating genetic risks, and some values for quantitative risk estimates are given. (U.K.). 13 refs., 2 figs., 1 tab
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Robinson, Joshua F; Port, Jesse A; Yu, Xiaozhong; Faustman, Elaine M
2010-10-01
To understand the complex etiology of developmental disorders, an understanding of both genetic and environmental risk factors is needed. Human and rodent genetic studies have identified a multitude of gene candidates for specific developmental disorders such as neural tube defects (NTDs). With the emergence of toxicogenomic-based assessments, scientists now also have the ability to compare and understand the expression of thousands of genes simultaneously across strain, time, and exposure in developmental models. Using a systems-based approach in which we are able to evaluate information from various parts and levels of the developing organism, we propose a framework for integrating genetic information with toxicogenomic-based studies to better understand gene-environmental interactions critical for developmental disorders. This approach has allowed us to characterize candidate genes in the context of variables critical for determining susceptibility such as strain, time, and exposure. Using a combination of toxicogenomic studies and complementary bioinformatic tools, we characterize NTD candidate genes during normal development by function (gene ontology), linked phenotype (disease outcome), location, and expression (temporally and strain-dependent). In addition, we show how environmental exposures (cadmium, methylmercury) can influence expression of these genes in a strain-dependent manner. Using NTDs as an example of developmental disorder, we show how simple integration of genetic information from previous studies into the standard microarray design can enhance analysis of gene-environment interactions to better define environmental exposure-disease pathways in sensitive and resistant mouse strains. © Wiley-Liss, Inc.
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Non-Genetic Determinants of Mosquito Competence for Malaria Parasites
Lefèvre, Thierry; Vantaux, Amélie; Dabiré, Kounbobr R.; Mouline, Karine; Cohuet, Anna
2013-01-01
Understanding how mosquito vectors and malaria parasites interact is of fundamental interest, and it also offers novel perspectives for disease control. Both the genetic and environmental contexts are known to affect the ability of mosquitoes to support malaria development and transmission, i.e., vector competence. Although the role of environment has long been recognized, much work has focused on host and parasite genetic effects. However, the last few years have seen a surge of studies revealing a great diversity of ways in which non-genetic factors can interfere with mosquito-Plasmodium interactions. Here, we review the current evidence for such environmentally mediated effects, including ambient temperature, mosquito diet, microbial gut flora, and infection history, and we identify additional factors previously overlooked in mosquito-Plasmodium interactions. We also discuss epidemiological implications, and the evolutionary consequences for vector immunity and parasite transmission strategies. Finally, we propose directions for further research and argue that an improved knowledge of non-genetic influences on mosquito-Plasmodium interactions could aid in implementing conventional malaria control measures and contribute to the design of novel strategies. PMID:23818841
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Non-genetic determinants of mosquito competence for malaria parasites.
Directory of Open Access Journals (Sweden)
Thierry Lefèvre
Full Text Available Understanding how mosquito vectors and malaria parasites interact is of fundamental interest, and it also offers novel perspectives for disease control. Both the genetic and environmental contexts are known to affect the ability of mosquitoes to support malaria development and transmission, i.e., vector competence. Although the role of environment has long been recognized, much work has focused on host and parasite genetic effects. However, the last few years have seen a surge of studies revealing a great diversity of ways in which non-genetic factors can interfere with mosquito-Plasmodium interactions. Here, we review the current evidence for such environmentally mediated effects, including ambient temperature, mosquito diet, microbial gut flora, and infection history, and we identify additional factors previously overlooked in mosquito-Plasmodium interactions. We also discuss epidemiological implications, and the evolutionary consequences for vector immunity and parasite transmission strategies. Finally, we propose directions for further research and argue that an improved knowledge of non-genetic influences on mosquito-Plasmodium interactions could aid in implementing conventional malaria control measures and contribute to the design of novel strategies.
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Directory of Open Access Journals (Sweden)
Apurv Goel
Full Text Available Date hub proteins have 1 or 2 interaction interfaces but many interaction partners. This raises the question of whether all partner proteins compete for the interaction interface of the hub or if the cell carefully regulates aspects of this process? Here, we have used real-time rendering of protein interaction networks to analyse the interactions of all the 1 or 2 interface hubs of Saccharomyces cerevisiae during the cell cycle. By integrating previously determined structural and gene expression data, and visually hiding the nodes (proteins and their edges (interactions during their troughs of expression, we predict when interactions of hubs and their partners are likely to exist. This revealed that 20 out of all 36 one- or two- interface hubs in the yeast interactome fell within two main groups. The first was dynamic hubs with static partners, which can be considered as 'competitive hubs'. Their interaction partners will compete for the interaction interface of the hub and the success of any interaction will be dictated by the kinetics of interaction (abundance and affinity and subcellular localisation. The second was static hubs with dynamic partners, which we term 'non-competitive hubs'. Regulatory mechanisms are finely tuned to lessen the presence and/or effects of competition between the interaction partners of the hub. It is possible that these regulatory processes may also be used by the cell for the regulation of other, non-cell cycle processes.
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Genetic variation and population structure of interleukin genes ...
Indian Academy of Sciences (India)
... phylogenetic analysis based on genetic distances between populations agreed with known social and cultural data ... thus, impact on community genetics (Bittles 2001, 2002). ... reflect an interaction between evolutionary and demographic.
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Directory of Open Access Journals (Sweden)
Alexandre eBureau
2015-07-01
Full Text Available Effects of genetic variants on the risk of complex diseases estimated from association studies are typically small. Nonetheless, variants may have important effects in presence of specific levels of environmental exposures, and when a trait related to the disease (endophenotype is either normal or impaired. We propose polytomous and transition models to represent the relationship between disease, endophenotype, genotype and environmental exposure in family studies. Model coefficients were estimated using generalized estimating equations and were used to derive gene-environment interaction effects and genotype effects at specific levels of exposure. In a simulation study, estimates of the effect of a genetic variant were substantially higher when both an endophenotype and an environmental exposure modifying the variant effect were taken into account, particularly under transition models, compared to the alternative of ignoring the endophenotype. Illustration of the proposed modeling with the metabolic syndrome, abdominal obesity, physical activity and polymorphisms in the NOX3 gene in the Quebec Family Study revealed that the positive association of the A allele of rs1375713 with the metabolic syndrome at high levels of physical activity was only detectable in subjects without abdominal obesity, illustrating the importance of taking into account the abdominal obesity endophenotype in this analysis.
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Understanding protein–protein interactions by genetic suppression
Indian Academy of Sciences (India)
Unknown
Protein–protein interactions influence many cellular processes and it is increasingly being felt that even a weak and ... In a bacterial system where the complete genome sequence is available, it is an arduous ... teins (primary mutations) are useful in these studies. ... of interaction of this antibiotic with the central enzyme.
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Directory of Open Access Journals (Sweden)
Jacob W. Bledsoe
2018-05-01
Full Text Available The microbiota of teleost fish has gained a great deal of research attention within the past decade, with experiments suggesting that both host-genetics and environment are strong ecological forces shaping the bacterial assemblages of fish microbiomes. Despite representing great commercial and scientific importance, the catfish within the family Ictaluridae, specifically the blue and channel catfish, have received very little research attention directed toward their gut-associated microbiota using 16S rRNA gene sequencing. Within this study we utilize multiple genetically distinct strains of blue and channel catfish, verified via microsatellite genotyping, to further quantify the role of host-genetics in shaping the bacterial communities in the fish gut, while maintaining environmental and husbandry parameters constant. Comparisons of the gut microbiota among the two catfish species showed no differences in bacterial species richness (observed and Chao1 or overall composition (weighted and unweighted UniFrac and UniFrac distances showed no correlation with host genetic distances (Rst according to Mantel tests. The microbiota of environmental samples (diet and water were found to be significantly more diverse than that of the catfish gut associated samples, suggesting that factors within the host were further regulating the bacterial communities, despite the lack of a clear connection between microbiota composition and host genotype. The catfish gut communities were dominated by the phyla Fusobacteria, Proteobacteria, and Firmicutes; however, differential abundance analysis between the two catfish species using analysis of composition of microbiomes detected two differential genera, Cetobacterium and Clostridium XI. The metagenomic pathway features inferred from our dataset suggests the catfish gut bacterial communities possess pathways beneficial to their host such as those involved in nutrient metabolism and antimicrobial biosynthesis, while
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Automated identification of social interaction criteria in Drosophila melanogaster.
Schneider, J; Levine, J D
2014-10-01
The study of social behaviour within groups has relied on fixed definitions of an 'interaction'. Criteria used in these definitions often involve a subjectively defined cut-off value for proximity, orientation and time (e.g. courtship, aggression and social interaction networks) and the same numerical values for these criteria are applied to all of the treatment groups within an experiment. One universal definition of an interaction could misidentify interactions within groups that differ in life histories, study treatments and/or genetic mutations. Here, we present an automated method for determining the values of interaction criteria using a pre-defined rule set rather than pre-defined values. We use this approach and show changing social behaviours in different manipulations of Drosophila melanogaster. We also show that chemosensory cues are an important modality of social spacing and interaction. This method will allow a more robust analysis of the properties of interacting groups, while helping us understand how specific groups regulate their social interaction space. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
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Gene-set analysis shows association between FMRP targets and autism spectrum disorder
Jansen, Arija; Dieleman, Gwen C; Smit, August B; Verhage, Matthijs; Verhulst, Frank C; Polderman, Tinca J C; Posthuma, Danielle
Autism spectrum disorder (ASD) is a heterogeneous group of disorders characterized by problems with social interaction, communication, and repetitive and restricted behavior. Despite its high heritability and the substantial progress made in elucidating genetic associations, the corresponding
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SNP interaction pattern identifier (SIPI)
DEFF Research Database (Denmark)
Lin, Hui Yi; Chen, Dung Tsa; Huang, Po Yu
2017-01-01
Motivation: Testing SNP-SNP interactions is considered as a key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped. Results: We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45...
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Demongeot, Jacques; Ben Amor, Hedi; Elena, Adrien; Gillois, Pierre; Noual, Mathilde; Sené, Sylvain
2009-01-01
Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability). We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode) of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression). We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime) or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control. PMID:20057955
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Directory of Open Access Journals (Sweden)
Sylvain Sené
2009-10-01
Full Text Available Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability. We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression. We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control.
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Song, Nan; Shin, Aesun; Oh, Jae Hwan; Kim, Jeongseon
2018-01-01
Background Genome-wide association studies (GWAS) have identified approximately 40 common genetic loci associated with colorectal cancer risk. To investigate possible gene-environment interactions (GEIs) between GWAS-identified single-nucleotide polymorphisms (SNPs) and alcohol consumption with respect to colorectal cancer, a hospital-based case-control study was conducted. Results Higher levels of alcohol consumption as calculated based on a standardized definition of a drink (1 drink=12.5g of ethanol) were associated with increased risk of colorectal cancer (OR=2.47, 95% CI=1.62-3.76 for heavy drinkers [>50g/day] compared to never drinkers; ptrendcolorectal cancer associated with the G allele of rs6687758 tended to increase among individuals in the heavier alcohol consumption strata. A statistically significant association between rs6687758 and colorectal cancer risk was observed among moderate alcohol drinkers who consumed between >12.5 and ≤50g of alcohol per day (OR=1.46, 95% CI=1.01-2.11). Methods A total of 2,109 subjects (703 colorectal cancer patients and 1,406 healthy controls) were recruited from the Korean National Cancer Center. For genotyping, 30 GWAS-identified SNPs were selected. A logistic regression model was used to evaluate associations of SNPs and alcohol consumption with colorectal cancer risk. We also tested GEIs between SNPs and alcohol consumption using a logistic model with multiplicative interaction terms. Conclusions Our results suggest that SNP rs6687758 at 1q41 may interact with alcohol consumption in the etiology of colorectal cancer. PMID:29464080
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Mycobacterium leprae–host-cell interactions and genetic determinants in leprosy: an overview
Pinheiro, Roberta Olmo; de Souza Salles, Jorgenilce; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira
2011-01-01
Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae–host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed. PMID:21366421
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Genetic analysis of the heparan modification network in Caenorhabditis elegans.
Townley, Robert A; Bülow, Hannes E
2011-05-13
Heparan sulfates (HS) are highly modified sugar polymers in multicellular organisms that function in cell adhesion and cellular responses to protein signaling. Functionally distinct, cell type-dependent HS modification patterns arise as the result of a conserved network of enzymes that catalyze deacetylations, sulfations, and epimerizations in specific positions of the sugar residues. To understand the genetic interactions of the enzymes during the HS modification process, we have measured the composition of HS purified from mutant strains of Caenorhabditis elegans. From these measurements we have developed a genetic network model of HS modification. We find the interactions to be highly recursive positive feed-forward and negative feedback loops. Our genetic analyses show that the HS C-5 epimerase hse-5, the HS 2-O-sulfotransferase hst-2, or the HS 6-O-sulfotransferase hst-6 inhibit N-sulfation. In contrast, hse-5 stimulates both 2-O- and 6-O-sulfation and, hst-2 and hst-6 inhibit 6-O- and 2-O-sulfation, respectively. The effects of hst-2 and hst-6 on N-sulfation, 6-O-sulfation, and 2-O-sulfation appear largely dependent on hse-5 function. This core of regulatory interactions is further modulated by 6-O-endosulfatase activity (sul-1). 47% of all 6-O-sulfates get removed from HS and this editing process is dependent on hst-2, thereby providing additional negative feedback between 2-O- and 6-O-sulfation. These findings suggest that the modification patterns are highly sensitive to the relative composition of the HS modification enzymes. Our comprehensive genetic analysis forms the basis of understanding the HS modification network in metazoans.
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Genetic Analysis of the Heparan Modification Network in Caenorhabditis elegans*
Townley, Robert A.; Bülow, Hannes E.
2011-01-01
Heparan sulfates (HS) are highly modified sugar polymers in multicellular organisms that function in cell adhesion and cellular responses to protein signaling. Functionally distinct, cell type-dependent HS modification patterns arise as the result of a conserved network of enzymes that catalyze deacetylations, sulfations, and epimerizations in specific positions of the sugar residues. To understand the genetic interactions of the enzymes during the HS modification process, we have measured the composition of HS purified from mutant strains of Caenorhabditis elegans. From these measurements we have developed a genetic network model of HS modification. We find the interactions to be highly recursive positive feed-forward and negative feedback loops. Our genetic analyses show that the HS C-5 epimerase hse-5, the HS 2-O-sulfotransferase hst-2, or the HS 6-O-sulfotransferase hst-6 inhibit N-sulfation. In contrast, hse-5 stimulates both 2-O- and 6-O-sulfation and, hst-2 and hst-6 inhibit 6-O- and 2-O-sulfation, respectively. The effects of hst-2 and hst-6 on N-sulfation, 6-O-sulfation, and 2-O-sulfation appear largely dependent on hse-5 function. This core of regulatory interactions is further modulated by 6-O-endosulfatase activity (sul-1). 47% of all 6-O-sulfates get removed from HS and this editing process is dependent on hst-2, thereby providing additional negative feedback between 2-O- and 6-O-sulfation. These findings suggest that the modification patterns are highly sensitive to the relative composition of the HS modification enzymes. Our comprehensive genetic analysis forms the basis of understanding the HS modification network in metazoans. PMID:21454666
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God and Genes in the Caring Professions: Clinician and Clergy Perceptions of Religion and Genetics
Bartlett, Virginia L; Johnson, Rolanda L
2013-01-01
Little is known about how care providers’ perceptions of religion and genetics affect interactions with patients/parishioners. This study investigates clinicians’ and clergy’s perceptions of and experiences with religion and genetics in their clinical and pastoral interactions. An exploratory qualitative study designed to elicit care providers’ descriptions of experiences with religion and genetics in clinical or pastoral interactions. Thirteen focus groups were conducted with members of the caring professions: physicians, nurses, and genetics counselors (clinicians), ministers and chaplains (clergy). Preliminary analysis of qualitative data is presented here. Preliminary analysis highlights four positions in professional perceptions of the relationship between science and faith. Further, differences among professional perceptions appear to influence perceptions of needed or available resources for interactions with religion and genetics. Clinicians’ and clergy’s perceptions of how religion and genetics relate are not defined solely by professional affiliation. These non-role-defined perceptions may affect clinical and pastoral interactions, especially regarding resources for patients and parishioners. PMID:19170091
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The genetic basis of local adaptation for pathogenic fungi in agricultural ecosystems.
Croll, Daniel; McDonald, Bruce A
2017-04-01
Local adaptation plays a key role in the evolutionary trajectory of host-pathogen interactions. However, the genetic architecture of local adaptation in host-pathogen systems is poorly understood. Fungal plant pathogens in agricultural ecosystems provide highly tractable models to quantify phenotypes and map traits to corresponding genomic loci. The outcome of crop-pathogen interactions is thought to be governed largely by gene-for-gene interactions. However, recent studies showed that virulence can be governed by quantitative trait loci and that many abiotic factors contribute to the outcome of the interaction. After introducing concepts of local adaptation and presenting examples from wild plant pathosystems, we focus this review on a major pathogen of wheat, Zymoseptoria tritici, to show how a multitude of traits can affect local adaptation. Zymoseptoria tritici adapted to different thermal environments across its distribution range, indicating that thermal adaptation may limit effective dispersal to different climates. The application of fungicides led to the rapid evolution of multiple, independent resistant populations. The degree of colony melanization showed strong pleiotropic effects with other traits, including trade-offs with colony growth rates and fungicide sensitivity. The success of the pathogen on its host can be assessed quantitatively by counting pathogen reproductive structures and measuring host damage based on necrotic lesions. Interestingly, these two traits can be weakly correlated and depend both on host and pathogen genotypes. Quantitative trait mapping studies showed that the genetic architecture of locally adapted traits varies from single loci with large effects to many loci with small individual effects. We discuss how local adaptation could hinder or accelerate the development of epidemics in agricultural ecosystems. © 2016 John Wiley & Sons Ltd.
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An investigation of genetic algorithms
International Nuclear Information System (INIS)
Douglas, S.R.
1995-04-01
Genetic algorithms mimic biological evolution by natural selection in their search for better individuals within a changing population. they can be used as efficient optimizers. This report discusses the developing field of genetic algorithms. It gives a simple example of the search process and introduces the concept of schema. It also discusses modifications to the basic genetic algorithm that result in species and niche formation, in machine learning and artificial evolution of computer programs, and in the streamlining of human-computer interaction. (author). 3 refs., 1 tab., 2 figs
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Biflorin induces cytotoxicity by DNA interaction in genetically different human melanoma cell lines.
Ralph, Ana Carolina Lima; Calcagno, Danielle Queiroz; da Silva Souza, Luciana Gregório; de Lemos, Telma Leda Gomes; Montenegro, Raquel Carvalho; de Arruda Cardoso Smith, Marília; de Vasconcellos, Marne Carvalho
2016-08-01
Cancer is a public health problem and the second leading cause of death worldwide. The incidence of cutaneous melanoma has been notably increasing, resulting in high aggressiveness and poor survival rates. Taking into account the antitumor activity of biflorin, a substance isolated from Capraria biflora L. roots that is cytotoxic in vitro and in vivo, this study aimed to demonstrate the action of biflorin against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of genetic alterations and mutations, such as the TP53, NRAS and BRAF genes. The results presented here indicate that biflorin reduces the viability of melanoma cell lines by DNA interactions. Biflorin causes single and double DNA strand breaks, consequently inhibiting cell cycle progression, replication and DNA repair and promoting apoptosis. Our data suggest that biflorin could be considered as a future therapeutic option for managing melanoma. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Jung, Su Yon; Sobel, Eric M; Papp, Jeanette C; Zhang, Zuo-Feng
2017-04-26
Impaired glucose metabolism-related genetic variants and traits likely interact with obesity and related lifestyle factors, influencing postmenopausal breast and colorectal cancer (CRC), but their interconnected pathways are not fully understood. By stratifying via obesity and lifestyles, we partitioned the total effect of glucose metabolism genetic variants on cancer risk into two putative mechanisms: 1) indirect (risk-associated glucose metabolism genetic variants mediated by glucose metabolism traits) and 2) direct (risk-associated glucose metabolism genetic variants through pathways other than glucose metabolism traits) effects. Using 16 single-nucleotide polymorphisms (SNPs) associated with glucose metabolism and data from 5379 postmenopausal women in the Women's Health Initiative Harmonized and Imputed Genome-Wide Association Studies, we retrospectively assessed the indirect and direct effects of glucose metabolism-traits (fasting glucose, insulin, and homeostatic model assessment-insulin resistance [HOMA-IR]) using two quantitative tests. Several SNPs were associated with breast cancer and CRC risk, and these SNP-cancer associations differed between non-obese and obese women. In both strata, the direct effect of cancer risk associated with the SNP accounted for the majority of the total effect for most SNPs, with roughly 10% of cancer risk due to the SNP that was from an indirect effect mediated by glucose metabolism traits. No apparent differences in the indirect (glucose metabolism-mediated) effects were seen between non-obese and obese women. It is notable that among obese women, 50% of cancer risk was mediated via glucose metabolism trait, owing to two SNPs: in breast cancer, in relation to GCKR through glucose, and in CRC, in relation to DGKB/TMEM195 through HOMA-IR. Our findings suggest that glucose metabolism genetic variants interact with obesity, resulting in altered cancer risk through pathways other than those mediated by glucose metabolism traits.
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Zhu, Ena C; Soundy, Timothy J; Hu, Yueshan
2017-05-01
Consuming excessive amounts of alcohol has the potential to modify an individual's brain and lead to alcohol dependence. Alcohol use leads to 88,000 deaths every year in the U.S. alone and can lead to other health issues including cancers, such as colorectal cancer, and mental health problems. While drinking behavior varies due to environmental factors, genetic factors also contribute to the risk of alcoholism. Certain genes affecting alcohol metabolism and neurotransmitters have been found to contribute to or inhibit the risk. Geneenvironment interactions may also play a role in the susceptibility of alcoholism. With a better understanding of the different components that can contribute to alcoholism, more personalized treatment could cater to the individual. This review discusses the major genetic factors and some small variants in other genes that contribute to alcoholism, as well as considers the gene-environmental interactions. Copyright© South Dakota State Medical Association.
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Kuno, Sotaro; Yoshida, Takashi; Kaneko, Takakazu; Sako, Yoshihiko
2012-08-01
Clustered regularly interspaced short palindromic repeats (CRISPR) confer sequence-dependent, adaptive resistance in prokaryotes against viruses and plasmids via incorporation of short sequences, called spacers, derived from foreign genetic elements. CRISPR loci are thus considered to provide records of past infections. To describe the host-parasite (i.e., cyanophages and plasmids) interactions involving the bloom-forming freshwater cyanobacterium Microcystis aeruginosa, we investigated CRISPR in four M. aeruginosa strains and in two previously sequenced genomes. The number of spacers in each locus was larger than the average among prokaryotes. All spacers were strain specific, except for a string of 11 spacers shared in two closely related strains, suggesting diversification of the loci. Using CRISPR repeat-based PCR, 24 CRISPR genotypes were identified in a natural cyanobacterial community. Among 995 unique spacers obtained, only 10 sequences showed similarity to M. aeruginosa phage Ma-LMM01. Of these, six spacers showed only silent or conservative nucleotide mutations compared to Ma-LMM01 sequences, suggesting a strategy by the cyanophage to avert CRISPR immunity dependent on nucleotide identity. These results imply that host-phage interactions can be divided into M. aeruginosa-cyanophage combinations rather than pandemics of population-wide infectious cyanophages. Spacer similarity also showed frequent exposure of M. aeruginosa to small cryptic plasmids that were observed only in a few strains. Thus, the diversification of CRISPR implies that M. aeruginosa has been challenged by diverse communities (almost entirely uncharacterized) of cyanophages and plasmids.
