WorldWideScience

Sample records for underlying genetic architecture

  1. A simple genetic architecture underlies morphological variation in dogs.

    Directory of Open Access Journals (Sweden)

    Adam R Boyko

    2010-08-01

    Full Text Available Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs. Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (< or = 3 explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.

  2. Determination of the Genetic Architecture Underlying Short Wavelength Sensitivity in Lake Malawi Cichlids.

    Science.gov (United States)

    Nandamuri, Sri Pratima; Dalton, Brian E; Carleton, Karen L

    2017-06-01

    African cichlids are an exemplary system to study organismal diversity and rapid speciation. Species differ in external morphology including jaw shape and body coloration, but also differ in sensory systems including vision. All cichlids have 7 cone opsin genes with species differing broadly in which opsins are expressed. The differential opsin expression results in closely related species with substantial differences in spectral sensitivity of their photoreceptors. In this work, we take a first step in determining the genetic basis of opsin expression in cichlids. Using a second generation cross between 2 species with different opsin expression patterns, we make a conservative estimate that short wavelength opsin expression is regulated by a few loci. Genetic mapping in 96 F2 hybrids provides clear evidence of a cis-regulatory region for SWS1 opsin that explains 34% of the variation in expression between the 2 species. Additionally, in situ hybridization has shown that SWS1 and SWS2B opsins are coexpressed in individual single cones in the retinas of F2 progeny. Results from this work will contribute to a better understanding of the genetic architecture underlying opsin expression. This knowledge will help answer long-standing questions about the evolutionary processes fundamental to opsin expression variation and how this contributes to adaptive cichlid divergence. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Genetic architecture of factors underlying partial resistance to Alternaria leaf blight in carrot.

    Science.gov (United States)

    Le Clerc, Valérie; Pawelec, Anna; Birolleau-Touchard, Christelle; Suel, Anita; Briard, Mathilde

    2009-05-01

    In most production areas, Alternaria leaf blight (ALB) is recognized as the most common and destructive foliage disease in carrot. To assess the genetic architecture of carrot ALB resistance, two parental coupling maps were developed with similar number of dominant markers (around 70), sizes (around 650 cM), densities (around 9.5 cM), and marker composition. The F(2:3) progenies were evaluated in field and tunnel for two scoring dates. The continuous distribution of the disease severity value indicated that ALB resistance is under polygenic control. Three QTLs regions were found on three linkage groups. Two of them were tunnel or field specific and were detected only at the second screening date suggesting that the expression of these two QTLs regions involved in resistance to Alternaria dauci might depend on environment and delay after infection.

  4. Evolutionary divergence of the genetic architecture underlying photoperiodism in the pitcher-plant mosquito, Wyeomyia smithii.

    Science.gov (United States)

    Lair, K P; Bradshaw, W E; Holzapfel, C M

    1997-12-01

    We determine the contribution of composite additive, dominance, and epistatic effects to the genetic divergence of photoperiodic response along latitudinal, altitudinal, and longitudinal gradients in the pitcher-plant mosquito, Wyeomyia smithii. Joint scaling tests of crosses between populations showed widespread epistasis as well as additive and dominance differences among populations. There were differences due to epistasis between an alpine population in North Carolina and populations in Florida, lowland North Carolina, and Maine. Longitudinal displacement resulted in differences due to epistasis between Florida and Alabama populations separated by 300 km but not between Maine and Wisconsin populations separated by 2000 km. Genetic differences between New Jersey and Ontario did not involve either dominance or epistasis and we estimated the minimum number of effective factors contributing to a difference in mean critical photoperiod of 5 SD between them as nE = 5. We propose that the genetic similarity of populations within a broad northern region is due to their more recent origin since recession of the Laurentide Ice Sheet and that the unique genetic architecture of each population is the result of both mutation and repeated migration-founder-flush episodes during the dispersal of W. smithii in North America. Our results suggest that differences in composite additive and dominance effects arise early in the genetic divergence of populations while differences due to epistasis accumulate after more prolonged isolation.

  5. Genetic variants associated with the root system architecture of oilseed rape (Brassica napus L.) under contrasting phosphate supply.

    Science.gov (United States)

    Wang, Xiaohua; Chen, Yanling; Thomas, Catherine L; Ding, Guangda; Xu, Ping; Shi, Dexu; Grandke, Fabian; Jin, Kemo; Cai, Hongmei; Xu, Fangsen; Yi, Bin; Broadley, Martin R; Shi, Lei

    2017-08-01

    Breeding crops with ideal root system architecture for efficient absorption of phosphorus is an important strategy to reduce the use of phosphate fertilizers. To investigate genetic variants leading to changes in root system architecture, 405 oilseed rape cultivars were genotyped with a 60K Brassica Infinium SNP array in low and high P environments. A total of 285 single-nucleotide polymorphisms were associated with root system architecture traits at varying phosphorus levels. Nine single-nucleotide polymorphisms corroborate a previous linkage analysis of root system architecture quantitative trait loci in the BnaTNDH population. One peak single-nucleotide polymorphism region on A3 was associated with all root system architecture traits and co-localized with a quantitative trait locus for primary root length at low phosphorus. Two more single-nucleotide polymorphism peaks on A5 for root dry weight at low phosphorus were detected in both growth systems and co-localized with a quantitative trait locus for the same trait. The candidate genes identified on A3 form a haplotype 'BnA3Hap', that will be important for understanding the phosphorus/root system interaction and for the incorporation into Brassica napus breeding programs. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  6. Quantitative trait loci in hop (Humulus lupulus L.) reveal complex genetic architecture underlying variation in sex, yield and cone chemistry.

    Science.gov (United States)

    McAdam, Erin L; Freeman, Jules S; Whittock, Simon P; Buck, Emily J; Jakse, Jernej; Cerenak, Andreja; Javornik, Branka; Kilian, Andrzej; Wang, Cai-Hong; Andersen, Dave; Vaillancourt, René E; Carling, Jason; Beatson, Ron; Graham, Lawrence; Graham, Donna; Darby, Peter; Koutoulis, Anthony

    2013-05-30

    genetic control of traits of current economic and breeding significance in hop and demonstrate the complex genetic architecture underlying variation in these traits. The linkage information obtained in this study, based on transferable markers, can be used to facilitate the validation of QTL, crucial to the success of MAS.

  7. RAD-QTL Mapping Reveals Both Genome-Level Parallelism and Different Genetic Architecture Underlying the Evolution of Body Shape in Lake Whitefish (Coregonus clupeaformis) Species Pairs.

    Science.gov (United States)

    Laporte, Martin; Rogers, Sean M; Dion-Côté, Anne-Marie; Normandeau, Eric; Gagnaire, Pierre-Alexandre; Dalziel, Anne C; Chebib, Jobran; Bernatchez, Louis

    2015-05-21

    Parallel changes in body shape may evolve in response to similar environmental conditions, but whether such parallel phenotypic changes share a common genetic basis is still debated. The goal of this study was to assess whether parallel phenotypic changes could be explained by genetic parallelism, multiple genetic routes, or both. We first provide evidence for parallelism in fish shape by using geometric morphometrics among 300 fish representing five species pairs of Lake Whitefish. Using a genetic map comprising 3438 restriction site-associated DNA sequencing single-nucleotide polymorphisms, we then identified quantitative trait loci underlying body shape traits in a backcross family reared in the laboratory. A total of 138 body shape quantitative trait loci were identified in this cross, thus revealing a highly polygenic architecture of body shape in Lake Whitefish. Third, we tested for evidence of genetic parallelism among independent wild populations using both a single-locus method (outlier analysis) and a polygenic approach (analysis of covariation among markers). The single-locus approach provided limited evidence for genetic parallelism. However, the polygenic analysis revealed genetic parallelism for three of the five lakes, which differed from the two other lakes. These results provide evidence for both genetic parallelism and multiple genetic routes underlying parallel phenotypic evolution in fish shape among populations occupying similar ecological niches. Copyright © 2015 Laporte et al.

  8. Genetic Regulation of Shoot Architecture.

    Science.gov (United States)

    Wang, Bing; Smith, Steven M; Li, Jiayang

    2018-03-19

    Shoot architecture is determined by the organization and activities of apical, axillary, intercalary, secondary, and inflorescence meristems and by the subsequent development of stems, leaves, shoot branches, and inflorescences. In this review, we discuss the unifying principles of hormonal and genetic control of shoot architecture including advances in our understanding of lateral branch outgrowth; control of stem elongation, thickness, and angle; and regulation of inflorescence development. We focus on recent progress made mainly in Arabidopsis thaliana, rice, pea, maize, and tomato, including the identification of new genes and mechanisms controlling shoot architecture. Key advances include elucidation of mechanisms by which strigolactones, auxins, and genes such as IDEAL PLANT ARCHITECTURE1 and TEOSINTE BRANCHED1 control shoot architecture. Knowledge now available provides a foundation for rational approaches to crop breeding and the generation of ideotypes with defined architectural features to improve performance and productivity. Expected final online publication date for the Annual Review of Plant Biology Volume 69 is April 29, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  9. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

    DEFF Research Database (Denmark)

    Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S

    2018-01-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns...... the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes...... in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely...

  10. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

    Science.gov (United States)

    Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

    2018-03-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

  11. Distinct genetic architecture underlies the emergence of sleep loss and prey-seeking behavior in the Mexican cavefish.

    Science.gov (United States)

    Yoshizawa, Masato; Robinson, Beatriz G; Duboué, Erik R; Masek, Pavel; Jaggard, James B; O'Quin, Kelly E; Borowsky, Richard L; Jeffery, William R; Keene, Alex C

    2015-02-20

    Sleep is characterized by extended periods of quiescence and reduced responsiveness to sensory stimuli. Animals ranging from insects to mammals adapt to environments with limited food by suppressing sleep and enhancing their response to food cues, yet little is known about the genetic and evolutionary relationship between these processes. The blind Mexican cavefish, Astyanax mexicanus is a powerful model for elucidating the genetic mechanisms underlying behavioral evolution. A. mexicanus comprises an extant ancestral-type surface dwelling morph and at least five independently evolved cave populations. Evolutionary convergence on sleep loss and vibration attraction behavior, which is involved in prey seeking, have been documented in cavefish raising the possibility that enhanced sensory responsiveness underlies changes in sleep. We established a system to study sleep and vibration attraction behavior in adult A. mexicanus and used high coverage quantitative trait loci (QTL) mapping to investigate the functional and evolutionary relationship between these traits. Analysis of surface-cave F2 hybrid fish and an outbred cave population indicates that independent genetic factors underlie changes in sleep/locomotor activity and vibration attraction behavior. High-coverage QTL mapping with genotyping-by-sequencing technology identify two novel QTL intervals that associate with locomotor activity and include the narcolepsy-associated tp53 regulating kinase. These QTLs represent the first genomic localization of locomotor activity in cavefish and are distinct from two QTLs previously identified as associating with vibration attraction behavior. Taken together, these results localize genomic regions underlying sleep/locomotor and sensory changes in cavefish populations and provide evidence that sleep loss evolved independently from enhanced sensory responsiveness.

  12. The genetic architecture of susceptibility to parasites.

    Science.gov (United States)

    Wilfert, Lena; Schmid-Hempel, Paul

    2008-06-30

    The antagonistic co-evolution of hosts and their parasites is considered to be a potential driving force in maintaining host genetic variation including sexual reproduction and recombination. The examination of this hypothesis calls for information about the genetic basis of host-parasite interactions - such as how many genes are involved, how big an effect these genes have and whether there is epistasis between loci. We here examine the genetic architecture of quantitative resistance in animal and plant hosts by concatenating published studies that have identified quantitative trait loci (QTL) for host resistance in animals and plants. Collectively, these studies show that host resistance is affected by few loci. We particularly show that additional epistatic interactions, especially between loci on different chromosomes, explain a majority of the effects. Furthermore, we find that when experiments are repeated using different host or parasite genotypes under otherwise identical conditions, the underlying genetic architecture of host resistance can vary dramatically - that is, involves different QTLs and epistatic interactions. QTLs and epistatic loci vary much less when host and parasite types remain the same but experiments are repeated in different environments. This pattern of variability of the genetic architecture is predicted by strong interactions between genotypes and corroborates the prevalence of varying host-parasite combinations over varying environmental conditions. Moreover, epistasis is a major determinant of phenotypic variance for host resistance. Because epistasis seems to occur predominantly between, rather than within, chromosomes, segregation and chromosome number rather than recombination via cross-over should be the major elements affecting adaptive change in host resistance.

  13. Genetic Architecture of Natural Variation Underlying Adult Foraging Behavior That Is Essential for Survival of Drosophila melanogaster.

    Science.gov (United States)

    Lee, Yuh Chwen G; Yang, Qian; Chi, Wanhao; Turkson, Susie A; Du, Wei A; Kemkemer, Claus; Zeng, Zhao-Bang; Long, Manyuan; Zhuang, Xiaoxi

    2017-05-01

    Foraging behavior is critical for the fitness of individuals. However, the genetic basis of variation in foraging behavior and the evolutionary forces underlying such natural variation have rarely been investigated. We developed a systematic approach to assay the variation in survival rate in a foraging environment for adult flies derived from a wild Drosophila melanogaster population. Despite being such an essential trait, there is substantial variation of foraging behavior among D. melanogaster strains. Importantly, we provided the first evaluation of the potential caveats of using inbred Drosophila strains to perform genome-wide association studies on life-history traits, and concluded that inbreeding depression is unlikely a major contributor for the observed large variation in adult foraging behavior. We found that adult foraging behavior has a strong genetic component and, unlike larval foraging behavior, depends on multiple loci. Identified candidate genes are enriched in those with high expression in adult heads and, demonstrated by expression knock down assay, are involved in maintaining normal functions of the nervous system. Our study not only identified candidate genes for foraging behavior that is relevant to individual fitness, but also shed light on the initial stage underlying the evolution of the behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. Towards a genetic architecture of cryptic genetic variation

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 84; Issue 3. Towards a genetic architecture of cryptic genetic variation and genetic assimilation: the contribution of K. G. Bateman. Ian Dworkin. Commentary on J. Genet. Classic Volume 84 Issue 3 December 2005 pp 223-226 ...

  15. Genetic architecture and functional characterization of genes underlying the rapid diversification of male external genitalia between Drosophila simulans and Drosophila mauritiana.

    Science.gov (United States)

    Tanaka, Kentaro M; Hopfen, Corinna; Herbert, Matthew R; Schlötterer, Christian; Stern, David L; Masly, John P; McGregor, Alistair P; Nunes, Maria D S

    2015-05-01

    Male sexual characters are often among the first traits to diverge between closely related species and identifying the genetic basis of such changes can contribute to our understanding of their evolutionary history. However, little is known about the genetic architecture or the specific genes underlying the evolution of male genitalia. The morphology of the claspers, posterior lobes, and anal plates exhibit striking differences between Drosophila mauritiana and D. simulans. Using QTL and introgression-based high-resolution mapping, we identified several small regions on chromosome arms 3L and 3R that contribute to differences in these traits. However, we found that the loci underlying the evolution of clasper differences between these two species are independent from those that contribute to posterior lobe and anal plate divergence. Furthermore, while most of the loci affect each trait in the same direction and act additively, we also found evidence for epistasis between loci for clasper bristle number. In addition, we conducted an RNAi screen in D. melanogaster to investigate if positional and expression candidate genes located on chromosome 3L, are also involved in genital development. We found that six of these genes, including components of Wnt signaling and male-specific lethal 3 (msl3), regulate the development of genital traits consistent with the effects of the introgressed regions where they are located and that thus represent promising candidate genes for the evolution these traits. Copyright © 2015 by the Genetics Society of America.

  16. Genetic architecture and the evolution of sex.

    Science.gov (United States)

    Lohaus, Rolf; Burch, Christina L; Azevedo, Ricardo B R

    2010-01-01

    Theoretical investigations of the advantages of sex have tended to treat the genetic architecture of organisms as static and have not considered that genetic architecture might coevolve with reproductive mode. As a result, some potential advantages of sex may have been missed. Using a gene network model, we recently showed that recombination imposes selection for robustness to mutation and that negative epistasis can evolve as a by-product of this selection. These results motivated a detailed exploration of the mutational deterministic hypothesis, a hypothesis in which the advantage of sex depends critically on epistasis. We found that sexual populations do evolve higher mean fitness and lower genetic load than asexual populations at equilibrium, and, under moderate stabilizing selection and large population size, these equilibrium sexual populations resist invasion by asexuals. However, we found no evidence that these long- and short-term advantages to sex were explained by the negative epistasis that evolved in our experiments. The long-term advantage of sex was that sexual populations evolved a lower deleterious mutation rate, but this property was not sufficient to account for the ability of sexual populations to resist invasion by asexuals. The ability to resist asexual invasion was acquired simultaneously with an increase in recombinational robustness that minimized the cost of sex. These observations provide the first direct evidence that sexual reproduction does indeed select for conditions that favor its own maintenance. Furthermore, our results highlight the importance of considering a dynamic view of the genetic architecture to understand the evolution of sex and recombination.

  17. Towards a genetic architecture of cryptic genetic variation and ...

    Indian Academy of Sciences (India)

    Unknown

    Far from being a historical curiosity, it appears that this phenotype may be a relevant and powerful model system for current studies of cryptic genetic varia- tion and possibly for examining allelic architecture of complex diseases. I will discuss what future research di- rections will allow for this possibility. Genetic assimilation.

  18. The Genetic Architecture of Barley Plant Stature

    Science.gov (United States)

    Alqudah, Ahmad M.; Koppolu, Ravi; Wolde, Gizaw M.; Graner, Andreas; Schnurbusch, Thorsten

    2016-01-01

    Plant stature in temperate cereals is predominantly controlled by tillering and plant height as complex agronomic traits, representing important determinants of grain yield. This study was designed to reveal the genetic basis of tillering at five developmental stages and plant height at harvest in 218 worldwide spring barley (Hordeum vulgare L.) accessions under greenhouse conditions. The accessions were structured based on row-type classes [two- vs. six-rowed] and photoperiod response [photoperiod-sensitive (Ppd-H1) vs. reduced photoperiod sensitivity (ppd-H1)]. Phenotypic analyses of both factors revealed profound between group effects on tiller development. To further verify the row-type effect on the studied traits, Six-rowed spike 1 (vrs1) mutants and their two-rowed progenitors were examined for tiller number per plant and plant height. Here, wild-type (Vrs1) plants were significantly taller and had more tillers than mutants suggesting a negative pleiotropic effect of this row-type locus on both traits. Our genome-wide association scans further revealed highly significant associations, thereby establishing a link between the genetic control of row-type, heading time, tillering, and plant height. We further show that associations for tillering and plant height are co-localized with chromosomal segments harboring known plant stature-related phytohormone and sugar-related genes. This work demonstrates the feasibility of the GWAS approach for identifying putative candidate genes for improving plant architecture. PMID:27446200

  19. The genetic architecture of type 2 diabetes

    NARCIS (Netherlands)