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Dopamine and dopamine receptor D1 associated with decreased social interaction.
Liu, Qiang; Shi, Jieyun; Lin, Rongfei; Wen, Tieqiao
2017-05-01
Deficits in social interaction are hallmarks of neurological and psychiatric disorders. However, its underlying mechanism is still unclear. Here, we show that the loss of dendritic cell factor 1 (Dcf1) in the nervous system of mice induces social interaction deficiency, autism-like behaviour, and influences social interaction via the dopamine system. Dopamine receptor D1 agonist rescues this social cognition phenotype, and improves short-term plasticity. Together, this study presents a new genetic mechanism that affects social interaction and may provide a new way to improve positive social interaction and treat autism spectrum disorders. Copyright © 2017 Elsevier B.V. All rights reserved.
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Can friends protect genetically vulnerable children from depression?
Brendgen, Mara; Vitaro, Frank; Bukowski, William M; Dionne, Ginette; Tremblay, Richard E; Boivin, Michel
2013-05-01
The study examined whether reciprocal friendship quantity or quality can mitigate genetic vulnerability for depression symptoms in children. The sample comprised 168 monozygotic twin pairs and 126 same-sex dizygotic twin pairs assessed in Grade 4 (mean age = 10.04 years). Friendship participation was measured via reciprocal nominations of close friendships within the classroom. Friendship quality was measured through self-reports. Depression symptoms were measured through teacher and peer reports. Genetic vulnerability for depression symptoms was unrelated to friendship participation or the number of reciprocal friends, but it was negatively related to positive friendship quality. In line with gene-environment interaction, genetic risk effects on depression symptoms were mitigated in girls who had at least one close reciprocal friend. In boys, only moderate main effects of genetic vulnerability and friendship participation were found but no interaction between them. However, among boys with at least one reciprocal friend, a greater number of friends was related to fewer depression symptoms whereas no cumulative effect of friendship was found for girls. Finally, positive friendship quality was related to fewer depression symptoms in girls and boys even when controlling for genetic risk. The findings emphasize the importance of teaching social interactional skills that promote high-quality friendship relations to help prevent the development of depression symptoms in children.
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The DNA of coral reef biodiversity: predicting and protecting genetic diversity of reef assemblages.
Selkoe, Kimberly A; Gaggiotti, Oscar E; Treml, Eric A; Wren, Johanna L K; Donovan, Mary K; Toonen, Robert J
2016-04-27
Conservation of ecological communities requires deepening our understanding of genetic diversity patterns and drivers at community-wide scales. Here, we use seascape genetic analysis of a diversity metric, allelic richness (AR), for 47 reef species sampled across 13 Hawaiian Islands to empirically demonstrate that large reefs high in coral cover harbour the greatest genetic diversity on average. We found that a species's life history (e.g. depth range and herbivory) mediates response of genetic diversity to seascape drivers in logical ways. Furthermore, a metric of combined multi-species AR showed strong coupling to species richness and habitat area, quality and stability that few species showed individually. We hypothesize that macro-ecological forces and species interactions, by mediating species turnover and occupancy (and thus a site's mean effective population size), influence the aggregate genetic diversity of a site, potentially allowing it to behave as an apparent emergent trait that is shaped by the dominant seascape drivers. The results highlight inherent feedbacks between ecology and genetics, raise concern that genetic resilience of entire reef communities is compromised by factors that reduce coral cover or available habitat, including thermal stress, and provide a foundation for new strategies for monitoring and preserving biodiversity of entire reef ecosystems. © 2016 The Authors.
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Directory of Open Access Journals (Sweden)
Brianne A Beisner
2011-01-01
Full Text Available The persistence of biological systems requires evolved mechanisms which promote stability. Cohesive primate social groups are one example of stable biological systems, which persist in spite of regular conflict. We suggest that genetic relatedness and its associated kinship structure are a potential source of stability in primate social groups as kinship structure is an important organizing principle in many animal societies. We investigated the effect of average genetic relatedness per matrilineal family on the stability of matrilineal grooming and agonistic interactions in 48 matrilines from seven captive groups of rhesus macaques. Matrilines with low average genetic relatedness show increased family-level instability such as: more sub-grouping in their matrilineal groom network, more frequent fighting with kin, and higher rates of wounding. Family-level instability in multiple matrilines within a group is further associated with group-level instability such as increased wounding. Stability appears to arise from the presence of clear matrilineal structure in the rhesus macaque group hierarchy, which is derived from cohesion among kin in their affiliative and agonistic interactions with each other. We conclude that genetic relatedness and kinship structure are an important source of group stability in animal societies, particularly when dominance and/or affilative interactions are typically governed by kinship.
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Wade, Christopher H; Wilfond, Benjamin S
2006-11-15
Several companies utilize direct-to-consumer (DTC) advertising for genetic tests and some, but not all, bypass clinician involvement by offering DTC purchase of the tests. This article examines how DTC marketing strategies may affect genetic counselors, using available cardiovascular disease susceptibility tests as an illustration. The interpretation of these tests is complex and includes consideration of clinical validity and utility, and the further complications of gene-environment interactions and pleiotropy. Although it is unclear to what extent genetic counselors will encounter clients who have been exposed to DTC marketing strategies, these strategies may influence genetic counseling interactions if they produce directed interest in specific tests and unrealistic expectations for the tests' capacity to predict disease. Often, a client's concern about risk for cardiovascular diseases is best addressed by established clinical tests and a family history assessment. Ethical dilemmas may arise for genetic counselors who consider whether to accept clients who request test interpretation or to order DTC-advertised tests that require a clinician's authorization. Genetic counselors' obligations to care for clients extend to interpreting DTC tests, although this obligation may be fulfilled by referral or consultation with specialists. Genetic counselors do not have an obligation to order DTC-advertised tests that have minimal clinical validity and utility at a client's request. This can be a justified restriction on autonomy based on consideration of risks to the client, the costs, and the implications for society. Published 2006 Wiley-Liss, Inc.
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Sonestedt, Emily; Hellstrand, Sophie; Drake, Isabel; Schulz, Christina-Alexandra; Ericson, Ulrika; Hlebowicz, Joanna; Persson, Margaretha M; Gullberg, Bo; Hedblad, Bo; Engström, Gunnar; Orho-Melander, Marju
2016-05-09
A high diet quality according to the Swedish nutrition recommendations is associated with a reduced risk of cardiovascular disease in the population-based Malmö Diet and Cancer cohort. To further clarify this protective association, we examined the association between high diet quality and change in triglycerides, high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) after 16 years of follow-up in 3152 individuals (61% women; 46-68 years at baseline). In addition, we examined if genetic risk scores composed of 80 lipid-associated genetic variants modify these associations. A diet quality index based on intakes of saturated fat, polyunsaturated fat, sucrose, fiber, fruit and vegetables, and fish was constructed. A high diet quality was associated with lower risk of developing high triglycerides (p = 0.02) and high LDL-C (p = 0.03) during follow-up compared with a low diet quality. We found an association between diet quality and long-term change in HDL-C only among those with lower genetic risk for low HDL-C as opposed to those with higher genetic risk (p-interaction = 0.04). Among those with lower genetic risk for low HDL-C, low diet quality was associated with decreased HDL-C during follow-up (p = 0.05). In conclusion, individuals with high adherence to the Swedish nutrition recommendation had lower risk of developing high triglycerides and LDL-C during 16 years of follow-up.
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The New Genetics and Natural versus Artificial Genetic Modification
Directory of Open Access Journals (Sweden)
Mae-Wan Ho
2013-11-01
Full Text Available The original rationale and impetus for artificial genetic modification was the “central dogma” of molecular biology that assumed DNA carries all the instructions for making an organism, which are transmitted via RNA to protein to biological function in linear causal chains. This is contrary to the reality of the “fluid genome” that has emerged since the mid-1970s. In order to survive, the organism needs to engage in natural genetic modification in real time, an exquisitely precise molecular dance of life with RNA and DNA responding to and participating in “downstream” biological functions. Artificial genetic modification, in contrast, is crude, imprecise, and interferes with the natural process. It drives natural systems towards maximum biosemiotic entropy as the perturbations are propagated and amplified through the complex cascades of interactions between subsystems that are essential for health and longevity.
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Hüls, Anke; Ickstadt, Katja; Schikowski, Tamara; Krämer, Ursula
2017-06-12
For the analysis of gene-environment (GxE) interactions commonly single nucleotide polymorphisms (SNPs) are used to characterize genetic susceptibility, an approach that mostly lacks power and has poor reproducibility. One promising approach to overcome this problem might be the use of weighted genetic risk scores (GRS), which are defined as weighted sums of risk alleles of gene variants. The gold-standard is to use external weights from published meta-analyses. In this study, we used internal weights from the marginal genetic effects of the SNPs estimated by a multivariate elastic net regression and thereby provided a method that can be used if there are no external weights available. We conducted a simulation study for the detection of GxE interactions and compared power and type I error of single SNPs analyses with Bonferroni correction and corresponding analysis with unweighted and our weighted GRS approach in scenarios with six risk SNPs and an increasing number of highly correlated (up to 210) and noise SNPs (up to 840). Applying weighted GRS increased the power enormously in comparison to the common single SNPs approach (e.g. 94.2% vs. 35.4%, respectively, to detect a weak interaction with an OR ≈ 1.04 for six uncorrelated risk SNPs and n = 700 with a well-controlled type I error). Furthermore, weighted GRS outperformed the unweighted GRS, in particular in the presence of SNPs without any effect on the phenotype (e.g. 90.1% vs. 43.9%, respectively, when 20 noise SNPs were added to the six risk SNPs). This outperforming of the weighted GRS was confirmed in a real data application on lung inflammation in the SALIA cohort (n = 402). However, in scenarios with a high number of noise SNPs (>200 vs. 6 risk SNPs), larger sample sizes are needed to avoid an increased type I error, whereas a high number of correlated SNPs can be handled even in small samples (e.g. n = 400). In conclusion, weighted GRS with weights from the marginal genetic effects of the
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Recurrent and multiple bladder tumors show conserved expression profiles
International Nuclear Information System (INIS)
Lindgren, David; Fioretos, Thoas; Månsson, Wiking; Höglund, Mattias; Gudjonsson, Sigurdur; Jee, Kowan Ja; Liedberg, Fredrik; Aits, Sonja; Andersson, Anna; Chebil, Gunilla; Borg, Åke; Knuutila, Sakari
2008-01-01
Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors. Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses. We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles. Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors
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Malone, Molly
2012-01-01
Most middle school students comprehend that organisms have adaptations that enable their survival and that successful adaptations prevail in a population over time. Yet they often miss that those bird beaks, moth-wing colors, or whatever traits are the result of random, normal genetic variations that just happen to confer a negative, neutral, or…
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Hida, Hirotake; Mouri, Akihiro; Noda, Yukihiro
2013-01-01
Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.
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Genetics of ischaemic stroke in young adults
Terni, Eva; Giannini, Nicola; Brondi, Marco; Montano, Vincenzo; Bonuccelli, Ubaldo; Mancuso, Michelangelo
2015-01-01
Background: Stroke may be a clinical expression of several inherited disorders in humans. Recognition of the underlined genetic disorders causing stroke is important for a correct diagnosis, for genetic counselling and, even if rarely, for a correct therapeutic management. Moreover, the genetics of complex diseases such the stroke, in which multiple genes interact with environmental risk factors to increase risk, has been revolutionized by the Genome-Wide Association Study (GWAS) approach. ...
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Journal of Genetics | Indian Academy of Sciences
Indian Academy of Sciences (India)
Home; Journals; Journal of Genetics; Volume 86; Issue 2. Complex genetic interactions govern the temporal effects of Antennapedia on antenna-to-leg transformations in Drosophila melanogaster. Ian Dworkin Wendy Lee Fiona Mccloskey Ellen Larsen. Research Article Volume 86 Issue 2 August 2007 pp 111-123 ...
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Gene–Lifestyle Interactions in Obesity
van Vliet-Ostaptchouk, Jana V.; Snieder, Harold; Lagou, Vasiliki
Obesity is a complex multifaceted disease resulting from interactions between genetics and lifestyle. The proportion of phenotypic variance ascribed to genetic variance is 0.4 to 0.7 for obesity and recent years have seen considerable success in identifying disease-susceptibility variants. Although
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Genetic architecture for susceptibility to gout in the KARE cohort study.
Shin, Jimin; Kim, Younyoung; Kong, Minyoung; Lee, Chaeyoung
2012-06-01
This study aimed to identify functional associations of cis-regulatory regions with gout susceptibility using data resulted from a genome-wide association study (GWAS), and to show a genetic architecture for gout with interaction effects among genes within each of the identified functions. The GWAS was conducted with 8314 control subjects and 520 patients with gout in the Korea Association REsource cohort. However, genetic associations with any individual nucleotide variants were not discovered by Bonferroni multiple testing in the GWAS (P>1.42 × 10(-7)). Genomic regions enrichment analysis was employed to identify functional associations of cis-regulatory regions. This analysis revealed several biological processes associated with gout susceptibility, and they were quite different from those with serum uric acid level. Epistasis for susceptibility to gout was estimated using entropy decomposition with selected genes within each biological process identified by the genomic regions enrichment analysis. Some epistases among nucleotide sequence variants for gout susceptibility were found to be larger than their individual effects. This study provided the first evidence that genetic factors for gout susceptibility greatly differed from those for serum uric acid level, which may suggest that research endeavors for identifying genetic factors for gout susceptibility should not be heavily dependent on pathogenesis of uric acid. Interaction effects between genes should be examined to explain a large portion of phenotypic variability for gout susceptibility.
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Citalopram for the Treatment of Agitation in Alzheimer Dementia: Genetic Influences.
Peters, Matthew E; Vaidya, Vijay; Drye, Lea T; Devanand, Davangere P; Mintzer, Jacobo E; Pollock, Bruce G; Porsteinsson, Anton P; Rosenberg, Paul B; Schneider, Lon S; Shade, David M; Weintraub, Daniel; Yesavage, Jerome; Lyketsos, Constantine G; Avramopoulos, Dimitri
2016-03-01
To assess potential genetic influences on citalopram treatment efficacy for agitation in individuals with Alzheimer dementia (AD). Six functional genetic variants were studied in the following genes: serotonin receptor 2A (HTR2A-T102C), serotonin receptor 2C (HTR2C-Cys23Ser), serotonin transporter (5HTT-LPR), brain-derived neurotropic factor (BDNF-Val66Met), apolipoprotein E (ε2, ε3, ε4 variants), and cytochrome P450 (CYP2C19). Treatment response by genotype was measured by (1) the agitation domain of the Neurobehavioral Rating Scale, (2) the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change scale (mADCS-CGIC), (3) the agitation domain of the Neuropsychiatric Inventory (NPI), and (4) the Cohen-Mansfield Agitation Inventory. We utilized data from the Citalopram for Agitation in Alzheimer's Disease (CitAD) database. CitAD was a 9-week randomized, double-blind, placebo-controlled multicenter clinical trial showing significant improvement in agitation and caregiver distress in patients treated with citalopram. Proportional odds logistic regression and mixed effects models were used to examine the above-mentioned outcome measures. Significant interactions were noted on the NPI agitation domain for HTR2A (likelihood ratio [LR] = 6.19, df = 2, P = .04) and the mADCS-CGIC for HTR2C (LR = 4.33, df = 2, P = .02) over 9 weeks. Treatment outcomes in CitAD showed modest, although statistically significant, influence of genetic variation at HTR2A and HTR2C loci. Future studies should continue to examine the interaction of known genetic variants with antidepressant treatment in patients with AD having agitation. © The Author(s) 2015.
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Gene interactions and genetics of blast resistance and yield ...
Indian Academy of Sciences (India)
2014-08-11
Aug 11, 2014 ... of chemical measures for the control and management of blast, which are not .... tion of genetic components of variation, epistasis model and gene effects in two .... and environmental variance is estimated from mean variance.
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Codon size reduction as the origin of the triplet genetic code.
Directory of Open Access Journals (Sweden)
Pavel V Baranov
Full Text Available The genetic code appears to be optimized in its robustness to missense errors and frameshift errors. In addition, the genetic code is near-optimal in terms of its ability to carry information in addition to the sequences of encoded proteins. As evolution has no foresight, optimality of the modern genetic code suggests that it evolved from less optimal code variants. The length of codons in the genetic code is also optimal, as three is the minimal nucleotide combination that can encode the twenty standard amino acids. The apparent impossibility of transitions between codon sizes in a discontinuous manner during evolution has resulted in an unbending view that the genetic code was always triplet. Yet, recent experimental evidence on quadruplet decoding, as well as the discovery of organisms with ambiguous and dual decoding, suggest that the possibility of the evolution of triplet decoding from living systems with non-triplet decoding merits reconsideration and further exploration. To explore this possibility we designed a mathematical model of the evolution of primitive digital coding systems which can decode nucleotide sequences into protein sequences. These coding systems can evolve their nucleotide sequences via genetic events of Darwinian evolution, such as point-mutations. The replication rates of such coding systems depend on the accuracy of the generated protein sequences. Computer simulations based on our model show that decoding systems with codons of length greater than three spontaneously evolve into predominantly triplet decoding systems. Our findings suggest a plausible scenario for the evolution of the triplet genetic code in a continuous manner. This scenario suggests an explanation of how protein synthesis could be accomplished by means of long RNA-RNA interactions prior to the emergence of the complex decoding machinery, such as the ribosome, that is required for stabilization and discrimination of otherwise weak triplet codon
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Wang, Tiange; Huang, Tao; Zheng, Yan; Rood, Jennifer; Bray, George A.; Sacks, Frank M.; Qi, Lu
2016-01-01
Objective Weight loss intervention through diet modification has been widely used to improve obesity-related hyperglycemia; however, little is known about whether genetic variation modifies the intervention effect. We examined the interaction between weight-loss diets and genetic variation of fasting glucose on changes in glycemic traits in a dietary intervention trial. Research Design and Methods The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial is a randomized, controlled 2-year weight-loss trial. We assessed overall genetic variation of fasting glucose by calculating a genetic risk score (GRS) based on 14 fasting glucose-associated single nucleotide polymorphisms, and examined the progression in fasting glucose and insulin levels, and insulin resistance and insulin sensitivity in 733 adults from this trial. Results The GRS was associated with 6-month changes in fasting glucose (Pfasting insulin (P=0.042), homeostasis model assessment of insulin resistance (HOMA-IR, P=0.009) and insulin sensitivity (HOMA-S, P=0.043). We observed significant interaction between the GRS and dietary fat on 6-month changes in fasting glucose, HOMA-IR and HOMA-S after multivariable adjustment (P-interaction=0.007, 0.045, and 0.028, respectively). After further adjustment for weight loss, the interaction remained significant on change in fasting glucose (P=0.015). In the high-fat diet group, participants in the highest GRS tertile showed increased fasting glucose, whereas participants in the lowest tertile showed decreased fasting glucose (P-trend<0.001); in contrast, the genetic association was not significant in the low-fat diet group (P-trend=0.087). Conclusions Our data suggest that participants with a higher genetic risk may benefit more by eating a low-fat diet to improve glucose metabolism. PMID:27113490
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Ibañez Cuadrado, Angela
2008-01-01
The addictions are common chronic psychiatric diseases which represent a serious worldwide public-health problem. They have a high prevalence and negative effects at individual, family and societal level, with a high sanitary cost. Epidemiological genetic research has revealed that addictions are moderately to highly heritable. Also the investigation has evidenced that environmental and genetic factors contribute to individual differences in vulnerability to addictions. Advances in the neurobiology of addiction joined to the development of new molecular genetic technologies, have led to the identification of a variety of underlying genes and pathways in addiction process, leading to the description of common molecular mechanisms in substance and behaviour dependencies. Identifying gene-environment interactions is a crucial issue in future research. Other major goal in genetic research is the identification of new therapeutic targets for treatment and prevention.
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Archaeal extrachromosomal genetic elements
DEFF Research Database (Denmark)
Wang, Haina; Peng, Nan; Shah, Shiraz Ali
2015-01-01
SUMMARY: Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes, such as spind......SUMMARY: Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes...... on archaeal ECEs has just started to unravel the molecular biology of these genetic entities and their interactions with archaeal hosts, it is expected to accelerate in the next decade....
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Tegeder, Irmgard
2016-12-01
Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech). This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016) [1].
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Directory of Open Access Journals (Sweden)
Rahul M. Phuke
2017-05-01
Full Text Available The low grain iron and zinc densities are well documented problems in food crops, affecting crop nutritional quality especially in cereals. Sorghum is a major source of energy and micronutrients for majority of population in Africa and central India. Understanding genetic variation, genotype × environment interaction and association between these traits is critical for development of improved cultivars with high iron and zinc. A total of 336 sorghum RILs (Recombinant Inbred Lines were evaluated for grain iron and zinc concentration along with other agronomic traits for 2 years at three locations. The results showed that large variability exists in RIL population for both micronutrients (Iron = 10.8 to 76.4 mg kg−1 and Zinc = 10.2 to 58.7 mg kg−1, across environments and agronomic traits. Genotype × environment interaction for both micronutrients (iron and zinc was highly significant. GGE biplots comparison for grain iron and zinc showed greater variation across environments. The results also showed that G × E was substantial for grain iron and zinc, hence wider testing needed for taking care of G × E interaction to breed micronutrient rich sorghum lines. Iron and zinc concentration showed high significant positive correlation (across environment = 0.79; p < 0.01 indicating possibility of simultaneous effective selection for both the traits. The RIL population showed good variability and high heritabilities (>0.60, in individual environments for Fe and Zn and other traits studied indicating its suitability to map QTL for iron and zinc.
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Directory of Open Access Journals (Sweden)
Ian M Willis
2008-07-01
Full Text Available Transcriptional repression of ribosomal components and tRNAs is coordinately regulated in response to a wide variety of environmental stresses. Part of this response involves the convergence of different nutritional and stress signaling pathways on Maf1, a protein that is essential for repressing transcription by RNA polymerase (pol III in Saccharomyces cerevisiae. Here we identify the functions buffering yeast cells that are unable to down-regulate transcription by RNA pol III. MAF1 genetic interactions identified in screens of non-essential gene-deletions and conditionally expressed essential genes reveal a highly interconnected network of 64 genes involved in ribosome biogenesis, RNA pol II transcription, tRNA modification, ubiquitin-dependent proteolysis and other processes. A survey of non-essential MAF1 synthetic sick/lethal (SSL genes identified six gene-deletions that are defective in transcriptional repression of ribosomal protein (RP genes following rapamycin treatment. This subset of MAF1 SSL genes included MED20 which encodes a head module subunit of the RNA pol II Mediator complex. Genetic interactions between MAF1 and subunits in each structural module of Mediator were investigated to examine the functional relationship between these transcriptional regulators. Gene expression profiling identified a prominent and highly selective role for Med20 in the repression of RP gene transcription under multiple conditions. In addition, attenuated repression of RP genes by rapamycin was observed in a strain deleted for the Mediator tail module subunit Med16. The data suggest that Mediator and Maf1 function in parallel pathways to negatively regulate RP mRNA and tRNA synthesis.