    Fuchsberger, Christian; Flannick, Jason; Teslovich, Tanya M.; Mahajan, Anubha; Agarwala, Vineeta; Gaulton, Kyle J.; Ma, Clement; Fontanillas, Pierre; Moutsianas, Loukas; McCarthy, Davis J.; Rivas, Manuel A.; Perry, John R. B.; Sim, Xueling; Blackwell, Thomas W.; Robertson, Neil R.; Rayner, N. William; Cingolani, Pablo; Locke, Adam E.; Fernandez Tajes, Juan; Highland, Heather M.; Dupuis, Josee; Chines, Peter S.; Lindgren, Cecilia M.; Hartl, Christopher; Jackson, Anne U.; Chen, Han; Huyghe, Jeroen R.; van de Bunt, Martijn; Pearson, Richard D.; Kumar, Ashish; Müller-Nurasyid, Martina; Grarup, Niels; Stringham, Heather M.; Gamazon, Eric R.; Lee, Jaehoon; Chen, Yuhui; Scott, Robert A.; Below, Jennifer E.; Chen, Peng; Huang, Jinyan; Go, Min Jin; Stitzel, Michael L.; Pasko, Dorota; Parker, Stephen C. J.; Varga, Tibor V.; Green, Todd; Beer, Nicola L.; Day-Williams, Aaron G.; Ferreira, Teresa; Fingerlin, Tasha; Horikoshi, Momoko; Hu, Cheng; Huh, Iksoo; Ikram, Mohammad Kamran; Kim, Bong-Jo; Kim, Yongkang; Kim, Young Jin; Kwon, Min-Seok; Lee, Juyoung; Lee, Selyeong; Lin, Keng-Han; Maxwell, Taylor J.; Nagai, Yoshihiko; Wang, Xu; Welch, Ryan P.; Yoon, Joon; Zhang, Weihua; Barzilai, Nir; Voight, Benjamin F.; Han, Bok-Ghee; Jenkinson, Christopher P.; Kuulasmaa, Teemu; Kuusisto, Johanna; Manning, Alisa; Ng, Maggie C. Y.; Palmer, Nicholette D.; Balkau, Beverley; Stancáková, Alena; Abboud, Hanna E.; Boeing, Heiner; Giedraitis, Vilmantas; Prabhakaran, Dorairaj; Gottesman, Omri; Scott, James; Carey, Jason; Kwan, Phoenix; Grant, George; Smith, Joshua D.; Neale, Benjamin M.; Purcell, Shaun; Butterworth, Adam S.; Howson, Joanna M. M.; Lee, Heung Man; Lu, Yingchang; Kwak, Soo-Heon; Zhao, Wei; Danesh, John; Lam, Vincent K. L.; Park, Kyong Soo; Saleheen, Danish; So, Wing Yee; Tam, Claudia H. T.; Afzal, Uzma; Aguilar, David; Arya, Rector; Aung, Tin; Chan, Edmund; Navarro, Carmen; Cheng, Ching-Yu; Palli, Domenico; Correa, Adolfo; Curran, Joanne E.; Rybin, Denis; Farook, Vidya S.; Fowler, Sharon P.; Freedman, Barry I.; Griswold, Michael; Hale, Daniel Esten; Hicks, Pamela J.; Khor, Chiea-Chuen; Kumar, Satish; Lehne, Benjamin; Thuillier, Dorothée; Lim, Wei Yen; Liu, Jianjun; van der Schouw, Yvonne T.; Loh, Marie; Musani, Solomon K.; Puppala, Sobha; Scott, William R.; Yengo, Loïc; Tan, Sian-Tsung; Taylor, Herman A.; Thameem, Farook; Wilson, Gregory; Wong, Tien Yin; Njølstad, Pål Rasmus; Levy, Jonathan C.; Mangino, Massimo; Bonnycastle, Lori L.; Schwarzmayr, Thomas; Fadista, João; Surdulescu, Gabriela L.; Herder, Christian; Groves, Christopher J.; Wieland, Thomas; Bork-Jensen, Jette; Brandslund, Ivan; Christensen, Cramer; Koistinen, Heikki A.; Doney, Alex S. F.; Kinnunen, Leena; Esko, Tõnu; Farmer, Andrew J.; Hakaste, Liisa; Hodgkiss, Dylan; Kravic, Jasmina; Lyssenko, Valeriya; Hollensted, Mette; Jørgensen, Marit E.; Jørgensen, Torben; Ladenvall, Claes; Justesen, Johanne Marie; Käräjämäki, Annemari; Kriebel, Jennifer; Rathmann, Wolfgang; Lannfelt, Lars; Lauritzen, Torsten; Narisu, Narisu; Linneberg, Allan; Melander, Olle; Milani, Lili; Neville, Matt; Orho-Melander, Marju; Qi, Lu; Qi, Qibin; Roden, Michael; Rolandsson, Olov; Swift, Amy; Rosengren, Anders H.; Stirrups, Kathleen; Wood, Andrew R.; Mihailov, Evelin; Blancher, Christine; Carneiro, Mauricio O.; Maguire, Jared; Poplin, Ryan; Shakir, Khalid; Fennell, Timothy; DePristo, Mark; Hrabé de Angelis, Martin; Deloukas, Panos; Gjesing, Anette P.; Jun, Goo; Nilsson, Peter; Murphy, Jacquelyn; Onofrio, Robert; Thorand, Barbara; Hansen, Torben; Meisinger, Christa; Hu, Frank B.; Isomaa, Bo; Karpe, Fredrik; Liang, Liming; Peters, Annette; Huth, Cornelia; O'Rahilly, Stephen P.; Palmer, Colin N. A.; Pedersen, Oluf; Rauramaa, Rainer; Tuomilehto, Jaakko; Salomaa, Veikko; Watanabe, Richard M.; Syvänen, Ann-Christine; Bergman, Richard N.; Bharadwaj, Dwaipayan; Bottinger, Erwin P.; Cho, Yoon Shin; Chandak, Giriraj R.; Chan, Juliana C. N.; Chia, Kee Seng; Daly, Mark J.; Ebrahim, Shah B.; Langenberg, Claudia; Elliott, Paul; Jablonski, Kathleen A.; Lehman, Donna M.; Jia, Weiping; Ma, Ronald C. W.; Pollin, Toni I.; Sandhu, Manjinder; Tandon, Nikhil; Froguel, Philippe; Barroso, Inês; teo, Yik Ying; Zeggini, Eleftheria; Loos, Ruth J. F.; Small, Kerrin S.; Ried, Janina S.; DeFronzo, Ralph A.; Grallert, Harald; Glaser, Benjamin; Metspalu, Andres; Wareham, Nicholas J.; Walker, Mark; Banks, Eric; Gieger, Christian; Ingelsson, Erik; Im, Hae Kyung; Illig, Thomas; Franks, Paul W.; Buck, Gemma; Trakalo, Joseph; Buck, David; Prokopenko, Inga; Mägi, Reedik; Lind, Lars; Farjoun, Yossi; Owen, Katharine R.; Gloyn, Anna L.; Strauch, Konstantin; Tuomi, Tiinamaija; Kooner, Jaspal Singh; Lee, Jong-Young; Park, Taesung; Donnelly, Peter; Morris, Andrew D.; Hattersley, Andrew T.; Bowden, Donald W.; Collins, Francis S.; Atzmon, Gil; Chambers, John C.; Spector, Timothy D.; Laakso, Markku; Strom, Tim M.; Bell, Graeme I.; Blangero, John; Duggirala, Ravindranath; Tai, E. Shyong; McVean, Gilean; Hanis, Craig L.; Wilson, James G.; Seielstad, Mark; Frayling, Timothy M.; Meigs, James B.; Cox, Nancy J.; Sladek, Rob; Lander, Eric S.; Gabriel, Stacey; Burtt, Noël P.; Mohlke, Karen L.; Meitinger, Thomas; Groop, Leif; Abecasis, Goncalo; Florez, Jose C.; Scott, Laura J.; Morris, Andrew P.; Kang, Hyun Min; Boehnke, Michael; Altshuler, David; McCarthy, Mark I.

    2016-01-01

    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate,

  20. Phenotypic evolution from genetic polymorphisms in a radial network architecture

    Directory of Open Access Journals (Sweden)

    Siegel Paul B

    2007-11-01

    Full Text Available Abstract Background The genetic architecture of a quantitative trait influences the phenotypic response to natural or artificial selection. One of the main objectives of genetic mapping studies is to identify the genetic factors underlying complex traits and understand how they contribute to phenotypic expression. Presently, we are good at identifying and locating individual loci with large effects, but there is a void in describing more complex genetic architectures. Although large networks of connected genes have been reported, there is an almost complete lack of information on how polymorphisms in these networks contribute to phenotypic variation and change. To date, most of our understanding comes from theoretical, model-based studies, and it remains difficult to assess how realistic their conclusions are as they lack empirical support. Results A previous study provided evidence that nearly half of the difference in eight-week body weight between two divergently selected lines of chickens was a result of four loci organized in a 'radial' network (one central locus interacting with three 'radial' loci that, in turn, only interacted with the central locus. Here, we study the relationship between phenotypic change and genetic polymorphism in this empirically detected network. We use a model-free approach to study, through individual-based simulations, the dynamic properties of this polymorphic and epistatic genetic architecture. The study provides new insights to how epistasis can modify the selection response, buffer and reveal effects of major loci leading to a progressive release of genetic variation. We also illustrate the difficulty of predicting genetic architecture from observed selection response, and discuss mechanisms that might lead to misleading conclusions on underlying genetic architectures from quantitative trait locus (QTL experiments in selected populations. Conclusion Considering both molecular (QTL and phenotypic (selection

  1. The genetic architecture of climatic adaptation of tropical cattle.

    Directory of Open Access Journals (Sweden)

    Laercio R Porto-Neto

    Full Text Available Adaptation of global food systems to climate change is essential to feed the world. Tropical cattle production, a mainstay of profitability for farmers in the developing world, is dominated by heat, lack of water, poor quality feedstuffs, parasites, and tropical diseases. In these systems European cattle suffer significant stock loss, and the cross breeding of taurine x indicine cattle is unpredictable due to the dilution of adaptation to heat and tropical diseases. We explored the genetic architecture of ten traits of tropical cattle production using genome wide association studies of 4,662 animals varying from 0% to 100% indicine. We show that nine of the ten have genetic architectures that include genes of major effect, and in one case, a single location that accounted for more than 71% of the genetic variation. One genetic region in particular had effects on parasite resistance, yearling weight, body condition score, coat colour and penile sheath score. This region, extending 20 Mb on BTA5, appeared to be under genetic selection possibly through maintenance of haplotypes by breeders. We found that the amount of genetic variation and the genetic correlations between traits did not depend upon the degree of indicine content in the animals. Climate change is expected to expand some conditions of the tropics to more temperate environments, which may impact negatively on global livestock health and production. Our results point to several important genes that have large effects on adaptation that could be introduced into more temperate cattle without detrimental effects on productivity.

  2. The genetic architecture of leaf number and its genetic relationship to flowering time in maize.

    Science.gov (United States)

    Li, Dan; Wang, Xufeng; Zhang, Xiangbo; Chen, Qiuyue; Xu, Guanghui; Xu, Dingyi; Wang, Chenglong; Liang, Yameng; Wu, Lishuan; Huang, Cheng; Tian, Jinge; Wu, Yaoyao; Tian, Feng

    2016-04-01

    The number of leaves and their distributions on plants are critical factors determining plant architecture in maize (Zea mays), and leaf number is frequently used as a measure of flowering time, a trait that is key to local environmental adaptation. Here, using a large set of 866 maize-teosinte BC2 S3 recombinant inbred lines genotyped by using 19,838 single nucleotide polymorphism markers, we conducted a comprehensive genetic dissection to assess the genetic architecture of leaf number and its genetic relationship to flowering time. We demonstrated that the two components of total leaf number, the number of leaves above (LA) and below (LB) the primary ear, were under relatively independent genetic control and might be subject to differential directional selection during maize domestication and improvement. Furthermore, we revealed that flowering time and leaf number are commonly regulated at a moderate level. The pleiotropy of the genes ZCN8, dlf1 and ZmCCT on leaf number and flowering time were validated by near-isogenic line analysis. Through fine mapping, qLA1-1, a major-effect locus that specifically affects LA, was delimited to a region with severe recombination suppression derived from teosinte. This study provides important insights into the genetic basis of traits affecting plant architecture and adaptation. The genetic independence of LA from LB enables the optimization of leaf number for ideal plant architecture breeding in maize. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  3. The genetic architecture of type 2 diabetes

    DEFF Research Database (Denmark)

    Fuchsberger, Christian; Flannick, Jason; Teslovich, Tanya M

    2016-01-01

    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate......,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome......-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes....

  4. Parametric and nonparametric statistical methods for genomic selection of traits with additive and epistatic genetic architectures.

    Science.gov (United States)

    Howard, Réka; Carriquiry, Alicia L; Beavis, William D

    2014-04-11

    Parametric and nonparametric methods have been developed for purposes of predicting phenotypes. These methods are based on retrospective analyses of empirical data consisting of genotypic and phenotypic scores. Recent reports have indicated that parametric methods are unable to predict phenotypes of traits with known epistatic genetic architectures. Herein, we review parametric methods including least squares regression, ridge regression, Bayesian ridge regression, least absolute shrinkage and selection operator (LASSO), Bayesian LASSO, best linear unbiased prediction (BLUP), Bayes A, Bayes B, Bayes C, and Bayes Cπ. We also review nonparametric methods including Nadaraya-Watson estimator, reproducing kernel Hilbert space, support vector machine regression, and neural networks. We assess the relative merits of these 14 methods in terms of accuracy and mean squared error (MSE) using simulated genetic architectures consisting of completely additive or two-way epistatic interactions in an F2 population derived from crosses of inbred lines. Each simulated genetic architecture explained either 30% or 70% of the phenotypic variability. The greatest impact on estimates of accuracy and MSE was due to genetic architecture. Parametric methods were unable to predict phenotypic values when the underlying genetic architecture was based entirely on epistasis. Parametric methods were slightly better than nonparametric methods for additive genetic architectures. Distinctions among parametric methods for additive genetic architectures were incremental. Heritability, i.e., proportion of phenotypic variability, had the second greatest impact on estimates of accuracy and MSE. Copyright © 2014 Howard et al.

  5. The genetic architecture of type 2 diabetes

    Science.gov (United States)

    Ma, Clement; Fontanillas, Pierre; Moutsianas, Loukas; McCarthy, Davis J; Rivas, Manuel A; Perry, John R B; Sim, Xueling; Blackwell, Thomas W; Robertson, Neil R; Rayner, N William; Cingolani, Pablo; Locke, Adam E; Tajes, Juan Fernandez; Highland, Heather M; Dupuis, Josee; Chines, Peter S; Lindgren, Cecilia M; Hartl, Christopher; Jackson, Anne U; Chen, Han; Huyghe, Jeroen R; van de Bunt, Martijn; Pearson, Richard D; Kumar, Ashish; Müller-Nurasyid, Martina; Grarup, Niels; Stringham, Heather M; Gamazon, Eric R; Lee, Jaehoon; Chen, Yuhui; Scott, Robert A; Below, Jennifer E; Chen, Peng; Huang, Jinyan; Go, Min Jin; Stitzel, Michael L; Pasko, Dorota; Parker, Stephen C J; Varga, Tibor V; Green, Todd; Beer, Nicola L; Day-Williams, Aaron G; Ferreira, Teresa; Fingerlin, Tasha; Horikoshi, Momoko; Hu, Cheng; Huh, Iksoo; Ikram, Mohammad Kamran; Kim, Bong-Jo; Kim, Yongkang; Kim, Young Jin; Kwon, Min-Seok; Lee, Juyoung; Lee, Selyeong; Lin, Keng-Han; Maxwell, Taylor J; Nagai, Yoshihiko; Wang, Xu; Welch, Ryan P; Yoon, Joon; Zhang, Weihua; Barzilai, Nir; Voight, Benjamin F; Han, Bok-Ghee; Jenkinson, Christopher P; Kuulasmaa, Teemu; Kuusisto, Johanna; Manning, Alisa; Ng, Maggie C Y; Palmer, Nicholette D; Balkau, Beverley; Stančáková, Alena; Abboud, Hanna E; Boeing, Heiner; Giedraitis, Vilmantas; Prabhakaran, Dorairaj; Gottesman, Omri; Scott, James; Carey, Jason; Kwan, Phoenix; Grant, George; Smith, Joshua D; Neale, Benjamin M; Purcell, Shaun; Butterworth, Adam S; Howson, Joanna M M; Lee, Heung Man; Lu, Yingchang; Kwak, Soo-Heon; Zhao, Wei; Danesh, John; Lam, Vincent K L; Park, Kyong Soo; Saleheen, Danish; So, Wing Yee; Tam, Claudia H T; Afzal, Uzma; Aguilar, David; Arya, Rector; Aung, Tin; Chan, Edmund; Navarro, Carmen; Cheng, Ching-Yu; Palli, Domenico; Correa, Adolfo; Curran, Joanne E; Rybin, Denis; Farook, Vidya S; Fowler, Sharon P; Freedman, Barry I; Griswold, Michael; Hale, Daniel Esten; Hicks, Pamela J; Khor, Chiea-Chuen; Kumar, Satish; Lehne, Benjamin; Thuillier, Dorothée; Lim, Wei Yen; Liu, Jianjun; van der Schouw, Yvonne T; Loh, Marie; Musani, Solomon K; Puppala, Sobha; Scott, William R; Yengo, Loïc; Tan, Sian-Tsung; Taylor, Herman A; Thameem, Farook; Wilson, Gregory; Wong, Tien Yin; Njølstad, Pål Rasmus; Levy, Jonathan C; Mangino, Massimo; Bonnycastle, Lori L; Schwarzmayr, Thomas; Fadista, João; Surdulescu, Gabriela L; Herder, Christian; Groves, Christopher J; Wieland, Thomas; Bork-Jensen, Jette; Brandslund, Ivan; Christensen, Cramer; Koistinen, Heikki A; Doney, Alex S F; Kinnunen, Leena; Esko, Tõnu; Farmer, Andrew J; Hakaste, Liisa; Hodgkiss, Dylan; Kravic, Jasmina; Lyssenko, Valeriya; Hollensted, Mette; Jørgensen, Marit E; Jørgensen, Torben; Ladenvall, Claes; Justesen, Johanne Marie; Käräjämäki, Annemari; Kriebel, Jennifer; Rathmann, Wolfgang; Lannfelt, Lars; Lauritzen, Torsten; Narisu, Narisu; Linneberg, Allan; Melander, Olle; Milani, Lili; Neville, Matt; Orho-Melander, Marju; Qi, Lu; Qi, Qibin; Roden, Michael; Rolandsson, Olov; Swift, Amy; Rosengren, Anders H; Stirrups, Kathleen; Wood, Andrew R; Mihailov, Evelin; Blancher, Christine; Carneiro, Mauricio O; Maguire, Jared; Poplin, Ryan; Shakir, Khalid; Fennell, Timothy; DePristo, Mark; de Angelis, Martin Hrabé; Deloukas, Panos; Gjesing, Anette P; Jun, Goo; Nilsson, Peter; Murphy, Jacquelyn; Onofrio, Robert; Thorand, Barbara; Hansen, Torben; Meisinger, Christa; Hu, Frank B; Isomaa, Bo; Karpe, Fredrik; Liang, Liming; Peters, Annette; Huth, Cornelia; O'Rahilly, Stephen P; Palmer, Colin N A; Pedersen, Oluf; Rauramaa, Rainer; Tuomilehto, Jaakko; Salomaa, Veikko; Watanabe, Richard M; Syvänen, Ann-Christine; Bergman, Richard N; Bharadwaj, Dwaipayan; Bottinger, Erwin P; Cho, Yoon Shin; Chandak, Giriraj R; Chan, Juliana C N; Chia, Kee Seng; Daly, Mark J; Ebrahim, Shah B; Langenberg, Claudia; Elliott, Paul; Jablonski, Kathleen A; Lehman, Donna M; Jia, Weiping; Ma, Ronald C W; Pollin, Toni I; Sandhu, Manjinder; Tandon, Nikhil; Froguel, Philippe; Barroso, Inês; Teo, Yik Ying; Zeggini, Eleftheria; Loos, Ruth J F; Small, Kerrin S; Ried, Janina S; DeFronzo, Ralph A; Grallert, Harald; Glaser, Benjamin; Metspalu, Andres; Wareham, Nicholas J; Walker, Mark; Banks, Eric; Gieger, Christian; Ingelsson, Erik; Im, Hae Kyung; Illig, Thomas; Franks, Paul W; Buck, Gemma; Trakalo, Joseph; Buck, David; Prokopenko, Inga; Mägi, Reedik; Lind, Lars; Farjoun, Yossi; Owen, Katharine R; Gloyn, Anna L; Strauch, Konstantin; Tuomi, Tiinamaija; Kooner, Jaspal Singh; Lee, Jong-Young; Park, Taesung; Donnelly, Peter; Morris, Andrew D; Hattersley, Andrew T; Bowden, Donald W; Collins, Francis S; Atzmon, Gil; Chambers, John C; Spector, Timothy D; Laakso, Markku; Strom, Tim M; Bell, Graeme I; Blangero, John; Duggirala, Ravindranath; Tai, E Shyong; McVean, Gilean; Hanis, Craig L; Wilson, James G; Seielstad, Mark; Frayling, Timothy M; Meigs, James B; Cox, Nancy J; Sladek, Rob; Lander, Eric S; Gabriel, Stacey; Burtt, Noël P; Mohlke, Karen L; Meitinger, Thomas; Groop, Leif; Abecasis, Goncalo; Florez, Jose C; Scott, Laura J; Morris, Andrew P; Kang, Hyun Min; Boehnke, Michael; Altshuler, David; McCarthy, Mark I

    2016-01-01

    The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes. PMID:27398621

  6. Genetic architecture: the shape of the genetic contribution to human traits and disease.

    Science.gov (United States)

    Timpson, Nicholas J; Greenwood, Celia M T; Soranzo, Nicole; Lawson, Daniel J; Richards, J Brent

    2018-02-01

    Genetic architecture describes the characteristics of genetic variation that are responsible for heritable phenotypic variability. It depends on the number of genetic variants affecting a trait, their frequencies in the population, the magnitude of their effects and their interactions with each other and the environment. Defining the genetic architecture of a complex trait or disease is central to the scientific and clinical goals of human genetics, which are to understand disease aetiology and aid in disease screening, diagnosis, prognosis and therapy. Recent technological advances have enabled genome-wide association studies and emerging next-generation sequencing studies to begin to decipher the nature of the heritable contribution to traits and disease. Here, we describe the types of genetic architecture that have been observed, how architecture can be measured and why an improved understanding of genetic architecture is central to future advances in the field.

  7. Genetic architecture of rainbow trout survival from egg to adult

    NARCIS (Netherlands)

    Vehvilainen, H.; Kause, A.; Quiton, C.; Kuukka-Anttila, H.; Koskinen, H.; Paananen, T.

    2010-01-01

    Survival from birth to a reproductive adult is a challenge that only robust individuals resistant to a variety of mortality factors will overcome. To assess whether survival traits share genetic architecture throughout the life cycle, we estimated genetic correlations for survival within fingerling

  8. Determination of nonlinear genetic architecture using compressed sensing.

    Science.gov (United States)

    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

  9. The Genetic Basis of Plant Architecture in 10 Maize Recombinant Inbred Line Populations.

    Science.gov (United States)

    Pan, Qingchun; Xu, Yuancheng; Li, Kun; Peng, Yong; Zhan, Wei; Li, Wenqiang; Li, Lin; Yan, Jianbing

    2017-10-01

    Plant architecture is a key factor affecting planting density and grain yield in maize ( Zea mays ). However, the genetic mechanisms underlying plant architecture in diverse genetic backgrounds have not been fully addressed. Here, we performed a large-scale phenotyping of 10 plant architecture-related traits and dissected the genetic loci controlling these traits in 10 recombinant inbred line populations derived from 14 diverse genetic backgrounds. Nearly 800 quantitative trait loci (QTLs) with major and minor effects were identified as contributing to the phenotypic variation of plant architecture-related traits. Ninety-two percent of these QTLs were detected in only one population, confirming the diverse genetic backgrounds of the mapping populations and the prevalence of rare alleles in maize. The numbers and effects of QTLs are positively associated with the phenotypic variation in the population, which, in turn, correlates positively with parental phenotypic and genetic variations. A large proportion (38.5%) of QTLs was associated with at least two traits, suggestive of the frequent occurrence of pleiotropic loci or closely linked loci. Key developmental genes, which previously were shown to affect plant architecture in mutant studies, were found to colocalize with many QTLs. Five QTLs were further validated using the segregating populations developed from residual heterozygous lines present in the recombinant inbred line populations. Additionally, one new plant height QTL, qPH3 , has been fine-mapped to a 600-kb genomic region where three candidate genes are located. These results provide insights into the genetic mechanisms controlling plant architecture and will benefit the selection of ideal plant architecture in maize breeding. © 2017 American Society of Plant Biologists. All Rights Reserved.

  10. Genetic architecture of ALS in Sardinia

    Science.gov (United States)

    Borghero, Giuseppe; Pugliatti, Maura; Marrosu, Francesco; Marrosu, Maria Giovanna; Murru, Maria Rita; Floris, Gianluca; Cannas, Antonino; Parish, Leslie D; Occhineri, Patrizia; Cau, Tea B.; Loi, Daniela; Ticca, Anna; Traccis, Sebastiano; Manera, Umberto; Canosa, Antonio; Moglia, Cristina; Calvo, Andrea; Barberis, Marco; Brunetti, Maura; Pliner, Hannah A; Renton, Alan E; Nalls, Mike A; Traynor, Bryan J; Restagno, Gabriella; Chiò, Adriano

    2014-01-01

    Conserved populations, such as Sardinians, displaying elevated rates of familial or sporadic ALS provide unique information on the genetics of the disease. Our aim was to describe the genetic profile of a consecutive series of ALS patients of Sardinian ancestry. All ALS patients of Sardinian ancestry, identified between 2008 and 2013 through the ITALSGEN consortium, were eligible to be included in the study. Patients and controls underwent the analysis of TARDBP, C9ORF72, SOD1, and FUS genes. Genetic mutations were identified in 155 out of 375 Sardinian ALS cases (41.3%), more commonly the p.A382T and p.G295S mutations of TARDBP, and the GGGGCC hexanucleotide repeat expansion of C9ORF72. One patient had both p.G295S and p.A382T mutation of TARDBP and eight carried both the heterozygous p.A382T mutation of TARDBP and a repeat expansion of C9ORF72. Patients carrying the p.A382T and the p.G295S mutations of TARDBP and the C9ORF72 repeat expansion shared distinct haplotypes across these loci. Patients with co-occurrence of C9ORF72 and TARDBP p.A382T missense mutation had a significantly lower age at onset and shorter survival. More than 40% of all cases on the island of Sardinia carry a mutation of an ALS-related gene, representing the highest percentage of ALS cases genetically explained outside of Scandinavia. Clinical phenotypes associated with different genetic mutations show some distinctive characteristics, but the heterogeneity between and among families carrying the same mutations implies that ALS manifestation is influenced by other genetic and non-genetic factors. PMID:25123918

  11. 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.

  12. Unraveling the genetic architecture of environmental variance of somatic cell score using high-density single nucleotide polymorphism and cow data from experimental farms

    NARCIS (Netherlands)

    Mulder, H.A.; Crump, R.E.; Calus, M.P.L.; Veerkamp, R.F.

    2013-01-01

    In recent years, it has been shown that not only is the phenotype under genetic control, but also the environmental variance. Very little, however, is known about the genetic architecture of environmental variance. The main objective of this study was to unravel the genetic architecture of the mean

  13. Bayesian dissection for genetic architecture of traits associated with ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-15

    Dec 15, 2009 ... Bayesian model selection technique was used to dissect genetic architecture for traits of interest. A total of 28 main-effect QTLs and 23 pairs of epistatic QTLs were detected for traits associated with nitrogen utilization efficiency. The proportions of phenotypic variation explained by the detected QTLs ranged.

  14. Genetic architecture of circulating lipid levels

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; Amin, Najaf; Isaacs, Aaron

    2011-01-01

    Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid...... the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify...... an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models...

  15. Formation process of Malaysian modern architecture under influence of nationalism

    OpenAIRE

    宇高, 雄志; 山崎, 大智

    2001-01-01

    This paper examines the Formation Process of Malaysian Modern Architecture under Influence of Nationalism,through the process of independence of Malaysia. The national style as "Malaysian national architecture" which hasengaged on background of political environment under the post colonial situation. Malaysian urban design is alsodetermined under the balance of both of ethnic culture and the national culture. In Malaysia, they decided to choosethe Malay ethnic culture as the national culture....

  16. The Genetic Architecture of Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Steven M. Prideaux

    2014-01-01

    Full Text Available Multiple myeloma is a malignant proliferation of monoclonal plasma cells leading to clinical features that include hypercalcaemia, renal dysfunction, anaemia, and bone disease (frequently referred to by the acronym CRAB which represent evidence of end organ failure. Recent evidence has revealed myeloma to be a highly heterogeneous disease composed of multiple molecularly-defined subtypes each with varying clinicopathological features and disease outcomes. The major division within myeloma is between hyperdiploid and nonhyperdiploid subtypes. In this division, hyperdiploid myeloma is characterised by trisomies of certain odd numbered chromosomes, namely, 3, 5, 7, 9, 11, 15, 19, and 21 whereas nonhyperdiploid myeloma is characterised by translocations of the immunoglobulin heavy chain alleles at chromosome 14q32 with various partner chromosomes, the most important of which being 4, 6, 11, 16, and 20. Hyperdiploid and nonhyperdiploid changes appear to represent early or even initiating mutagenic events that are subsequently followed by secondary aberrations including copy number abnormalities, additional translocations, mutations, and epigenetic modifications which lead to plasma cell immortalisation and disease progression. The following review provides a comprehensive coverage of the genetic and epigenetic events contributing to the initiation and progression of multiple myeloma and where possible these abnormalities have been linked to disease prognosis.

  17. The Genetic Architecture of Murine Glutathione Transferases.

    Directory of Open Access Journals (Sweden)

    Lu Lu

    Full Text Available Glutathione S-transferase (GST genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6 and DBA2/J (D2--the BXD family--was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01 with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes.

  18. Assessing the genetic architecture of epithelial ovarian cancer histological subtypes

    DEFF Research Database (Denmark)

    Cuellar-Partida, Gabriel; Lu, Yi; Dixon, Suzanne C

    2016-01-01

    Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent...... studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian...

  19. Genetic Architecture of Conspicuous Red Ornaments in Female Threespine Stickleback

    Directory of Open Access Journals (Sweden)

    Lengxob Yong

    2016-03-01

    Full Text Available Explaining the presence of conspicuous female ornaments that take the form of male-typical traits has been a longstanding challenge in evolutionary biology. Such female ornaments have been proposed to evolve via both adaptive and nonadaptive evolutionary processes. Determining the genetic underpinnings of female ornaments is important for elucidating the mechanisms by which such female traits arise and persist in natural populations, but detailed information about their genetic basis is still scarce. In this study, we investigated the genetic architecture of two ornaments, the orange-red throat and pelvic spine, in the threespine stickleback (Gasterosteus aculeatus. Throat coloration is male-specific in ancestral marine populations but has evolved in females in some derived stream populations, whereas sexual dimorphism in pelvic spine coloration is variable among populations. We find that ornaments share a common genetic architecture between the sexes. At least three independent genomic regions contribute to red throat coloration, and harbor candidate genes related to pigment production and pigment cell differentiation. One of these regions is also associated with spine coloration, indicating that both ornaments might be mediated partly via pleiotropic genetic mechanisms.

  20. Genetic analysis of agronomic traits associated with plant architecture by QTL mapping in maize.

    Science.gov (United States)

    Zheng, Z P; Liu, X H

    2013-04-17

    Maize (Zea mays L.) is one of the most important cereal crops worldwide, and increasing the grain yield and biomass has been among the most important goals of maize production. The plant architecture can determine the grain yield and biomass to some extent; however, the genetic basis of the link between the plant architecture and grain yield/biomass is unclear. In this study, an immortal F9 recombinant inbred line population, derived from the cross Mo17 x Huangzao4, was used to detect quantitative trait loci (QTLs) for 3 traits associated with plant architecture under two nitrogen regimes: plant height, ear height, and leaf number. As a result, 8 and 10 QTLs were identified under the high nitrogen regime and low nitrogen regime, respectively. These QTLs mapped to chromosomes 1 (six QTLs), 2 (one QTL), 3 (one QTL), 7 (two QTLs), and 9 (eight QTLs), and had different genetic distances to their closest markers, ranging from 0 to 22.0 cM, explaining 4.7 to 20.5% of the phenotypic variance. Because of an additive effect, 9 and 9 could make the phenotypic values of traits increase and decrease to some extent, respectively. These results are beneficial for understanding the genetic basis of agronomic traits associated with plant architecture and for performing marker-assisted selection in maize breeding programs.

  1. Improved multilayer OLED architecture using evolutionary genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Quirino, W.G. [LADOR - Laboratorio de Dispositivos Organicos, Dimat - Inmetro, Duque de Caxias, RJ (Brazil); Teixeira, K.C. [LADOR - Laboratorio de Dispositivos Organicos, Dimat - Inmetro, Duque de Caxias, RJ (Brazil); LOEM - Laboratorio de Optoeletronica Molecular, Physics Department, Pontifical Catholic University of Rio de Janeiro, 22453-900, Rio de Janeiro, RJ (Brazil); Legnani, C. [LADOR - Laboratorio de Dispositivos Organicos, Dimat - Inmetro, Duque de Caxias, RJ (Brazil); Calil, V.L. [LADOR - Laboratorio de Dispositivos Organicos, Dimat - Inmetro, Duque de Caxias, RJ (Brazil); LOEM - Laboratorio de Optoeletronica Molecular, Physics Department, Pontifical Catholic University of Rio de Janeiro, 22453-900, Rio de Janeiro, RJ (Brazil); Messer, B.; Neto, O.P. Vilela; Pacheco, M.A.C. [ICA - Laboratorio de Inteligencia Computacional Aplicada, Electrical Engineering Department, Pontifical Catholic University of Rio de Janeiro, 22451-900, Rio de Janeiro, RJ (Brazil); Cremona, M., E-mail: cremona@fis.puc-rio.b [LADOR - Laboratorio de Dispositivos Organicos, Dimat - Inmetro, Duque de Caxias, RJ (Brazil); LOEM - Laboratorio de Optoeletronica Molecular, Physics Department, Pontifical Catholic University of Rio de Janeiro, 22453-900, Rio de Janeiro, RJ (Brazil)

    2009-12-31

    Organic light-emitting diodes (OLEDs) constitute a new class of emissive devices, which present high efficiency and low voltage operation, among other advantages over current technology. Multilayer architecture (M-OLED) is generally used to optimize these devices, specially overcoming the suppression of light emission due to the exciton recombination near the metal layers. However, improvement in recombination, transport and charge injection can also be achieved by blending electron and hole transporting layers into the same one. Graded emissive region devices can provide promising results regarding quantum and power efficiency and brightness, as well. The massive number of possible model configurations, however, suggests that a search algorithm would be more suitable for this matter. In this work, multilayer OLEDs were simulated and fabricated using Genetic Algorithms (GAs) as evolutionary strategy to improve their efficiency. Genetic Algorithms are stochastic algorithms based on genetic inheritance and Darwinian strife to survival. In our simulations, it was assumed a 50 nm width graded region, divided into five equally sized layers. The relative concentrations of the materials within each layer were optimized to obtain the lower V/J{sup 0.5} ratio, where V is the applied voltage and J the current density. The best M-OLED architecture obtained by genetic algorithm presented a V/J{sup 0.5} ratio nearly 7% lower than the value reported in the literature. In order to check the experimental validity of the improved results obtained in the simulations, two M-OLEDs with different architectures were fabricated by thermal deposition in high vacuum environment. The results of the comparison between simulation and some experiments are presented and discussed.

  2. Improved multilayer OLED architecture using evolutionary genetic algorithm

    International Nuclear Information System (INIS)

    Quirino, W.G.; Teixeira, K.C.; Legnani, C.; Calil, V.L.; Messer, B.; Neto, O.P. Vilela; Pacheco, M.A.C.; Cremona, M.

    2009-01-01

    Organic light-emitting diodes (OLEDs) constitute a new class of emissive devices, which present high efficiency and low voltage operation, among other advantages over current technology. Multilayer architecture (M-OLED) is generally used to optimize these devices, specially overcoming the suppression of light emission due to the exciton recombination near the metal layers. However, improvement in recombination, transport and charge injection can also be achieved by blending electron and hole transporting layers into the same one. Graded emissive region devices can provide promising results regarding quantum and power efficiency and brightness, as well. The massive number of possible model configurations, however, suggests that a search algorithm would be more suitable for this matter. In this work, multilayer OLEDs were simulated and fabricated using Genetic Algorithms (GAs) as evolutionary strategy to improve their efficiency. Genetic Algorithms are stochastic algorithms based on genetic inheritance and Darwinian strife to survival. In our simulations, it was assumed a 50 nm width graded region, divided into five equally sized layers. The relative concentrations of the materials within each layer were optimized to obtain the lower V/J 0.5 ratio, where V is the applied voltage and J the current density. The best M-OLED architecture obtained by genetic algorithm presented a V/J 0.5 ratio nearly 7% lower than the value reported in the literature. In order to check the experimental validity of the improved results obtained in the simulations, two M-OLEDs with different architectures were fabricated by thermal deposition in high vacuum environment. The results of the comparison between simulation and some experiments are presented and discussed.

  3. Towards a genetic architecture of cryptic genetic variation and ...

    Indian Academy of Sciences (India)

    Unknown

    Under the guidance of Waddington, K. G. Bateman. (1959) repeated and extended the original experiments on the selection of the vein phenocopies in a ... of the anterior crossvein (acvl) as well as the ectopic ex- pression of additional crossveins. Bateman did indeed demonstrate that Waddington's initial observations for ...

  4. The quantitative genetic architecture of the bold-shy continuum in zebrafish, Danio rerio.

    Directory of Open Access Journals (Sweden)

    Mary E Oswald

    Full Text Available In studies of consistent individual differences (personality along the bold-shy continuum, a pattern of behavioral correlations frequently emerges: individuals towards the bold end of the continuum are more likely to utilize risky habitat, approach potential predators, and feed under risky conditions. Here, we address the hypothesis that observed phenotypic correlations among component behaviors of the bold-shy continuum are a result of underlying genetic correlations (quantitative genetic architecture. We used a replicated three-generation pedigree of zebrafish (Danio rerio to study three putative components of the bold-shy continuum: horizontal position, swim level, and feeding latency. We detected significant narrow-sense heritabilities as well as significant genetic and phenotypic correlations among all three behaviors, such that fish selected for swimming at the front of the tank swam closer to the observer, swam higher in the water column, and fed more quickly than fish selected for swimming at the back of the tank. Further, the lines varied in their initial open field behavior (swim level and activity level. The quantitative genetic architecture of the bold-shy continuum indicates that the multivariate behavioral phenotype characteristic of a "bold" personality type may be a result of correlated evolution via underlying genetic correlations.

  5. Alleles versus mutations: Understanding the evolution of genetic architecture requires a molecular perspective on allelic origins.

    Science.gov (United States)

    Remington, David L

    2015-12-01

    Perspectives on the role of large-effect quantitative trait loci (QTL) in the evolution of complex traits have shifted back and forth over the past few decades. Different sets of studies have produced contradictory insights on the evolution of genetic architecture. I argue that much of the confusion results from a failure to distinguish mutational and allelic effects, a limitation of using the Fisherian model of adaptive evolution as the lens through which the evolution of adaptive variation is examined. A molecular-based perspective reveals that allelic differences can involve the cumulative effects of many mutations plus intragenic recombination, a model that is supported by extensive empirical evidence. I discuss how different selection regimes could produce very different architectures of allelic effects under a molecular-based model, which may explain conflicting insights on genetic architecture from studies of variation within populations versus between divergently selected populations. I address shortcomings of genome-wide association study (GWAS) practices in light of more suitable models of allelic evolution, and suggest alternate GWAS strategies to generate more valid inferences about genetic architecture. Finally, I discuss how adopting more suitable models of allelic evolution could help redirect research on complex trait evolution toward addressing more meaningful questions in evolutionary biology. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  6. The Molecular Genetic Architecture of Self-Employment

    Science.gov (United States)

    van der Loos, Matthijs J. H. M.; Rietveld, Cornelius A.; Eklund, Niina; Koellinger, Philipp D.; Rivadeneira, Fernando; Abecasis, Gonçalo R.; Ankra-Badu, Georgina A.; Baumeister, Sebastian E.; Benjamin, Daniel J.; Biffar, Reiner; Blankenberg, Stefan; Boomsma, Dorret I.; Cesarini, David; Cucca, Francesco; de Geus, Eco J. C.; Dedoussis, George; Deloukas, Panos; Dimitriou, Maria; Eiriksdottir, Guðny; Eriksson, Johan; Gieger, Christian; Gudnason, Vilmundur; Höhne, Birgit; Holle, Rolf; Hottenga, Jouke-Jan; Isaacs, Aaron; Järvelin, Marjo-Riitta; Johannesson, Magnus; Kaakinen, Marika; Kähönen, Mika; Kanoni, Stavroula; Laaksonen, Maarit A.; Lahti, Jari; Launer, Lenore J.; Lehtimäki, Terho; Loitfelder, Marisa; Magnusson, Patrik K. E.; Naitza, Silvia; Oostra, Ben A.; Perola, Markus; Petrovic, Katja; Quaye, Lydia; Raitakari, Olli; Ripatti, Samuli; Scheet, Paul; Schlessinger, David; Schmidt, Carsten O.; Schmidt, Helena; Schmidt, Reinhold; Senft, Andrea; Smith, Albert V.; Spector, Timothy D.; Surakka, Ida; Svento, Rauli; Terracciano, Antonio; Tikkanen, Emmi; van Duijn, Cornelia M.; Viikari, Jorma; Völzke, Henry; Wichmann, H. -Erich; Wild, Philipp S.; Willems, Sara M.; Willemsen, Gonneke; van Rooij, Frank J. A.; Groenen, Patrick J. F.; Uitterlinden, André G.; Hofman, Albert; Thurik, A. Roy

    2013-01-01

    Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable–entrepreneurship–that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg 2/σP 2 = 25%, h 2 = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with pentrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases. PMID:23593239

  7. The molecular genetic architecture of self-employment.

    Directory of Open Access Journals (Sweden)

    Matthijs J H M van der Loos

    Full Text Available Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g(2/σ(P(2 = 25%, h(2 = 55%. However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10(-5 were tested in a replication sample (n = 3,271, but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039. Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.

  8. Genetic architecture of gene expression in ovine skeletal muscle.

    Science.gov (United States)

    Kogelman, Lisette J A; Byrne, Keren; Vuocolo, Tony; Watson-Haigh, Nathan S; Kadarmideen, Haja N; Kijas, James W; Oddy, Hutton V; Gardner, Graham E; Gondro, Cedric; Tellam, Ross L

    2011-12-15

    In livestock populations the genetic contribution to muscling is intensively monitored in the progeny of industry sires and used as a tool in selective breeding programs. The genes and pathways conferring this genetic merit are largely undefined. Genetic variation within a population has potential, amongst other mechanisms, to alter gene expression via cis- or trans-acting mechanisms in a manner that impacts the functional activities of specific pathways that contribute to muscling traits. By integrating sire-based genetic merit information for a muscling trait with progeny-based gene expression data we directly tested the hypothesis that there is genetic structure in the gene expression program in ovine skeletal muscle. The genetic performance of six sires for a well defined muscling trait, longissimus lumborum muscle depth, was measured using extensive progeny testing and expressed as an Estimated Breeding Value by comparison with contemporary sires. Microarray gene expression data were obtained for longissimus lumborum samples taken from forty progeny of the six sires (4-8 progeny/sire). Initial unsupervised hierarchical clustering analysis revealed strong genetic architecture to the gene expression data, which also discriminated the sire-based Estimated Breeding Value for the trait. An integrated systems biology approach was then used to identify the major functional pathways contributing to the genetics of enhanced muscling by using both Estimated Breeding Value weighted gene co-expression network analysis and a differential gene co-expression network analysis. The modules of genes revealed by these analyses were enriched for a number of functional terms summarised as muscle sarcomere organisation and development, protein catabolism (proteosome), RNA processing, mitochondrial function and transcriptional regulation. This study has revealed strong genetic structure in the gene expression program within ovine longissimus lumborum muscle. The balance between

  9. Sex differences in genetic architecture of complex phenotypes?

    Directory of Open Access Journals (Sweden)

    Jacqueline M Vink

    Full Text Available We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA studies of complex phenotypes. If different genes play a role across sex, GWA studies should consider the effect of genetic variants separately in men and women, which affects statistical power. Twin and family studies offer an opportunity to compare resemblance between opposite-sex family members to the resemblance between same-sex relatives, thereby presenting a test of quantitative and qualitative sex differences in the genetic architecture of complex traits. We analyzed data on lifestyle, personality, psychiatric disorder, health, growth, development and metabolic traits in dizygotic (DZ same-sex and opposite-sex twins, as these siblings are perfectly matched for age and prenatal exposures. Sample size varied from slightly over 300 subjects for measures of brain function such as EEG power to over 30,000 subjects for childhood psychopathology and birth weight. For most phenotypes, sample sizes were large, with an average sample size of 9027 individuals. By testing whether the resemblance in DZ opposite-sex pairs is the same as in DZ same-sex pairs, we obtain evidence for genetic qualitative sex-differences in the genetic architecture of complex traits for 4% of phenotypes. We conclude that for most traits that were examined, the current evidence is that same the genes are operating in men and women.

  10. Genetic architecture of male sterility and segregation distortion in Drosophila pseudoobscura Bogota-USA hybrids.

    Science.gov (United States)

    Phadnis, Nitin

    2011-11-01

    Understanding the genetic basis of reproductive isolation between recently diverged species is a central problem in evolutionary genetics. Here, I present analyses of the genetic architecture underlying hybrid male sterility and segregation distortion between the Bogota and USA subspecies of Drosophila pseudoobscura. Previously, a single gene, Overdrive (Ovd), was shown to be necessary but not sufficient for both male sterility and segregation distortion in F(1) hybrids between these subspecies, requiring several interacting partner loci for full manifestation of hybrid phenomena. I map these partner loci separately on the Bogota X chromosome and USA autosomes using a combination of different mapping strategies. I find that hybrid sterility involves a single hybrid incompatibility of at least seven interacting partner genes that includes three large-effect loci. Segregation distortion involves three loci on the Bogota X chromosome and one locus on the autosomes. The genetic bases of hybrid sterility and segregation distortion are at least partially--but not completely--overlapping. My results lay the foundation for fine-mapping experiments to identify the complete set of genes that interact with Overdrive. While individual genes that cause hybrid sterility or inviability have been identified in a few cases, my analysis provides a comprehensive look at the genetic architecture of all components of a hybrid incompatibility underlying F(1) hybrid sterility. Such an analysis would likely be unfeasible for most species pairs due to their divergence time and emphasizes the importance of young species pairs such as the D. pseudoobscura subspecies studied here.

  11. Genetic architecture of winter hardiness and frost tolerance in triticale.

    Directory of Open Access Journals (Sweden)

    Wenxin Liu

    Full Text Available Abiotic stress experienced by autumn-sown crops during winter is of great economic importance as it can have a severe negative impact on yield. In this study, we investigated the genetic architecture of winter hardiness and frost tolerance in triticale. To this end, we used a large mapping population of 647 DH lines phenotyped for both traits in combination with genome-wide marker data. Employing multiple-line cross QTL mapping, we identified nine main effect QTL for winter hardiness and frost tolerance of which six were overlapping between both traits. Three major QTL were identified on chromosomes 5A, 1B and 5R. In addition, an epistasis scan revealed the contribution of epistasis to the genetic architecture of winter hardiness and frost tolerance in triticale. Taken together, our results show that winter hardiness and frost tolerance are complex traits that can be improved by phenotypic selection, but also that genomic approaches hold potential for a knowledge-based improvement of these important traits in elite triticale germplasm.