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Knowledge of Genetics and Attitudes toward Genetic Testing among College Students in Saudi Arabia.
Olwi, Duaa; Merdad, Leena; Ramadan, Eman
2016-01-01
Genetic testing has been gradually permeating the practice of medicine. Health-care providers may be confronted with new genetic approaches that require genetically informed decisions which will be influenced by patients' knowledge of genetics and their attitudes toward genetic testing. This study assesses the knowledge of genetics and attitudes toward genetic testing among college students. A cross-sectional study was conducted using a multistage stratified sample of 920 senior college students enrolled at King Abdulaziz University, Saudi Arabia. Information regarding knowledge of genetics, attitudes toward genetic testing, and sociodemographic data were collected using a self-administered questionnaire. In general, students had a good knowledge of genetics but lacked some fundamentals of genetics. The majority of students showed positive attitudes toward genetic testing, but some students showed negative attitudes toward certain aspects of genetic testing such as resorting to abortion in the case of an untreatable major genetic defect in an unborn fetus. The main significant predictors of knowledge were faculty, gender, academic year, and some prior awareness of 'genetic testing'. The main significant predictors of attitudes were gender, academic year, grade point average, and some prior awareness of 'genetic testing'. The knowledge of genetics among college students was higher than has been reported in other studies, and the attitudes toward genetic testing were fairly positive. Genetics educational programs that target youths may improve knowledge of genetics and create a public perception that further supports genetic testing. © 2016 S. Karger AG, Basel.
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Fan, Qiao; Wojciechowski, Robert; Kamran Ikram, M.; Cheng, Ching-Yu; Chen, Peng; Zhou, Xin; Pan, Chen-Wei; Khor, Chiea-Chuen; Tai, E-Shyong; Aung, Tin; Wong, Tien-Yin; Teo, Yik-Ying; Saw, Seang-Mei
2014-01-01
Refractive error is a complex ocular trait governed by both genetic and environmental factors and possibly their interplay. Thus far, data on the interaction between genetic variants and environmental risk factors for refractive errors are largely lacking. By using findings from recent genome-wide association studies, we investigated whether the main environmental factor, education, modifies the effect of 40 single nucleotide polymorphisms on refractive error among 8461 adults from five studies including ethnic Chinese, Malay and Indian residents of Singapore. Three genetic loci SHISA6-DNAH9, GJD2 and ZMAT4-SFRP1 exhibited a strong association with myopic refractive error in individuals with higher secondary or university education (SHISA6-DNAH9: rs2969180 A allele, β = −0.33 D, P = 3.6 × 10–6; GJD2: rs524952 A allele, β = −0.31 D, P = 1.68 × 10−5; ZMAT4-SFRP1: rs2137277 A allele, β = −0.47 D, P = 1.68 × 10−4), whereas the association at these loci was non-significant or of borderline significance in those with lower secondary education or below (P for interaction: 3.82 × 10−3–4.78 × 10−4). The evidence for interaction was strengthened when combining the genetic effects of these three loci (P for interaction = 4.40 × 10−8), and significant interactions with education were also observed for axial length and myopia. Our study shows that low level of education may attenuate the effect of risk alleles on myopia. These findings further underline the role of gene–environment interactions in the pathophysiology of myopia. PMID:24014484
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Genetic influences are virtually absent for trust.
Directory of Open Access Journals (Sweden)
Paul A M Van Lange
Full Text Available Over the past decades, numerous twin studies have revealed moderate to high heritability estimates for individual differences in a wide range of human traits, including cognitive ability, psychiatric disorders, and personality traits. Even factors that are generally believed to be environmental in nature have been shown to be under genetic control, albeit modest. Is such heritability also present in social traits that are conceptualized as causes and consequences of social interactions or in other ways strongly shaped by behavior of other people? Here we examine a population-based sample of 1,012 twins and relatives. We show that the genetic influence on generalized trust in other people (trust-in-others: h2 = 5%, ns, and beliefs regarding other people's trust in the self (trust-in-self: h2 = 13%, ns, is virtually absent. As test-retest reliability for both scales were found to be moderate or high (r = .76 and r = .53, respectively in an independent sample, we conclude that all variance in trust is likely to be accounted for by non-shared environmental influences. We show that, relative to cognitive abilities, psychiatric disorders, and classic personality variables, genetic influences are smaller for trust, and propose that experiences with or observations of the behavior of other people shape trust more strongly than other traits.
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Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis
Colizzi, Marco; Iyegbe, Conrad; Powell, John; Ursini, Gianluca; Porcelli, Annamaria; Bonvino, Aurora; Taurisano, Paolo; Romano, Raffaella; Masellis, Rita; Blasi, Giuseppe; Morgan, Craig; Aitchison, Katherine; Mondelli, Valeria; Luzi, Sonija; Kolliakou, Anna; David, Anthony; Murray, Robin M.; Bertolino, Alessandro; Forti, Marta Di
2015-01-01
Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects’ sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22–7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39–16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis use. PMID:25829376
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Journal of Genetics | Indian Academy of Sciences
Indian Academy of Sciences (India)
Home; Journals; Journal of Genetics. LIANG WANG. Articles written in Journal of Genetics. Volume 92 Issue 3 December 2013 pp 395-402 Research Article. Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene × gender interaction · Ke-Sheng Wang Liang Wang Xuefeng Liu Min Zeng.
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Jacobson, Kristen C; Hoffman, Christy L; Vasilopoulos, Terrie; Kremen, William S; Panizzon, Matthew S; Grant, Michael D; Lyons, Michael J; Xian, Hong; Franz, Carol E
2012-12-01
There is growing evidence that pet ownership and human-animal interaction (HAI) have benefits for human physical and psychological well-being. However, there may be pre-existing characteristics related to patterns of pet ownership and interactions with pets that could potentially bias results of research on HAI. The present study uses a behavioral genetic design to estimate the degree to which genetic and environmental factors contribute to individual differences in frequency of play with pets among adult men. Participants were from the ongoing longitudinal Vietnam Era Twin Study of Aging (VETSA), a population-based sample of 1,237 monozygotic (MZ) and dizygotic (DZ) twins aged 51-60 years. Results demonstrate that MZ twins have higher correlations than DZ twins on frequency of pet play, suggesting that genetic factors play a role in individual differences in interactions with pets. Structural equation modeling revealed that, according to the best model, genetic factors accounted for as much as 37% of the variance in pet play, although the majority of variance (63-71%) was due to environmental factors that are unique to each twin. Shared environmental factors, which would include childhood exposure to pets, overall accounted for influenced characteristics.
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Directory of Open Access Journals (Sweden)
Tim eKarl
2013-08-01
Full Text Available Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors. In recent years, an increasing number of researchers worldwide have started investigating the ‘two-hit hypothesis’ of schizophrenia predicting that genetic and environmental risk factors (GxE interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. This mini review will focus on recent advancements in the field made by challenging mutant and transgenic rodent models for the schizophrenia candidate gene neuregulin 1 (NRG1 with particular environmental factors. It will outline results obtained from mouse and rat models for various Nrg1 isoforms/isoform types (e.g. transmembrane domain Nrg1, Type II Nrg1, which have been exposed to different forms of stress (acute versus chronic, restraint versus social and housing conditions (standard laboratory versus minimally enriched housing. These studies suggest Nrg1 as a prime candidate for GxE interactions in schizophrenia rodent models and that the use of rodent models will enable a better understanding of GxE interactions and the underlying mechanisms.
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Directory of Open Access Journals (Sweden)
Huang Yung-Fen
2012-02-01
Full Text Available Abstract Background Proanthocyanidins (PAs, or condensed tannins, are flavonoid polymers, widespread throughout the plant kingdom, which provide protection against herbivores while conferring organoleptic and nutritive values to plant-derived foods, such as wine. However, the genetic basis of qualitative and quantitative PA composition variation is still poorly understood. To elucidate the genetic architecture of the complex grape PA composition, we first carried out quantitative trait locus (QTL analysis on a 191-individual pseudo-F1 progeny. Three categories of PA variables were assessed: total content, percentages of constitutive subunits and composite ratio variables. For nine functional candidate genes, among which eight co-located with QTLs, we performed association analyses using a diversity panel of 141 grapevine cultivars in order to identify causal SNPs. Results Multiple QTL analysis revealed a total of 103 and 43 QTLs, respectively for seed and skin PA variables. Loci were mainly of additive effect while some loci were primarily of dominant effect. Results also showed a large involvement of pairwise epistatic interactions in shaping PA composition. QTLs for PA variables in skin and seeds differed in number, position, involvement of epistatic interaction and allelic effect, thus revealing different genetic determinisms for grape PA composition in seeds and skin. Association results were consistent with QTL analyses in most cases: four out of nine tested candidate genes (VvLAR1, VvMYBPA2, VvCHI1, VvMYBPA1 showed at least one significant association with PA variables, especially VvLAR1 revealed as of great interest for further functional investigation. Some SNP-phenotype associations were observed only in the diversity panel. Conclusions This study presents the first QTL analysis on grape berry PA composition with a comparison between skin and seeds, together with an association study. Our results suggest a complex genetic control for PA
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Jackson, Anne U.; Monda, Keri L.; Kilpeläinen, Tuomas O.; Esko, Tõnu; Mägi, Reedik; Li, Shengxu; Workalemahu, Tsegaselassie; Feitosa, Mary F.; Croteau-Chonka, Damien C.; Day, Felix R.; Fall, Tove; Ferreira, Teresa; Gustafsson, Stefan; Locke, Adam E.; Mathieson, Iain; Scherag, Andre; Vedantam, Sailaja; Wood, Andrew R.; Liang, Liming; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Karpe, Fredrik; Min, Josine L.; Nicholson, George; Clegg, Deborah J.; Person, Thomas; Krohn, Jon P.; Bauer, Sabrina; Buechler, Christa; Eisinger, Kristina; Bonnefond, Amélie; Froguel, Philippe; Hottenga, Jouke-Jan; Prokopenko, Inga; Waite, Lindsay L.; Harris, Tamara B.; Smith, Albert Vernon; Shuldiner, Alan R.; McArdle, Wendy L.; Caulfield, Mark J.; Munroe, Patricia B.; Grönberg, Henrik; Chen, Yii-Der Ida; Li, Guo; Beckmann, Jacques S.; Johnson, Toby; Thorsteinsdottir, Unnur; Teder-Laving, Maris; Khaw, Kay-Tee; Wareham, Nicholas J.; Zhao, Jing Hua; Amin, Najaf; Oostra, Ben A.; Kraja, Aldi T.; Province, Michael A.; Cupples, L. Adrienne; Heard-Costa, Nancy L.; Kaprio, Jaakko; Ripatti, Samuli; Surakka, Ida; Collins, Francis S.; Saramies, Jouko; Tuomilehto, Jaakko; Jula, Antti; Salomaa, Veikko; Erdmann, Jeanette; Hengstenberg, Christian; Loley, Christina; Schunkert, Heribert; Lamina, Claudia; Wichmann, H. Erich; Albrecht, Eva; Gieger, Christian; Hicks, Andrew A.; Johansson, Åsa; Pramstaller, Peter P.; Kathiresan, Sekar; Speliotes, Elizabeth K.; Penninx, Brenda; Hartikainen, Anna-Liisa; Jarvelin, Marjo-Riitta; Gyllensten, Ulf; Boomsma, Dorret I.; Campbell, Harry; Wilson, James F.; Chanock, Stephen J.; Farrall, Martin; Goel, Anuj; Medina-Gomez, Carolina; Rivadeneira, Fernando; Estrada, Karol; Uitterlinden, André G.; Hofman, Albert; Zillikens, M. Carola; den Heijer, Martin; Kiemeney, Lambertus A.; Maschio, Andrea; Hall, Per; Tyrer, Jonathan; Teumer, Alexander; Völzke, Henry; Kovacs, Peter; Tönjes, Anke; Mangino, Massimo; Spector, Tim D.; Hayward, Caroline; Rudan, Igor; Hall, Alistair S.; Samani, Nilesh J.; Attwood, Antony Paul; Sambrook, Jennifer G.; Hung, Joseph; Palmer, Lyle J.; Lokki, Marja-Liisa; Sinisalo, Juha; Boucher, Gabrielle; Huikuri, Heikki; Lorentzon, Mattias; Ohlsson, Claes; Eklund, Niina; Eriksson, Johan G.; Barlassina, Cristina; Rivolta, Carlo; Nolte, Ilja M.; Snieder, Harold; Van der Klauw, Melanie M.; Van Vliet-Ostaptchouk, Jana V.; Gejman, Pablo V.; Shi, Jianxin; Jacobs, Kevin B.; Wang, Zhaoming; Bakker, Stephan J. L.; Mateo Leach, Irene; Navis, Gerjan; van der Harst, Pim; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Yang, Jian; Chasman, Daniel I.; Ridker, Paul M.; Rose, Lynda M.; Lehtimäki, Terho; Raitakari, Olli; Absher, Devin; Iribarren, Carlos; Basart, Hanneke; Hovingh, Kees G.; Hyppönen, Elina; Power, Chris; Anderson, Denise; Beilby, John P.; Hui, Jennie; Jolley, Jennifer; Sager, Hendrik; Bornstein, Stefan R.; Schwarz, Peter E. H.; Kristiansson, Kati; Perola, Markus; Lindström, Jaana; Swift, Amy J.; Uusitupa, Matti; Atalay, Mustafa; Lakka, Timo A.; Rauramaa, Rainer; Bolton, Jennifer L.; Fowkes, Gerry; Fraser, Ross M.; Price, Jackie F.; Fischer, Krista; KrjutÅ¡kov, Kaarel; Metspalu, Andres; Mihailov, Evelin; Langenberg, Claudia; Luan, Jian'an; Ong, Ken K.; Chines, Peter S.; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Edkins, Sarah; Franks, Paul W.; Hallmans, Göran; Shungin, Dmitry; Morris, Andrew David; Palmer, Colin N. A.; Erbel, Raimund; Moebus, Susanne; Nöthen, Markus M.; Pechlivanis, Sonali; Hveem, Kristian; Narisu, Narisu; Hamsten, Anders; Humphries, Steve E.; Strawbridge, Rona J.; Tremoli, Elena; Grallert, Harald; Thorand, Barbara; Illig, Thomas; Koenig, Wolfgang; Müller-Nurasyid, Martina; Peters, Annette; Boehm, Bernhard O.; Kleber, Marcus E.; März, Winfried; Winkelmann, Bernhard R.; Kuusisto, Johanna; Laakso, Markku; Arveiler, Dominique; Cesana, Giancarlo; Kuulasmaa, Kari; Virtamo, Jarmo; Yarnell, John W. G.; Kuh, Diana; Wong, Andrew; Lind, Lars; de Faire, Ulf; Gigante, Bruna; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Dedoussis, George; Dimitriou, Maria; Kolovou, Genovefa; Kanoni, Stavroula; Stirrups, Kathleen; Bonnycastle, Lori L.; Njølstad, Inger; Wilsgaard, Tom; Ganna, Andrea; Rehnberg, Emil; Hingorani, Aroon; Kivimaki, Mika; Kumari, Meena; Assimes, Themistocles L.; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Frayling, Timothy; Groop, Leif C.; Haritunians, Talin; Hunter, David; Ingelsson, Erik; Kaplan, Robert; Mohlke, Karen L.; O'Connell, Jeffrey R.; Schlessinger, David; Strachan, David P.; Stefansson, Kari; van Duijn, Cornelia M.; Abecasis, Gonçalo R.; McCarthy, Mark I.; Hirschhorn, Joel N.; Qi, Lu; Loos, Ruth J. F.; Lindgren, Cecilia M.; North, Kari E.; Heid, Iris M.
2013-01-01
Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10−8), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits. PMID:23754948
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Directory of Open Access Journals (Sweden)
Joshua C Randall
2013-06-01
Full Text Available Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals and took forward 348 SNPs into follow-up (additional 137,052 individuals in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%, including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9 and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG, all of which were genome-wide significant in women (P<5×10(-8, but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.
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Directory of Open Access Journals (Sweden)
Paul M B Medina
Full Text Available BACKGROUND: Neurons require precise cytoskeletal regulation within neurites, containing microtubule tracks for cargo transport in axons and dendrites or within synapses containing organized actin. Due to the unique architecture and specialized function of neurons, neurons are particularly susceptible to perturbation of the cytoskeleton. Numerous actin-binding proteins help maintain proper cytoskeletal regulation. METHODOLOGY/PRINCIPAL FINDINGS: From a Drosophila forward genetic screen, we identified a mutation in capulet--encoding a conserved actin-binding protein--that causes abnormal aggregates of actin within dendrites. Through interaction studies, we demonstrate that simultaneous genetic inactivation of capulet and kinesin heavy chain, a microtubule motor protein, produces elongate cofilin-actin rods within dendrites but not axons. These rods resemble actin-rich structures induced in both mammalian neurodegenerative and Drosophila Alzheimer's models, but have not previously been identified by loss of function mutations in vivo. We further demonstrate that mitochondria, which are transported by Kinesin, have impaired distribution along dendrites in a capulet mutant. While Capulet and Cofilin may biochemically cooperate in certain circumstances, in neuronal dendrites they genetically antagonize each other. CONCLUSIONS/SIGNIFICANCE: The present study is the first molecularly defined loss of function demonstration of actin-cofilin rods in vivo. This study suggests that simultaneous, seemingly minor perturbations in neuronal dendrites can synergize producing severe abnormalities affecting actin, microtubules and mitochondria/energy availability in dendrites. Additionally, as >90% of Alzheimer's and Parkinson's cases are sporadic this study suggests mechanisms by which multiple mutations together may contribute to neurodegeneration instead of reliance on single mutations to produce disease.
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Spatial genetic structure across a hybrid zone between European rabbit subspecies
Directory of Open Access Journals (Sweden)
Fernando Alda
2014-09-01
Full Text Available The Iberian Peninsula is the only region in the world where the two existing subspecies of the European rabbit (Oryctolagus cuniculus naturally occur and hybridize. In this study we explore the relative roles of historical and contemporary processes in shaping the spatial genetic structure of the rabbit across its native distribution range, and how they differently affect each subspecies and the hybrid zone. For that purpose we obtained multilocus genotypes and mitochondrial DNA data from 771 rabbits across most of the distribution range of the European rabbit in Spain. Based on the nuclear markers we observed a hierarchical genetic structure firstly comprised by two genetic groups, largely congruent with the mitochondrial lineages and subspecies distributions (O. c. algirus and O. c. cuniculus, which were subsequently subdivided into seven genetic groups. Geographic distance alone emerged as an important factor explaining genetic differentiation across the whole range, without the need to invoke for the effect for geographical barriers. Additionally, the significantly positive spatial correlation up to a distance of only 100 km supported the idea that differentiation at a local level is of greater importance when considering the species overall genetic structure. When looking at the subspecies, northern populations of O. c. cuniculus showed more spatial genetic structure and differentiation than O. c. algirus. This could be due to local geographic barriers, limited resources, soil type and/or social behavior limiting dispersal. The hybrid zone showed similar genetic structure to the southern populations but a larger introgression from the northern lineage genome. These differences have been attributed to selection against the hybrids rather than to behavioral differences between subspecies. Ultimately, the genetic structure of the rabbit in its native distribution range is the result of an ensemble of factors, from geographical and ecological
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Energy Technology Data Exchange (ETDEWEB)
Cai, Liquan; Wang, Dan [Department of Urology, The University of Pittsburgh, 5200 Centre Avenue, Pittsburgh, PA 15216 (United States); Fisher, Alfred L., E-mail: fishera2@uthscsa.edu [Division of Geriatrics, Gerontology, and Palliative Medicine, Department of Medicine, UTHSCSA, San Antonio, TX 78229 (United States); Center for Healthy Aging, UTHSCSA, San Antonio, TX 78229 (United States); GRECC, STVAHCS, San Antonio, TX 78229 (United States); Wang, Zhou, E-mail: wangz2@upmc.edu [Department of Urology, The University of Pittsburgh, 5200 Centre Avenue, Pittsburgh, PA 15216 (United States); GRECC, STVAHCS, San Antonio, TX 78229 (United States)
2014-05-02
Highlights: • RNAi screen identified genetic enhancers for the C. elegans homolog of EAF2. • EAF2 and RBBP4 proteins physically bind to each other and alter transcription. • Overexpression of EAF2 and RBBP4 induces the cell death in prostate cancer cells. - Abstract: The tumor suppressor EAF2 is regulated by androgen signaling and associated with prostate cancer. While EAF2 and its partner ELL have been shown to be members of protein complexes involved in RNA polymerase II transcriptional elongation, the biologic roles for EAF2 especially with regards to the development of cancer remains poorly understood. We have previously identified the eaf-1 gene in Caenorhabditiselegans as the ortholog of EAF2, and shown that eaf-1 interacts with the ELL ortholog ell-1 to control development and fertility in worms. To identify genetic pathways that interact with eaf-1, we screened RNAi libraries consisting of transcription factors, phosphatases, and chromatin-modifying factors to identify genes which enhance the effects of eaf-1(tm3976) on fertility. From this screen, we identified lin-53, hmg-1.2, pha-4, ruvb-2 and set-6 as hits. LIN-53 is the C. elegans ortholog of human retinoblastoma binding protein 4/7 (RBBP 4/7), which binds to the retinoblastoma protein and inhibits the Ras signaling pathway. We find that lin-53 showed a synthetic interaction with eaf-1(tm3976) where knockdown of lin-53 in an eaf-1(tm3976) mutant resulted in sterile worms. This phenotype may be due to cell death as the treated worms contain degenerated embryos with increased expression of the ced-1:GFP cell death marker. Further we find that the interaction between eaf-1 and lin-53/RBBP4/7 also exists in vertebrates, which is reflected by the formation of a protein complex between EAF2 and RBBP4/7. Finally, overexpression of either human EAF2 or RBBP4 in LNCaP cells induced the cell death while knockdown of EAF2 in LNCaP enhanced cell proliferation, indicating an important role of EAF2 in
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Biological pathways and genetic mechanisms involved in social functioning.
Ordoñana, Juan R; Bartels, Meike; Boomsma, Dorret I; Cella, David; Mosing, Miriam; Oliveira, Joao R; Patrick, Donald L; Veenhoven, Ruut; Wagner, Gert G; Sprangers, Mirjam A G
2013-08-01
To describe the major findings in the literature regarding associations between biological and genetic factors and social functioning, paying special attention to: (1) heritability studies on social functioning and related concepts; (2) hypothesized biological pathways and genetic variants that could be involved in social functioning, and (3) the implications of these results for quality-of-life research. A search of Web of Science and PubMed databases was conducted using combinations of the following keywords: genetics, twins, heritability, social functioning, social adjustment, social interaction, and social dysfunction. Variability in the definitions and measures of social functioning was extensive. Moderate to high heritability was reported for social functioning and related concepts, including prosocial behavior, loneliness, and extraversion. Disorders characterized by impairments in social functioning also show substantial heritability. Genetic variants hypothesized to be involved in social functioning are related to the network of brain structures and processes that are known to affect social cognition and behavior. Better knowledge and understanding about the impact of genetic factors on social functioning is needed to help us to attain a more comprehensive view of health-related quality-of-life (HRQOL) and will ultimately enhance our ability to identify those patients who are vulnerable to poor social functioning.