  12. Genetic architecture of gene transcription in two Atlantic salmon (Salmo salar) populations.

    Science.gov (United States)

    He, X; Houde, A L S; Pitcher, T E; Heath, D D

    2017-08-01

    Gene expression regulation has an important role in short-term acclimation and long-term adaptation to changing environments. However, the genetic architecture of gene expression has received much less attention than that of traditional phenotypic traits. In this study, we used a 5 × 5 full-factorial breeding design within each of two Atlantic salmon (Salmo salar) populations to characterize the genetic architecture of gene transcription. The two populations (LaHave and Sebago) are being used for reintroduction efforts into Lake Ontario, Canada. We used high-throughput quantitative real-time PCR to measure gene transcription levels for 22 genes in muscle tissue of Atlantic salmon fry. We tested for population differences in gene transcription and partitioned the transcription variance into additive genetic, non-additive genetic and maternal effects within each population. Interestingly, average additive genetic effects for gene transcription were smaller than those reported for traditional phenotypic traits in salmonids, suggesting that the evolutionary potential of gene transcription is lower than that of traditional traits. Contrary to expectations for early life stage traits, maternal effects were small. In general, the LaHave population had higher additive genetic effects for gene transcription than the Sebago population had, indicating that the LaHave fish have a higher adaptive potential to respond to the novel selection pressures associated with reintroduction into a novel environment. This study highlights not only the profound variation in gene transcription possible among salmonid populations but also the among-population variation in the underlying genetic architecture of such traits.

  13. The genetic architecture of UV floral patterning in sunflower.

    Science.gov (United States)

    Moyers, Brook T; Owens, Gregory L; Baute, Gregory J; Rieseberg, Loren H

    2017-07-01

    The patterning of floral ultraviolet (UV) pigmentation varies both intra- and interspecifically in sunflowers and many other plant species, impacts pollinator attraction, and can be critical to reproductive success and crop yields. However, the genetic basis for variation in UV patterning is largely unknown. This study examines the genetic architecture for proportional and absolute size of the UV bullseye in Helianthus argophyllus , a close relative of the domesticated sunflower. A camera modified to capture UV light (320-380 nm) was used to phenotype floral UV patterning in an F 2 mapping population, then quantitative trait loci (QTL) were identified using genotyping-by-sequencing and linkage mapping. The ability of these QTL to predict the UV patterning of natural population individuals was also assessed. Proportional UV pigmentation is additively controlled by six moderate effect QTL that are predictive of this phenotype in natural populations. In contrast, UV bullseye size is controlled by a single large effect QTL that also controls flowerhead size and co-localizes with a major flowering time QTL in Helianthus . The co-localization of the UV bullseye size QTL, flowerhead size QTL and a previously known flowering time QTL may indicate a single highly pleiotropic locus or several closely linked loci, which could inhibit UV bullseye size from responding to selection without change in correlated characters. The genetic architecture of proportional UV pigmentation is relatively simple and different from that of UV bullseye size, and so should be able to respond to natural or artificial selection independently. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  14. Conservatism and novelty in the genetic architecture of adaptation in Heliconius butterflies.

    Science.gov (United States)

    Huber, B; Whibley, A; Poul, Y L; Navarro, N; Martin, A; Baxter, S; Shah, A; Gilles, B; Wirth, T; McMillan, W O; Joron, M

    2015-05-01

    Understanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima.

  15. Genetic architecture of carbon isotope composition and growth in Eucalyptus across multiple environments.

    Science.gov (United States)

    Bartholomé, Jérôme; Mabiala, André; Savelli, Bruno; Bert, Didier; Brendel, Oliver; Plomion, Christophe; Gion, Jean-Marc

    2015-06-01

    In the context of climate change, the water-use efficiency (WUE) of highly productive tree varieties, such as eucalypts, has become a major issue for breeding programmes. This study set out to dissect the genetic architecture of carbon isotope composition (δ(13) C), a proxy of WUE, across several environments. A family of Eucalyptus urophylla × E. grandis was planted in three trials and phenotyped for δ(13) C and growth traits. High-resolution genetic maps enabled us to target genomic regions underlying δ(13) C quantitative trait loci (QTLs) on the E. grandis genome. Of the 15 QTLs identified for δ(13) C, nine were stable across the environments and three displayed significant QTL-by-environment interaction, suggesting medium to high genetic determinism for this trait. Only one colocalization was found between growth and δ(13) C. Gene ontology (GO) term enrichment analysis suggested candidate genes related to foliar δ(13) C, including two involved in the regulation of stomatal movements. This study provides the first report of the genetic architecture of δ(13) C and its relation to growth in Eucalyptus. The low correlations found between the two traits at phenotypic and genetic levels suggest the possibility of improving the WUE of Eucalyptus varieties without having an impact on breeding for growth. © 2015 CIRAD. New Phytologist © 2015 New Phytologist Trust.

  16. Genetic architecture of variation in the lateral line sensory system of threespine sticklebacks.

    Science.gov (United States)

    Wark, Abigail R; Mills, Margaret G; Dang, Lam-Ha; Chan, Yingguang Frank; Jones, Felicity C; Brady, Shannon D; Absher, Devin M; Grimwood, Jane; Schmutz, Jeremy; Myers, Richard M; Kingsley, David M; Peichel, Catherine L

    2012-09-01

    Vertebrate sensory systems have evolved remarkable diversity, but little is known about the underlying genetic mechanisms. The lateral line sensory system of aquatic vertebrates is a promising model for genetic investigations of sensory evolution because there is extensive variation within and between species, and this variation is easily quantified. In the present study, we compare the lateral line sensory system of threespine sticklebacks (Gasterosteus aculeatus) from an ancestral marine and a derived benthic lake population. We show that lab-raised individuals from these populations display differences in sensory neuromast number, neuromast patterning, and groove morphology. Using genetic linkage mapping, we identify regions of the genome that influence different aspects of lateral line morphology. Distinct loci independently affect neuromast number on different body regions, suggesting that a modular genetic structure underlies the evolution of peripheral receptor number in this sensory system. Pleiotropy and/or tight linkage are also important, as we identify a region on linkage group 21 that affects multiple aspects of lateral line morphology. Finally, we detect epistasis between a locus on linkage group 4 and a locus on linkage group 21; interactions between these loci contribute to variation in neuromast pattern. Our results reveal a complex genetic architecture underlying the evolution of the stickleback lateral line sensory system. This study further uncovers a genetic relationship between sensory morphology and non-neural traits (bony lateral plates), creating an opportunity to investigate morphological constraints on sensory evolution in a vertebrate model system.

  17. The genetic architecture of fitness in a seed beetle: assessing the potential for indirect genetic benefits of female choice

    DEFF Research Database (Denmark)

    Bilde, T.; Friberg, U.; Maklakov, A.A.

    2008-01-01

    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......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...

  18. Integrative genetic analysis suggests that skin color modifies the genetic architecture of melanoma.

    Science.gov (United States)

    Hulur, Imge; Skol, Andrew D; Gamazon, Eric R; Cox, Nancy J; Onel, Kenan

    2017-01-01

    Melanoma is the deadliest form of skin cancer and presents a significant health care burden in many countries. In addition to ultraviolet radiation in sunlight, the main causal factor for melanoma, genetic factors also play an important role in melanoma susceptibility. Although genome-wide association studies have identified many single nucleotide polymorphisms associated with melanoma, little is known about the proportion of disease risk attributable to these loci and their distribution throughout the genome. Here, we investigated the genetic architecture of melanoma in 1,888 cases and 990 controls of European non-Hispanic ancestry. We estimated the overall narrow-sense heritability of melanoma to be 0.18 (P < 0.03), indicating that genetics contributes significantly to the risk of sporadically-occurring melanoma. We then demonstrated that only a small proportion of this risk is attributable to known risk variants, suggesting that much remains unknown of the role of genetics in melanoma. To investigate further the genetic architecture of melanoma, we partitioned the heritability by chromosome, minor allele frequency, and functional annotations. We showed that common genetic variation contributes significantly to melanoma risk, with a risk model defined by a handful of genomic regions rather than many risk loci distributed throughout the genome. We also demonstrated that variants affecting gene expression in skin account for a significant proportion of the heritability, and are enriched among melanoma risk loci. Finally, by incorporating skin color into our analyses, we observed both a shift in significance for melanoma-associated loci and an enrichment of expression quantitative trait loci among melanoma susceptibility variants. These findings suggest that skin color may be an important modifier of melanoma risk. We speculate that incorporating skin color and other non-genetic factors into genetic studies may allow for an improved understanding of melanoma

  19. Genetic architecture of obesity and related metabolic traits-recent insights from isolated populations.

    Science.gov (United States)

    Andersen, Mette Korre; Grarup, Niels; Moltke, Ida; Albrechtsen, Anders; Hansen, Torben

    2018-03-03

    In this mini-review, we give an overview of what is known about the genetic architecture of obesity and related metabolic traits with a primary focus on recent insights from studies of historically small and isolated populations. We start by briefly explaining what genetic architecture is and why studies of isolated populations in general are valuable if we want a complete picture of the genetic architecture of diseases and other traits among humans. Then we contrast what is known about the genetic architecture of obesity and related metabolic traits among large outbred populations, like Europeans, with results from recent studies of isolated populations. Finally, we briefly discuss the perspectives of studying isolated populations to gain insight into genetic architecture in humans. Copyright © 2018. Published by Elsevier Ltd.

  20. Urban landscape architecture design under the view of sustainable development

    Science.gov (United States)

    Chen, WeiLin

    2017-08-01

    The concept of sustainable development in modern city landscape design advocates landscape architecture, which is the main development direction in the field of landscape design. They are also effective measures to promote the sustainable development of city garden. Based on this, combined with the connotation of sustainable development and sustainable design, this paper analyzes and discusses the design of urban landscape under the concept of sustainable development.

  1. Development and Genetic Control of Plant Architecture and Biomass in the Panicoid Grass, Setaria.

    Directory of Open Access Journals (Sweden)

    Margarita Mauro-Herrera

    Full Text Available The architecture of a plant affects its ability to compete for light and to respond to environmental stresses, thus affecting overall fitness and productivity. Two components of architecture, branching and height, were studied in 182 F7 recombinant inbred lines (RILs at the vegetative, flowering and mature developmental stages in the panicoid C4 model grass system, Setaria. The RIL population was derived from a cross between domesticated S. italica (foxtail millet and its wild relative S. viridis (green foxtail. In both field and greenhouse trials the wild parent was taller initially, started branching earlier, and flowered earlier, while the domesticated parent was shorter initially, but flowered later, producing a robust tall plant architecture with more nodes and leaves on the main culm and few or no branches. Biomass was highly correlated with height of the plant and number of nodes on the main culm, and generally showed a negative relationship with branch number. However, several of the RILs with the highest biomass in both trials were significantly more branched than the domesticated parent of the cross. Quantitative trait loci (QTL analyses indicate that both height and branching are controlled by multiple genetic regions, often with QTL for both traits colocalizing in the same genomic regions. Genomic positions of several QTL colocalize with QTL in syntenic regions in other species and contain genes known to control branching and height in sorghum, maize, and switchgrass. Included in these is the ortholog of the rice SD-1 semi-dwarfing gene, which underlies one of the major Setaria height QTL. Understanding the relationships between height and branching patterns in Setaria, and their genetic control, is an important step to gaining a comprehensive knowledge of the development and genetic regulation of panicoid grass architecture.

  2. Genetic architecture of skin and eye color in an African-European admixed population.

    Directory of Open Access Journals (Sweden)

    Sandra Beleza

    2013-03-01

    Full Text Available Variation in human skin and eye color is substantial and especially apparent in admixed populations, yet the underlying genetic architecture is poorly understood because most genome-wide studies are based on individuals of European ancestry. We study pigmentary variation in 699 individuals from Cape Verde, where extensive West African/European admixture has given rise to a broad range in trait values and genomic ancestry proportions. We develop and apply a new approach for measuring eye color, and identify two major loci (HERC2[OCA2] P = 2.3 × 10(-62, SLC24A5 P = 9.6 × 10(-9 that account for both blue versus brown eye color and varying intensities of brown eye color. We identify four major loci (SLC24A5 P = 5.4 × 10(-27, TYR P = 1.1 × 10(-9, APBA2[OCA2] P = 1.5 × 10(-8, SLC45A2 P = 6 × 10(-9 for skin color that together account for 35% of the total variance, but the genetic component with the largest effect (~44% is average genomic ancestry. Our results suggest that adjacent cis-acting regulatory loci for OCA2 explain the relationship between skin and eye color, and point to an underlying genetic architecture in which several genes of moderate effect act together with many genes of small effect to explain ~70% of the estimated heritability.

  3. Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures

    Science.gov (United States)

    Koch, Manja; Baurecht, Hansjörg; Ried, Janina S.; Rodriguez, Elke; Schlesinger, Sabrina; Volks, Natalie; Gieger, Christian; Rückert, Ina-Maria; Heinrich, Luise; Willenborg, Christina; Smith, Catherine; Peters, Annette; Thorand, Barbara; Koenig, Wolfgang; Lamina, Claudia; Jansen, Henning; Kronenberg, Florian; Seissler, Jochen; Thiery, Joachim; Rathmann, Wolfgang; Schunkert, Heribert; Erdmann, Jeanette; Barker, Jonathan; Nair, Rajan P; Tsoi, Lam C; Elder, James T; Mrowietz, Ulrich; Weichenthal, Michael; Mucha, Sören; Schreiber, Stefan; Franke, Andre; Schmitt, Jochen; Lieb, Wolfgang; Weidinger, Stephan

    2015-01-01

    Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4.185) and a prospective cohort of German Health Insurance beneficiaries (n=1.811.098). A potential genetic overlap was explored using genome-wide data from >22.000 coronary artery disease (CAD) and >4.000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3.717 controls. Controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odd’s ratio OR=2.36; 95% confidence interval CI=1.26–4.41) and myocardial infarction (MI, OR=2.26, 95% CI=1.03–4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk RR=1.11; 95%CI=1.08–1.14) and MI (RR=1.14; 95%CI=1.06–1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the MHC, there was no evidence for genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct. PMID:25599394

  4. Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes.

    Directory of Open Access Journals (Sweden)

    Esterina ePascale

    2016-04-01

    Full Text Available The microtubule-associated protein tau (MAPT region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease. Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; 2 =9.9; OR,1.7; 95% CI, 1.2-2.4; p=0.002. The effect was more evident in non tremor dominant PD subjects (NTD-PD (82 vs 69.5%; 2 =13.6; OR, 2.03; 95% CI, 1.4-3; p=0.0003, while no difference emerged between PD subgroup of tremor dominant patients (TD-PD and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p=0.007, OR 2.9; 95%CI 1.3-6.3. Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype.

  5. Genetic Architecture and Candidate Genes Identified for Follicle Number in Chicken.

    Science.gov (United States)

    Shen, Manman; Sun, Hongyan; Qu, Liang; Ma, Meng; Dou, Taocun; Lu, Jian; Guo, Jun; Hu, Yuping; Wang, Xingguo; Li, Yongfeng; Wang, Kehua; Yang, Ning

    2017-11-27

    Follicular development has a major impact on reproductive performance. Most previous researchers focused on molecular mechanisms of follicular development. The genetic architecture underlying the number of follicle, however, has yet not to be thoroughly defined in chicken. Here we report a genome-wide association study for the genetic architecture determining the numbers of follicles in a large F 2 resource population. The results showed heritability were low to moderate (0.05-0.28) for number of pre-ovulatory follicles (POF), small yellow follicles (SYF) and atresia follicles (AF). The highly significant SNPs associated with SYF were mainly located on GGA17 and GGA28. Only four significant SNPs were identified for POF on GGA1. The variance partitioned across chromosomes and chromosome lengths had a linear relationship for SYF (R 2  = 0.58). The enriched genes created by the closest correspondent significant SNPs were found to be involved in biological pathways related to cell proliferation, cell cycle and cell survival. Two promising candidate genes, AMH and RGS3, were suggested to be prognostic biomarkers for SYF. In conclusion, this study offers the first evidence of genetic variance and positional candidate genes which influence the number of SYF in chicken. These identified informative SNPs may facilitate selection for an improved reproductive performance of laying hens.

  6. Improved reactor regulating system logical architecture using genetic algorithm

    Directory of Open Access Journals (Sweden)

    Hyo-Sub Shim

    2017-12-01

    Full Text Available An improved Reactor Regulating System (RRS logic architecture, which is combined with genetic algorithm (GA, is implemented in this work. It is devised to provide an optimal solution to the current RRS. The current system works desirably and has contributed to safe and stable nuclear power plant operation. However, during the ascent and descent section of the reactor power, the RRS output reveals a relatively high steady-state error, and the output also carries a considerable level of overshoot. In an attempt to consolidate conservatism and minimize the error, this work proposes to apply GA to RRS and suggests reconfiguring the system. Prior to the use of GA, reverse engineering is implemented to build a Simulink-based RRS model. Reengineering is followed to produce a newly configured RRS to generate an output that has a reduced steady-state error and diminished overshoot level. A full-scope APR1400 simulator is used to examine the dynamic behaviors of RRS and to build the RRS Simulink model.

  7. Mapping the genetic architecture of gene expression in human liver.

    Directory of Open Access Journals (Sweden)

    Eric E Schadt

    2008-05-01

    Full Text Available Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large

  8. Effect of genetic architecture on the prediction accuracy of quantitative traits in samples of unrelated individuals.

    Science.gov (United States)

    Morgante, Fabio; Huang, Wen; Maltecca, Christian; Mackay, Trudy F C

    2018-02-10

    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.

  9. Genetic architecture of age at maturity can generate divergent and disruptive harvest-induced evolution.

    Science.gov (United States)

    Kuparinen, Anna; Hutchings, Jeffrey A

    2017-01-19

    Life-history traits are generally assumed to be inherited quantitatively. Fishing that targets large, old individuals is expected to decrease age at maturity. In Atlantic salmon (Salmo salar), it has recently been discovered that sea age at maturity is under strong control by a single locus with sexually dimorphic expression of heterozygotes, which makes it less intuitive to predict how life histories respond to selective fishing. We explore evolutionary responses to fishing in Atlantic salmon, using eco-evolutionary simulations with two alternative scenarios for the genetic architecture of age at maturity: (i) control by multiple loci with additive effects and (ii) control by one locus with sexually dimorphic expression. We show that multi-locus control leads to unidirectional evolution towards earlier maturation, whereas single-locus control causes largely divergent and disruptive evolution of age at maturity without a clear phenotypic trend but a wide range of alternative evolutionary trajectories and greater trait variability within trajectories. Our results indicate that the range of evolutionary responses to selective fishing can be wider than previously thought and that a lack of phenotypic trend need not imply that evolution has not occurred. These findings underscore the role of genetic architecture of life-history traits in understanding how human-induced selection can shape target populations.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).

  10. Genetic architecture of wild soybean (Glycine soja) response to soybean cyst nematode (Heterodera glycines).

    Science.gov (United States)

    Zhang, Hengyou; Song, Qijian; Griffin, Joshua D; Song, Bao-Hua

    2017-12-01

    The soybean cyst nematode (SCN) is one of the most destructive pathogens of soybean plants worldwide. Host-plant resistance is an environmentally friendly method to mitigate SCN damage. To date, the resistant soybean cultivars harbor limited genetic variation, and some are losing resistance. Thus, a better understanding of the genetic mechanisms of the SCN resistance, as well as developing diverse resistant soybean cultivars, is urgently needed. In this study, a genome-wide association study (GWAS) was conducted using 1032 wild soybean (Glycine soja) accessions with over 42,000 single-nucleotide polymorphisms (SNPs) to understand the genetic architecture of G. soja resistance to SCN race 1. Ten SNPs were significantly associated with the response to race 1. Three SNPs on chromosome 18 were localized within the previously identified quantitative trait loci (QTLs), and two of which were localized within a strong linkage disequilibrium block encompassing a nucleotide-binding (NB)-ARC disease resistance gene (Glyma.18G102600). Genes encoding methyltransferases, the calcium-dependent signaling protein, the leucine-rich repeat kinase family protein, and the NB-ARC disease resistance protein, were identified as promising candidate genes. The identified SNPs and candidate genes can not only shed light on the molecular mechanisms underlying SCN resistance, but also can facilitate soybean improvement employing wild genetic resources.

  11. Genetic architecture of artemisinin-resistant Plasmodium falciparum

    Science.gov (United States)

    Miotto, Olivo; Amato, Roberto; Ashley, Elizabeth A; MacInnis, Bronwyn; Almagro-Garcia, Jacob; Amaratunga, Chanaki; Lim, Pharath; Mead, Daniel; Oyola, Samuel O; Dhorda, Mehul; Imwong, Mallika; Woodrow, Charles; Manske, Magnus; Stalker, Jim; Drury, Eleanor; Campino, Susana; Amenga-Etego, Lucas; Thanh, Thuy-Nhien Nguyen; Tran, Hien Tinh; Ringwald, Pascal; Bethell, Delia; Nosten, Francois; Phyo, Aung Pyae; Pukrittayakamee, Sasithon; Chotivanich, Kesinee; Chuor, Char Meng; Nguon, Chea; Suon, Seila; Sreng, Sokunthea; Newton, Paul N; Mayxay, Mayfong; Khanthavong, Maniphone; Hongvanthong, Bouasy; Htut, Ye; Han, Kay Thwe; Kyaw, Myat Phone; Faiz, Md Abul; Fanello, Caterina I; Onyamboko, Marie; Mokuolu, Olugbenga A; Jacob, Christopher G; Takala-Harrison, Shannon; Plowe, Christopher V; Day, Nicholas P; Dondorp, Arjen M; Spencer, Chris C A; McVean, Gilean; Fairhurst, Rick M; White, Nicholas J; Kwiatkowski, Dominic P

    2015-01-01

    We report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin, the frontline antimalarial drug. Across 15 locations in Southeast Asia, we identified at least 20 mutations in kelch13 (PF3D7_1343700) affecting the encoded propeller and BTB/POZ domains, which were associated with a slow parasite clearance rate after treatment with artemisinin derivatives. Nonsynonymous polymorphisms in fd (ferredoxin), arps10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt (chloroquine resistance transporter) also showed strong associations with artemisinin resistance. Analysis of the fine structure of the parasite population showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic background on which kelch13 mutations are particularly likely to arise and that they correlate with the contemporary geographical boundaries and population frequencies of artemisinin resistance. These findings indicate that the risk of new resistance-causing mutations emerging is determined by specific predisposing genetic factors in the underlying parasite population. PMID:25599401

  12. Genetic architecture of artemisinin-resistant Plasmodium falciparum.

    Science.gov (United States)

    Miotto, Olivo; Amato, Roberto; Ashley, Elizabeth A; MacInnis, Bronwyn; Almagro-Garcia, Jacob; Amaratunga, Chanaki; Lim, Pharath; Mead, Daniel; Oyola, Samuel O; Dhorda, Mehul; Imwong, Mallika; Woodrow, Charles; Manske, Magnus; Stalker, Jim; Drury, Eleanor; Campino, Susana; Amenga-Etego, Lucas; Thanh, Thuy-Nhien Nguyen; Tran, Hien Tinh; Ringwald, Pascal; Bethell, Delia; Nosten, Francois; Phyo, Aung Pyae; Pukrittayakamee, Sasithon; Chotivanich, Kesinee; Chuor, Char Meng; Nguon, Chea; Suon, Seila; Sreng, Sokunthea; Newton, Paul N; Mayxay, Mayfong; Khanthavong, Maniphone; Hongvanthong, Bouasy; Htut, Ye; Han, Kay Thwe; Kyaw, Myat Phone; Faiz, Md Abul; Fanello, Caterina I; Onyamboko, Marie; Mokuolu, Olugbenga A; Jacob, Christopher G; Takala-Harrison, Shannon; Plowe, Christopher V; Day, Nicholas P; Dondorp, Arjen M; Spencer, Chris C A; McVean, Gilean; Fairhurst, Rick M; White, Nicholas J; Kwiatkowski, Dominic P

    2015-03-01

    We report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin, the frontline antimalarial drug. Across 15 locations in Southeast Asia, we identified at least 20 mutations in kelch13 (PF3D7_1343700) affecting the encoded propeller and BTB/POZ domains, which were associated with a slow parasite clearance rate after treatment with artemisinin derivatives. Nonsynonymous polymorphisms in fd (ferredoxin), arps10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt (chloroquine resistance transporter) also showed strong associations with artemisinin resistance. Analysis of the fine structure of the parasite population showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic background on which kelch13 mutations are particularly likely to arise and that they correlate with the contemporary geographical boundaries and population frequencies of artemisinin resistance. These findings indicate that the risk of new resistance-causing mutations emerging is determined by specific predisposing genetic factors in the underlying parasite population.

  13. Genetic Components of Root Architecture Remodeling in Response to Salt Stress

    KAUST Repository

    Julkowska, Magdalena

    2017-11-07

    Salinity of the soil is highly detrimental to plant growth. Plants respond by a redistribution of root mass between main and lateral roots, yet the genetic machinery underlying this process is still largely unknown. Here, we describe the natural variation among 347 Arabidopsis thaliana accessions in root system architecture (RSA) and identify the traits with highest natural variation in their response to salt. Salt-induced changes in RSA were associated with 100 genetic loci using genome-wide association studies (GWAS). Two candidate loci associated with lateral root development were validated and further investigated. Changes in CYP79B2 expression in salt stress positively correlated with lateral root development in accessions, and cyp79b2 cyp79b3 double mutants developed fewer and shorter lateral roots under salt stress, but not in control conditions. By contrast, high HKT1 expression in the root repressed lateral root development, which could be partially rescued by addition of potassium. The collected data and Multi-Variate analysis of multiple RSA traits, available through the Salt_NV_Root App, capture root responses to salinity. Together, our results provide a better understanding of effective RSA remodeling responses, and the genetic components involved, for plant performance in stress conditions.

  14. Genetic Architecture of Anther Extrusion in Spring and Winter Wheat

    Directory of Open Access Journals (Sweden)

    Quddoos H. Muqaddasi

    2017-05-01

    Full Text Available Hybrid wheat breeding is gaining prominence worldwide because it ensures higher and more static yield than conventionally bred varieties. The cleistogamous floral architecture of wheat (Triticum aestivum L. impedes anthers inside the floret, making it largely an inbreeder. For hybrid seed production, high anther extrusion is needed to promote cross pollination and to ensure a high level of pollen availability for the seed plant. This study, therefore, aimed at the genetic dissection of anther extrusion (AE in panels of spring (SP, and winter wheat (WP accessions by genome wide association studies (GWAS. We performed GWAS to identify the SNP markers potentially linked with AE in each panel separately. Phenotypic data were collected for 3 years for each panel. The average levels of Pearson's correlation (r among all years and their best linear unbiased estimates (BLUEs within both panels were high (r(SP = 0.75, P < 0.0001;r(WP = 0.72, P < 0.0001. Genotypic data (with minimum of 0.05 minor allele frequency applied included 12,066 and 12,191 SNP markers for SP and WP, respectively. Both genotypes and environment influenced the magnitude of AE. In total, 23 significant (|log10(P| > 3.0 marker trait associations (MTAs were detected (SP = 11; WP = 12. Anther extrusion behaved as a complex trait with significant markers having either favorable or unfavorable additive effects and imparting minor to moderate levels of phenotypic variance (R2(SP = 9.75−14.24%; R2 (WP = 9.44−16.98%. All mapped significant markers as well as the markers within their significant linkage disequilibrium (r2 ≥ 0.30 regions were blasted against wheat genome assembly (IWGSC1+popseq to find the corresponding genes and their high confidence descriptions were retrieved. These genes and their orthologs in Hordeum vulgare, Brachypodium distachyon, Oryza sativa, and Sorghum bicolor revealed syntenic genomic regions potentially involved in flowering-related traits. Moreover, the

  15. Genetic architecture of domestication-related traits in maize

    Science.gov (United States)

    Strong directional selection occurred during the domestication of maize from its wild ancestor teosinte, reducing its genetic diversity, particularly at genes controlling domestication-related traits. Nevertheless, variability for some domestication-related traits is maintained in maize. The genet...

  16. Genetic architecture and balancing selection: the life and death of differentiated variants.

    Science.gov (United States)

    Llaurens, Violaine; Whibley, Annabel; Joron, Mathieu

    2017-05-01

    Balancing selection describes any form of natural selection, which results in the persistence of multiple variants of a trait at intermediate frequencies within populations. By offering up a snapshot of multiple co-occurring functional variants and their interactions, systems under balancing selection can reveal the evolutionary mechanisms favouring the emergence and persistence of adaptive variation in natural populations. We here focus on the mechanisms by which several functional variants for a given trait can arise, a process typically requiring multiple epistatic mutations. We highlight how balancing selection can favour specific features in the genetic architecture and review the evolutionary and molecular mechanisms shaping this architecture. First, balancing selection affects the number of loci underlying differentiated traits and their respective effects. Control by one or few loci favours the persistence of differentiated functional variants by limiting intergenic recombination, or its impact, and may sometimes lead to the evolution of supergenes. Chromosomal rearrangements, particularly inversions, preventing adaptive combinations from being dissociated are increasingly being noted as features of such systems. Similarly, due to the frequency of heterozygotes maintained by balancing selection, dominance may be a key property of adaptive variants. High heterozygosity and limited recombination also influence associated genetic load, as linked recessive deleterious mutations may be sheltered. The capture of deleterious elements in a locus under balancing selection may reinforce polymorphism by further promoting heterozygotes. Finally, according to recent genomewide scans, balanced polymorphism might be more pervasive than generally thought. We stress the need for both functional and ecological studies to characterize the evolutionary mechanisms operating in these systems. © 2017 John Wiley & Sons Ltd.

  17. Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations

    NARCIS (Netherlands)

    Santure, Anna W.; Poissant, Jocelyn; Cauwer, De Isabelle; Oers, Van Kees; Robinson, Matthew R.; Quinn, John L.; Groenen, M.A.M.; Visser, M.E.; Sheldon, Ben C.; Slate, Jon

    2015-01-01

    Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar

  18. Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations

    NARCIS (Netherlands)

    Santure, Anna W; Poissant, Jocelyn; De Cauwer, Isabelle; van Oers, Kees; Robinson, Matthew R; Quinn, John L; Groenen, Martien A M; Visser, Marcel E; Sheldon, Ben C; Slate, Jon

    2015-01-01

    Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic

  19. QTL analysis reveals the genetic architecture of domestication traits in Crisphead lettuce

    NARCIS (Netherlands)

    Hartman, Y.; Hooftman, D.A.P.; Schranz, M.E.; van Tienderen, P.H.

    2013-01-01

    The genetic architecture of crop domestication is generally characterized by three trends: relatively few genomic regions with major QTL effects are involved, QTL are often clustered, and alleles derived from the crop do not always contribute to the crop phenotype. We have investigated the genetic

  20. Long-term response to genomic selection: effects of estimation method and reference population structure for different genetic architectures.

    Science.gov (United States)

    Bastiaansen, John W M; Coster, Albart; Calus, Mario P L; van Arendonk, Johan A M; Bovenhuis, Henk

    2012-01-24

    Genomic selection has become an important tool in the genetic improvement of animals and plants. The objective of this study was to investigate the impacts of breeding value estimation method, reference population structure, and trait genetic architecture, on long-term response to genomic selection without updating marker effects. Three methods were used to estimate genomic breeding values: a BLUP method with relationships estimated from genome-wide markers (GBLUP), a Bayesian method, and a partial least squares regression method (PLSR). A shallow (individuals from one generation) or deep reference population (individuals from five generations) was used with each method. The effects of the different selection approaches were compared under four different genetic architectures for the trait under selection. Selection was based on one of the three genomic breeding values, on pedigree BLUP breeding values, or performed at random. Selection continued for ten generations. Differences in long-term selection response were small. For a genetic architecture with a very small number of three to four quantitative trait loci (QTL), the Bayesian method achieved a response that was 0.05 to 0.1 genetic standard deviation higher than other methods in generation 10. For genetic architectures with approximately 30 to 300 QTL, PLSR (shallow reference) or GBLUP (deep reference) had an average advantage of 0.2 genetic standard deviation over the Bayesian method in generation 10. GBLUP resulted in 0.6% and 0.9% less inbreeding than PLSR and BM and on average a one third smaller reduction of genetic variance. Responses in early generations were greater with the shallow reference population while long-term response was not affected by reference population structure. The ranking of estimation methods was different with than without selection. Under selection, applying GBLUP led to lower inbreeding and a smaller reduction of genetic variance while a similar response to selection was

  1. Worms under stress: unravelling genetic complex traits through perturbation

    NARCIS (Netherlands)

    Rodriguez Sanchez, M.

    2014-01-01

    The genetic architecture of an organism could be considered ‘the most amazing piece of engineering’ existing in nature. Looking from a certain distance, the genetic complexity of an organism could be described as an immense jigsaw puzzle. As in a real jigsaw, the connection between two pieces

  2. Genetic Architecture of Charcoal Rot (Macrophomina phaseolina Resistance in Soybean Revealed Using a Diverse Panel

    Directory of Open Access Journals (Sweden)

    Sara M. Coser

    2017-09-01

    Full Text Available Charcoal rot (CR disease caused by Macrophomina phaseolina is responsible for significant yield losses in soybean production. Among the methods available for controlling this disease, breeding for resistance is the most promising. Progress in breeding efforts has been slow due to the insufficient information available on the genetic mechanisms related to resistance. Genome-wide association studies (GWAS enable unraveling the genetic architecture of resistance and identification of causal genes. The aims of this study were to identify new sources of resistance to CR in a collection of 459 diverse plant introductions from the USDA Soybean Germplasm Core Collection using field and greenhouse screenings, and to conduct GWAS to identify candidate genes and associated molecular markers. New sources for CR resistance were identified from both field and greenhouse screening from maturity groups I, II, and III. Five significant single nucleotide polymorphism (SNP and putative candidate genes related to abiotic and biotic stress responses are reported from the field screening; while greenhouse screening revealed eight loci associated with eight candidate gene families, all associated with functions controlling plant defense response. No overlap of markers or genes was observed between field and greenhouse screenings suggesting a complex molecular mechanism underlying resistance to CR in soybean with varied response to different environments; but our findings provide useful information for advancing breeding for CR resistance as well as the genetic mechanism of resistance.

  3. Genetic architecture of life history traits and environment-specific trade-offs.

    Science.gov (United States)

    Haselhorst, Monia S H; Edwards, Christine E; Rubin, Matthew J; Weinig, Cynthia

    2011-10-01

    Life history theory predicts the evolution of trait combinations that enhance fitness, and the occurrence of trade-offs depends in part on the magnitude of variation in growth rate or acquisition. Using recombinant inbred lines, we examined the genetic architecture of age and size at reproduction across abiotic conditions encountered by cultivars and naturalized populations of Brassica rapa. We found that genotypes are plastic to seasonal setting, such that reproduction was accelerated under conditions encountered by summer annual populations and genetic variances for age at reproduction varied across simulated seasonal settings. Using an acquisition-allocation model, we predicted the likelihood of trade-offs. Consistent with predicted relationships, we observed a trade-off where early maturity is associated with small size at maturity under simulated summer and fall annual conditions but not under winter annual conditions. The trade-off in the summer annual setting was observed despite significant genotypic variation in growth rate, which is often expected to decouple age and size at reproduction because rapidly growing genotypes could mature early and attain a larger size relative to slowly growing genotypes that mature later. The absence of a trade-off in the winter setting is presumably attributable to the absence of genotypic differences in age at reproduction. We observed QTL for age at reproduction that jointly regulated size at reproduction in both the summer and fall annual settings, but these QTL were environment-specific (i.e. different QTL contributed to the trade-off in the fall vs. summer annual settings). Thus, at least some of the genetic mechanisms underlying observed trade-offs differed across environments. © 2011 Blackwell Publishing Ltd.

  4. Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets.

    Directory of Open Access Journals (Sweden)

    Niels Grarup

    2013-06-01

    Full Text Available Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B(12 (B12 and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B(12 and folate measurements, respectively. We found six novel loci associating with serum B(12 (CD320, TCN2, ABCD4, MMAA, MMACHC or folate levels (FOLR3 and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR. Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B(12 and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B(12 or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations.

  5. Genetic Architecture of Vitamin B12 and Folate Levels Uncovered Applying Deeply Sequenced Large Datasets

    Science.gov (United States)

    Thorleifsson, Gudmar; Ahluwalia, Tarunveer S.; Steinthorsdottir, Valgerdur; Bjarnason, Helgi; Gudbjartsson, Daniel F.; Magnusson, Olafur T.; Sparsø, Thomas; Albrechtsen, Anders; Kong, Augustine; Masson, Gisli; Tian, Geng; Cao, Hongzhi; Nie, Chao; Kristiansen, Karsten; Husemoen, Lise Lotte; Thuesen, Betina; Li, Yingrui; Nielsen, Rasmus; Linneberg, Allan; Olafsson, Isleifur; Eyjolfsson, Gudmundur I.; Jørgensen, Torben; Wang, Jun; Hansen, Torben; Thorsteinsdottir, Unnur; Stefánsson, Kari; Pedersen, Oluf

    2013-01-01

    Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B12 (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B12 and folate measurements, respectively. We found six novel loci associating with serum B12 (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B12 and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B12 or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations. PMID:23754956

  6. Genetic architecture and postzygotic reproductive isolation: evolution of Bateson-Dobzhansky-Muller incompatibilities in a polygenic model.

    Science.gov (United States)

    Fierst, Janna L; Hansen, Thomas F

    2010-03-01

    The Bateson-Dobzhansky-Muller model predicts that postzygotic isolation evolves due to the accumulation of incompatible epistatic interactions, but few studies have quantified the relationship between genetic architecture and patterns of reproductive divergence. We examined how the direction and magnitude of epistatic interactions in a polygenic trait under stabilizing selection influenced the evolution of hybrid incompatibilities. We found that populations evolving independently under stabilizing selection experienced suites of compensatory allelic changes that resulted in genetic divergence between populations despite the maintenance of a stable, high-fitness phenotype. A small number of loci were then incompatible with multiple alleles in the genetic background of the hybrid and the identity of these incompatibility loci changed over the evolution of the populations. For F(1) hybrids, reduced fitness evolved in a window of intermediate strengths of epistatic interactions, but F(2) and backcross hybrids evolved reduced fitness across weak and moderate strengths of epistasis due to segregation variance. Strong epistatic interactions constrained the allelic divergence of parental populations and prevented the development of reproductive isolation. Because many traits with varying genetic architectures must be under stabilizing selection, our results indicate that polygenetic drift is a plausible hypothesis for the evolution of postzygotic reproductive isolation.

  7. An analysis of genetic architecture in populations of Ponderosa Pine

    Science.gov (United States)

    Yan B. Linhart; Jeffry B. Mitton; Kareen B. Sturgeon; Martha L. Davis

    1981-01-01

    Patterns of genetic variation were studied in three populations of ponderosa pine in Colorado by using electrophoretically variable protein loci. Significant genetic differences were found between separate clusters of trees and between age classes within populations. In addition, data indicate that differential cone production and differential animal damage have...

  8. A Genetic Programming Approach to Reconfigure a Morphological Image Processing Architecture

    Directory of Open Access Journals (Sweden)

    Emerson Carlos Pedrino

    2011-01-01

    Full Text Available Mathematical morphology supplies powerful tools for low-level image analysis. Many applications in computer vision require dedicated hardware for real-time execution. The design of morphological operators for a given application is not a trivial one. Genetic programming is a branch of evolutionary computing, and it is consolidating as a promising method for applications of digital image processing. The main objective of genetic programming is to discover how computers can learn to solve problems without being programmed for that. In this paper, the development of an original reconfigurable architecture using logical, arithmetic, and morphological instructions generated automatically by a genetic programming approach is presented. The developed architecture is based on FPGAs and has among the possible applications, automatic image filtering, pattern recognition and emulation of unknown filter. Binary, gray, and color image practical applications using the developed architecture are presented and the results are compared with similar techniques found in the literature.

  9. Genetic and Molecular Mechanisms of Quantitative Trait Loci Controlling Maize Inflorescence Architecture.

    Science.gov (United States)

    Li, Manfei; Zhong, Wanshun; Yang, Fang; Zhang, Zuxin

    2018-03-01

    The establishment of inflorescence architecture is critical for the reproduction of flowering plant species. The maize plant generates two types of inflorescences, the tassel and the ear, and their architectures have a large effect on grain yield and yield-related traits that are genetically controlled by quantitative trait loci (QTLs). Since ear and tassel architecture are deeply affected by the activity of inflorescence meristems, key QTLs and genes regulating meristematic activity have important impacts on inflorescence development and show great potential for optimizing grain yield. Isolation of yield trait-related QTLs is challenging, but these QTLs have direct application in maize breeding. Additionally, characterization and functional dissection of QTLs can provide genetic and molecular knowledge of quantitative variation in inflorescence architecture. In this review, we summarize currently identified QTLs responsible for the establishment of ear and tassel architecture and discuss the potential genetic control of four ear-related and four tassel-related traits. In recent years, several inflorescence architecture-related QTLs have been characterized at the gene level. We review the mechanisms of these characterized QTLs.

  10. Genetic analysis of loose cluster architecture in grapevine

    Directory of Open Access Journals (Sweden)

    Richter Robert

    2017-01-01

    Full Text Available Loose cluster architecture is a well known trait supporting Botrytis resilience by permitting a faster drying of bunches. Furthermore, a loose bunch enables a better application of fungicides into the cluster. The analysis of 150 F1 plants of the superior breeding line GF.GA-47-42 (‘Bacchus' x ‘Seyval blanc' crossed with ‘Villard blanc' segregating for compactness of the cluster was used for QTL analysis. Plenty of QTL were identified reproducibly for two years, QTLs stable over three growing seasons were identified for rachis length, peduncle length, and pedicel length. In a second approach ‘Pinot noir' clones showing variation for cluster architecture were analyzed for differential gene expression. Grown in three different German viticultural areas, loose versus compact clustered ‘Pinot noir' clones showed in gene expression experiments a candidate gene expressed fivefold higher in loosely clustered clones between stages BBCH57 and BBCH71.

  11. Architecture

    OpenAIRE

    Clear, Nic

    2014-01-01

    When discussing science fiction’s relationship with architecture, the usual practice is to look at the architecture “in” science fiction—in particular, the architecture in SF films (see Kuhn 75-143) since the spaces of literary SF present obvious difficulties as they have to be imagined. In this essay, that relationship will be reversed: I will instead discuss science fiction “in” architecture, mapping out a number of architectural movements and projects that can be viewed explicitly as scien...

  12. Insights into the genetic architecture of morphological traits in two passerine bird species.

    Science.gov (United States)

    Silva, C N S; McFarlane, S E; Hagen, I J; Rönnegård, L; Billing, A M; Kvalnes, T; Kemppainen, P; Rønning, B; Ringsby, T H; Sæther, B-E; Qvarnström, A; Ellegren, H; Jensen, H; Husby, A

    2017-09-01

    Knowledge about the underlying genetic architecture of phenotypic traits is needed to understand and predict evolutionary dynamics. The number of causal loci, magnitude of the effects and location in the genome are, however, still largely unknown. Here, we use genome-wide single-nucleotide polymorphism (SNP) data from two large-scale data sets on house sparrows and collared flycatchers to examine the genetic architecture of different morphological traits (tarsus length, wing length, body mass, bill depth, bill length, total and visible badge size and white wing patches). Genomic heritabilities were estimated using relatedness calculated from SNPs. The proportion of variance captured by the SNPs (SNP-based heritability) was lower in house sparrows compared with collared flycatchers, as expected given marker density (6348 SNPs in house sparrows versus 38 689 SNPs in collared flycatchers). Indeed, after downsampling to similar SNP density and sample size, this estimate was no longer markedly different between species. Chromosome-partitioning analyses demonstrated that the proportion of variance explained by each chromosome was significantly positively related to the chromosome size for some traits and, generally, that larger chromosomes tended to explain proportionally more variation than smaller chromosomes. Finally, we found two genome-wide significant associations with very small-effect sizes. One SNP on chromosome 20 was associated with bill length in house sparrows and explained 1.2% of phenotypic variation (V P ), and one SNP on chromosome 4 was associated with tarsus length in collared flycatchers (3% of V P ). Although we cannot exclude the possibility of undetected large-effect loci, our results indicate a polygenic basis for morphological traits.

  13. Current Understanding of the Genetic Architecture of Rhegmatogenous Retinal Detachment.

    Science.gov (United States)

    Johnston, Timothy; Chandra, Aman; Hewitt, Alex W

    2016-06-01

    Rhegmatogenous retinal detachment (RRD) is a common and potentially blinding surgical retinal disease. While the precise molecular mechanisms leading to RRD are poorly understood, there is an increasing body of literature supporting the role of heritable factors in the pathogenesis of the condition. Much work has been undertaken investigating genes important in syndromic forms of RRD (e.g., Stickler, Wagner Syndrome, etc.) and research pertaining to genetic investigations of idiopathic or non-syndromic RRD has also recently been reported. To date, at least 12 genetic loci have been implicated in the development of syndromes of which RRD is a feature. A recent GWAS identified five loci implicated in the development of idiopathic RRD.This article provides an overview of the genetic mechanisms of both syndromic and idiopathic RRD. The genetics of predisposing conditions, such as myopia and lattice degeneration, are also discussed.