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Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.
Raabe, T; Olivier, J P; Dickson, B J; Liu, X; Gish, G D; Pawson, T; Hafen, E
1995-01-01
The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. We have used a combined biochemical and genetic approach to study the interactions between Sev, Drk and Sos. We show that Tyr2546 in the cytoplasmic tail of Sev is r...
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Conceptualizing genetic counseling as psychotherapy in the era of genomic medicine.
Austin, Jehannine; Semaka, Alicia; Hadjipavlou, George
2014-12-01
Discussions about genetic contributions to medical illness have become increasingly commonplace. Physicians and other health-care providers in all quarters of medicine, from oncology to psychiatry, routinely field questions about the genetic basis of the medical conditions they treat. Communication about genetic testing and risk also enter into these conversations, as knowledge about genetics is increasingly expected of all medical specialists. Attendant to this evolving medical landscape is some uncertainty regarding the future of the genetic counseling profession, with the potential for both increases and decreases in demand for genetic counselors being possible outcomes. This emerging uncertainty provides the opportunity to explicitly conceptualize the potentially distinct value and contributions of the genetic counselor over and above education about genetics and risk that may be provided by other health professionals. In this paper we suggest conceptualizing genetic counseling as a highly circumscribed form of psychotherapy in which effective communication of genetic information is a central therapeutic goal. While such an approach is by no means new--in 1979 Seymour Kessler explicitly described genetic counseling as a "kind of psychotherapeutic encounter," an "interaction with a psychotherapeutic potential"--we expand on his view, and provide research evidence in support of our position. We review available evidence from process and outcome studies showing that genetic counseling is a therapeutic encounter that cannot be reduced to one where the counselor performs a simple "conduit for information" function, without losing effectiveness. We then discuss potential barriers that may have impeded greater uptake of a psychotherapeutic model of practice, and close by discussing implications for practice.
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Transfer of genetic information via isolated mammalian chromosomes
G.J. Wullems
1976-01-01
textabstractRecombination of genetic information from different origin has provided insight in many aspects of the genetic mechanisms of the living cell. These aspects concern the location of genes on chromosomes, the regulation of gene expression and the interaction of different genes in the
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Llewellyn, Clare H; Fildes, Alison
2017-03-01
There is considerable variability in human body weight, despite the ubiquity of the 'obesogenic' environment. Human body weight has a strong genetic basis and it has been hypothesised that genetic susceptibility to the environment explains variation in human body weight, with differences in appetite being implicated as the mediating mechanism; so-called 'behavioural susceptibility theory' (BST), first described by Professor Jane Wardle. This review summarises the evidence for the role of appetite as a mediator of genetic risk of obesity. Variation in appetitive traits is observable from infancy, drives early weight gain and is highly heritable in infancy and childhood. Obesity-related common genetic variants identified through genome-wide association studies show associations with appetitive traits, and appetite mediates part of the observed association between genetic risk and adiposity. Obesity results from an interaction between genetic susceptibility to overeating and exposure to an 'obesogenic' food environment.
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Directory of Open Access Journals (Sweden)
Vijay P Bondre
2016-01-01
Interpretation & conclusions: Our results showed that the full-length genome sequence generated from an Indian HSV-1 isolate shared close genetic relationship with the American KOS and Chinese CR38 strains which belonged to the Asian genetic lineage. Recombination analysis of Indian isolate demonstrated multiple recombination crossover points throughout the genome. This full-length genome sequence amplified from the Indian isolate would be helpful to study HSV evolution, genetic basis of differential pathogenesis, host-virus interactions and viral factors contributing towards differential clinical outcome in human infections.
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Genetic ancestry-smoking interactions and lung function in African Americans: a cohort study.
Directory of Open Access Journals (Sweden)
Melinda C Aldrich
Full Text Available BACKGROUND: Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV₁ per pack-year of smoking (-5.7 ml FEV₁/ smoking pack-year compared with smokers with lower African ancestry (-4.6 ml in FEV₁/ smoking pack-year (interaction P value = 0.17. Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV(1 decline in Health ABC and independently replicated in CARDIA. CONCLUSIONS/SIGNIFICANCE: African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.
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van Hoek, Mandy; Langendonk, Janneke G.; de Rooij, Susanne R.; Sijbrands, Eric J. G.; Roseboom, Tessa J.
2009-01-01
OBJECTIVE: Fetal malnutrition may predispose to type 2 diabetes through gene programming and developmental changes. Previous studies showed that these effects may be modulated by genetic variation. Genome-wide association studies discovered and replicated a number of type 2 diabetes-associated
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Journal of Genetics | Indian Academy of Sciences
Indian Academy of Sciences (India)
... yet simple way to follow a set of interacting proteins. Such a reversion site need not necessarily be geometrically close to the primary mutation site. pp 131-132 Book review. The genetics of sheep · J. H. Edwards · More Details Fulltext PDF. pp 133-134 Book review. Evolutionary genetics: from molecules to morphology.
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Dataset on genetic and physiological adults׳ responses to social distress.
Bonassi, Andrea; Ghilardi, Tommaso; Truzzi, Anna; Cataldo, Ilaria; Azhari, Atiqah; Setoh, Peipei; Shinohara, Kazuyuki; Esposito, Gianluca
2017-08-01
Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR) and serotonin transporter (5-HTTLPR) polymorphisms), and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos) we assessed participants׳ ( N = 42 males) heart rate (HR) and peripheral nose temperature, which index state of arousal and readiness to action. Self-reported questionnaires were used to evaluate participants' interactional patterns towards peers (Attachment Style Questionnaire, Feeney et al., 1994[1]), and the quality of bond with intimate partners (Experiences in Close Relationships Scale, Fraley et al., 2000 [2]). To assess participants׳ genetic predispositions, the OXTR gene (regions rs53576, and rs2254298) and the 5-HTTLPR gene (region SLC6A4) were genotyped. The data set is made publicly available to enable critical or extended analyzes.
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Dataset on genetic and physiological adults׳ responses to social distress
Directory of Open Access Journals (Sweden)
Andrea Bonassi
2017-08-01
Full Text Available Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR and serotonin transporter (5-HTTLPR polymorphisms, and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos we assessed participants׳ (N = 42 males heart rate (HR and peripheral nose temperature, which index state of arousal and readiness to action. Self-reported questionnaires were used to evaluate participants’ interactional patterns towards peers (Attachment Style Questionnaire, Feeney et al., 1994 [1], and the quality of bond with intimate partners (Experiences in Close Relationships Scale, Fraley et al., 2000 [2]. To assess participants׳ genetic predispositions, the OXTR gene (regions rs53576, and rs2254298 and the 5-HTTLPR gene (region SLC6A4 were genotyped. The data set is made publicly available to enable critical or extended analyzes.
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Peer Influence, Genetic Propensity, and Binge Drinking: A Natural Experiment and a Replication.
Guo, Guang; Li, Yi; Wang, Hongyu; Cai, Tianji; Duncan, Greg J
2015-11-01
The authors draw data from the College Roommate Study (ROOM) and the National Longitudinal Study of Adolescent Health to investigate gene-environment interaction effects on youth binge drinking. In ROOM, the environmental influence was measured by the precollege drinking behavior of randomly assigned roommates. Random assignment safeguards against friend selection and removes the threat of gene-environment correlation that makes gene-environment interaction effects difficult to interpret. On average, being randomly assigned a drinking peer as opposed to a nondrinking peer increased college binge drinking by 0.5-1.0 episodes per month, or 20%-40% the average amount of binge drinking. However, this peer influence was found only among youths with a medium level of genetic propensity for alcohol use; those with either a low or high genetic propensity were not influenced by peer drinking. A replication of the findings is provided in data drawn from Add Health. The study shows that gene-environment interaction analysis can uncover social-contextual effects likely to be missed by traditional sociological approaches.
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Genetic susceptibility to Grave's disease.
Li, Hong; Chen, Qiuying
2013-06-01
The variety of clinical presentations of eye changes in patients with Graves' disease (GD) suggests that complex interactions between genetic, environmental, endogenous and local factors influence the severity of Graves' ophthalmopathy (GO). It is thought that the development of GO might be influenced by genetic factors and environmental factors, such as cigarette smoking. At present, however, the role of genetic factors in the development of GO is not known. On the basis of studies with candidate genes and other genetic approaches, several susceptibility loci in GO have been proposed, including immunological genes, human leukocyte antigen (HLA), cytotoxic T-lymphocyte antigen-4 (CTLA-4), regulatory T-cell genes and thyroid-specific genes. This review gives a brief overview of the current range of major susceptibility genes found for GD.
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DEFF Research Database (Denmark)
Arneborg, N.; Siegumfeldt, H.; Andersen, G.H.
2005-01-01
Applying a newly developed user-interactive optical trapping system, we controllably surrounded individual cells of one yeast species, Hanseniaspora uvarum, with viable cells of another yeast species, Saccharomyces cerevisiae, thus creating a confinement of the former. Growth of surrounded and non......-surrounded H. uvarum cells was followed under a microscope by determining their generation time. The average generation time of surrounded H. uvarum cells was 15% higher than that of non-surrounded cells thereby showing that the confinement imposed by viable S. cerevisiae cells on H. uvarum inhibits growth...
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Challenges and Opportunities in Genome-Wide Environmental Interaction (GWEI) studies
Aschard, Hugues; Lutz, Sharon; Maus, Bärbel; Duell, Eric J.; Fingerlin, Tasha; Chatterjee, Nilanjan; Kraft, Peter; Van Steen, Kristel
2012-01-01
The interest in performing gene-environment interaction studies has seen a significant increase with the increase of advanced molecular genetics techniques. Practically, it became possible to investigate the role of environmental factors in disease risk and hence to investigate their role as genetic effect modifiers. The understanding that genetics is important in the uptake and metabolism of toxic substances is an example of how genetic profiles can modify important environmental risk factors to disease. Several rationales exist to set up gene-environment interaction studies and the technical challenges related to these studies – when the number of environmental or genetic risk factors is relatively small – has been described before. In the post-genomic era, it is now possible to study thousands of genes and their interaction with the environment. This brings along a whole range of new challenges and opportunities. Despite a continuing effort in developing efficient methods and optimal bioinformatics infrastructures to deal with the available wealth of data, the challenge remains how to best present and analyze Genome-Wide Environmental Interaction (GWEI) studies involving multiple genetic and environmental factors. Since GWEIs are performed at the intersection of statistical genetics, bioinformatics and epidemiology, usually similar problems need to be dealt with as for Genome-Wide Association gene-gene Interaction (GWAI) studies. However, additional complexities need to be considered which are typical for large-scale epidemiological studies, but are also related to “joining” two heterogeneous types of data in explaining complex disease trait variation or for prediction purposes. PMID:22760307
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Determination of nonlinear genetic architecture using compressed sensing.
Ho, Chiu Man; Hsu, Stephen D H
2015-01-01
One of the fundamental problems of modern genomics is to extract the genetic architecture of a complex trait from a data set of individual genotypes and trait values. Establishing this important connection between genotype and phenotype is complicated by the large number of candidate genes, the potentially large number of causal loci, and the likely presence of some nonlinear interactions between different genes. Compressed Sensing methods obtain solutions to under-constrained systems of linear equations. These methods can be applied to the problem of determining the best model relating genotype to phenotype, and generally deliver better performance than simply regressing the phenotype against each genetic variant, one at a time. We introduce a Compressed Sensing method that can reconstruct nonlinear genetic models (i.e., including epistasis, or gene-gene interactions) from phenotype-genotype (GWAS) data. Our method uses L1-penalized regression applied to nonlinear functions of the sensing matrix. The computational and data resource requirements for our method are similar to those necessary for reconstruction of linear genetic models (or identification of gene-trait associations), assuming a condition of generalized sparsity, which limits the total number of gene-gene interactions. An example of a sparse nonlinear model is one in which a typical locus interacts with several or even many others, but only a small subset of all possible interactions exist. It seems plausible that most genetic architectures fall in this category. We give theoretical arguments suggesting that the method is nearly optimal in performance, and demonstrate its effectiveness on broad classes of nonlinear genetic models using simulated human genomes and the small amount of currently available real data. A phase transition (i.e., dramatic and qualitative change) in the behavior of the algorithm indicates when sufficient data is available for its successful application. Our results indicate
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Genetics Home Reference: Crohn disease
... JH. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012 Nov 1; ... Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical ...
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Directory of Open Access Journals (Sweden)
Irmgard Tegeder
2016-12-01
Full Text Available Progranulin deficiency in humans is associated with neurodegeneration. Its mechanisms are not yet fully understood. We performed a Yeast-2-Hybrid screen using human full-length progranulin as bait to assess the interactions of progranulin. Progranulin was screened against human fetal brain and human bone marrow libraries using the standard Matchmaker technology (Clontech. This article contains the full Y2H data table, including blast results and sequences, a sorted table according to selection criteria for likely positive, putatively positive, likely false and false preys, and tables showing the gene ontology terms associated with the likely and putative preys of the brain and bone marrow libraries. The interactions with autophagy proteins were confirmed and functionally analyzed in "Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy" (C. Altmann, S. Hardt, C. Fischer, J. Heidler, H.Y. Lim, A. Haussler, B. Albuquerque, B. Zimmer, C. Moser, C. Behrends, F. Koentgen, I. Wittig, M.H. Schmidt, A.M. Clement, T. Deller, I. Tegeder, 2016 [1].
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GENE X ENVIRONMENT INTERACTIONS IN SCHIZOPHRENIA AND BIPOLAR DISORDER:EVIDENCE FROM NEUROIMAGING
Directory of Open Access Journals (Sweden)
Pierre Alexis Geoffroy
2013-10-01
Full Text Available Introduction: Schizophrenia (SZ and Bipolar disorder (BD are considered as severe multifactorial diseases, stemming from genetic and environmental influences. Growing evidence supports gene x environment (GxE interactions in these disorders and neuroimaging studies can help us to understand how those factors mechanistically interact. No reviews synthesized the existing data of neuroimaging studies in these issues.Methods: We conduct a systematic review on the neuroimaging studies exploring GxE interactions relative to SZ or BD in PubMed.Results: First results of the influence of genetic and environmental risks on brain structures came from monozygotic twin pairs concordant and discordant for SZ or BD. Few structural magnetic resonance imaging (sMRI studies have explored the GxE interactions. No other imaging methods were found. Two main GxE interactions on brain volumes have arisen. First, an interaction between genetic liability to SZ and obstetric complications on gray matter, cerebrospinal fluid and hippocampal volumes. Second, cannabis use and genetic liability interaction effects on cortical thickness and white matter volumes.Conclusion: Combining GxE interactions and neuroimaging domains is a promising approach. Genetic risk and environmental exposures such as cannabis or obstetrical complications seem to interact leading to specific neuroimaging cerebral alterations in SZ. They are suggestive of GxE interactions that confer phenotypic abnormalities in SZ and possibly BD. We need further, larger neuroimaging studies of GxE interactions for which we may propose a framework focusing on GxE interactions data already known to have a clinical effect such as infections, early stress, urbanicity and substance abuse.
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Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP.
Warth, Arne; Kloor, Matthias; Schirmacher, Peter; Bläker, Hendrik
2011-04-01
Characterization of tumor genetics and epigenetics allows to stratify a tumor entity according to molecular pathways and may shed light on the interactions of different types of DNA alterations during tumorigenesis. Small intestinal adenocarcinoma is rare, and to date the interrelation of genomic instability and epigenetics has not been investigated in this tumor type. We therefore analyzed 37 primary small bowel carcinomas with known microsatellite instability and KRAS status for chromosomal instability using comparative genomic hybridization, for the presence of aberrant methylation (CpG island methylation phenotype) by methylation-specific polymerase chain reaction, and for BRAF mutations. Chromosomal instability was detected in 22 of 37 (59%) tumors (3 of 9 microsatellite instable, and 19 of 28 microsatellite stable carcinomas). Nine carcinomas (24%) were microsatellite and chromosomally stable. High-level DNA methylation was found in 16% of chromosomal instable tumors and in 44% of both microsatellite instable and microsatellite and chromosomally stable carcinomas. KRAS was mutated in 55, 0, and 10% of chromosomal instable, microsatellite instable, and microsatellite and chromosomally stable tumors, respectively whereas the frequencies of BRAF mutations were 6% for chromosomal instable and 22% for both microsatellite instable and microsatellite and chromosomally stable carcinomas. In conclusion, in this study we show that chromosomal instable carcinomas of the small intestine are distinguished from microsatellite instable and microsatellite and chromosomally stable tumors by a high frequency of KRAS mutations, low frequencies of CpG island methylation phenotype, and BRAF mutations. In microsatellite instable and microsatellite and chromosomally stable cancers, CpG island methylation phenotype and BRAF/KRAS mutations are similarly distributed, indicating common mechanisms of tumor initiation or progression in their molecular pathogenesis.
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Application of molecular genetic tools for forest pathology
Mee-Sook Kim; John Hanna; Amy Ross-Davis; Ned Klopfenstein
2012-01-01
In recent years, advances in molecular genetics have provided powerful tools to address critical issues in forest pathology to help promote resilient forests. Although molecular genetic tools are initially applied to understand individual components of forest pathosystems, forest pathosystems involve dynamic interactions among biotic and abiotic components of the...
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Genetic Interactions Between the Meiosis-Specific Cohesin Components, STAG3, REC8, and RAD21L.
Ward, Ayobami; Hopkins, Jessica; Mckay, Matthew; Murray, Steve; Jordan, Philip W
2016-06-01
Cohesin is an essential structural component of chromosomes that ensures accurate chromosome segregation during mitosis and meiosis. Previous studies have shown that there are cohesin complexes specific to meiosis, required to mediate homologous chromosome pairing, synapsis, recombination, and segregation. Meiosis-specific cohesin complexes consist of two structural maintenance of chromosomes proteins (SMC1α/SMC1β and SMC3), an α-kleisin protein (RAD21, RAD21L, or REC8), and a stromal antigen protein (STAG1, 2, or 3). STAG3 is exclusively expressed during meiosis, and is the predominant STAG protein component of cohesin complexes in primary spermatocytes from mouse, interacting directly with each α-kleisin subunit. REC8 and RAD21L are also meiosis-specific cohesin components. Stag3 mutant spermatocytes arrest in early prophase ("zygotene-like" stage), displaying failed homolog synapsis and persistent DNA damage, as a result of unstable loading of cohesin onto the chromosome axes. Interestingly, Rec8, Rad21L double mutants resulted in an earlier "leptotene-like" arrest, accompanied by complete absence of STAG3 loading. To assess genetic interactions between STAG3 and α-kleisin subunits RAD21L and REC8, our lab generated Stag3, Rad21L, and Stag3, Rec8 double knockout mice, and compared them to the Rec8, Rad21L double mutant. These double mutants are phenotypically distinct from one another, and more severe than each single knockout mutant with regards to chromosome axis formation, cohesin loading, and sister chromatid cohesion. The Stag3, Rad21L, and Stag3, Rec8 double mutants both progress further into prophase I than the Rec8, Rad21L double mutant. Our genetic analysis demonstrates that cohesins containing STAG3 and REC8 are the main complex required for centromeric cohesion, and RAD21L cohesins are required for normal clustering of pericentromeric heterochromatin. Furthermore, the STAG3/REC8 and STAG3/RAD21L cohesins are the primary cohesins required for
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Social Relationships Moderate Genetic Influences on Heavy Drinking in Young Adulthood.
Barr, Peter B; Salvatore, Jessica E; Maes, Hermine H; Korhonen, Tellervo; Latvala, Antti; Aliev, Fazil; Viken, Richard; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M
2017-11-01
Social relationships, such as committed partnerships, limit risky behaviors like heavy drinking, in part, because of increased social control. The current analyses examine whether involvement in committed relationships or social support extend beyond a main effect to limit genetic liability in heavy drinking (gene-environment interaction) during young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (n = 3,269), we tested whether involvement in romantic partnerships or social support moderated genetic influences on heavy drinking using biometric twin modeling for gene-environment interaction. Involvement in a romantic partnership was associated with a decline in genetic variance in both males and females, although the overall magnitude of genetic influence was greater in males. Sex differences emerged for social support: increased social support was associated with increased genetic influence for females and reduced genetic influence for males. These findings demonstrate that social relationships are important moderators of genetic influences on young adult alcohol use. Mechanisms of social control that are important in limiting genetic liability during adolescence extend into young adulthood. In addition, although some relationships limit genetic liability equally, others, such as extensive social networks, may operate differently across sex.
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iDoRNA: An Interacting Domain-based Tool for Designing RNA-RNA Interaction Systems
Directory of Open Access Journals (Sweden)
Jittrawan Thaiprasit
2016-03-01
Full Text Available RNA-RNA interactions play a crucial role in gene regulation in living organisms. They have gained increasing interest in the field of synthetic biology because of their potential applications in medicine and biotechnology. However, few novel regulators based on RNA-RNA interactions with desired structures and functions have been developed due to the challenges of developing design tools. Recently, we proposed a novel tool, called iDoDe, for designing RNA-RNA interacting sequences by first decomposing RNA structures into interacting domains and then designing each domain using a stochastic algorithm. However, iDoDe did not provide an optimal solution because it still lacks a mechanism to optimize the design. In this work, we have further developed the tool by incorporating a genetic algorithm (GA to find an RNA solution with maximized structural similarity and minimized hybridized RNA energy, and renamed the tool iDoRNA. A set of suitable parameters for the genetic algorithm were determined and found to be a weighting factor of 0.7, a crossover rate of 0.9, a mutation rate of 0.1, and the number of individuals per population set to 8. We demonstrated the performance of iDoRNA in comparison with iDoDe by using six RNA-RNA interaction models. It was found that iDoRNA could efficiently generate all models of interacting RNAs with far more accuracy and required far less computational time than iDoDe. Moreover, we compared the design performance of our tool against existing design tools using forty-four RNA-RNA interaction models. The results showed that the performance of iDoRNA is better than RiboMaker when considering the ensemble defect, the fitness score and computation time usage. However, it appears that iDoRNA is outperformed by NUPACK and RNAiFold 2.0 when considering the ensemble defect. Nevertheless, iDoRNA can still be an useful alternative tool for designing novel RNA-RNA interactions in synthetic biology research. The source code of i
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Awareness of Cancer Susceptibility Genetic Testing
Mai, Phuong L.; Vadaparampil, Susan Thomas; Breen, Nancy; McNeel, Timothy S.; Wideroff, Louise; Graubard, Barry I.
2014-01-01
Background Genetic testing for several cancer susceptibility syndromes is clinically available; however, existing data suggest limited population awareness of such tests. Purpose To examine awareness regarding cancer genetic testing in the U.S. population aged ≥25 years in the 2000, 2005, and 2010 National Health Interview Surveys. Methods The weighted percentages of respondents aware of cancer genetic tests, and percent changes from 2000–2005 and 2005–2010, overall and by demographic, family history, and healthcare factors were calculated. Interactions were used to evaluate the patterns of change in awareness between 2005 and 2010 among subgroups within each factor. To evaluate associations with awareness in 2005 and 2010, percentages were adjusted for covariates using multiple logistic regression. The analysis was performed in 2012. Results Awareness decreased from 44.4% to 41.5% (pAwareness increased between 2005 and 2010 in most subgroups, particularly among individuals in the South (p-interaction=0.03) or with a usual place of care (p-interaction=0.01). In 2005 and 2010, awareness was positively associated with personal or family cancer history and high perceived cancer risk, and inversely associated with racial/ethnic minorities, age 25–39 or ≥60 years, male gender, lower education and income levels, public or no health insurance, and no provider contact in 12 months. Conclusions Despite improvement from 2005 to 2010, ≤50% of the U.S. adult population was aware of cancer genetic testing in 2010. Notably, disparities persist for racial/ethnic minorities and individuals with limited health care access or income. PMID:24745633
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Genetic improvement of beef cattle in the United States: cattle, people and their interaction.