  14. Inferring genetic architecture of complex traits using Bayesian integrative analysis of genome and transcriptiome data

    DEFF Research Database (Denmark)

    Ehsani, Alireza; Sørensen, Peter; Pomp, Daniel

    2012-01-01

    -modal distribution of genomic values collapses, when gene expressions are added to the model Conclusions With increased availability of various -omics data, integrative approaches are promising tools for understanding the genetic architecture of complex traits. Partitioning of explained variances at the chromosome......Background To understand the genetic architecture of complex traits and bridge the genotype-phenotype gap, it is useful to study intermediate -omics data, e.g. the transcriptome. The present study introduces a method for simultaneous quantification of the contributions from single nucleotide...

  15. Leaf shape evolution has a similar genetic architecture in three edaphic specialists within the Mimulus guttatus species complex.

    Science.gov (United States)

    Ferris, Kathleen G; Rushton, Tullia; Greenlee, Anna B; Toll, Katherine; Blackman, Benjamin K; Willis, John H

    2015-08-01

    The genetic basis of leaf shape has long interested botanists because leaf shape varies extensively across the plant kingdom and this variation is probably adaptive. However, knowledge of the genetic architecture of leaf shape variation in natural populations remains limited. This study examined the genetic architecture of leaf shape diversification among three edaphic specialists in the Mimulus guttatus species complex. Lobed and narrow leaves have evolved from the entire, round leaves of M. guttatus in M. laciniatus, M. nudatus and a polymorphic serpentine M. guttatus population (M2L). Bulk segregant analysis and next-generation sequencing were used to map quantitative trait loci (QTLs) that underlie leaf shape in an M. laciniatus × M. guttatus F2 population. To determine whether the same QTLs contribute to leaf shape variation in M. nudatus and M2L, F2s from M. guttatus × M. nudatus and lobed M2L × unlobed M. guttatus crosses were genotyped at QTLs from the bulk segregant analysis. Narrow and lobed leaf shapes in M. laciniatus, M. nudatus and M. guttatus are controlled by overlapping genetic regions. Several promising leaf shape candidate genes were found under each QTL. The evolution of divergent leaf shape has taken place multiple times in the M. guttatus species complex and is associated with the occupation of dry, rocky environments. The genetic architecture of elongated and lobed leaves is similar across three species in this group. This may indicate that parallel genetic evolution from standing variation or new mutations is responsible for the putatively adaptive leaf shape variation in Mimulus. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Complex Genotype by Environment interactions and changing genetic architectures across thermal environments in the Australian field cricket, Teleogryllus oceanicus

    Science.gov (United States)

    2011-01-01

    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 reared at the cooler

  17. Complex Genotype by Environment interactions and changing genetic architectures across thermal environments in the Australian field cricket, Teleogryllus oceanicus

    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

  18. Genetic architecture of gene expression in ovine skeletal muscle

    DEFF Research Database (Denmark)

    Kogelman, Lisette Johanna Antonia; Byrne, Keren; Vuocolo, Tony

    2011-01-01

    weighted gene co-expression network analysis and a differential gene co-expression network analysis. The modules of genes revealed by these analyses were enriched for a number of functional terms summarised as muscle sarcomere organisation and development, protein catabolism (proteosome), RNA processing...... has potential, amongst other mechanisms, to alter gene expression via cis- or trans-acting mechanisms in a manner that impacts the functional activities of specific pathways that contribute to muscling traits. By integrating sire-based genetic merit information for a muscling trait with progeny......-based gene expression data we directly tested the hypothesis that there is genetic structure in the gene expression program in ovine skeletal muscle.Results: The genetic performance of six sires for a well defined muscling trait, longissimus lumborum muscle depth, was measured using extensive progeny testing...

  19. Genetic Architecture of Charcoal Rot (Macrophomina phaseolina) Resistance in Soybean Revealed Using a Diverse Panel

    OpenAIRE

    Coser, Sara M.; Chowda Reddy, R. V.; Zhang, Jiaoping; Mueller, Daren S.; Mengistu, Alemu; Wise, Kiersten A.; Allen, Tom W.; Singh, Arti; Singh, Asheesh K.

    2017-01-01

    Charcoal rot (CR) disease caused by Macrophomina phaseolina is responsible for significant yield losses in soybean production. Among the methods available for controlling this disease, breeding for resistance is the most promising. Progress in breeding efforts has been slow due to the insufficient information available on the genetic mechanisms related to resistance. Genome-wide association studies (GWAS) enable unraveling the genetic architecture of resistance and identification of causal ge...

  20. Genetic architecture of seed longevity in bread wheat (Triticum ...

    Indian Academy of Sciences (India)

    2017-01-20

    Jan 20, 2017 ... SPSS v17.0 software (SPSS Inc. 1999). Candidate genes mapping within a genomic region associated with a trait were identified from the deletion bin maps prepared in wheat cv. Chinese Spring (http://wheat.pw.usda.gov/pubs/2004/. Genetics/Bioinfo/). 3. Results. 3.1 Genomic distribution of DArT markers.

  1. Genetic architecture of flowering time variation in Brachypodium distachyon

    Science.gov (United States)

    The transition to reproductive development is a crucial step of a plant’s life cycle, and the timing of this transition is an important factor in crop yields. Here, we report new insights into the genetic control of natural variation in flowering time in Brachypodium distachyon, a non-domesticated c...

  2. Bayesian dissection for genetic architecture of traits associated with ...

    African Journals Online (AJOL)

    Nitrogen is one of the key important nutrients in rice production. High rice grain yield is greatly dependent upon economic nitrogen input and genetic factors. In order to locate quantitative loci for traits associated with nitrogen utilization efficiency in rice, F9 recombinant inbred lines derived from a Korean tongil type ...

  3. Genetic architectures of seropositive and seronegative rheumatic diseases.

    Science.gov (United States)

    Kirino, Yohei; Remmers, Elaine F

    2015-07-01

    Rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and some other rheumatic diseases are genetically complex, with evidence of familial clustering, but not of Mendelian inheritance. These diseases are thought to result from contributions and interactions of multiple genetic and nongenetic risk factors, which have small effects individually. Genome-wide association studies (GWAS) of large collections of data from cases and controls have revealed many genetic factors that contribute to non-Mendelian rheumatic diseases, thus providing insights into associated molecular mechanisms. This Review summarizes methods for the identification of gene variants that influence genetically complex diseases and focuses on what we have learned about the rheumatic diseases for which GWAS have been reported. Our review of the disease-associated loci identified to date reveals greater sharing of risk loci among the groups of seropositive (diseases in which specific autoantibodies are often present) or seronegative diseases than between these two groups. The nature of the shared and discordant loci suggests important similarities and differences among these diseases.

  4. Genetic architecture of kernel composition in global sorghum germplasm

    Science.gov (United States)

    Sorghum [Sorghum bicolor (L.) Moench] is an important cereal crop for dryland areas in the United States and for small-holder farmers in Africa. Natural variation of sorghum grain composition (protein, fat, and starch) between accessions can be used for crop improvement, but the genetic controls are...

  5. The genetic and regulatory architecture of ERBB3-type 1 diabetes susceptibility locus

    DEFF Research Database (Denmark)

    Kaur, Simranjeet; Mirza, Aashiq H.; Brorsson, Caroline Anna

    2016-01-01

    -producing INS-1E cells and the genetic and regulatory architecture of the ERBB3 locus to provide insights to how rs2292239 may confer disease susceptibility. rs2292239 strongly correlated with residual β-cell function and metabolic control in children with T1D. ERBB3 locus associated lncRNA (NONHSAG011351...

  6. The Genetic and Environmental Factors Underlying Hypospadias

    Science.gov (United States)

    Pask, Andrew; Heloury, Yves; Sinclair, Andrew H.

    2016-01-01

    Hypospadias results from a failure of urethral closure in the male phallus and affects 1 in 200–300 boys. It is thought to be due to a combination of genetic and environmental factors. The development of the penis progresses in 2 stages: an initial hormone-independent phase and a secondary hormone-dependent phase. Here, we review the molecular pathways that contribute to each of these stages, drawing on studies from both human and mouse models. Hypospadias can occur when normal development of the phallus is disrupted, and we provide evidence that mutations in genes underlying this developmental process are causative. Finally, we discuss the environmental factors that may contribute to hypospadias and their potential immediate and transgen erational epigenetic impacts. PMID:26613581

  7. Interactions within the MHC contribute to the genetic architecture of celiac disease.

    Science.gov (United States)

    Goudey, Benjamin; Abraham, Gad; Kikianty, Eder; Wang, Qiao; Rawlinson, Dave; Shi, Fan; Haviv, Izhak; Stern, Linda; Kowalczyk, Adam; Inouye, Michael

    2017-01-01

    Interaction analysis of GWAS can detect signal that would be ignored by single variant analysis, yet few robust interactions in humans have been detected. Recent work has highlighted interactions in the MHC region between known HLA risk haplotypes for various autoimmune diseases. To better understand the genetic interactions underlying celiac disease (CD), we have conducted exhaustive genome-wide scans for pairwise interactions in five independent CD case-control studies, using a rapid model-free approach to examine over 500 billion SNP pairs in total. We found 14 independent interaction signals within the MHC region that achieved stringent replication criteria across multiple studies and were independent of known CD risk HLA haplotypes. The strongest independent CD interaction signal corresponded to genes in the HLA class III region, in particular PRRC2A and GPANK1/C6orf47, which are known to contain variants for non-Hodgkin's lymphoma and early menopause, co-morbidities of celiac disease. Replicable evidence for statistical interaction outside the MHC was not observed. Both within and between European populations, we observed striking consistency of two-locus models and model distribution. Within the UK population, models of CD based on both interactions and additive single-SNP effects increased explained CD variance by approximately 1% over those of single SNPs. The interactions signal detected across the five cohorts indicates the presence of novel associations in the MHC region that cannot be detected using additive models. Our findings have implications for the determination of genetic architecture and, by extension, the use of human genetics for validation of therapeutic targets.

  8. Gene Pools and the Genetic Architecture of Domesticated Cowpea

    Directory of Open Access Journals (Sweden)

    Bao-Lam Huynh

    2013-11-01

    Full Text Available Cowpea [ (L. Walp.] is a major tropical legume crop grown in warm to hot areas throughout the world and especially important to the people of sub-Saharan Africa where the crop was domesticated. To date, relatively little is understood about its domestication origins and patterns of genetic variation. In this study, a worldwide collection of cowpea landraces and African ancestral wild cowpea was genotyped with more than 1200 single nucleotide polymorphism markers. Bayesian inference revealed the presence of two major gene pools in cultivated cowpea in Africa. Landraces from gene pool 1 are mostly distributed in western Africa while the majority of gene pool 2 are located in eastern Africa. Each gene pool is most closely related to wild cowpea in the same geographic region, indicating divergent domestication processes leading to the formation of two gene pools. The total genetic variation within landraces from countries outside Africa was slightly greater than within African landraces. Accessions from Asia and Europe were more related to those from western Africa while accessions from the Americas appeared more closely related to those from eastern Africa. This delineation of cowpea germplasm into groups of genetic relatedness will be valuable for guiding introgression efforts in breeding programs and for improving the efficiency of germplasm management.

  9. The Multi-allelic Genetic Architecture of a Variance-Heterogeneity Locus for Molybdenum Concentration in Leaves Acts as a Source of Unexplained Additive Genetic Variance.

    Directory of Open Access Journals (Sweden)

    Simon K G Forsberg

    2015-11-01

    Full Text Available Genome-wide association (GWA analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or "missing heritability". Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1, and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975 as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations.

  10. Genetic Architecture of Milk, Fat, Protein, Mastitis and Fertility Studied using NGS Data in Holstein Cattle

    DEFF Research Database (Denmark)

    Sahana, Goutam; Janss, Luc; Guldbrandtsen, Bernt

    The use of genomic information in genetic evaluation has revolutionized dairy cattle breeding. It remains a major challenge to understand the genetic basis of variation for quantitative traits. Here, we study the genetic architecture for milk, fat, protein, mastitis and fertility indices in dairy...... cattle using NGS variants. The analysis was done using a linear mixed model (LMM) and a Bayesian mixture model (BMM). The top 10 QTL identified by LMM analyses explained 22.61, 23.86, 10.88, 18.58 and 14.83% of the total genetic variance for these traits respectively. Trait-specific sets of 4,964 SNPs...... from NGS variants (most ‘associated’ SNP for each 0.5 Mbp bin) explained 81.0, 81.6, 85.0, 60.4 and 70.9% of total genetic variance for milk, fat, protein, mastitis and fertility indices when analyzed simultaneously by BMM...

  11. Genetic architecture of spring and autumn phenology in Salix

    Science.gov (United States)

    2014-01-01

    Background In woody plants from temperate regions, adaptation to the local climate results in annual cycles of growth and dormancy, and optimal regulation of these cycles are critical for growth, long-term survival, and competitive success. In this study we have investigated the genetic background to growth phenology in a Salix pedigree by assessing genetic and phenotypic variation in growth cessation, leaf senescence and bud burst in different years and environments. A previously constructed linkage map using the same pedigree and anchored to the annotated genome of P. trichocarpa was improved in target regions and used for QTL analysis of the traits. The major aims in this study were to map QTLs for phenology traits in Salix, and to identify candidate genes in QTL hot spots through comparative mapping with the closely related Populus trichocarpa. Results All traits varied significantly among genotypes and the broad-sense heritabilities ranged between 0.5 and 0.9, with the highest for leaf senescence. In total across experiment and years, 80 QTLs were detected. For individual traits, the QTLs explained together from 21.5 to 56.5% of the variation. Generally each individual QTL explained a low amount of the variation but three QTLs explained above 15% of the variation with one QTL for leaf senescence explaining 34% of the variation. The majority of the QTLs were recurrently identified across traits, years and environments. Two hotspots were identified on linkage group (LG) II and X where narrow QTLs for all traits co-localized. Conclusions This study provides the most detailed analysis of QTL detection for phenology in Salix conducted so far. Several hotspot regions were found where QTLs for different traits and QTLs for the same trait but identified during different years co-localised. Many QTLs co-localised with QTLs found in poplar for similar traits that could indicate common pathways for these traits in Salicaceae. This study is an important first step in

  12. Genetic architecture of seed longevity in bread wheat

    Indian Academy of Sciences (India)

    Some, but not all, of these regions were associated with variation for both natural and experimental ageing, implyingsome non-congruency obtains between these two forms of testing for longevity. The genes underlying longevityappear to be independent of known genes determining dormancy and pre-harvest sprouting.

  13. The genetic architecture of adaptations to high altitude in Ethiopia.

    Science.gov (United States)

    Alkorta-Aranburu, Gorka; Beall, Cynthia M; Witonsky, David B; Gebremedhin, Amha; Pritchard, Jonathan K; Di Rienzo, Anna

    2012-01-01

    Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome-wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, in the Amhara, SNP rs10803083 is associated with hemoglobin levels at genome-wide levels of significance. No significant genotype association was observed for oxygen saturation levels in either ethnic group. Approaches based on allele frequency divergence did not detect outliers in candidate hypoxia genes, but the most differentiated variants between high- and lowlanders have a clear role in pathogen defense. Interestingly, a significant excess of allele frequency divergence was consistently detected for genes involved in cell cycle control and DNA damage and repair, thus pointing to new pathways for high altitude adaptations. Finally, a comparison of CpG methylation levels between high- and lowlanders found several significant signals at individual genes in the Oromo.

  14. Systems-level quantification of division timing reveals a common genetic architecture controlling asynchrony and fate asymmetry.

    Science.gov (United States)

    Ho, Vincy Wing Sze; Wong, Ming-Kin; An, Xiaomeng; Guan, Daogang; Shao, Jiaofang; Ng, Hon Chun Kaoru; Ren, Xiaoliang; He, Kan; Liao, Jinyue; Ang, Yingjin; Chen, Long; Huang, Xiaotai; Yan, Bin; Xia, Yiji; Chan, Leanne Lai Hang; Chow, King Lau; Yan, Hong; Zhao, Zhongying

    2015-06-10

    Coordination of cell division timing is crucial for proper cell fate specification and tissue growth. However, the differential regulation of cell division timing across or within cell types during metazoan development remains poorly understood. To elucidate the systems-level genetic architecture coordinating division timing, we performed a high-content screening for genes whose depletion produced a significant reduction in the asynchrony of division between sister cells (ADS) compared to that of wild-type during Caenorhabditis elegans embryogenesis. We quantified division timing using 3D time-lapse imaging followed by computer-aided lineage analysis. A total of 822 genes were selected for perturbation based on their conservation and known roles in development. Surprisingly, we find that cell fate determinants are not only essential for establishing fate asymmetry, but also are imperative for setting the ADS regardless of cellular context, indicating a common genetic architecture used by both cellular processes. The fate determinants demonstrate either coupled or separate regulation between the two processes. The temporal coordination appears to facilitate cell migration during fate specification or tissue growth. Our quantitative dataset with cellular resolution provides a resource for future analyses of the genetic control of spatial and temporal coordination during metazoan development. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  15. The genetic architecture of disease resistance in plants and the maintenance of recombination by parasites.

    Science.gov (United States)

    Kover, P X; Caicedo, A L

    2001-01-01

    Parasites represent strong selection on host populations because they are ubiquitous and can drastically reduce host fitness. It has been hypothesized that parasite selection could explain the widespread occurrence of recombination because it is a coevolving force that favours new genetic combinations in the host. A review of deterministic models for the maintenance of recombination reveals that for recombination to be favoured, multiple genes that interact with each other must be under selection. To evaluate whether parasite selection can explain the maintenance of recombination, we review 85 studies that investigated the genetic architecture of plant disease resistance and discuss whether they conform to the requirements that emerge from theoretical models. General characteristics of disease resistance in plants and problems in evaluating resistance experimentally are also discussed. We found strong evidence that disease resistance in plants is determined by multiple loci. Furthermore, in most cases where loci were tested for interactions, epistasis between loci that affect resistance was found. However, we found weak support for the idea that specific allelic combinations determine resistance to different host genotypes and there was little data on whether epistasis between resistance genes is negative or positive. Thus, the current data indicate that it is possible that parasite selection can favour recombination, but more studies in natural populations that specifically address the nature of the interactions between resistance genes are necessary. The data summarized here suggest that disease resistance is a complex trait and that environmental effects and fitness trade-offs should be considered in future models of the coevolutionary dynamics of host and parasites.

  16. Network architecture underlying maximal separation of neuronal representations

    Directory of Open Access Journals (Sweden)

    Ron A Jortner

    2013-01-01

    Full Text Available One of the most basic and general tasks faced by all nervous systems is extracting relevant information from the organism’s surrounding world. While physical signals available to sensory systems are often continuous, variable, overlapping and noisy, high-level neuronal representations used for decision-making tend to be discrete, specific, invariant, and highly separable. This study addresses the question of how neuronal specificity is generated. Inspired by experimental findings on network architecture in the olfactory system of the locust, I construct a highly simplified theoretical framework which allows for analytic solution of its key properties. For generalized feed-forward systems, I show that an intermediate range of connectivity values between source- and target-populations leads to a combinatorial explosion of wiring possibilities, resulting in input spaces which are, by their very nature, exquisitely sparsely populated. In particular, connection probability ½, as found in the locust antennal-lobe–mushroom-body circuit, serves to maximize separation of neuronal representations across the target Kenyon-cells, and explains their specific and reliable responses. This analysis yields a function expressing response specificity in terms of lower network-parameters; together with appropriate gain control this leads to a simple neuronal algorithm for generating arbitrarily sparse and selective codes and linking network architecture and neural coding. I suggest a way to easily construct ecologically meaningful representations from this code.

  17. Accounting for genetic architecture improves sequence based genomic prediction for a Drosophila fitness trait.

    Science.gov (United States)

    Ober, Ulrike; Huang, Wen; Magwire, Michael; Schlather, Martin; Simianer, Henner; Mackay, Trudy F C

    2015-01-01

    The ability to predict quantitative trait phenotypes from molecular polymorphism data will revolutionize evolutionary biology, medicine and human biology, and animal and plant breeding. Efforts to map quantitative trait loci have yielded novel insights into the biology of quantitative traits, but the combination of individually significant quantitative trait loci typically has low predictive ability. Utilizing all segregating variants can give good predictive ability in plant and animal breeding populations, but gives little insight into trait biology. Here, we used the Drosophila Genetic Reference Panel to perform both a genome wide association analysis and genomic prediction for the fitness-related trait chill coma recovery time. We found substantial total genetic variation for chill coma recovery time, with a genetic architecture that differs between males and females, a small number of molecular variants with large main effects, and evidence for epistasis. Although the top additive variants explained 36% (17%) of the genetic variance among lines in females (males), the predictive ability using genomic best linear unbiased prediction and a relationship matrix using all common segregating variants was very low for females and zero for males. We hypothesized that the low predictive ability was due to the mismatch between the infinitesimal genetic architecture assumed by the genomic best linear unbiased prediction model and the true genetic architecture of chill coma recovery time. Indeed, we found that the predictive ability of the genomic best linear unbiased prediction model is markedly improved when we combine quantitative trait locus mapping with genomic prediction by only including the top variants associated with main and epistatic effects in the relationship matrix. This trait-associated prediction approach has the advantage that it yields biologically interpretable prediction models.

  18. Accounting for genetic architecture improves sequence based genomic prediction for a Drosophila fitness trait.

    Directory of Open Access Journals (Sweden)

    Ulrike Ober

    Full Text Available The ability to predict quantitative trait phenotypes from molecular polymorphism data will revolutionize evolutionary biology, medicine and human biology, and animal and plant breeding. Efforts to map quantitative trait loci have yielded novel insights into the biology of quantitative traits, but the combination of individually significant quantitative trait loci typically has low predictive ability. Utilizing all segregating variants can give good predictive ability in plant and animal breeding populations, but gives little insight into trait biology. Here, we used the Drosophila Genetic Reference Panel to perform both a genome wide association analysis and genomic prediction for the fitness-related trait chill coma recovery time. We found substantial total genetic variation for chill coma recovery time, with a genetic architecture that differs between males and females, a small number of molecular variants with large main effects, and evidence for epistasis. Although the top additive variants explained 36% (17% of the genetic variance among lines in females (males, the predictive ability using genomic best linear unbiased prediction and a relationship matrix using all common segregating variants was very low for females and zero for males. We hypothesized that the low predictive ability was due to the mismatch between the infinitesimal genetic architecture assumed by the genomic best linear unbiased prediction model and the true genetic architecture of chill coma recovery time. Indeed, we found that the predictive ability of the genomic best linear unbiased prediction model is markedly improved when we combine quantitative trait locus mapping with genomic prediction by only including the top variants associated with main and epistatic effects in the relationship matrix. This trait-associated prediction approach has the advantage that it yields biologically interpretable prediction models.

  19. Correlations between genet architecture and some life history features in three species of Solidago.

    Science.gov (United States)

    Schmid, B; Puttick, G M; Burgess, K H; Bazzaz, F A

    1988-04-01

    Members of the genus Solidago are among the most widely studied model systems in plant population biology. A comparative study of Solidago canadensis, S. altissima, and S. gigantea in an experimental garden showed that the three species had different patterns of shoot growth and development, leaf morphology and physiology, and biomass allocation at harvest. These differences were also found in the field. Contrary to some current taxonomic usage, our results show that S. canadensis should ecologically be treated as a separate taxon distinct from S. altissima, and that the latter may be grouped together with S. gigantea. Many of the biological differences between S. canadensis and the other two taxa, such as differential investment into sexual reproduction versus clonal growth, may be explained by differences in genet architecture. These architectures concern high compared to lower within-genet shoot density resulting from differences in rhizome lengths among the taxa (shorter in S. canadensis than in S. altissima and S. gigantea).

  20. Understanding the genetic and epigenetic architecture in complex network of rice flowering pathways.

    Science.gov (United States)

    Sun, Changhui; Chen, Dan; Fang, Jun; Wang, Pingrong; Deng, Xiaojian; Chu, Chengcai

    2014-12-01

    Although the molecular basis of flowering time control is well dissected in the long day (LD) plant Arabidopsis, it is still largely unknown in the short day (SD) plant rice. Rice flowering time (heading date) is an important agronomic trait for season adaption and grain yield, which is affected by both genetic and environmental factors. During the last decade, as the nature of florigen was identified, notable progress has been made on exploration how florigen gene expression is genetically controlled. In Arabidopsis expression of certain key flowering integrators such as FLOWERING LOCUS C (FLC) and FLOWERING LOCUS T (FT) are also epigenetically regulated by various chromatin modifications, however, very little is known in rice on this aspect until very recently. This review summarized the advances of both genetic networks and chromatin modifications in rice flowering time control, attempting to give a complete view of the genetic and epigenetic architecture in complex network of rice flowering pathways.

  1. Dissecting the genetic architecture of F-1 hybrid sterility in house mice

    OpenAIRE

    Dzúr-Gejdošová, M. (Mária); Šimeček, P. (Petr); Gregorová, S. (Soňa); Bhattacharyya, T. (Tanmoy); Forejt, J. (Jiří)

    2012-01-01

    Hybrid sterility as a postzygotic reproductive isolation mechanism has been studied for over 80 years, yet the first identifications of hybrid sterility genes in Drosophila and mouse are quite recent. To study the genetic architecture of F-1 hybrid sterility between young subspecies of house mouse Mus m. domesticus and M. m. musculus, we conducted QTL analysis of a backcross between inbred strains representing these two subspecies and probed the role of individual chromosomes in hybrid steril...

  2. The Genetic Architecture of Liver Enzyme Levels: GGT, ALT and AST

    OpenAIRE

    van Beek, Jenny H. D. A.; de Moor, Marleen H. M.; de Geus, Eco J. C.; Lubke, Gitta H.; Vink, Jacqueline M.; Willemsen, Gonneke; Boomsma, Dorret I.

    2013-01-01

    High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were ass...

  3. Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits

    NARCIS (Netherlands)

    P. Henneman (Peter); Y.S. Aulchenko (Yurii); R.R. Frants (Rune); I.V. Zorkoltseva (Irina); M.C. Zillikens (Carola); M. Frölich (Marijke); B.A. Oostra (Ben); J.A.P. Willems van Dijk (Ko); P. Tikka-Kleemola (Päivi)

    2010-01-01

    textabstractOBJECTIVE - Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity

  4. Genetic Architecture of Flooding Tolerance in the Dry Bean Middle-American Diversity Panel

    Directory of Open Access Journals (Sweden)

    Ali Soltani

    2017-07-01

    Full Text Available Flooding is a devastating abiotic stress that endangers crop production in the twenty-first century. Because of the severe susceptibility of common bean (Phaseolus vulgaris L. to flooding, an understanding of the genetic architecture and physiological responses of this crop will set the stage for further improvement. However, challenging phenotyping methods hinder a large-scale genetic study of flooding tolerance in common bean and other economically important crops. A greenhouse phenotyping protocol was developed to evaluate the flooding conditions at early stages. The Middle-American diversity panel (n = 272 of common bean was developed to capture most of the diversity exits in North American germplasm. This panel was evaluated for seven traits under both flooded and non-flooded conditions at two early developmental stages. A subset of contrasting genotypes was further evaluated in the field to assess the relationship between greenhouse and field data under flooding condition. A genome-wide association study using ~150 K SNPs was performed to discover genomic regions associated with multiple physiological responses. The results indicate a significant strong correlation (r > 0.77 between greenhouse and field data, highlighting the reliability of greenhouse phenotyping method. Black and small red beans were the least affected by excess water at germination stage. At the seedling stage, pinto and great northern genotypes were the most tolerant. Root weight reduction due to flooding was greatest in pink and small red cultivars. Flooding reduced the chlorophyll content to the greatest extent in the navy bean cultivars compared with other market classes. Races of Durango/Jalisco and Mesoamerica were separated by both genotypic and phenotypic data indicating the potential effect of eco-geographical variations. Furthermore, several loci were identified that potentially represent the antagonistic pleiotropy. The GWAS analysis revealed peaks at Pv08

  5. Genome-wide study of an elite rice pedigree reveals a complex history of genetic architecture for breeding improvement.

    Science.gov (United States)

    Chen, Shaoxia; Lin, Zechuan; Zhou, Degui; Wang, Chongrong; Li, Hong; Yu, Renbo; Deng, Hanchao; Tang, Xiaoyan; Zhou, Shaochuan; Wang Deng, Xing; He, Hang

    2017-04-04

    Improving breeding has been widely utilized in crop breeding and contributed to yield and quality improvement, yet few researches have been done to analyze genetic architecture underlying breeding improvement comprehensively. Here, we collected genotype and phenotype data of 99 cultivars from the complete pedigree including Huanghuazhan, an elite, high-quality, conventional indica rice that has been grown over 4.5 million hectares in southern China and from which more than 20 excellent cultivars have been derived. We identified 1,313 selective sweeps (SSWs) revealing four stage-specific selection patterns corresponding to improvement preference during 65 years, and 1113 conserved Huanghuazhan traceable blocks (cHTBs) introduced from different donors and conserved in >3 breeding generations were the core genomic regions for superior performance of Huanghuazhan. Based on 151 quantitative trait loci (QTLs) identified for 13 improved traits in the pedigree, we reproduced their improvement process in silico, highlighting improving breeding works well for traits controlled by major/major + minor effect QTLs, but was inefficient for traits controlled by QTLs with complex interactions or explaining low levels of phenotypic variation. These results indicate long-term breeding improvement is efficient to construct superior genetic architecture for elite performance, yet molecular breeding with designed genotype of QTLs can facilitate complex traits improvement.

  6. Generator scheduling under competitive environment using genetic ...

    African Journals Online (AJOL)

    In this paper, genetic algorithm (GA) is used to solve the GENCOs profit based unit commitment problem (PBUCP) in a dayahead competitive electricity markets considering power and reserve generations simultaneously, whereas enhanced lambda iteration (ELI) method is used to solve the economic dispatch (ED) ...

  7. Intraspecific Genetic dynamics under Climate Change

    DEFF Research Database (Denmark)

    Florez Rodriguez, Alexander

    Climate change has a deep influence on the maintenance and generation of global biodiversity. Past contractions, expansions and shifts in species’ ranges drove to changes in species genetic diversity. Noteworthy, the interaction among: climate change, range, population size and extinction is ofte...

  8. The between-population genetic architecture of growth, maturation, and plasticity in Atlantic salmon.

    Science.gov (United States)

    Debes, Paul Vincent; Fraser, Dylan John; Yates, Matthew; Hutchings, Jeffrey A

    2014-04-01

    The between-population genetic architecture for growth and maturation has not been examined in detail for many animal species despite its central importance in understanding hybrid fitness. We studied the genetic architecture of population divergence in: (i) maturation probabilities at the same age; (ii) size at age and growth, while accounting for maturity status and sex; and (iii) growth plasticity in response to environmental factors, using divergent wild and domesticated Atlantic salmon (Salmo salar). Our work examined two populations and their multigenerational hybrids in a common experimental arrangement in which salinity and quantity of suspended sediments were manipulated to mimic naturally occurring environmental variation. Average specific growth rates across environments differed among crosses, maturity groups, and cross-by-maturity groups, but a growth-rate reduction in the presence of suspended sediments was equal for all groups. Our results revealed both additive and nonadditive outbreeding effects for size at age and for growth rates that differed with life stage, as well as the presence of different sex- and size-specific maturation probabilities between populations. The major implication of our work is that estimates of the genetic architecture of growth and maturation can be biased if one does not simultaneously account for temporal changes in growth and for different maturation probabilities between populations. Namely, these correlated traits interact differently within each population and between sexes and among generations, due to nonadditive effects and a level of independence in the genetic control for traits. Our results emphasize the challenges to investigating and predicting phenotypic changes resulting from between-population outbreeding.

  9. Genetic architecture of retinal and macular degenerative diseases: the promise and challenges of next-generation sequencing

    Science.gov (United States)

    2013-01-01

    Inherited retinal degenerative diseases (RDDs) display wide variation in their mode of inheritance, underlying genetic defects, age of onset, and phenotypic severity. Molecular mechanisms have not been delineated for many retinal diseases, and treatment options are limited. In most instances, genotype-phenotype correlations have not been elucidated because of extensive clinical and genetic heterogeneity. Next-generation sequencing (NGS) methods, including exome, genome, transcriptome and epigenome sequencing, provide novel avenues towards achieving comprehensive understanding of the genetic architecture of RDDs. Whole-exome sequencing (WES) has already revealed several new RDD genes, whereas RNA-Seq and ChIP-Seq analyses are expected to uncover novel aspects of gene regulation and biological networks that are involved in retinal development, aging and disease. In this review, we focus on the genetic characterization of retinal and macular degeneration using NGS technology and discuss the basic framework for further investigations. We also examine the challenges of NGS application in clinical diagnosis and management. PMID:24112618

  10. Genome-wide prediction of traits with different genetic architecture through efficient variable selection.

    Science.gov (United States)

    Wimmer, Valentin; Lehermeier, Christina; Albrecht, Theresa; Auinger, Hans-Jürgen; Wang, Yu; Schön, Chris-Carolin

    2013-10-01

    In genome-based prediction there is considerable uncertainty about the statistical model and method required to maximize prediction accuracy. For traits influenced by a small number of quantitative trait loci (QTL), predictions are expected to benefit from methods performing variable selection [e.g., BayesB or the least absolute shrinkage and selection operator (LASSO)] compared to methods distributing effects across the genome [ridge regression best linear unbiased prediction (RR-BLUP)]. We investigate the assumptions underlying successful variable selection by combining computer simulations with large-scale experimental data sets from rice (Oryza sativa L.), wheat (Triticum aestivum L.), and Arabidopsis thaliana (L.). We demonstrate that variable selection can be successful when the number of phenotyped individuals is much larger than the number of causal mutations contributing to the trait. We show that the sample size required for efficient variable selection increases dramatically with decreasing trait heritabilities and increasing extent of linkage disequilibrium (LD). We contrast and discuss contradictory results from simulation and experimental studies with respect to superiority of variable selection methods over RR-BLUP. Our results demonstrate that due to long-range LD, medium heritabilities, and small sample sizes, superiority of variable selection methods cannot be expected in plant breeding populations even for traits like FRIGIDA gene expression in Arabidopsis and flowering time in rice, assumed to be influenced by a few major QTL. We extend our conclusions to the analysis of whole-genome sequence data and infer upper bounds for the number of causal mutations which can be identified by LASSO. Our results have major impact on the choice of statistical method needed to make credible inferences about genetic architecture and prediction accuracy of complex traits.

  11. The genetic architecture of ecological adaptation: intraspecific variation in host plant use by the lepidopteran crop pest Chloridea virescens.

    Science.gov (United States)

    Oppenheim, Sara J; Gould, Fred; Hopper, Keith R

    2018-03-01

    Intraspecific variation in ecologically important traits is a cornerstone of Darwin's theory of evolution by natural selection. The evolution and maintenance of this variation depends on genetic architecture, which in turn determines responses to natural selection. Some models suggest that traits with complex architectures are less likely to respond to selection than those with simple architectures, yet rapid divergence has been observed in such traits. The simultaneous evolutionary lability and genetic complexity of host plant use in the Lepidopteran subfamily Heliothinae suggest that architecture may not constrain ecological adaptation in this group. Here we investigate the response of Chloridea virescens, a generalist that feeds on diverse plant species, to selection for performance on a novel host, Physalis angulata (Solanaceae). P. angulata is the preferred host of Chloridea subflexa, a narrow specialist on the genus Physalis. In previous experiments, we found that the performance of C. subflexa on P. angulata depends on many loci of small effect distributed throughout the genome, but whether the same architecture would be involved in the generalist's adoption of P. angulata was unknown. Here we report a rapid response to selection in C. virescens for performance on P. angulata, and establish that the genetic architecture of intraspecific variation is quite similar to that of the interspecific differences in terms of the number, distribution, and effect sizes of the QTL involved. We discuss the impact of genetic architecture on the ability of Heliothine moths to respond to varying ecological selection pressures.

  12. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains

    Science.gov (United States)

    Bennett, Brian J.; Davis, Richard C.; Civelek, Mete; Orozco, Luz; Wu, Judy; Qi, Hannah; Pan, Calvin; Packard, René R. Sevag; Eskin, Eleazar; Yan, Mujing; Kirchgessner, Todd; Wang, Zeneng; Li, Xinmin; Gregory, Jill C.; Hazen, Stanley L.; Gargalovic, Peter S.; Lusis, Aldons J.

    2015-01-01

    Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression

  13. Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains.

    Directory of Open Access Journals (Sweden)

    Brian J Bennett

    2015-12-01

    Full Text Available Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP. The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden and human cholesteryl ester transfer protein (CETP. The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear

  14. The genetic architecture of traits associated with the evolution of self-pollination in Mimulus.

    Science.gov (United States)

    Fishman, Lila; Beardsley, Paul M; Stathos, Angela; Williams, Charles F; Hill, Jeffrey P

    2015-01-01

    Quantitative trait locus (QTL) mapping is a first step toward understanding the genetic basis of adaptive evolution and may also reveal reproductive incompatibilities unique to hybrids. In plants, the shift from outcrossing to self-pollination is common, providing the opportunity for comparisons of QTL architecture among parallel evolutionary transitions. We used QTL mapping in hybrids between the bee-pollinated monkeyflower Mimulus lewisii and the closely related selfer Mimulus parishii to determine the genetic basis of divergence in floral traits and flowering time associated with mating-system evolution, and to characterize hybrid anther sterility. We found a moderately polygenic and highly directional basis for floral size evolution, suggesting adaptation from standing variation or in pursuit of a moving optimum, whereas only a few major loci accounted for substantial flowering-time divergence. Cytonuclear incompatibilities caused hybrid anther sterility, confounding estimation of reproductive organ QTLs. The genetic architecture of floral traits associated with selfing in M. parishii was primarily polygenic, as in other QTL studies of this transition, but in contrast to the previously characterized oligogenic basis of a pollinator shift in close relatives. Hybrid anther sterility appeared parallel at the molecular level to previously characterized incompatibilities, but also raised new questions about cytonuclear co-evolution in plants. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  15. The genetic architecture of liver enzyme levels: GGT, ALT and AST.

    Science.gov (United States)

    van Beek, Jenny H D A; de Moor, Marleen H M; de Geus, Eco J C; Lubke, Gitta H; Vink, Jacqueline M; Willemsen, Gonneke; Boomsma, Dorret I

    2013-07-01

    High levels of liver enzymes GGT, ALT and AST are predictive of disease and all-cause mortality and can reflect liver injury, fatty liver and/or oxidative stress. Variation in GGT, ALT and AST levels is heritable. Moderation of the heritability of these liver enzymes by age and sex has not often been explored, and it is not clear to what extent non-additive genetic and shared environmental factors may play a role. To examine the genetic architecture of GGT, ALT and AST, plasma levels were assessed in a large sample of twins, their siblings, parents and spouses (N = 8,371; age range 18-90). For GGT and ALT, but not for AST, genetic structural equation modeling showed evidence for quantitative sex differences in the genetic architecture. There was no evidence for qualitative sex differences, i.e. the same genes were expressed in males and females. Both additive and non-additive genetic factors were important for GGT in females (total heritability h(2) 60 %) and AST in both sexes (total h(2) 43 %). The heritability of GGT in males and ALT for both sexes was due to additive effects only (GGT males 30 %; ALT males 40 %, females 22 %). Evidence emerged for shared environmental factors influencing GGT in the male offspring generation (variance explained 28 %). Thus, the same genes influence liver enzyme levels across sex and age, but their relative contribution to the variation in GGT and ALT differs in males and females and for GGT across age. Given adequate sample sizes these results suggest that genome-wide association studies may result in the detection of new susceptibility loci for liver enzyme levels when pooling results over sex and age.

  16. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

    NARCIS (Netherlands)

    Morris, Andrew P.; Voight, Benjamin F.; Teslovich, Tanya M.; Ferreira, Teresa; Segrè, Ayellet V.; Steinthorsdottir, Valgerdur; Strawbridge, Rona J.; Khan, Hassan; Grallert, Harald; Mahajan, Anubha; Prokopenko, Inga; Kang, Hyun Min; Dina, Christian; Esko, Tonu; Fraser, Ross M.; Kanoni, Stavroula; Kumar, Ashish; Lagou, Vasiliki; Langenberg, Claudia; Luan, Jian'an; Lindgren, Cecilia M.; Müller-Nurasyid, Martina; Pechlivanis, Sonali; Rayner, N. William; Scott, Laura J.; Wiltshire, Steven; Yengo, Loic; Kinnunen, Leena; Rossin, Elizabeth J.; Raychaudhuri, Soumya; Johnson, Andrew D.; Dimas, Antigone S.; Loos, Ruth J. F.; Vedantam, Sailaja; Chen, Han; Florez, Jose C.; Fox, Caroline; Liu, Ching-Ti; Rybin, Denis; Couper, David J.; Kao, Wen Hong L.; Li, Man; Cornelis, Marilyn C.; Kraft, Peter; Sun, Qi; van Dam, Rob M.; Stringham, Heather M.; Chines, Peter S.; Fischer, Krista; Fontanillas, Pierre; Holmen, Oddgeir L.; Hunt, Sarah E.; Jackson, Anne U.; Kong, Augustine; Lawrence, Robert; Meyer, Julia; Perry, John R. B.; Platou, Carl G. P.; Potter, Simon; Rehnberg, Emil; Robertson, Neil; Sivapalaratnam, Suthesh; Stančáková, Alena; Stirrups, Kathleen; Thorleifsson, Gudmar; Tikkanen, Emmi; Wood, Andrew R.; Almgren, Peter; Atalay, Mustafa; Benediktsson, Rafn; Bonnycastle, Lori L.; Burtt, Noël; Carey, Jason; Charpentier, Guillaume; Crenshaw, Andrew T.; Doney, Alex S. F.; Dorkhan, Mozhgan; Edkins, Sarah; Emilsson, Valur; Eury, Elodie; Forsen, Tom; Gertow, Karl; Gigante, Bruna; Grant, George B.; Groves, Christopher J.; Guiducci, Candace; Herder, Christian; Hreidarsson, Astradur B.; Hui, Jennie; James, Alan; Jonsson, Anna; Rathmann, Wolfgang; Klopp, Norman; Kravic, Jasmina; Krjutškov, Kaarel; Langford, Cordelia; Leander, Karin; Lindholm, Eero; Lobbens, Stéphane; Männistö, Satu; Mirza, Ghazala; Mühleisen, Thomas W.; Musk, Bill; Parkin, Melissa; Rallidis, Loukianos; Saramies, Jouko; Sennblad, Bengt; Shah, Sonia; Sigurðsson, Gunnar; Silveira, Angela; Steinbach, Gerald; Thorand, Barbara; Trakalo, Joseph; Veglia, Fabrizio; Wennauer, Roman; Winckler, Wendy; Zabaneh, Delilah; Campbell, Harry; van Duijn, Cornelia; Uitterlinden, Andre G.; Hofman, Albert; Sijbrands, Eric; Abecasis, Goncalo R.; Owen, Katharine R.; Zeggini, Eleftheria; Trip, Mieke D.; Forouhi, Nita G.; Syvänen, Ann-Christine; Eriksson, Johan G.; Peltonen, Leena; Nöthen, Markus M.; Balkau, Beverley; Palmer, Colin N. A.; Lyssenko, Valeriya; Tuomi, Tiinamaija; Isomaa, Bo; Hunter, David J.; Qi, Lu; Shuldiner, Alan R.; Roden, Michael; Barroso, Ines; Wilsgaard, Tom; Beilby, John; Hovingh, Kees; Price, Jackie F.; Wilson, James F.; Rauramaa, Rainer; Lakka, Timo A.; Lind, Lars; Dedoussis, George; Njølstad, Inger; Pedersen, Nancy L.; Khaw, Kay-Tee; Wareham, Nicholas J.; Keinanen-Kiukaanniemi, Sirkka M.; Saaristo, Timo E.; Korpi-Hyövälti, Eeva; Saltevo, Juha; Laakso, Markku; Kuusisto, Johanna; Metspalu, Andres; Collins, Francis S.; Mohlke, Karen L.; Bergman, Richard N.; Tuomilehto, Jaakko; Boehm, Bernhard O.; Gieger, Christian; Hveem, Kristian; Cauchi, Stephane; Froguel, Philippe; Baldassarre, Damiano; Tremoli, Elena; Humphries, Steve E.; Saleheen, Danish; Danesh, John; Ingelsson, Erik; Ripatti, Samuli; Salomaa, Veikko; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Peters, Annette; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Morris, Andrew D.; Donnelly, Peter J.; Frayling, Timothy M.; Hattersley, Andrew T.; Boerwinkle, Eric; Melander, Olle; Kathiresan, Sekar; Nilsson, Peter M.; Deloukas, Panos; Thorsteinsdottir, Unnur; Groop, Leif C.; Stefansson, Kari; Hu, Frank; Pankow, James S.; Dupuis, Josée; Meigs, James B.; Altshuler, David; Boehnke, Michael; McCarthy, Mark I.