Willham, R L
1982-03-01
The purpose of this essay is to develop a historic perspective of the beef cattle population and the legion of people directing its genetic change so that future leadership can increase the rate of breeding technology assimilation. Use of cattle for beef to feed millions is relatively recent. The beef industry of the United States has a rich, romantic heritage that combined Spanish exploitation with British tradition. Spanish cattle became adapted as the Texas longhorn and the European cattle became indigenous. Breeds developed in Britain replaced both. The Zebu was introduced to produce cattle adapted to the Gulf Coast. Selection for early maturity in the British breeds promoted by livestock shows was ended by the dwarf gene. The Charolais breed demonstrated growth potential. Then in 1967, Continental European breeds were imported, given an array of biological types from which to select. Beef cattle breeding research expanded after the second world war through the three regional projects. Performance Registry International was the focal point for performance. The Beef Improvement Federation produced guidelines for recording beef performance including those for national sire evaluation. U.S. Meat Animal Research Center evaluated the several newly introduced breeds. To date, breeding researchers have developed breeding technology for the use by breeder. The major breed association are keeping and utilizing performance records. The genetic structure of the beef breeds is being altered by the use of AI such that genetic change can be made rapidly by the use of superior sires evaluated on their progeny in many herds.
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The Genetic Ancestry of African Americans, Latinos, and European Americans across the United States
Bryc, Katarzyna; Durand, Eric Y.; Macpherson, J. Michael; Reich, David; Mountain, Joanna L.
2015-01-01
Over the past 500 years, North America has been the site of ongoing mixing of Native Americans, European settlers, and Africans (brought largely by the trans-Atlantic slave trade), shaping the early history of what became the United States. We studied the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans who are 23andMe customers and show that the legacy of these historical interactions is visible in the genetic ancestry of present-day Americans. We document pervasive mixed ancestry and asymmetrical male and female ancestry contributions in all groups studied. We show that regional ancestry differences reflect historical events, such as early Spanish colonization, waves of immigration from many regions of Europe, and forced relocation of Native Americans within the US. This study sheds light on the fine-scale differences in ancestry within and across the United States and informs our understanding of the relationship between racial and ethnic identities and genetic ancestry. PMID:25529636
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DEFF Research Database (Denmark)
Schoeps, Anja; Rudolph, Anja; Seibold, Petra
2014-01-01
recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714......,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three...... in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8...
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Genetic effects of nonionizing electromagnetic fields
International Nuclear Information System (INIS)
Lai, Henry
2001-01-01
Due to the increased use of electricity and wireless communication devices, there is a concern on whether exposure to nonionizing electromagnetic fields (50/60 Hz fields and radiofrequency radiation) can lead to harmful health effects, particularly, genetic effects and cancer development. This presentation will review recent research on genetic effects of power line frequency and radiofrequency electromagnetic fields. Even though the mechanism of interaction is still unknown, there is increasing evidence that these electromagnetic fields at low intensities can cause genetic damage in cells. There is also evidence suggesting that the effects are caused by oxidative stress. (author)
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Klippel, Annelie; Reininghaus, Ulrich; Viechtbauer, Wolfgang; Decoster, Jeroen; Delespaul, Philippe; Derom, Cathérine; de Hert, Marc; Jacobs, Nele; Menne-Lothmann, Claudia; Rutten, Bart; Thiery, Evert; van Os, Jim; van Winkel, Ruud; Myin-Germeys, Inez; Wichers, Marieke
2018-02-23
Adolescents and young adults are highly focused on peer evaluation, but little is known about sources of their differential sensitivity. We examined to what extent sensitivity to peer evaluation is influenced by interacting environmental and genetic factors. A sample of 354 healthy adolescent twin pairs (n = 708) took part in a structured, laboratory task in which they were exposed to peer evaluation. The proportion of the variance in sensitivity to peer evaluation due to genetic and environmental factors was estimated, as was the association with specific a priori environmental risk factors. Differences in sensitivity to peer evaluation between adolescents were explained mainly by non-shared environmental influences. The results on shared environmental influences were not conclusive. No impact of latent genetic factors or gene-environment interactions was found. Adolescents with lower self-rated positions on the social ladder or who reported to have been bullied more severely showed significantly stronger responses to peer evaluation. Not genes, but subjective social status and past experience of being bullied seem to impact sensitivity to peer evaluation. This suggests that altered response to peer evaluation is the outcome of cumulative sensitization to social interactions.
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Histone modifications influence mediator interactions with chromatin
Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.
2011-01-01
The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760
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Song, Minsun; Wheeler, William; Caporaso, Neil E; Landi, Maria Teresa; Chatterjee, Nilanjan
2018-03-01
Genome-wide association studies (GWAS) are now routinely imputed for untyped single nucleotide polymorphisms (SNPs) based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score test for genetic association. In this paper, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene-environment interactions. We focus on case-control association studies where inference for an underlying logistic regression model can be performed using alternative methods that rely on varying degree on an assumption of gene-environment independence in the underlying population. As increasingly large-scale GWAS are being performed through consortia effort where it is preferable to share only summary-level information across studies, we also describe simple mechanisms for implementing score tests based on standard meta-analysis of "one-step" maximum-likelihood estimates across studies. Applications of the methods in simulation studies and a dataset from GWAS of lung cancer illustrate ability of the proposed methods to maintain type-I error rates for the underlying testing procedures. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene-environment interactions under the assumption of gene-environment independence. Methods are made available for public use through CGEN R software package. © 2017 WILEY PERIODICALS, INC.
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Interaction between microbiome and host genetics in psoriatic arthritis.
Chimenti, Maria Sole; Perricone, Carlo; Novelli, Lucia; Caso, Francesco; Costa, Luisa; Bogdanos, Dimitrios; Conigliaro, Paola; Triggianese, Paola; Ciccacci, Cinzia; Borgiani, Paola; Perricone, Roberto
2018-03-01
Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, seen in combination with psoriasis. Both genetic and environmental factors are responsible for the development of PsA, however little is known about the different weight of these two distinctive components in the pathogenesis of the disease. Genomic variability in PsA is associated with the disease and/or some peculiar clinical phenotypes. Candidate genes involved are crucial in inflammation, immune system, and epithelial permeability. Moreover, the genesis and regulation of inflammation are influenced by the composition of the human intestinal microbiome that is able to modulate both mucosal and systemic immune system. It is possible that pro-inflammatory responses initiated in gut mucosa could contribute to the induction and progression of autoimmune conditions. Given such premises, the aim of this review is to summarize immune-mediated response and specific bacterial changes in the composition of fecal microbiota in PsA patients and to analyze the relationships between bacterial changes, immune system, and host genetic background. Copyright © 2018 Elsevier B.V. All rights reserved.
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Host genetics affect microbial ecosystems via host immunity.
El Kafsi, Hela; Gorochov, Guy; Larsen, Martin
2016-10-01
Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.
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Biological General Repository for Interaction Datasets (BioGRID)
U.S. Department of Health & Human Services — BioGRID is an online interaction repository with data on raw protein and genetic interactions from major model organism species. All interaction data are freely...
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Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits.
Shi, Huwenbo; Mancuso, Nicholas; Spendlove, Sarah; Pasaniuc, Bogdan
2017-11-02
Although genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions disproportionately contribute to the genome-wide correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach requires GWAS summary data only and makes no distributional assumption on the causal variant effect sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 36 quantitative traits, and identified 25 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 6 genomic regions that contribute to the genetic correlation of 10 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we report the distribution of local genetic correlations across the genome for 55 pairs of traits that show putative causal relationships. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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Non-genetic effects on growth characteristics of Brahman cattle
Directory of Open Access Journals (Sweden)
Nicacia Hernández-Hernández
2015-01-01
Full Text Available Objective. To determine how some non-genetic factors influence weights at birth (BW, weaning (WW and yearling (YW of Brahman calves. Materials and methods. Data corresponding to 58257, 57045 and 40364 for BW, WW and YW, respectively, were analyzed. The models included the effects of year and season of birth and sex, and were considered simple interactions. Results. All effects were significant (p0.05 on WW. The average general BW, WW and YW were 32±3.2, 188±37.7 and 291±56.8 kg, respectively. Variables evaluated that take into account the year of birth show a trend to increase weight each year. In relation to the birth season on BW and YW, it was observed that calves born during the rainy season were heavier than those born during the dry season. Similarly, male calves were heavier than females at birth, weaning and one year of age. The effects of the analyzed interactions were significant (p0.05 for BW and WW. Conclusions. The studied non-genetic factors were important and should be taken into account in management strategies when striving to increase the efficiency of the productive system.
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Directory of Open Access Journals (Sweden)
Mary P. Metcalf
2010-01-01
Full Text Available Background: It is increasingly important that physicians have a thorough understanding of the basic science of human genetics and the ethical, legal and social implications (ELSI associated with genetic testing and counseling. Methods: The authors developed a series of web-based courses for medical students on these topics. The course modules are interactive, emphasize clinical case studies, and can easily be incorporated into existing medical school curricula. Results: Results of a ‘real world’ effectiveness trial indicate that the courses have a statistically significant effect on knowledge, attitude, intended behavior and self-efficacy related to genetic testing (p<0.001; N varies between 163 and 596 for each course. Conclusions: The results indicate that this curriculum is an effective tool for educating medical students on the ELSI associated with genetic testing and for promoting positive changes in students' confidence, counseling attitudes and behaviors.
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Crawford, Kerri M; Rudgers, Jennifer A
2013-05-01
Plant biodiversity is being lost at a rapid rate. This has spurred much interest in elucidating the consequences of this loss for higher trophic levels. Experimental tests have shown that both plant species diversity and genetic diversity within a plant species can influence arthropod community structure. However, the majority of these studies have been conducted in separate systems, so their relative importance is currently unresolved. Furthermore, potential interactions between the two levels of diversity, which likely occur in natural systems, have not been investigated. To clarify these issues, we conducted three experiments in a freshwater sand dune ecosystem. We (1) independently manipulated plant species diversity, (2) independently manipulated genetic diversity within the dominant plant species, Ammophila breviligulata, and (3) jointly manipulated genetic diversity within the dominant plant and species diversity. We found that genetic diversity within the dominant plant species, Ammophila breviligulata, more strongly influenced arthropod communities than plant species diversity, but this effect was dependent on the presence of other species. In species mixtures, A. breviligulata genetic diversity altered overall arthropod community composition, and arthropod richness and abundance peaked at the highest level of genetic diversity. Positive nonadditive effects of diversity were detected, suggesting that arthropods respond to emergent properties of diverse plant communities. However, in the independent manipulations where A. breviligulata was alone, effects of genetic diversity were weaker, with only arthropod richness responding. In contrast, plant species diversity only influenced arthropods when A. breviligulata was absent, and then only influenced herbivore abundance. In addition to showing that genetic diversity within a dominant plant species can have large effects on arthropod community composition, these results suggest that understanding how species
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Cruz Neto, Oswaldo; Aguiar, Antonio V; Twyford, Alex D; Neaves, Linda E; Pennington, R Toby; Lopes, Ariadna V
2014-01-01
Planting of native trees for habitat restoration is a widespread practice, but the consequences for the retention and transmission of genetic diversity in planted and natural populations are unclear. Using Inga vera subsp. affinis as a model species, we genotyped five natural and five planted populations in the Atlantic forest of northeastern Brazil at polymorphic microsatellite loci. We studied the breeding system and population structure to test how much genetic diversity is retained in planted relative to natural populations. We then genotyped seedlings from these populations to test whether genetic diversity in planted populations is restored by outcrossing to natural populations of I. vera. The breeding system of natural I. vera populations was confirmed to be highly outcrossing (t = 0.92; FIS = -0.061, P = 0.04), with populations showing weak population substructure (FST = 0.028). Genetic diversity in planted populations was 50% less than that of natural populations (planted: AR = 14.9, HO = 0.865 and natural: AR = 30.8, HO = 0.655). However, seedlings from planted populations showed a 30% higher allelic richness relative to their parents (seedlings AR = 10.5, parents AR = 7.6). Understanding the processes and interactions that shape this system are necessary to provide ecologically sensible goals and successfully restore hyper-fragmented habitats. Future restoration plans for I. vera must consider the genetic diversity of planted populations and the potential for gene flow between natural populations in the landscape, in order to preserve ecological interactions (i.e. pollination), and promote opportunities for outcrossing.
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A novel test for gene-ancestry interactions in genome-wide association data.
Directory of Open Access Journals (Sweden)
Joanna L Davies
Full Text Available Genome-wide association study (GWAS data on a disease are increasingly available from multiple related populations. In this scenario, meta-analyses can improve power to detect homogeneous genetic associations, but if there exist ancestry-specific effects, via interactions on genetic background or with a causal effect that co-varies with genetic background, then these will typically be obscured. To address this issue, we have developed a robust statistical method for detecting susceptibility gene-ancestry interactions in multi-cohort GWAS based on closely-related populations. We use the leading principal components of the empirical genotype matrix to cluster individuals into "ancestry groups" and then look for evidence of heterogeneous genetic associations with disease or other trait across these clusters. Robustness is improved when there are multiple cohorts, as the signal from true gene-ancestry interactions can then be distinguished from gene-collection artefacts by comparing the observed interaction effect sizes in collection groups relative to ancestry groups. When applied to colorectal cancer, we identified a missense polymorphism in iron-absorption gene CYBRD1 that associated with disease in individuals of English, but not Scottish, ancestry. The association replicated in two additional, independently-collected data sets. Our method can be used to detect associations between genetic variants and disease that have been obscured by population genetic heterogeneity. It can be readily extended to the identification of genetic interactions on other covariates such as measured environmental exposures. We envisage our methodology being of particular interest to researchers with existing GWAS data, as ancestry groups can be easily defined and thus tested for interactions.
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Genetic interaction studies are a powerful approach to identify functional interactions between genes. This approach can reveal networks of regulatory hubs and connect uncharacterized genes to well-studied pathways. However, this approach has previously been limited to simple gene inactivation studies. Here, we present an orthogonal CRISPR/Cas-mediated genetic interaction approach that allows the systematic activation of one gene while simultaneously knocking out a second gene in the same cell.
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International Nuclear Information System (INIS)
Abrahamson, S.; Bender, M.; Denniston, C.; Schull, W.
1985-01-01
Modeling analyses are used to predict the outcomes for two nuclear power plant accident scenarios, the first in which the population received a chronic dose of 0.1 Gy (10 rad) over a 50 year period, the second in which an equivalent population receives acute dose of 2 Gy. In both cases the analyses are projected over a period of five generations. The risk analysis takes on two major forms: the increase in genetic disease that would be observed in the immediate offspring of the exposed population, and the subsequent transmission of the newly induced mutations through future generations. The classes of genetic diseases studied are: dominant gene mutation, X-linked gene mutation, chromosome disorders and multifactorial disorders which involve the interaction of many mutant genes and environmental factors. 28 references, 3 figures, 5 tables
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Genetics and evolution of colour patterns in reptiles.
Olsson, Mats; Stuart-Fox, Devi; Ballen, Cissy
2013-01-01
The study of coloration in the polyphyletic reptilians has flourished in the last two decades, in particular with respect to the underlying genetics of colour traits, the function of colours in social interactions, and ongoing selection on these traits in the wild. The taxonomic bias, however, is profound: at this level of resolution almost all available information is for diurnal lizards. Therefore, we focus on case studies, for which there are as complete causal sequences of colour evolution as possible, from phenotypic expression of variation in colour, to ongoing selection in the wild. For work prior to 1992 and for a broader coverage of reptilian coloration we refer the readers to Cooper and Greenburg's (Biology of the Reptilia, 1992) review. There are seven major conclusions we would like to emphasise: (a) visual systems in diurnal lizards are broadly conserved but among the wider range of reptiles in general, there is functionally important variation in the number and type of photoreceptors, spectral tuning of photopigments and optical properties of the eye; (b) coloration in reptiles is a function of complex interactions between structural and pigmentary components, with implications for both proximate control and condition dependence of colour expression; (c) studies of colour-variable species have enabled estimates of heritability of colour and colour patterns, which often show a simple Mendelian pattern of inheritance; (d) colour-polymorphic lizard species sometimes, but not always, show striking differences in genetically encoded reproductive tactics and provide useful models for studying the evolution and maintenance of polymorphism; (e) both male and female colours are sometimes, but not always, a significant component of socio-sexual signalling, often based on multiple traits; (f) evidence for effects of hormones and condition on colour expression, and trade-offs with immunocompetence and parasite load, is variable; (g) lizards show fading of colours
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Evidence for Gender-Dependent Genotype by Environment Interaction in Adult Depression.
Molenaar, Dylan; Middeldorp, Christel M; Willemsen, Gonneke; Ligthart, Lannie; Nivard, Michel G; Boomsma, Dorret I
2015-10-14
Depression in adults is heritable with about 40 % of the phenotypic variance due to additive genetic effects and the remaining phenotypic variance due to unique (unshared) environmental effects. Common environmental effects shared by family members are rarely found in adults. One possible explanation for this finding is that there is an interaction between genes and the environment which may mask effects of the common environment. To test this hypothesis, we investigated genotype by environment interaction in a large sample of female and male adult twins aged 18-70 years. The anxious depression subscale of the Adult Self Report from the Achenbach System of Empirically Based Assessment (Achenbach and Rescorla in Manual for the ASEBA adult: forms and profiles, 2003) was completed by 13,022 twins who participate in longitudinal studies of the Netherlands Twin Register. In a single group analysis, we found genotype by unique environment interaction, but no genotype by common environment interaction. However, when conditioning on gender, we observed genotype by common environment interaction in men, with larger common environmental variance in men who are genetically less at risk to develop depression. Although the effect size of the interaction is characterized by large uncertainty, the results show that there is at least some variance due to the common environment in adult depression in men.
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A novel statistic for genome-wide interaction analysis.
Directory of Open Access Journals (Sweden)
Xuesen Wu
2010-09-01
Full Text Available Although great progress in genome-wide association studies (GWAS has been made, the significant SNP associations identified by GWAS account for only a few percent of the genetic variance, leading many to question where and how we can find the missing heritability. There is increasing interest in genome-wide interaction analysis as a possible source of finding heritability unexplained by current GWAS. However, the existing statistics for testing interaction have low power for genome-wide interaction analysis. To meet challenges raised by genome-wide interactional analysis, we have developed a novel statistic for testing interaction between two loci (either linked or unlinked. The null distribution and the type I error rates of the new statistic for testing interaction are validated using simulations. Extensive power studies show that the developed statistic has much higher power to detect interaction than classical logistic regression. The results identified 44 and 211 pairs of SNPs showing significant evidence of interactions with FDR<0.001 and 0.001
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Quantum-genetic theory of the hafure of malignant tumors
International Nuclear Information System (INIS)
Ovsyannikov, V.A.
1984-01-01
It is shown, that all interactions, which can cause a transformation in genetic code of a cell, from energy viewpoint should possess quantum energy from 4 to 10 eV, i.e. they should be referred to radiations of UV range. All the reasons known presently, which cause initial carcinomas, are accompanied by UV radiation in the range. The mechanism of UV radiation interaction with living cells, mechanism of genetic code transformation and mechanism of appearance and development of initial and secondary carcinomas are considered
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Gonda, X; Eszlari, N; Kovacs, D; Anderson, I M; Deakin, J F W; Juhasz, G; Bagdy, G
2016-05-03
Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings.
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Maternal environment affects the genetic basis of seed dormancy in Arabidopsis thaliana.
Postma, Froukje M; Ågren, Jon
2015-02-01
The genetic basis of seed dormancy, a key life history trait important for adaptive evolution in plant populations, has yet been studied only using seeds produced under controlled conditions in greenhouse environments. However, dormancy is strongly affected by maternal environmental conditions, and interactions between seed genotype and maternal environment have been reported. Consequently, the genetic basis of dormancy of seeds produced under natural field conditions remains unclear. We examined the effect of maternal environment on the genetic architecture of seed dormancy using a recombinant inbred line (RIL) population derived from a cross between two locally adapted populations of Arabidopsis thaliana from Italy and Sweden. We mapped quantitative trait loci (QTL) for dormancy of seeds produced in the greenhouse and at the native field sites of the parental genotypes. The Italian genotype produced seeds with stronger dormancy at fruit maturation than did the Swedish genotype in all three environments, and the maternal field environments induced higher dormancy levels compared to the greenhouse environment in both genotypes. Across the three maternal environments, a total of nine dormancy QTL were detected, three of which were only detected among seeds matured in the field, and six of which showed significant QTL × maternal environment interactions. One QTL had a large effect on dormancy across all three environments and colocalized with the candidate gene DOG1. Our results demonstrate the importance of studying the genetic basis of putatively adaptive traits under relevant conditions. © 2015 John Wiley & Sons Ltd.
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Mucosal Interactions Between Genetics, Diet And Microbiome In Inflammatory Bowel Diseases
Directory of Open Access Journals (Sweden)
Abigail Basson
2016-08-01
Full Text Available Numerous reviews have discussed gut microbiota composition changes during inflammatory bowel diseases (IBD, particularly Crohn’s disease (CD. However, most studies address the observed effects by focusing on studying the univariate connection between disease and dietary-induced alterations to gut microbiota composition. The possibility that these effects may reflect a number of other interconnected (i.e. pantropic mechanisms, activated in parallel, particularly concerning various bacterial metabolites, is in the process of been elucidated. Progress seems however hampered by various difficult-to-study factors interacting at the mucosal level. Here we highlight some of such factors that merit consideration, namely; 1 the contribution of host genetics and diet in altering gut microbiome, and in turn, the crosstalk among secondary metabolic pathways; 2 the interdependence between the amount of dietary fat, the fatty acid composition, the effects of timing and route of administration on gut microbiota community, and the impact of microbiota-derived fatty acids; 3 the effect of diet on bile acid composition, and the modulator role of bile acids on the gut microbiota; 4 the impact of endogenous and exogenous intestinal micronutrients and metabolites, and 5 the need to consider food associated toxins and chemicals which can introduce confounding immune modulating elements (e.g., antioxidant and phytochemicals in oils and proteins. These concepts, which are not mutually exclusive, are herein illustrated paying special emphasis on physiologically inter-related processes.
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DEFF Research Database (Denmark)
Tomas Mas, Carmen; Sanchez Sanchez, Juan Jose; Barbaro, Anna
2008-01-01
BACKGROUND: Due to its history, with a high number of migration events, the Mediterranean basin represents a challenging area for population genetic studies. A large number of genetic studies have been carried out in the Mediterranean area using different markers but no consensus has been reached...
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Costantini, Federica; Carlesi, Lorenzo; Abbiati, Marco
2013-01-01
While shallow water red coral populations have been overharvested in the past, nowadays, commercial harvesting shifted its pressure on mesophotic organisms. An understanding of red coral population structure, particularly larval dispersal patterns and connectivity among harvested populations is paramount to the viability of the species. In order to determine patterns of genetic spatial structuring of deep water Corallium rubrum populations, for the first time, colonies found between 58-118 m depth within the Tyrrhenian Sea were collected and analyzed. Ten microsatellite loci and two regions of mitochondrial DNA (mtMSH and mtC) were used to quantify patterns of genetic diversity within populations and to define population structuring at spatial scales from tens of metres to hundreds of kilometres. Microsatellites showed heterozygote deficiencies in all populations. Significant levels of genetic differentiation were observed at all investigated spatial scales, suggesting that populations are likely to be isolated. This differentiation may by the results of biological interactions, occurring within a small spatial scale and/or abiotic factors acting at a larger scale. Mitochondrial markers revealed significant genetic structuring at spatial scales greater then 100 km showing the occurrence of a barrier to gene flow between northern and southern Tyrrhenian populations. These findings provide support for the establishment of marine protected areas in the deep sea and off-shore reefs, in order to effectively maintain genetic diversity of mesophotic red coral populations.
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Genetics: A New Landscape for Medical Geography
Carrel, Margaret; Emch, Michael
2014-01-01
The emergence and re-emergence of human pathogens resistant to medical treatment will present a challenge to the international public health community in the coming decades. Geography is uniquely positioned to examine the progressive evolution of pathogens across space and through time, and to link molecular change to interactions between population and environmental drivers. Landscape as an organizing principle for the integration of natural and cultural forces has a long history in geography, and, more specifically, in medical geography. Here, we explore the role of landscape in medical geography, the emergent field of landscape genetics, and the great potential that exists in the combination of these two disciplines. We argue that landscape genetics can enhance medical geographic studies of local-level disease environments with quantitative tests of how human-environment interactions influence pathogenic characteristics. In turn, such analyses can expand theories of disease diffusion to the molecular scale and distinguish the important factors in ecologies of disease that drive genetic change of pathogens. PMID:24558292
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The Information Content of Discrete Functions and Their Application in Genetic Data Analysis.
Sakhanenko, Nikita A; Kunert-Graf, James; Galas, David J
2017-12-01
The complex of central problems in data analysis consists of three components: (1) detecting the dependence of variables using quantitative measures, (2) defining the significance of these dependence measures, and (3) inferring the functional relationships among dependent variables. We have argued previously that an information theory approach allows separation of the detection problem from the inference of functional form problem. We approach here the third component of inferring functional forms based on information encoded in the functions. We present here a direct method for classifying the functional forms of discrete functions of three variables represented in data sets. Discrete variables are frequently encountered in data analysis, both as the result of inherently categorical variables and from the binning of continuous numerical variables into discrete alphabets of values. The fundamental question of how much information is contained in a given function is answered for these discrete functions, and their surprisingly complex relationships are illustrated. The all-important effect of noise on the inference of function classes is found to be highly heterogeneous and reveals some unexpected patterns. We apply this classification approach to an important area of biological data analysis-that of inference of genetic interactions. Genetic analysis provides a rich source of real and complex biological data analysis problems, and our general methods provide an analytical basis and tools for characterizing genetic problems and for analyzing genetic data. We illustrate the functional description and the classes of a number of common genetic interaction modes and also show how different modes vary widely in their sensitivity to noise.
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[Genetics of congenital heart diseases].
Bonnet, Damien
2017-06-01
Developmental genetics of congenital heart diseases has evolved from analysis of serial slices in embryos towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population-based analysis to screening for mutations in candidates genes identified in animal models. Close cooperation between molecular embryologists, pathologists involved in heart development and pediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects. The genetic model for congenital heart disease has to be revised to favor a polygenic origin rather than a monogenic one. The main mechanism is altered genic dosage that can account for heart diseases in chromosomal anomalies as well as in point mutations in syndromic and isolated congenital heart diseases. The use of big data grouping information from cardiac development, interactions between genes and proteins, epigenetic factors such as chromatin remodeling or DNA methylation is the current source for improving our knowledge in the field and to give clues for future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Deconstructing host-pathogen interactions in Drosophila
Directory of Open Access Journals (Sweden)
Ethan Bier
2012-01-01
Full Text Available Many of the cellular mechanisms underlying host responses to pathogens have been well conserved during evolution. As a result, Drosophila can be used to deconstruct many of the key events in host-pathogen interactions by using a wealth of well-developed molecular and genetic tools. In this review, we aim to emphasize the great leverage provided by the suite of genomic and classical genetic approaches available in flies for decoding details of host-pathogen interactions; these findings can then be applied to studies in higher organisms. We first briefly summarize the general strategies by which Drosophila resists and responds to pathogens. We then focus on how recently developed genome-wide RNA interference (RNAi screens conducted in cells and flies, combined with classical genetic methods, have provided molecular insight into host-pathogen interactions, covering examples of bacteria, fungi and viruses. Finally, we discuss novel strategies for how flies can be used as a tool to examine how specific isolated virulence factors act on an intact host.
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Molnos, Sophie; Baumbach, Clemens; Wahl, Simone; Müller-Nurasyid, Martina; Strauch, Konstantin; Wang-Sattler, Rui; Waldenberger, Melanie; Meitinger, Thomas; Adamski, Jerzy; Kastenmüller, Gabi; Suhre, Karsten; Peters, Annette; Grallert, Harald; Theis, Fabian J; Gieger, Christian
2017-09-29
Genome-wide association studies allow us to understand the genetics of complex diseases. Human metabolism provides information about the disease-causing mechanisms, so it is usual to investigate the associations between genetic variants and metabolite levels. However, only considering genetic variants and their effects on one trait ignores the possible interplay between different "omics" layers. Existing tools only consider single-nucleotide polymorphism (SNP)-SNP interactions, and no practical tool is available for large-scale investigations of the interactions between pairs of arbitrary quantitative variables. We developed an R package called pulver to compute p-values for the interaction term in a very large number of linear regression models. Comparisons based on simulated data showed that pulver is much faster than the existing tools. This is achieved by using the correlation coefficient to test the null-hypothesis, which avoids the costly computation of inversions. Additional tricks are a rearrangement of the order, when iterating through the different "omics" layers, and implementing this algorithm in the fast programming language C++. Furthermore, we applied our algorithm to data from the German KORA study to investigate a real-world problem involving the interplay among DNA methylation, genetic variants, and metabolite levels. The pulver package is a convenient and rapid tool for screening huge numbers of linear regression models for significant interaction terms in arbitrary pairs of quantitative variables. pulver is written in R and C++, and can be downloaded freely from CRAN at https://cran.r-project.org/web/packages/pulver/ .
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Prenatal screening and genetics
DEFF Research Database (Denmark)
Alderson, P; Aro, A R; Dragonas, T
2001-01-01
Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...
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Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity.
Directory of Open Access Journals (Sweden)
Vijee Mohan
Full Text Available Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS, carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1 involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima'D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future.
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Standing genetic variation in host preference for mutualist microbial symbionts.
Simonsen, Anna K; Stinchcombe, John R
2014-12-22
Many models of mutualisms show that mutualisms are unstable if hosts lack mechanisms enabling preferential associations with mutualistic symbiotic partners over exploitative partners. Despite the theoretical importance of mutualism-stabilizing mechanisms, we have little empirical evidence to infer their evolutionary dynamics in response to exploitation by non-beneficial partners. Using a model mutualism-the interaction between legumes and nitrogen-fixing soil symbionts-we tested for quantitative genetic variation in plant responses to mutualistic and exploitative symbiotic rhizobia in controlled greenhouse conditions. We found significant broad-sense heritability in a legume host's preferential association with mutualistic over exploitative symbionts and selection to reduce frequency of associations with exploitative partners. We failed to detect evidence that selection will favour the loss of mutualism-stabilizing mechanisms in the absence of exploitation, as we found no evidence for a fitness cost to the host trait or indirect selection on genetically correlated traits. Our results show that genetic variation in the ability to preferentially reduce associations with an exploitative partner exists within mutualisms and is under selection, indicating that micro-evolutionary responses in mutualism-stabilizing traits in the face of rapidly evolving mutualistic and exploitative symbiotic bacteria can occur in natural host populations. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
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Salvatore, Jessica E; Aliev, Fazil; Edwards, Alexis C; Evans, David M; Macleod, John; Hickman, Matthew; Lewis, Glyn; Kendler, Kenneth S; Loukola, Anu; Korhonen, Tellervo; Latvala, Antti; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M
2014-04-10
Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems-derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female)-predicted alcohol problems earlier in development (age 14) in an independent sample (FinnTwin12; n = 1162; 53% female). We then tested whether environmental factors (parental knowledge and peer deviance) moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07-0.08, all p-values ≤ 0.01). Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b), p-values (p), and percent of variance (R2) accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%; b = 0.94, p = 0.04, R2 = 0.30%, respectively). Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs) contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes.
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Directory of Open Access Journals (Sweden)
Jessica E. Salvatore
2014-04-01
Full Text Available Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems—derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female—predicted alcohol problems earlier in development (age 14 in an independent sample (FinnTwin12; n = 1162; 53% female. We then tested whether environmental factors (parental knowledge and peer deviance moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07–0.08, all p-values ≤ 0.01. Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b, p-values (p, and percent of variance (R2 accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%; b = 0.94, p = 0.04, R2 = 0.30%, respectively. Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes.
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Functional modules by relating protein interaction networks and gene expression.
Tornow, Sabine; Mewes, H W
2003-11-01
Genes and proteins are organized on the basis of their particular mutual relations or according to their interactions in cellular and genetic networks. These include metabolic or signaling pathways and protein interaction, regulatory or co-expression networks. Integrating the information from the different types of networks may lead to the notion of a functional network and functional modules. To find these modules, we propose a new technique which is based on collective, multi-body correlations in a genetic network. We calculated the correlation strength of a group of genes (e.g. in the co-expression network) which were identified as members of a module in a different network (e.g. in the protein interaction network) and estimated the probability that this correlation strength was found by chance. Groups of genes with a significant correlation strength in different networks have a high probability that they perform the same function. Here, we propose evaluating the multi-body correlations by applying the superparamagnetic approach. We compare our method to the presently applied mean Pearson correlations and show that our method is more sensitive in revealing functional relationships.
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Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis.
Colizzi, Marco; Iyegbe, Conrad; Powell, John; Ursini, Gianluca; Porcelli, Annamaria; Bonvino, Aurora; Taurisano, Paolo; Romano, Raffaella; Masellis, Rita; Blasi, Giuseppe; Morgan, Craig; Aitchison, Katherine; Mondelli, Valeria; Luzi, Sonija; Kolliakou, Anna; David, Anthony; Murray, Robin M; Bertolino, Alessandro; Di Forti, Marta
2015-09-01
Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects' sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22-7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39-16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis use. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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Structured parenting of toddlers at high versus low genetic risk: two pathways to child problems.
Leve, Leslie D; Harold, Gordon T; Ge, Xiaojia; Neiderhiser, Jenae M; Shaw, Daniel; Scaramella, Laura V; Reiss, David
2009-11-01
Little is known about how parenting might offset genetic risk to prevent the onset of child problems during toddlerhood. We used a prospective adoption design to separate genetic and environmental influences and test whether associations between structured parenting and toddler behavior problems were conditioned by genetic risk for psychopathology. The sample included 290 linked sets of adoptive families and birth mothers and 95 linked birth fathers. Genetic risk was assessed via birth mother and birth father psychopathology (anxiety, depression, antisociality, and drug use). Structured parenting was assessed via microsocial coding of adoptive mothers' behavior during a cleanup task. Toddler behavior problems were assessed with the Child Behavior Checklist. Controlling for temperamental risk at 9 months, there was an interaction between birth mother psychopathology and adoptive mothers' parenting on toddler behavior problems at 18 months. The interaction indicated two pathways to child problems: structured parenting was beneficial for toddlers at high genetic risk but was related to behavior problems for toddlers at low genetic risk. This crossover interaction pattern was replicated with birth father psychopathology as the index of genetic risk. The effects of structured parenting on toddler behavior problems varied as a function of genetic risk. Children at genetic risk might benefit from parenting interventions during toddlerhood that enhance structured parenting.
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2006-08-01
Infertility and reproductive genetic risk are both increasing in our societies because of lifestyle changes and possibly environmental factors. Owing to the magnitude of the problem, they have implications not only at the individual and family levels but also at the community level. This leads to an increasing demand for access to assisted reproduction technology (ART) and genetic services, especially when the cause of infertility may be genetic in origin. The increasing application of genetics in reproductive medicine and vice versa requires closer collaboration between the two disciplines. ART and genetics are rapidly evolving fields where new technologies are currently introduced without sufficient knowledge of their potential long-term effects. As for any medical procedures, there are possible unexpected effects which need to be envisaged to make sure that the balance between benefits and risks is clearly on the benefit side. The development of ART and genetics as scientific activities is creating an opportunity to understand the early stages of human development, which is leading to new and challenging findings/knowledge. However, there are opinions against investigating the early stages of development in humans who deserve respect and attention. For all these reasons, these two societies, European Society of Human Genetics (ESHG) and European Society of Human Reproduction and Embryology (ESHRE), have joined efforts to explore the issues at stake and to set up recommendations to maximize the benefit for the couples in need and for the community.
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... genetic counselor can help you work through the pros and cons of genetic testing based on your ... showing symptoms or what their progression will be. Technology is changing rapidly and costs of testing are ...
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Clinical and genetic characterization of six cases with complete ...
Indian Academy of Sciences (India)
JING HE
2017-08-31
Aug 31, 2017 ... The molecular study of the AR gene facilitated the understanding of the mechanism of CAIS and provided the genetic ... recessive genetic disease, which is characterized by par- .... the interaction of AR protein and androgenic hormone. .... in a brazilian cohort: Five novel mutations in the androgen receptor ...
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Kidson, S H; Ballo, R; Greenberg, L J
2016-05-25
Genetics and cell biology are very prominent areas of biological research with rapid advances being driven by a flood of theoretical, technological and informational knowledge. Big biology and small biology continue to feed off each other. In this paper, we provide a brief overview of the productive interactions that have taken place between human geneticists and cell biologists at UCT, and credit is given to the enabling environment created led by Prof. Peter Beighton. The growth of new disciplines and disciplinary mergers that have swept away division of the past to make new exciting syntheses are discussed. We show how our joint research has benefitted from worldwide advances in developmental genetics, cloning and stem cell technologies, genomics, bioinformatics and imaging. We conclude by describing the role of the UCT Stem Cell Initiative and show how we are using induced pluripotent cells to carry out disease-in-the- dish studies on retinal degeneration and fibrosis.
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Directory of Open Access Journals (Sweden)
Struchalin Maksim V
2012-01-01
Full Text Available Abstract Background Hundreds of new loci have been discovered by genome-wide association studies of human traits. These studies mostly focused on associations between single locus and a trait. Interactions between genes and between genes and environmental factors are of interest as they can improve our understanding of the genetic background underlying complex traits. Genome-wide testing of complex genetic models is a computationally demanding task. Moreover, testing of such models leads to multiple comparison problems that reduce the probability of new findings. Assuming that the genetic model underlying a complex trait can include hundreds of genes and environmental factors, testing of these models in genome-wide association studies represent substantial difficulties. We and Pare with colleagues (2010 developed a method allowing to overcome such difficulties. The method is based on the fact that loci which are involved in interactions can show genotypic variance heterogeneity of a trait. Genome-wide testing of such heterogeneity can be a fast scanning approach which can point to the interacting genetic variants. Results In this work we present a new method, SVLM, allowing for variance heterogeneity analysis of imputed genetic variation. Type I error and power of this test are investigated and contracted with these of the Levene's test. We also present an R package, VariABEL, implementing existing and newly developed tests. Conclusions Variance heterogeneity analysis is a promising method for detection of potentially interacting loci. New method and software package developed in this work will facilitate such analysis in genome-wide context.
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DEFF Research Database (Denmark)
Larsen, L H; Rose, C S; Sparsø, T
2007-01-01
The estrogen-related receptor alpha (ERRalpha or NR3B1) is a transcription factor from the nuclear receptor super-family, group III. The gene encoding ERRalpha (ESRRA) is located on chromosome 11q13, a region showing genetic linkage to body mass index and fat percentage. Through interaction...
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Genetic predisposition for radiation-induced bone tumors
International Nuclear Information System (INIS)
Rosemann, M.; Luz, A.; Kuosaite, V.; Favor, J.; Atkinson, M.J.; Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Neuherberg
1999-01-01
The interaction between environmental factors and genetic determinants is crucial for the development of malignant tumours. However, the hereditary factors involved in the development of cancer that have been recognised so far are only responsible for at the most ten percent of tumours. It is still a matter of dispute whether the remaining 90 percent - so-called sporadic tumours - really have a cause that is free of genetic influence. There are good reasons for believing that there are a large number of genes in the human genome that confer resistance or susceptibility for tumorigenesis, and thus lead to natural genetic variability. (orig.) [de
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Hybrid male sterility in rice is due to epistatic interactions with a pollen killer locus.
Kubo, Takahiko; Yoshimura, Atsushi; Kurata, Nori
2011-11-01
In intraspecific crosses between cultivated rice (Oryza sativa) subspecies indica and japonica, the hybrid male sterility gene S24 causes the selective abortion of male gametes carrying the japonica allele (S24-j) via an allelic interaction in the heterozygous hybrids. In this study, we first examined whether male sterility is due solely to the single locus S24. An analysis of near-isogenic lines (NIL-F(1)) showed different phenotypes for S24 in different genetic backgrounds. The S24 heterozygote with the japonica genetic background showed male semisterility, but no sterility was found in heterozygotes with the indica background. This result indicates that S24 is regulated epistatically. A QTL analysis of a BC(2)F(1) population revealed a novel sterility locus that interacts with S24 and is found on rice chromosome 2. The locus was named Epistatic Factor for S24 (EFS). Further genetic analyses revealed that S24 causes male sterility when in combination with the homozygous japonica EFS allele (efs-j). The results suggest that efs-j is a recessive sporophytic allele, while the indica allele (EFS-i) can dominantly counteract the pollen sterility caused by S24 heterozygosity. In summary, our results demonstrate that an additional epistatic locus is an essential element in the hybrid sterility caused by allelic interaction at a single locus in rice. This finding provides a significant contribution to our understanding of the complex molecular mechanisms underlying hybrid sterility and microsporogenesis.
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Genetic control of organ shape and tissue polarity.
Directory of Open Access Journals (Sweden)
Amelia A Green
2010-11-01
Full Text Available The mechanisms by which genes control organ shape are poorly understood. In principle, genes may control shape by modifying local rates and/or orientations of deformation. Distinguishing between these possibilities has been difficult because of interactions between patterns, orientations, and mechanical constraints during growth. Here we show how a combination of growth analysis, molecular genetics, and modelling can be used to dissect the factors contributing to shape. Using the Snapdragon (Antirrhinum flower as an example, we show how shape development reflects local rates and orientations of tissue growth that vary spatially and temporally to form a dynamic growth field. This growth field is under the control of several dorsoventral genes that influence flower shape. The action of these genes can be modelled by assuming they modulate specified growth rates parallel or perpendicular to local orientations, established by a few key organisers of tissue polarity. Models in which dorsoventral genes only influence specified growth rates do not fully account for the observed growth fields and shapes. However, the data can be readily explained by a model in which dorsoventral genes also modify organisers of tissue polarity. In particular, genetic control of tissue polarity organisers at ventral petal junctions and distal boundaries allows both the shape and growth field of the flower to be accounted for in wild type and mutants. The results suggest that genetic control of tissue polarity organisers has played a key role in the development and evolution of shape.
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Moonesinghe, Ramal; Ioannidis, John PA; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J
2012-01-01
Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene–environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal. PMID:22333905
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Moonesinghe, Ramal; Ioannidis, John P A; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J
2012-08-01
Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene-environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal.
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Friendship Experiences and Anxiety Among Children: A Genetically Informed Study.
Poirier, Catherine Serra; Brendgen, Mara; Girard, Alain; Vitaro, Frank; Dionne, Ginette; Boivin, Michel
2016-01-01
This study examined (a) whether, in line with a gene-environment correlation (rGE), a genetic disposition for anxiety puts children at risk of having anxious friends or having no reciprocal friends; (b) to what extent these friendship experiences are related to anxiety symptoms, when controlling for sex and genetic disposition for this trait; and (c) the additive and interactive predictive links of the reciprocal best friend's anxiety symptoms and of friendship quality with children's anxiety symptoms. Using a genetically informed design based on 521 monozygotic and ic twins (264 girls; 87% of European descent) assessed in Grade 4 (M age = 10.04 years, SD = .26), anxiety symptoms and perceived friendship quality were measured with self-report questionnaires. Results indicated that, in line with rGE, children with a strong genetic disposition for anxiety were more likely to have anxious friends than nonanxious friends. Moreover, controlling for their genetic risk for anxiety, children with anxious friends showed higher levels of anxiety symptoms than children with nonanxious friends but did not differ from those without reciprocal friends. Additional analyses suggested a possible contagion of anxiety symptoms between reciprocal best friends when perceived negative features of friendship were high. These results underline the importance of teaching strategies such as problem solving that enhance friendship quality to limit the potential social contagion of anxiety symptoms.
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LENUS (Irish Health Repository)
Casey, Fergal
2011-08-22
Abstract Background Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. Results We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. Conclusion We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.
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Clinical and genetic aspects of familial isolated pituitary adenomas
Directory of Open Access Journals (Sweden)
Vladimir Vasilev
2012-01-01
Full Text Available Pituitary adenomas represent a group of functionally diverse neoplasms with relatively high prevalence in the general population. Most occur sporadically, but inherited genetic predisposing factors are increasingly recognized. Familial isolated pituitary adenoma is a recently defined clinical entity, and is characterized by hereditary presentation of pituitary adenomas in the absence of clinical and genetic features of syndromic disease such as multiple endocrine neoplasia type 1 and Carney complex. Familial isolated pituitary adenoma is inherited in an autosomal dominant manner and accounted for approximately 2-3% of pituitary tumors in some series. Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds. Pituitary adenomas with mutations of the aryl-hydrocarbon interacting protein gene are predominantly somatotropinomas and prolactinomas, but non-functioning adenomas, Cushing disease, and thyrotropinoma may also occur. These tumors may present as macroadenomas in young patients and are often relatively difficult to control. Furthermore, recent evidence indicates that aryl-hydrocarbon interacting protein gene mutations occur in >10% of patients with sporadic macroadenomas that occur before 30 years of age, and in >20% of children with macroadenomas. Genetic screening for aryl-hydrocarbon interacting protein gene mutations is warranted in selected high-risk patients who may benefit from early recognition and follow-up.
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Energy Technology Data Exchange (ETDEWEB)
Terano, Takao [Univ. of Tsukuba, Tokyo (Japan); Ishino, Yoko [Univ. of Tokyo (Japan)
1996-12-31
This paper describes a novel method to acquire efficient decision rules from questionnaire data using both simulated breeding and inductive learning techniques. The basic ideas of the method are that simulated breeding is used to get the effective features from the questionnaire data and that inductive learning is used to acquire simple decision rules from the data. The simulated breeding is one of the Genetic Algorithm (GA) based techniques to subjectively or interactively evaluate the qualities of offspring generated by genetic operations. In this paper, we show a basic interactive version of the method and two variations: the one with semi-automated GA phases and the one with the relatively evaluation phase via the Analytic Hierarchy Process (AHP). The proposed method has been qualitatively and quantitatively validated by a case study on consumer product questionnaire data.
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Wetlands explain most in the genetic divergence pattern of Oncomelania hupensis.
Liang, Lu; Liu, Yang; Liao, Jishan; Gong, Peng
2014-10-01
Understanding the divergence patterns of hosts could shed lights on the prediction of their parasite transmission. No effort has been devoted to understand the drivers of genetic divergence pattern of Oncomelania hupensis, the only intermediate host of Schistosoma japonicum. Based on a compilation of two O. hupensis gene datasets covering a wide geographic range in China and an array of geographical distance and environmental dissimilarity metrics built from earth observation data and ecological niche modeling, we conducted causal modeling analysis via simple, partial Mantel test and local polynomial fitting to understand the interactions among isolation-by-distance, isolation-by-environment, and genetic divergence. We found that geography contributes more to genetic divergence than environmental isolation, and among all variables involved, wetland showed the strongest correlation with the genetic pairwise distances. These results suggested that in China, O. hupensis dispersal is strongly linked to the distribution of wetlands, and the current divergence pattern of both O. hupensis and schistosomiasis might be altered due to the changed wetland pattern with the accomplishment of the Three Gorges Dam and the South-to-North water transfer project. Copyright © 2014 Elsevier B.V. All rights reserved.
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Schwabe, Inga; Boomsma, Dorret I; van den Berg, Stéphanie M
2017-12-01
Genotype by environment interaction in behavioral traits may be assessed by estimating the proportion of variance that is explained by genetic and environmental influences conditional on a measured moderating variable, such as a known environmental exposure. Behavioral traits of interest are often measured by questionnaires and analyzed as sum scores on the items. However, statistical results on genotype by environment interaction based on sum scores can be biased due to the properties of a scale. This article presents a method that makes it possible to analyze the actually observed (phenotypic) item data rather than a sum score by simultaneously estimating the genetic model and an item response theory (IRT) model. In the proposed model, the estimation of genotype by environment interaction is based on an alternative parametrization that is uniquely identified and therefore to be preferred over standard parametrizations. A simulation study shows good performance of our method compared to analyzing sum scores in terms of bias. Next, we analyzed data of 2,110 12-year-old Dutch twin pairs on mathematical ability. Genetic models were evaluated and genetic and environmental variance components estimated as a function of a family's socio-economic status (SES). Results suggested that common environmental influences are less important in creating individual differences in mathematical ability in families with a high SES than in creating individual differences in mathematical ability in twin pairs with a low or average SES.
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Arenas, I. A.; Tremblay, J.; Deslauriers, B.; Sandoval, J.; Šeda, O.; Gaudet, D.; Merlo, E.; Kotchen, T.; Cowley, A. W.
2013-01-01
Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation. PMID:23269701
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Animal models of gene-environment interactions in schizophrenia.
Ayhan, Yavuz; Sawa, Akira; Ross, Christopher A; Pletnikov, Mikhail V
2009-12-07
The pathogenesis of schizophrenia and related mental illnesses likely involves multiple interactions between susceptibility genes of small effects and environmental factors. Gene-environment interactions occur across different stages of neurodevelopment to produce heterogeneous clinical and pathological manifestations of the disease. The main obstacle for mechanistic studies of gene-environment interplay has been the paucity of appropriate experimental systems for elucidating the molecular pathways that mediate gene-environment interactions relevant to schizophrenia. Recent advances in psychiatric genetics and a plethora of experimental data from animal studies allow us to suggest a new approach to gene-environment interactions in schizophrenia. We propose that animal models based on identified genetic mutations and measurable environment factors will help advance studies of the molecular mechanisms of gene-environment interplay.
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Genetics of Schizophrenia: Historical Insights and Prevailing Evidence.
van de Leemput, J; Hess, J L; Glatt, S J; Tsuang, M T
2016-01-01
Schizophrenia's (SZ's) heritability and familial transmission have been known for several decades; however, despite the clear evidence for a genetic component, it has been very difficult to pinpoint specific causative genes. Even so genetic studies have taught us a lot, even in the pregenomic era, about the molecular underpinnings and disease-relevant pathways. Recurring themes emerged revealing the involvement of neurodevelopmental processes, glutamate regulation, and immune system differential activation in SZ etiology. The recent emergence of epigenetic studies aimed at shedding light on the biological mechanisms underlying SZ has provided another layer of information in the investigation of gene and environment interactions. However, this epigenetic insight also brings forth another layer of complexity to the (epi)genomic landscape such as interactions between genetic variants, epigenetic marks-including cross-talk between DNA methylation and histone modification processes-, gene expression regulation, and environmental influences. In this review, we seek to synthesize perspectives, including limitations and obstacles yet to overcome, from genetic and epigenetic literature on SZ through a qualitative review of risk factors and prevailing hypotheses. Encouraged by the findings of both genetic and epigenetic studies to date, as well as the continued development of new technologies to collect and interpret large-scale studies, we are left with a positive outlook for the future of elucidating the molecular genetic mechanisms underlying SZ and other complex neuropsychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.
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International Nuclear Information System (INIS)
Shahid, M.Q.; Xiong, C.Z.; Juan, L.Y.; Ming, X.H.
2011-01-01
Genetic analysis and genotype-by-environment interaction for important traits of auto tetraploid rice were evaluated by additive, dominance and additive X additive model. It was show n that genetic effects had more influence on grain yield and other quantitative traits of auto tetraploid rice than genotypic environment interaction. Plant height, panicle length, seed set , grain yield, dry matter production and 1000-grain weight we re mainly regulated by dominance variance. Additive and additive X additive gene action constructed the main proportion of genetic variance for heading date (flowering), number of panicles, grains per panicle, grain length, however grain width was supposed to be affected by additive X additive and dominance variance. Flag leaf length and width, fresh weight, peduncle length, unfilled grains and awn length were greatly influenced by genotypic environment interaction. Heading date produced highly negative heterosis over mid parent (H pm) and better parent ( H pb), whereas H pm and H pb were detected to be highly positive and significant for grain yield, seed set, peduncle length, filled grains and 1000-grain weight in F/sub 1/ and F/sub 2/ generations. The results indicated that auto tetraploid hybrids 96025 X Jackson (indica/japonica), 96025 X Linglun (indica/indica) and Linglun X Jackson (indica/japonica) showed highly significant hybrid vigor with improved seed set percentage and grain yield. These results suggest that intra-specific auto tetraploid rice hybrids have more hybrid vigor as compared to intra-sub specific auto tetraploid rice hybrids and auto tetraploid rice has the potential to be used for further studies and commercial application. (author)
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McNamara, J P
2012-06-01
The role of the dairy cow is to help provide high-quality protein and other nutrients for humans. We must select and manage cows with the goal of reaching the greatest possible efficiency for any given environment. We have increased efficiency tremendously over the years, yet the variation in productive and reproductive efficiency among animals is still quite large. In part this is because of a lack of full integration of genetic, nutritional, and reproductive biology into management decisions. However, integration across these disciplines is increasing as biological research findings show more specific control points at which genetics, nutrition, and reproduction interact. An ordered systems biology approach that focuses on why and how cells regulate energy and N use and on how and why organs interact by endocrine and neurocrine mechanisms will speed improvements in efficiency. More sophisticated dairy managers will demand better information to improve the efficiency of their animals. Using genetic improvement and proper animal management to improve milk productive and reproductive efficiency requires a deeper understanding of metabolic processes during the transition period. Using existing metabolic models, we can design experiments specifically to integrate new data from transcriptional arrays into models that describe nutrient use in farm animals. A systems modeling approach can help focus our research to make faster and large advances in efficiency and show directly how this can be applied on the farms.
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Empathy in early childhood: genetic, environmental, and affective contributions.
Knafo, Ariel; Zahn-Waxler, Carolyn; Davidov, Maayan; Van Hulle, Carol; Robinson, JoAnn L; Rhee, Soo Hyun
2009-06-01
We investigated the genetic and environmental origins of children's empathy toward a distress victim and its correlates with emotional symptoms and affective knowledge. The cognitive (hypothesis testing) and affective (empathic concern) empathy of 122 twin pairs in response to simulated pain by an adult examiner was observed at 3.5 years of age. Moderate (0.19 to 0.44) heritabilities were estimated for individual differences in empathy, and the nonshared environment and error accounted for the rest of the variance. Hypothesis testing and empathic concern were moderately correlated, mainly through overlapping genetic effects. Although children's affective knowledge did not correlate with their empathy, affective knowledge interacted with mother-rated emotional symptoms in predicting empathy; knowledge about emotions was associated with greater empathy in children low in emotional symptoms. In contrast, among children with high degrees of emotional symptoms, those with better affective knowledge tended to show lower empathy.
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Genetics and epigenetics of obesity.
Herrera, Blanca M; Keildson, Sarah; Lindgren, Cecilia M
2011-05-01
Obesity results from interactions between environmental and genetic factors. Despite a relatively high heritability of common, non-syndromic obesity (40-70%), the search for genetic variants contributing to susceptibility has been a challenging task. Genome wide association (GWA) studies have dramatically changed the pace of detection of common genetic susceptibility variants. To date, more than 40 genetic variants have been associated with obesity and fat distribution. However, since these variants do not fully explain the heritability of obesity, other forms of variation, such as epigenetics marks, must be considered. Epigenetic marks, or "imprinting", affect gene expression without actually changing the DNA sequence. Failures in imprinting are known to cause extreme forms of obesity (e.g. Prader-Willi syndrome), but have also been convincingly associated with susceptibility to obesity. Furthermore, environmental exposures during critical developmental periods can affect the profile of epigenetic marks and result in obesity. We review the most recent evidence for genetic and epigenetic mechanisms involved in the susceptibility and development of obesity. Only a comprehensive understanding of the underlying genetic and epigenetic mechanisms, and the metabolic processes they govern, will allow us to manage, and eventually prevent, obesity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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Gene-lifestyle interaction and type 2 diabetes
DEFF Research Database (Denmark)
Langenberg, Claudia; Sharp, Stephen J; Franks, Paul W
2014-01-01
the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS: The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would......BACKGROUND: Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify...
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Genetics of Parkinson’s Disease - A Clinical Perspective
Directory of Open Access Journals (Sweden)
Sang-Myung Cheon
2012-10-01
Full Text Available Discovering genes following Medelian inheritance, such as autosomal dominant-synuclein and leucine-rich repeat kinase 2 gene, or autosomal recessive Parkin, P-TEN-induced putative kinase 1 gene and Daisuke-Junko 1 gene, has provided great insights into the pathogenesis of Parkinson’s disease (PD. Genes found to be associated with PD through investigating genetic polymorphisms or via the whole genome association studies suggest that such genes could also contribute to an increased risk of PD in the general population. Some environmental factors have been found to be associated with genetic factors in at-risk patients, further implicating the role of gene-environment interactions in sporadic PD. There may be confusion for clinicians facing rapid progresses of genetic understanding in PD. After a brief review of PD genetics, we will discuss the insight of new genetic discoveries to clinicians, the implications of ethnic differences in PD genetics and the role of genetic testing for general clinicians managing PD patients.
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Marks, Laura R.; Reddinger, Ryan M.; Hakansson, Anders P.
2012-01-01
ABSTRACT Transformation of genetic material between bacteria was first observed in the 1920s using Streptococcus pneumoniae as a model organism. Since then, the mechanism of competence induction and transformation has been well characterized, mainly using planktonic bacteria or septic infection models. However, epidemiological evidence suggests that genetic exchange occurs primarily during pneumococcal nasopharyngeal carriage, which we have recently shown is associated with biofilm growth, and is associated with cocolonization with multiple strains. However, no studies to date have comprehensively investigated genetic exchange during cocolonization in vitro and in vivo or the role of the nasopharyngeal environment in these processes. In this study, we show that genetic exchange during dual-strain carriage in vivo is extremely efficient (10−2) and approximately 10,000,000-fold higher than that measured during septic infection (10−9). This high transformation efficiency was associated with environmental conditions exclusive to the nasopharynx, including the lower temperature of the nasopharynx (32 to 34°C), limited nutrient availability, and interactions with epithelial cells, which were modeled in a novel biofilm model in vitro that showed similarly high transformation efficiencies. The nasopharyngeal environmental factors, combined, were critical for biofilm formation and induced constitutive upregulation of competence genes and downregulation of capsule that promoted transformation. In addition, we show that dual-strain carriage in vivo and biofilms formed in vitro can be transformed during colonization to increase their pneumococcal fitness and also, importantly, that bacteria with lower colonization ability can be protected by strains with higher colonization efficiency, a process unrelated to genetic exchange. PMID:23015736
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Indirect genetic effects and kin recognition
DEFF Research Database (Denmark)
Alemu, Setegn Worku; Berg, Peer; Janss, Luc
2014-01-01
Social interactions among individuals are widespread, both in natural and domestic populations. As a result, trait values of individuals may be affected by genes in other individuals, a phenomenon known as indirect genetic effects (IGEs). IGEs can be estimated using linear mixed models. The tradi......Social interactions among individuals are widespread, both in natural and domestic populations. As a result, trait values of individuals may be affected by genes in other individuals, a phenomenon known as indirect genetic effects (IGEs). IGEs can be estimated using linear mixed models...... present a reduced model that yields estimates of the total heritable effects on kin, on non-kin and on all social partners of an individual, as well as the total heritable variance for response to selection. Finally we discuss the consequences of analysing data in which IGEs depend on relatedness using...
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Genetic structure of Antioquia Holstein from two SNPs and association with dairy traits
Directory of Open Access Journals (Sweden)
Stephania Madrid G
2015-11-01
Full Text Available Objective. Analyze the structure and genetic differentiation of a population of Antioquia Holstein cows from the polymorphisms A192G of INHA and A-320T of FSHR, and explore the association of the genotypic combinations with milk traits. Materials and methods. 1240 lactations of 356 animals from 9 herds in 6 municipalities of Antioquia were analyzed. Genotyping was performed by PCR-RFLP. Structure and genetic diversity parameters were determined using GenAlex software. The association of genotypes combinations with productive and reproductive traits was explored through a linear mixed model. Results. SNP A192G showed a frequency of 0.534 and 0.466 for A and G alleles respectively and SNP A-320T had a frequency of 0.660 far A allele and 0.339 for T allele, this way the population is in HWE. The FST, FIS and FIT values were 0.059, 0.285 and 0.328 respectively indicating a moderate genetic differentiation between subpopulations. The A-320T SNP showed significant effect on milk yield. Fat and protein percentage, calving interval and services per conception were not affected by these polymorphisms or their interaction. Conclusions. Phenotypic selection made on this population has not been strong enough to generate noticeable changes in allele frequencies of these polymorphisms or deviations from Hardy-Weinberg equilibrium. The interaction of these polymorphisms has no significant effect on the characteristics of zootechnical interest, so its use in programs of molecular marker assisted selection is not recommended.
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Directory of Open Access Journals (Sweden)
Federica Costantini
Full Text Available While shallow water red coral populations have been overharvested in the past, nowadays, commercial harvesting shifted its pressure on mesophotic organisms. An understanding of red coral population structure, particularly larval dispersal patterns and connectivity among harvested populations is paramount to the viability of the species. In order to determine patterns of genetic spatial structuring of deep water Corallium rubrum populations, for the first time, colonies found between 58-118 m depth within the Tyrrhenian Sea were collected and analyzed. Ten microsatellite loci and two regions of mitochondrial DNA (mtMSH and mtC were used to quantify patterns of genetic diversity within populations and to define population structuring at spatial scales from tens of metres to hundreds of kilometres. Microsatellites showed heterozygote deficiencies in all populations. Significant levels of genetic differentiation were observed at all investigated spatial scales, suggesting that populations are likely to be isolated. This differentiation may by the results of biological interactions, occurring within a small spatial scale and/or abiotic factors acting at a larger scale. Mitochondrial markers revealed significant genetic structuring at spatial scales greater then 100 km showing the occurrence of a barrier to gene flow between northern and southern Tyrrhenian populations. These findings provide support for the establishment of marine protected areas in the deep sea and off-shore reefs, in order to effectively maintain genetic diversity of mesophotic red coral populations.
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Genetic determination of human facial morphology: links between cleft-lips and normal variation.
Boehringer, Stefan; van der Lijn, Fedde; Liu, Fan; Günther, Manuel; Sinigerova, Stella; Nowak, Stefanie; Ludwig, Kerstin U; Herberz, Ruth; Klein, Stefan; Hofman, Albert; Uitterlinden, Andre G; Niessen, Wiro J; Breteler, Monique M B; van der Lugt, Aad; Würtz, Rolf P; Nöthen, Markus M; Horsthemke, Bernhard; Wieczorek, Dagmar; Mangold, Elisabeth; Kayser, Manfred
2011-11-01
Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 × 10(-4)), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P=0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.
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Preimplantation genetic screening.
Harper, Joyce C
2018-03-01
Preimplantation genetic diagnosis was first successfully performed in 1989 as an alternative to prenatal diagnosis for couples at risk of transmitting a genetic or chromosomal abnormality, such as cystic fibrosis, to their child. From embryos generated in vitro, biopsied cells are genetically tested. From the mid-1990s, this technology has been employed as an embryo selection tool for patients undergoing in vitro fertilisation, screening as many chromosomes as possible, in the hope that selecting chromosomally normal embryos will lead to higher implantation and decreased miscarriage rates. This procedure, preimplantation genetic screening, was initially performed using fluorescent in situ hybridisation, but 11 randomised controlled trials of screening using this technique showed no improvement in in vitro fertilisation delivery rates. Progress in genetic testing has led to the introduction of array comparative genomic hybridisation, quantitative polymerase chain reaction, and next generation sequencing for preimplantation genetic screening, and three small randomised controlled trials of preimplantation genetic screening using these new techniques indicate a modest benefit. Other trials are still in progress but, regardless of their results, preimplantation genetic screening is now being offered globally. In the near future, it is likely that sequencing will be used to screen the full genetic code of the embryo.
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Bureau, Alexandre; Duchesne, Thierry
2015-12-01
Splitting extended families into their component nuclear families to apply a genetic association method designed for nuclear families is a widespread practice in familial genetic studies. Dependence among genotypes and phenotypes of nuclear families from the same extended family arises because of genetic linkage of the tested marker with a risk variant or because of familial specificity of genetic effects due to gene-environment interaction. This raises concerns about the validity of inference conducted under the assumption of independence of the nuclear families. We indeed prove theoretically that, in a conditional logistic regression analysis applicable to disease cases and their genotyped parents, the naive model-based estimator of the variance of the coefficient estimates underestimates the true variance. However, simulations with realistic effect sizes of risk variants and variation of this effect from family to family reveal that the underestimation is negligible. The simulations also show the greater efficiency of the model-based variance estimator compared to a robust empirical estimator. Our recommendation is therefore, to use the model-based estimator of variance for inference on effects of genetic variants.
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Hruby, Adela; Ngwa, Julius S.; Renström, Frida; Wojczynski, Mary K.; Ganna, Andrea; Hallmans, Göran; Houston, Denise K.; Jacques, Paul F.; Kanoni, Stavroula; Lehtimäki, Terho; Lemaitre, Rozenn N.; Manichaikul, Ani; North, Kari E.; Ntalla, Ioanna; Sonestedt, Emily; Tanaka, Toshiko; van Rooij, Frank J. A.; Bandinelli, Stefania; Djoussé, Luc; Grigoriou, Efi; Johansson, Ingegerd; Lohman, Kurt K.; Pankow, James S.; Raitakari, Olli T.; Riserus, Ulf; Yannakoulia, Mary; Zillikens, M. Carola; Hassanali, Neelam; Liu, Yongmei; Mozaffarian, Dariush; Papoutsakis, Constantina; Syvänen, Ann-Christine; Uitterlinden, André G.; Viikari, Jorma; Groves, Christopher J.; Hofman, Albert; Lind, Lars; McCarthy, Mark I.; Mikkilä, Vera; Mukamal, Kenneth; Franco, Oscar H.; Borecki, Ingrid B.; Cupples, L. Adrienne; Dedoussis, George V.; Ferrucci, Luigi; Hu, Frank B.; Ingelsson, Erik; Kähönen, Mika; Kao, W. H. Linda; Kritchevsky, Stephen B.; Orho-Melander, Marju; Prokopenko, Inga; Rotter, Jerome I.; Siscovick, David S.; Witteman, Jacqueline C. M.; Franks, Paul W.; Meigs, James B.; McKeown, Nicola M.; Nettleton, Jennifer A.
2013-01-01
Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = −0.009 mmol/L (95% CI: −0.013, −0.005), P magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. PMID:23343670
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Genetics and psychopharmacology: prospects for individualized treatment.
Nnadi, Charles U; Goldberg, Joseph F; Malhotra, Anil K
2005-01-01
This article provides a clear and succinct description of the components of inheritance, such as trait transmission, genetic variability, and gene interaction. Genetic sequences constitute the prime focus of pharmacogenetic studies. Variations in drug-metabolizing enzyme systems tend to be monogenic, whereas the pharmacologic effects of medications appear to be polygenic, i.e., complex phenotypes shaped by the interaction of genes and environment. Translated into clinical terms, a history of a good response to a drug in a close relative of a patient is presumed to predict a good response to the same medication by the patient. This seems to hold for antidepressants, antipsychotics, and lithium, but the evidential studies generally have meaningful limitations. Bit by bit, information about the relationship between particular genetic formations and the effectiveness of these medications as well as their side effects, is appearing. The authors cite a number of examples, one such being an association between impaired antidepressant activity and the short allele of SLC6A4. This research promises to strengthen the accuracy, effectiveness, safety, and cost of our psychopharmacological practices.
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Tieleman, B. I.; Versteegh, M. A.; Helm, B.; Dingemanse, N. J.; Volff, Jean-Nicolas
2009-01-01
Phenotypic variation in physiological traits, such as energy metabolism, is commonly subjected to adaptive interpretations, but little is known about the heritable basis or genetic correlations among physiological traits in non-domesticated species. Basal metabolic rate (BMR) and body mass are
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Directory of Open Access Journals (Sweden)
Angeline S Andrew
Full Text Available Bladder cancer is the 4(th most common cancer among men in the U.S. We analyzed variant genotypes hypothesized to modify major biological processes involved in bladder carcinogenesis, including hormone regulation, apoptosis, DNA repair, immune surveillance, metabolism, proliferation, and telomere maintenance. Logistic regression was used to assess the relationship between genetic variation affecting these processes and susceptibility in 563 genotyped urothelial cell carcinoma cases and 863 controls enrolled in a case-control study of incident bladder cancer conducted in New Hampshire, U.S. We evaluated gene-gene interactions using Multifactor Dimensionality Reduction (MDR and Statistical Epistasis Network analysis. The 3'UTR flanking variant form of the hormone regulation gene HSD3B2 was associated with increased bladder cancer risk in the New Hampshire population (adjusted OR 1.85 95%CI 1.31-2.62. This finding was successfully replicated in the Texas Bladder Cancer Study with 957 controls, 497 cases (adjusted OR 3.66 95%CI 1.06-12.63. The effect of this prevalent SNP was stronger among males (OR 2.13 95%CI 1.40-3.25 than females (OR 1.56 95%CI 0.83-2.95, (SNP-gender interaction P = 0.048. We also identified a SNP-SNP interaction between T-cell activation related genes GATA3 and CD81 (interaction P = 0.0003. The fact that bladder cancer incidence is 3-4 times higher in males suggests the involvement of hormone levels. This biologic process-based analysis suggests candidate susceptibility markers and supports the theory that disrupted hormone regulation plays a role in bladder carcinogenesis.
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Genetic and Biochemical Characterization of the MinC-FtsZ Interaction in Bacillus subtilis
Castellen, Patricia; Nogueira, Maria Luiza C.; Bettini, Jefferson; Portugal, Rodrigo V.; Zeri, Ana Carolina M.; Gueiros-Filho, Frederico J.
2013-01-01
Cell division in bacteria is regulated by proteins that interact with FtsZ and modulate its ability to polymerize into the Z ring structure. The best studied of these regulators is MinC, an inhibitor of FtsZ polymerization that plays a crucial role in the spatial control of Z ring formation. Recent work established that E. coli MinC interacts with two regions of FtsZ, the bottom face of the H10 helix and the extreme C-terminal peptide (CTP). Here we determined the binding site for MinC on Bacillus subtilis FtsZ. Selection of a library of FtsZ mutants for survival in the presence of Min overexpression resulted in the isolation of 13 Min-resistant mutants. Most of the substitutions that gave rise to Min resistance clustered around the H9 and H10 helices in the C-terminal domain of FtsZ. In addition, a mutation in the CTP of B. subtilis FtsZ also produced MinC resistance. Biochemical characterization of some of the mutant proteins showed that they exhibited normal polymerization properties but reduced interaction with MinC, as expected for binding site mutations. Thus, our study shows that the overall architecture of the MinC-FtsZ interaction is conserved in E. coli and B. subtilis. Nevertheless, there was a clear difference in the mutations that conferred Min resistance, with those in B. subtilis FtsZ pointing to the side of the molecule rather than to its polymerization interface. This observation suggests that the mechanism of Z ring inhibition by MinC differs in both species. PMID:23577149
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Wuchty, Stefan
2006-05-23
While the analysis of unweighted biological webs as diverse as genetic, protein and metabolic networks allowed spectacular insights in the inner workings of a cell, biological networks are not only determined by their static grid of links. In fact, we expect that the heterogeneity in the utilization of connections has a major impact on the organization of cellular activities as well. We consider a web of interactions between protein domains of the Protein Family database (PFAM), which are weighted by a probability score. We apply metrics that combine the static layout and the weights of the underlying interactions. We observe that unweighted measures as well as their weighted counterparts largely share the same trends in the underlying domain interaction network. However, we only find weak signals that weights and the static grid of interactions are connected entities. Therefore assuming that a protein interaction is governed by a single domain interaction, we observe strong and significant correlations of the highest scoring domain interaction and the confidence of protein interactions in the underlying interactions of yeast and fly. Modeling an interaction between proteins if we find a high scoring protein domain interaction we obtain 1, 428 protein interactions among 361 proteins in the human malaria parasite Plasmodium falciparum. Assessing their quality by a logistic regression method we observe that increasing confidence of predicted interactions is accompanied by high scoring domain interactions and elevated levels of functional similarity and evolutionary conservation. Our results indicate that probability scores are randomly distributed, allowing to treat static grid and weights of domain interactions as separate entities. In particular, these finding confirms earlier observations that a protein interaction is a matter of a single interaction event on domain level. As an immediate application, we show a simple way to predict potential protein interactions
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A strategy analysis for genetic association studies with known inbreeding
Directory of Open Access Journals (Sweden)
del Giacco Stefano
2011-07-01
Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is
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Physiology and Genetics of Tree-Phytophage Interactions
Frances Lieutier; William J. Mattson; Michael R. Wagner
1999-01-01
Interactions between trees and phytophagous organisms represent an important fundamental process in the evolution of forest ecosystems. Through evolutionary time, the special traits of trees have lead the herbivore populations to differentiate and evolve in order to cope with the variability in natural resistance mechanisms of their hosts. Conversely, damage by...
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Guo, Guang; Fu, Yilan; Lee, Hedwig; Cai, Tianji; Harris, Kathleen Mullan; Li, Yi
2013-01-01
Self-reported race is generally considered the basis for racial classification in social surveys, including the U.S. census. Drawing on recent advances in human molecular genetics and social science perspectives of socially constructed race, our study takes into account both genetic bio-ancestry and social context in understanding racial classification. This article accomplishes two objectives. First, our research establishes geographic genetic bio-ancestry as a component of racial classification. Second, it shows how social forces trump biology in racial classification and/or how social context interacts with bio-ancestry in shaping racial classification. The findings were replicated in two racially and ethnically diverse data sets: the College Roommate Study (N = 2,065) and the National Longitudinal Study of Adolescent Health (N = 2,281). PMID:24019100
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Bioengineering a non-genotoxic vector for genetic modification of mesenchymal stem cells.
Chen, Xuguang; Nomani, Alireza; Patel, Niket; Nouri, Faranak S; Hatefi, Arash
2018-01-01
Vectors used for stem cell transfection must be non-genotoxic, in addition to possessing high efficiency, because they could potentially transform normal stem cells into cancer-initiating cells. The objective of this research was to bioengineer an efficient vector that can be used for genetic modification of stem cells without any negative somatic or genetic impact. Two types of multifunctional vectors, namely targeted and non-targeted were genetically engineered and purified from E. coli. The targeted vectors were designed to enter stem cells via overexpressed receptors. The non-targeted vectors were equipped with MPG and Pep1 cell penetrating peptides. A series of commercial synthetic non-viral vectors and an adenoviral vector were used as controls. All vectors were evaluated for their efficiency and impact on metabolic activity, cell membrane integrity, chromosomal aberrations (micronuclei formation), gene dysregulation, and differentiation ability of stem cells. The results of this study showed that the bioengineered vector utilizing VEGFR-1 receptors for cellular entry could transfect mesenchymal stem cells with high efficiency without inducing genotoxicity, negative impact on gene function, or ability to differentiate. Overall, the vectors that utilized receptors as ports for cellular entry (viral and non-viral) showed considerably better somato- and genosafety profiles in comparison to those that entered through electrostatic interaction with cellular membrane. The genetically engineered vector in this study demonstrated that it can be safely and efficiently used to genetically modify stem cells with potential applications in tissue engineering and cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.
Raabe, T; Olivier, J P; Dickson, B; Liu, X; Gish, G D; Pawson, T; Hafen, E
1995-06-01
The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. We have used a combined biochemical and genetic approach to study the interactions between Sev, Drk and Sos. We show that Tyr2546 in the cytoplasmic tail of Sev is required for Drk binding, probably because it provides a recognition site for the Drk SH2 domain. Interestingly, a mutation at this site does not completely block Sev function in vivo. This may suggest that Sev can signal in a Drk-independent, parallel pathway or that Drk can also bind to an intermediate docking protein. Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. We show that the N-terminal Drk SH3 domain is primarily responsible for binding to the tail of Sos in vitro, and for signalling to Ras in vivo.
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Directory of Open Access Journals (Sweden)
Jorge Luis Pérez-Fuentes
2016-05-01
Full Text Available Tilapia is the second most widely cultivated species in the international scope, due to their fast growing and breeding capacity in captivity. Its biggest problem is the unpredictability of the productive performance of varieties in different environments and management types. For this reason, the productive performance of three lines: Oreochromis niloticus (N, red Oreochromis mossambicus (M and Rocky Mountain (R, cultured in five sites in two environments (Presses: Miguel de la Madrid and Miguel Aleman in the State of Oaxaca, Mexico was compared. Cages with dimensions between 18 and 48 m3 with stocking density of 7 to 28 fish m-3 were used. Feeding varied depending on the producers (1 to 3 portions a day/cage (300 to 1200 g of feed. Total length (TL, weight (P, survival (SUP and fillet yield (RF were evaluated in each genetic line. Results from physicochemical parameters of water, environments of culture and production efficiency of the strains indicated no significant differences, except for weight gain (g between sites of culture. However, it was considered that the differences were mainly due to handling during the culture, rather than the genetic line. Genetic lines showed similar performance (Tilapia R: LT 16.5 ± 3.1 cm, P 99.0± 46.6 g, 28 % RF, SUP 91.6 %. Tilapia N: LT 16.7 ± 3.7 cm, P 98.2 ± 40.9, RF 23 % SUP 86 %. Tilapia M: LT 15.4 ± 4.6 cm, P 100.1 ± 112.5 g, 30 % RF, SUP 91.6 %. Under the conditions evaluated, type of management could influence the efficiency of the culture more than the genetic line.
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Transgene x environment interactions in genetically modified wheat.
Zeller, Simon L; Kalinina, Olena; Brunner, Susanne; Keller, Beat; Schmid, Bernhard
2010-07-12
The introduction of transgenes into plants may cause unintended phenotypic effects which could have an impact on the plant itself and the environment. Little is published in the scientific literature about the interrelation of environmental factors and possible unintended effects in genetically modified (GM) plants. We studied transgenic bread wheat Triticum aestivum lines expressing the wheat Pm3b gene against the fungus powdery mildew Blumeria graminis f.sp. tritici. Four independent offspring pairs, each consisting of a GM line and its corresponding non-GM control line, were grown under different soil nutrient conditions and with and without fungicide treatment in the glasshouse. Furthermore, we performed a field experiment with a similar design to validate our glasshouse results. The transgene increased the resistance to powdery mildew in all environments. However, GM plants reacted sensitive to fungicide spraying in the glasshouse. Without fungicide treatment, in the glasshouse GM lines had increased vegetative biomass and seed number and a twofold yield compared with control lines. In the field these results were reversed. Fertilization generally increased GM/control differences in the glasshouse but not in the field. Two of four GM lines showed up to 56% yield reduction and a 40-fold increase of infection with ergot disease Claviceps purpurea compared with their control lines in the field experiment; one GM line was very similar to its control. Our results demonstrate that, depending on the insertion event, a particular transgene can have large effects on the entire phenotype of a plant and that these effects can sometimes be reversed when plants are moved from the glasshouse to the field. However, it remains unclear which mechanisms underlie these effects and how they may affect concepts in molecular plant breeding and plant evolutionary ecology.
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Transgene x environment interactions in genetically modified wheat.
Directory of Open Access Journals (Sweden)
Simon L Zeller
Full Text Available BACKGROUND: The introduction of transgenes into plants may cause unintended phenotypic effects which could have an impact on the plant itself and the environment. Little is published in the scientific literature about the interrelation of environmental factors and possible unintended effects in genetically modified (GM plants. METHODS AND FINDINGS: We studied transgenic bread wheat Triticum aestivum lines expressing the wheat Pm3b gene against the fungus powdery mildew Blumeria graminis f.sp. tritici. Four independent offspring pairs, each consisting of a GM line and its corresponding non-GM control line, were grown under different soil nutrient conditions and with and without fungicide treatment in the glasshouse. Furthermore, we performed a field experiment with a similar design to validate our glasshouse results. The transgene increased the resistance to powdery mildew in all environments. However, GM plants reacted sensitive to fungicide spraying in the glasshouse. Without fungicide treatment, in the glasshouse GM lines had increased vegetative biomass and seed number and a twofold yield compared with control lines. In the field these results were reversed. Fertilization generally increased GM/control differences in the glasshouse but not in the field. Two of four GM lines showed up to 56% yield reduction and a 40-fold increase of infection with ergot disease Claviceps purpurea compared with their control lines in the field experiment; one GM line was very similar to its control. CONCLUSIONS: Our results demonstrate that, depending on the insertion event, a particular transgene can have large effects on the entire phenotype of a plant and that these effects can sometimes be reversed when plants are moved from the glasshouse to the field. However, it remains unclear which mechanisms underlie these effects and how they may affect concepts in molecular plant breeding and plant evolutionary ecology.
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Genetic basis of autism: is there a way forward?
Eapen, Valsamma
2011-05-01
This paper outlines some of the key findings from genetic research carried out in the last 12-18 months, which indicate that autism spectrum disorder (ASD) is a complex disorder involving interactions between genetic, epigenetic and environmental factors. The current literature highlights the presence of genetic and phenotypic heterogeneity in ASD with a number of underlying pathogenetic mechanisms. In this regard, there are at least three phenotypic presentations with distinct genetic underpinnings: autism plus phenotype characterized by syndromic ASD caused by rare, single-gene disorders; broad autism phenotype caused by genetic variations in single or multiple genes, each of these variations being common and distributed continually in the general population, but resulting in varying clinical phenotypes when it reaches a certain threshold through complex gene-gene and gene-environment interactions; and severe and specific phenotype caused by 'de-novo' mutations in the patient or transmitted through asymptomatic carriers of such mutation. Understanding the neurobiological processes by which genotypes become phenotypes, along with the advances in developmental neuroscience and neuronal networks at the cellular and molecular level, is paving the way for translational research involving targeted interventions of affected molecular pathways and early intervention programs that promote normal brain responses to stimuli and alter the developmental trajectory.
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DEFF Research Database (Denmark)
Buch, Line Hjortø; Sørensen, Morten Kargo; Berg, Peer
2012-01-01
We tested the following hypotheses: (i) breeding schemes with genomic selection are superior to breeding schemes without genomic selection regarding annual genetic gain of the aggregate genotype (ΔGAG), annual genetic gain of the functional traits and rate of inbreeding per generation (ΔF), (ii......) a positive interaction exists between the use of genotypic information and a short generation interval on ΔGAG and (iii) the inclusion of an indicator trait in the selection index will only result in a negligible increase in ΔGAG if genotypic information about the breeding goal trait is known. We examined......, greater contributions of the functional trait to ΔGAG and lower ΔF than the two breeding schemes without genomic selection. Thus, the use of genotypic information may lead to more sustainable breeding schemes. In addition, a short generation interval increases the effect of using genotypic information...
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Pharmacokinetic interactions between contraceptives and antiepileptic drugs
DEFF Research Database (Denmark)
Sabers, A.
2008-01-01
The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (M) pose potential risks of unintended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin...... AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number...... of co-variants such as co-medication of other drugs, as well as genetic and environmental factors. It is therefore recommended that change in OC use is assisted by AED monitoring whenever possible. (C) 2007 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved Udgivelsesdato: 2008/3...
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Pervasive sharing of genetic effects in autoimmune disease.
Directory of Open Access Journals (Sweden)
Chris Cotsapas
2011-08-01
Full Text Available Genome-wide association (GWA studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs and risk of common autoimmune and inflammatory (immune-mediated diseases, some of which are shared between two diseases. Along with epidemiological and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes. We have developed a novel statistic for Cross Phenotype Meta-Analysis (CPMA which detects association of a SNP to multiple, but not necessarily all, phenotypes. With it, we find evidence that 47/107 (44% immune-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P(CPMA<0.01. We also show that distinct groups of interacting proteins are encoded near SNPs which predispose to the same subsets of diseases; we propose these as the mechanistic basis of shared disease risk. We are thus able to leverage genetic data across diseases to construct biological hypotheses about the underlying mechanism of pathogenesis.
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International Nuclear Information System (INIS)
Bender, M.A.; Abrahamson, S.; Denniston, C.; Schull, W.J.
1989-01-01
In this chapter, we present a comprehensive analysis of the major classes of genetic diseases that would be increased as a result of an increased gonadal radiation exposure to a human population. The risk analysis takes on two major forms: the increase in genetic disease that would be observed in the immediate offspring of the exposed population, and the subsequent transmission of the newly induced mutations through future generations. The major classes of genetic disease will be induced at different frequencies, and will also impact differentially in terms of survivability and fertility on the affected individuals and their descendants. Some classes of disease will be expected to persist for only a few generations at most. Other types of genetic disease will persist through a longer period. The classes of genetic diseases studied are: dominant gene mutation, X-linked gene mutation, chromosome disorders and multifactorial disorders which involve the interaction of many mutant genes and environmental factors. For each of these classes we have derived the general equations of mutation induction for the male and female germ cells of critical importance in the mutation process. The frequency of induced mutations will be determined initially by the dose received, the type of radiation and, to some extent at high dose, by the manner in which the dose is received. We have used the modeling analyses to predict the outcomes for two nuclear power plant accident scenarios, the first in which the population receives a chronic dose of 0.1 Gy (10 rad) over a 50-year period, the second in which an equivalent population receives an acute dose of 2 Gy. In both cases the analyses are projected over a period of five generations
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Public understandings of genetics and health.
Condit, C M
2010-01-01
This review of adult public understandings of genetics related to health indicates that the public's understandings overlap with those of professionals in some areas, but not others. Specifically, the majority of the world's people who have been studied understand genetics through the lens of heredity, not in terms of the structural and functional nature of genes. Public understandings of hereditary processes are influenced by models of social relationships and by experiential familiarity with particular conditions as much as by academic research results. Most people hold a fairly strong belief that many health conditions are substantially influenced by both genes and other factors. However, they do not have a stable understanding of the nature of gene-environment interactions. People in cultures where science is not a prominent cultural mode are even less likely to hold the belief structures of professional geneticists. In some areas--notably with regard to racialization of genetic medicine and characterizations of genetic variations as 'mutations'--at least some members of the public strongly reject some geneticists' constructions. Public understanding of details pertinent to genetic testing generally appears to be weak.
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Randall, J.C.; Winkler, T.W.; Kutalik, Z.; Berndt, S.I.; Jackson, A.U.; Monda, K.L.; Kilpeläinen, T.O.; Esko, T.; Mägi, R.; Li, S.; Workalemahu, T.; Feitosa, M.F.; Croteau-Chonka, D.C.; Day, F.R.; Fall, T.; Ferreira, T.; Gustafsson, S.; Locke, A.E.; Mathieson, I.; Scherag, A.; Vedantam, S.; Wood, A.R.; Liang, L.; Steinthorsdottir, V.; Thorleifsson, G.; Dermitzakis, E.T.; Dimas, A.S.; Karpe, F.; Min, J.L.; Nicholson, G.; Clegg, D.J.; Person, T.; Krohn, J.P.; Bauer, S.; Buechler, C.; Eisinger, K.; Bonnefond, A.; Froguel, P.; Hottenga, J.J.; Prokopenko, I.; Waite, L.L.; Harris, T.B.; Smith, A.V.; Shuldiner, A.R.; McArdle, W.L.; Caulfield, M.J.; Munroe, P.B.; Grönberg, H.; Chen, Y.D.; Li, G.; Beckmann, J.S.; Johnson, T.; Thorsteinsdottir, U.; Teder-Laving, M.; Khaw, K.T.; Wareham, N.J.; Zhao, J.H.; Amin, N.; Oostra, B.A.; Kraja, A.T.; Province, M.A.; Cupples, L.A.; Heard-Costa, N.L.; Kaprio, J.; Ripatti, S.; Surakka, I.; Collins, F.S.; Saramies, J.; Tuomilehto, J.; Jula, A.; Salomaa, V.; Erdmann, J.; Hengstenberg, C.; Loley, C.; Schunkert, H.; Lamina, C.; Wichmann, H.E.; Albrecht, E.; Gieger, C.; Hicks, A.A.; Johansson, A.; Pramstaller, P.P.; Kathiresan, S.; Speliotes, E.K.; Penninx, B.W.J.H.; Hartikainen, A.L.; Järvelin, M.R.; Gyllensten, U.; Boomsma, D.I.; Campbell, H.; Wilson, J.F.; Chanock, S.J.; Farrall, M.; Goel, A.; Medina-Gomez, C.; Rivadeneira, F.; Estrada, K.; Uitterlinden, A.G.; Hofman, A.; Zillikens, M.C.; den Heijer, M.; Kiemeney, L.A.; Maschio, A.; Hall, P.; Tyrer, J.; Teumer, A.; Völzke, H.; Kovacs, P.; Tönjes, A.; Mangino, M.; Spector, T.D.; Hayward, C.; Rudan, I.; Hall, A.S.; Samani, N.J.; Attwood, A.P.; Sambrook, J.G.; Hung, J.; Palmer, L.J.; Lokki, M.L.; Sinisalo, J.; Boucher, G.; Huikuri, H.V.; Lorentzon, M.; Ohlsson, C.; Eklund, N.; Eriksson, J.G.; Barlassina, C.; Rivolta, C.; Nolte, I.M.; Snieder, H.; van der Klauw, M.M.; van Vliet-Ostaptchouk, J.V.; Gejman, P.V.; Shi, J.; Jacobs, K.B.; Wang, Z.; Bakker, S.J.; Mateo Leach, I.; Navis, G.; van der Harst, P.; Martin, N.G.; Medland, S.E.; Montgomery, G.W.; Yang, J.; Chasman, D.I.; Ridker, P.M.; Rose, L.M.; Lehtimäki, T.; Raitakari, O.; Absher, D.; Iribarren, C.; Basart, H.; Hovingh, K.G.; Hyppönen, E.; Power, C.; Anderson, D.; Beilby, J.P.; Hui, J.; Jolley, J.; Sager, H.; Bornstein, S.R.; Schwarz, P.E.; Kristiansson, K.; Perola, M.; Lindström, J.; Swift, A.J.; Uusitupa, M.; Atalay, M.; Lakka, T.A.; Rauramaa, R.; Bolton, J.L.; Fowkes, G.; Fraser, R.M.; Price, J.F.; Fischer, K.; Krjuta Kov, K.; Metspalu, A.; Mihailov, E.; Langenberg, C.; Luan, J.; Ong, K.K.; Chines, P.S.; Keinanen-Kiukaanniemie, S.; Saaristo, T.E.; Edkins, S.; Franks, P.W.; Hallmans, G.; Shungin, D.; Morris, A.D.; Palmer, C.N.A.; Erbel, R.; Moebus, S.; Nöthen, M.M.; Pechlivanis, S.; Hveem, K.; Narisu, N.; Hamsten, A.; Humphries, S.E.; Strawbridge, R.J.; Tremoli, E.; Grallert, H.; Thorand, B.; Illig, T.; Koenig, W.; Müller-Nurasyid, M.; Peters, A.; Boehm, B.O.; Kleber, M.E.; März, W.; Winkelmann, B.R.; Kuusisto, J.; Laakso, M.; Arveiler, D.; Cesana, G.; Kuulasmaa, K.; Virtamo, J.; Yarnell, J.W.; Kuh, D; Wong, A.; Lind, L.; de Faire, U.; Gigante, B.; Magnusson, P.K.E.; Pedersen, N.L.; Dedoussis, G.; Dimitriou, M.; Kolovou, G.; Kanoni, S.; Stirrups, K.; Bonnycastle, L.L.; Njolstad, I.; Wilsgaard, T.; Ganna, A.; Rehnberg, E.; Hingorani, A.D.; Kivimaki, M.; Kumari, M.; Assimes, T.L.; Barroso, I.; Boehnke, M.; Borecki, I.B.; Deloukas, P.; Fox, C.S.; Frayling, T.M.; Groop, L.C.; Haritunians, T.; Hunter, D.; Ingelsson, E.; Kaplan, R.; Mohlke, K.L.; O'Connell, J.R.; Schlessinger, D.; Strachan, D.P.; Stefansson, K.; van Duijn, C.M.; Abecasis, G.R.; McCarthy, M.I.; Hirschhorn, J.N.; Qi, L.; Loos, R.J.; Lindgren, C.M.; North, K.E.; Heid, I.M.
2013-01-01
Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723