    2012-01-01

    To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D

  17. Genetic architecture of male floral traits required for hybrid wheat breeding.

    Science.gov (United States)

    Boeven, Philipp H G; Longin, C Friedrich H; Leiser, Willmar L; Kollers, Sonja; Ebmeyer, Erhard; Würschum, Tobias

    2016-12-01

    This study revealed a complex genetic architecture of male floral traits in wheat, and Rht-D1 was identified as the only major QTL. Genome-wide prediction approaches but also phenotypic recurrent selection appear promising to increase outcrossing ability required for hybrid wheat seed production. Hybrid wheat breeding is a promising approach to increase grain yield and yield stability. However, the identification of lines with favorable male floral characteristics required for hybrid seed production currently poses a severe bottleneck for hybrid wheat breeding. This study therefore aimed to unravel the genetic architecture of floral traits and to assess the potential of genomic approaches to accelerate their improvement. To this end, we employed a panel of 209 diverse winter wheat lines assessed for male floral traits and genotyped with genome-wide markers as well as for Rht-B1 and Rht-D1. We found the highest proportion of explained genotypic variance for the Rht-D1 locus (11-24 %), for which the dwarfing allele Rht-D1b had a negative effect on anther extrusion, visual anther extrusion and pollen mass. The genome-wide scan detected only few QTL with small or medium effects, indicating a complex genetic architecture. Consequently, marker-assisted selection yielded only moderate prediction abilities (0.44-0.63), mainly relying on Rht-D1. Genomic selection based on weighted ridge-regression best linear unbiased prediction achieved higher prediction abilities of up to 0.70 for anther extrusion. In conclusion, recurrent phenotypic selection appears most cost-effective for the initial improvement of floral traits in wheat, while genome-wide prediction approaches may be worthwhile when complete marker profiles are already available in a hybrid wheat breeding program.

  18. GPA-MDS: A Visualization Approach to Investigate Genetic Architecture among Phenotypes Using GWAS Results.

    Science.gov (United States)

    Wei, Wei; Ramos, Paula S; Hunt, Kelly J; Wolf, Bethany J; Hardiman, Gary; Chung, Dongjun

    2016-01-01

    Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. Recently, there has been accumulating evidence suggesting that different complex traits share a common risk basis, namely, pleiotropy. Previously, a statistical method, namely, GPA (Genetic analysis incorporating Pleiotropy and Annotation), was developed to improve identification of risk variants and to investigate pleiotropic structure through a joint analysis of multiple GWAS datasets. While GPA provides a statistically rigorous framework to evaluate pleiotropy between phenotypes, it is still not trivial to investigate genetic relationships among a large number of phenotypes using the GPA framework. In order to address this challenge, in this paper, we propose a novel approach, GPA-MDS, to visualize genetic relationships among phenotypes using the GPA algorithm and multidimensional scaling (MDS). This tool will help researchers to investigate common etiology among diseases, which can potentially lead to development of common treatments across diseases. We evaluate the proposed GPA-MDS framework using a simulation study and apply it to jointly analyze GWAS datasets examining 18 unique phenotypes, which helps reveal the shared genetic architecture of these phenotypes.

  19. The signal processing architecture underlying subjective reports of sensory awareness.

    Science.gov (United States)

    Maniscalco, Brian; Lau, Hakwan

    2016-01-01

    What is the relationship between perceptual information processing and subjective perceptual experience? Empirical dissociations between stimulus identification performance and subjective reports of stimulus visibility are crucial for shedding light on this question. We replicated a finding that metacontrast masking can produce such a dissociation (Lau and Passingham, 2006), and report a novel finding that this paradigm can also dissociate stimulus identification performance from the efficacy with which visibility ratings predict task performance. We explored various hypotheses about the relationship between perceptual task performance and visibility rating by implementing them in computational models and using formal model comparison techniques to assess which ones best captured the unusual patterns in the data. The models fell into three broad categories: Single Channel models, which hold that task performance and visibility ratings are based on the same underlying source of information; Dual Channel models, which hold that there are two independent processing streams that differentially contribute to task performance and visibility rating; and Hierarchical models, which hold that a late processing stage generates visibility ratings by evaluating the quality of early perceptual processing. Taking into account the quality of data fitting and model complexity, we found that Hierarchical models perform best at capturing the observed behavioral dissociations. Because current theories of visual awareness map well onto these different model structures, a formal comparison between them is a powerful approach for arbitrating between the different theories.

  20. Sex differences in the genetic architecture of lifespan in a seed beetle: extreme inbreeding extends male lifespan

    DEFF Research Database (Denmark)

    Bilde, T.; Maklakov, Alexei A.; Meisner, Katrine

    2009-01-01

    Background Sex differences in lifespan are ubiquitous throughout the animal kingdom but the causes underlying this phenomenon remain poorly understood. Several explanations based on asymmetrical inheritance patterns (sex chromosomes or mitochondrial DNA) have been proposed, but these ideas have...... rarely been tested experimentally. Alternatively, sexual dimorphism in lifespan could result from sex-specific selection, caused by fundamental differences in how males and females optimize their fitness by allocating resources into current and future reproduction. Results Here we used sex......-specific responses to inbreeding to study the genetic architecture of lifespan and mortality rates in Callosobruchus maculatus, a seed beetle that shows sexual dimorphism in lifespan. Two independent assays revealed opposing sex-specific responses to inbreeding. The combined data set showed that inbred males live...

  1. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.

    Directory of Open Access Journals (Sweden)

    Lea K Davis

    2013-10-01

    Full Text Available The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD and Tourette Syndrome (TS, using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12 for TS, and 0.37 (se = 0.07, p = 1.5e-07 for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum for which we had available expression quantitative trait loci (eQTLs. Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002. These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

  2. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

    Science.gov (United States)

    Davis, Lea K.; Yu, Dongmei; Keenan, Clare L.; Gamazon, Eric R.; Konkashbaev, Anuar I.; Derks, Eske M.; Neale, Benjamin M.; Yang, Jian; Lee, S. Hong; Evans, Patrick; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrio, Gabriel Bedoya; Bienvenu, Oscar J.; Bloch, Michael H.; Blom, Rianne M.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond; Cappi, Carolina; Cardona Silgado, Julio C.; Cath, Danielle C.; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Conti, David V.; Cook, Edwin H.; Coric, Vladimir; Cullen, Bernadette A.; Deforce, Dieter; Delorme, Richard; Dion, Yves; Edlund, Christopher K.; Egberts, Karin; Falkai, Peter; Fernandez, Thomas V.; Gallagher, Patience J.; Garrido, Helena; Geller, Daniel; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Haddad, Stephen; Heiman, Gary A.; Hemmings, Sian M. J.; Hounie, Ana G.; Illmann, Cornelia; Jankovic, Joseph; Jenike, Michael A.; Kennedy, James L.; King, Robert A.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Macciardi, Fabio; McCracken, James T.; McGrath, Lauren M.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Ochoa, William Cornejo; Ophoff, Roel A.; Osiecki, Lisa; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias J.; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosàrio, Maria C.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Ruiz-Linares, Andres; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, E.; Tischfield, Jay A.; Valencia Duarte, Ana V.; Vallada, Homero; Van Nieuwerburgh, Filip; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Miguel, Euripedes C.; McMahon, William; Wagner, Michael; Nicolini, Humberto; Posthuma, Danielle; Hanna, Gregory L.; Heutink, Peter; Denys, Damiaan; Arnold, Paul D.; Oostra, Ben A.; Nestadt, Gerald; Freimer, Nelson B.; Pauls, David L.; Wray, Naomi R.

    2013-01-01

    The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures. PMID:24204291

  3. Global optimization driven by genetic algorithms for disruption predictors based on APODIS architecture

    International Nuclear Information System (INIS)

    Rattá, G.A.; Vega, J.; Murari, A.; Dormido-Canto, S.; Moreno, R.

    2016-01-01

    Highlights: • A global optimization method based on genetic algorithms was developed. • It allowed improving the prediction of disruptions using APODIS architecture. • It also provides the potential opportunity to develop a spectrum of future predictors using different training datasets. • The future analysis of how their structures reassemble and evolve in each test may help to improve the development of disruption predictors for ITER. - Abstract: Since year 2010, the APODIS architecture has proven its accuracy predicting disruptions in JET tokamak. Nevertheless, it has shown margins for improvements, fact indisputable after the enhanced performances achieved in posterior upgrades. In this article, a complete optimization driven by Genetic Algorithms (GA) is applied to it aiming at considering all possible combination of signals, signal features, quantity of models, their characteristics and internal parameters. This global optimization targets the creation of the best possible system with a reduced amount of required training data. The results harbor no doubts about the reliability of the global optimization method, allowing to outperform the ones of previous versions: 91.77% of predictions (89.24% with an anticipation higher than 10 ms) with a 3.55% of false alarms. Beyond its effectiveness, it also provides the potential opportunity to develop a spectrum of future predictors using different training datasets.

  4. Global optimization driven by genetic algorithms for disruption predictors based on APODIS architecture

    Energy Technology Data Exchange (ETDEWEB)

    Rattá, G.A., E-mail: giuseppe.ratta@ciemat.es [Laboratorio Nacional de Fusión, CIEMAT, Madrid (Spain); Vega, J. [Laboratorio Nacional de Fusión, CIEMAT, Madrid (Spain); Murari, A. [Consorzio RFX, Associazione EURATOM/ENEA per la Fusione, Padua (Italy); Dormido-Canto, S. [Dpto. de Informática y Automática, Universidad Nacional de Educación a Distancia, Madrid (Spain); Moreno, R. [Laboratorio Nacional de Fusión, CIEMAT, Madrid (Spain)

    2016-11-15

    Highlights: • A global optimization method based on genetic algorithms was developed. • It allowed improving the prediction of disruptions using APODIS architecture. • It also provides the potential opportunity to develop a spectrum of future predictors using different training datasets. • The future analysis of how their structures reassemble and evolve in each test may help to improve the development of disruption predictors for ITER. - Abstract: Since year 2010, the APODIS architecture has proven its accuracy predicting disruptions in JET tokamak. Nevertheless, it has shown margins for improvements, fact indisputable after the enhanced performances achieved in posterior upgrades. In this article, a complete optimization driven by Genetic Algorithms (GA) is applied to it aiming at considering all possible combination of signals, signal features, quantity of models, their characteristics and internal parameters. This global optimization targets the creation of the best possible system with a reduced amount of required training data. The results harbor no doubts about the reliability of the global optimization method, allowing to outperform the ones of previous versions: 91.77% of predictions (89.24% with an anticipation higher than 10 ms) with a 3.55% of false alarms. Beyond its effectiveness, it also provides the potential opportunity to develop a spectrum of future predictors using different training datasets.

  5. A service-oriented architecture for integrating the modeling and formal verification of genetic regulatory networks

    Science.gov (United States)

    2009-01-01

    Background The study of biological networks has led to the development of increasingly large and detailed models. Computer tools are essential for the simulation of the dynamical behavior of the networks from the model. However, as the size of the models grows, it becomes infeasible to manually verify the predictions against experimental data or identify interesting features in a large number of simulation traces. Formal verification based on temporal logic and model checking provides promising methods to automate and scale the analysis of the models. However, a framework that tightly integrates modeling and simulation tools with model checkers is currently missing, on both the conceptual and the implementational level. Results We have developed a generic and modular web service, based on a service-oriented architecture, for integrating the modeling and formal verification of genetic regulatory networks. The architecture has been implemented in the context of the qualitative modeling and simulation tool GNA and the model checkers NUSMV and CADP. GNA has been extended with a verification module for the specification and checking of biological properties. The verification module also allows the display and visual inspection of the verification results. Conclusions The practical use of the proposed web service is illustrated by means of a scenario involving the analysis of a qualitative model of the carbon starvation response in E. coli. The service-oriented architecture allows modelers to define the model and proceed with the specification and formal verification of the biological properties by means of a unified graphical user interface. This guarantees a transparent access to formal verification technology for modelers of genetic regulatory networks. PMID:20042075

  6. Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures.

    Science.gov (United States)

    Cassatella, Daniele; Howard, Sasha R; Acierno, James S; Xu, Cheng; Papadakis, Georgios E; Santoni, Federico A; Dwyer, Andrew A; Santini, Sara; Sykiotis, Gerasimos P; Chambion, Caroline; Meylan, Jenny; Marino, Laura; Favre, Lucie; Li, Jiankang; Liu, Xuanzhu; Zhang, Jianguo; Bouloux, Pierre-Marc; Geyter, Christian De; Paepe, Anne De; Dhillo, Waljit S; Ferrara, Jean-Marc; Hauschild, Michael; Lang-Muritano, Mariarosaria; Lemke, Johannes R; Flück, Christa; Nemeth, Attila; Phan-Hug, Franziska; Pignatelli, Duarte; Popovic, Vera; Pekic, Sandra; Quinton, Richard; Szinnai, Gabor; l'Allemand, Dagmar; Konrad, Daniel; Sharif, Saba; Iyidir, Özlem Turhan; Stevenson, Brian J; Yang, Huanming; Dunkel, Leo; Pitteloud, Nelly

    2018-04-01

    Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. Exome sequencing data were used to identify rare variants in known genes in CHH ( n  = 116), CDGP ( n  = 72) and control cohorts ( n  = 36 874 ExAC and n  = 405 CoLaus). Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P  = 7.6 × 10 -11 ) or controls (18%, P  = 5.5 × 10 -12 ). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P  = 0.002) and controls (2%, P  = 6.4 × 10 -7 ). Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty. © 2018 The authors.

  7. The genetic architecture of hybridisation between two lineages of greenshell mussels.

    Science.gov (United States)

    Gardner, J P A; Wei, K-J

    2015-03-01

    A multidisciplinary approach has identified sigmoidal genetic clines on the east and west coasts in central New Zealand where low-density ecological interactions occur between northern and southern lineages of the endemic greenshell mussel, Perna canaliculus. The sigmoidal clines indicate the existence of a mussel hybrid zone in a region of genetic discontinuities for many continuously distributed coastal taxa, in particular marine invertebrates. Examination of the genetic architecture of the hybrid zone revealed the differential contribution of individual microsatellite loci and/or alleles to defining the zone of interaction and no evidence of increased allelic richness or heterozygosity inside versus outside the hybrid zone. Genomics cline analysis identified one locus in particular (Pcan1-27) as being different from neutral expectations, thereby contributing to lineage differentiation. Estimates of contemporary gene flow revealed very high levels of within-lineage self-recruitment and a hybrid zone composed mostly (~85%) of northern immigrants. Broad scale interpretation of these results is consistent with a zone of genetic interaction that was generated between 0.3 and 1.3 million years before present at a time of pronounced global sea-level change. At that time, the continuous distribution of the greenshell mussel was split into northern and southern groups, which differentiated to become distinct lineages, and which have subsequently been reunited (secondary contact) resulting in the generation of the hybrid zone at ~42°S.

  8. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

    DEFF Research Database (Denmark)

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address...... this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested...... that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We...

  9. Defeating the Warrior: genetic architecture of triticale resistance against a novel aggressive yellow rust race.

    Science.gov (United States)

    Losert, Dominik; Maurer, Hans Peter; Leiser, Willmar L; Würschum, Tobias

    2017-04-01

    Genome-wide association mapping of resistance against the novel, aggressive 'Warrior' race of yellow rust in triticale revealed a genetic architecture with some medium-effect QTL and a quantitative component, which in combination confer high levels of resistance on both leaves and ears. Yellow rust is an important destructive fungal disease in small grain cereals and the exotic 'Warrior' race has recently conquered Europe. The aim of this study was to investigate the genetic architecture of yellow rust resistance in hexaploid winter triticale as the basis for a successful resistance breeding. To this end, a diverse panel of 919 genotypes was evaluated for yellow rust infection on leaves and ears in multi-location field trials and genotyped by genotyping-by-sequencing as well as for known Yr resistance loci. Genome-wide association mapping identified ten quantitative trait loci (QTL) for yellow rust resistance on the leaves and seven of these also for ear resistance. The total genotypic variance explained by the QTL amounted to 44.0% for leaf and 26.0% for ear resistance. The same three medium-effect QTL were identified for both traits on chromosomes 1B, 2B, and 7B. Interestingly, plants pyramiding the resistance allele of all three medium-effect QTL were generally most resistant, but constitute less than 5% of the investigated triticale breeding material. Nevertheless, a genome-wide prediction yielded a higher predictive ability than prediction based on these three QTL. Taken together, our results show that yellow rust resistance in winter triticale is genetically complex, including both medium-effect QTL as well as a quantitative resistance component. Resistance to the novel 'Warrior' race of this fungal pathogen is consequently best achieved by recurrent selection in the field based on identified resistant lines and can potentially be assisted by genomic approaches.

  10. Complex genetic architecture of cardiac disease in a wild type inbred strain of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Zhi Zhang

    Full Text Available Natural populations of the fruit fly, Drosophila melanogaster, segregate genetic variation that leads to cardiac disease phenotypes. One nearly isogenic line from a North Carolina peach orchard, WE70, is shown to harbor two genetically distinct heart phenotypes: elevated incidence of arrhythmias, and a dramatically constricted heart diameter in both diastole and systole, with resemblance to restrictive cardiomyopathy in humans. Assuming the source to be rare variants of large effect, we performed Bulked Segregant Analysis using genomic DNA hybridization to Affymetrix chips to detect single feature polymorphisms, but found that the mutant phenotypes are more likely to have a polygenic basis. Further mapping efforts revealed a complex architecture wherein the constricted cardiomyopathy phenotype was observed in individual whole chromosome substitution lines, implying that variants on both major autosomes are sufficient to produce the phenotype. A panel of 170 Recombinant Inbred Lines (RIL was generated, and a small subset of mutant lines selected, but these each complemented both whole chromosome substitutions, implying a non-additive (epistatic contribution to the "disease" phenotype. Low coverage whole genome sequencing was also used to attempt to map chromosomal regions contributing to both the cardiomyopathy and arrhythmia, but a polygenic architecture had to be again inferred to be most likely. These results show that an apparently simple rare phenotype can have a complex genetic basis that would be refractory to mapping by deep sequencing in pedigrees. We present this as a cautionary tale regarding assumptions related to attempts to map new disease mutations on the assumption that probands carry a single causal mutation.

  11. Genetic architecture of seed longevity in bread wheat (Triticum aestivum L.).

    Science.gov (United States)

    Arif, Mian Abdur Rehman; Nagel, Manuela; Lohwasser, Ulrike; Borner, Andreas

    2017-03-01

    The deterioration in the quality of ex situ conserved seed over time reflects a combination of both physical and chemical changes. Intraspecific variation for longevity is, at least in part, under genetic control. Here, the grain of 183 bread wheat accessions maintained under low-temperature storage at the IPK-Gatersleben genebank over some decades have been tested for their viability, along with that of fresh grain subjected to two standard artificial ageing procedures. A phenotype-genotype association analysis, conducted to reveal the genetic basis of the observed variation between accessions, implicated many regions of the genome, underling the genetic complexity of the trait. Some, but not all, of these regions were associated with variation for both natural and experimental ageing, implying some non-congruency obtains between these two forms of testing for longevity. The genes underlying longevity appear to be independent of known genes determining dormancy and pre-harvest sprouting.

  12. Genetic architecture of sex determination in fish: Applications to sex ratio control in aquaculture

    Directory of Open Access Journals (Sweden)

    Paulino eMartínez

    2014-09-01

    Full Text Available Controlling the sex ratio is essential in finfish farming. A balanced sex ratio is usually good for broodstock management, since it enables to develop appropriate breeding schemes. However, in some species the production of monosex populations is desirable because the existence of sexual dimorphism, primarily in growth or first time of sexual maturation, but also in color or shape, can render one sex more valuable. The knowledge of the genetic architecture of sex determination (SD is convenient for controlling sex ratio and for the implementation of breeding programs. Unlike mammals and birds, which show highly conserved master genes that control a conserved genetic network responsible for gonad differentiation (GD, a huge diversity of SD mechanisms has been reported in fish. Despite theory predictions, more than one gene is in many cases involved in fish SD and genetic differences have been observed in the GD network. Environmental factors also play a relevant role and epigenetic mechanisms are becoming increasingly recognized for the establishment and maintenance of the GD pathways. Although major genetic factors are frequently involved in fish SD, these observations strongly suggest that SD in this group resembles a complex trait. Accordingly, the application of quantitative genetics combined with genomic tools is desirable to address its study and in fact, when applied, it has frequently demonstrated a multigene trait interacting with environmental factors in model and cultured fish species. This scenario has notable implications for aquaculture and, depending upon the species, from chromosome manipulation or environmental control techniques up to classical selection or marker assisted selection programs, are being applied. In this review, we selected four relevant species or fish groups to illustrate this diversity and hence the technologies that can be used by the industry for the control of sex ratio: turbot and European sea bass, two

  13. Artificial Selection Response due to Polygenic Adaptation from a Multilocus, Multiallelic Genetic Architecture.

    Science.gov (United States)

    Zan, Yanjun; Sheng, Zheya; Lillie, Mette; Rönnegård, Lars; Honaker, Christa F; Siegel, Paul B; Carlborg, Örjan

    2017-10-01

    The ability of a population to adapt to changes in their living conditions, whether in nature or captivity, often depends on polymorphisms in multiple genes across the genome. In-depth studies of such polygenic adaptations are difficult in natural populations, but can be approached using the resources provided by artificial selection experiments. Here, we dissect the genetic mechanisms involved in long-term selection responses of the Virginia chicken lines, populations that after 40 generations of divergent selection for 56-day body weight display a 9-fold difference in the selected trait. In the F15 generation of an intercross between the divergent lines, 20 loci explained >60% of the additive genetic variance for the selected trait. We focused particularly on fine-mapping seven major QTL that replicated in this population and found that only two fine-mapped to single, bi-allelic loci; the other five contained linked loci, multiple alleles or were epistatic. This detailed dissection of the polygenic adaptations in the Virginia lines provides a deeper understanding of the range of different genome-wide mechanisms that have been involved in these long-term selection responses. The results illustrate that the genetic architecture of a highly polygenic trait can involve a broad range of genetic mechanisms, and that this can be the case even in a small population bred from founders with limited genetic diversity. © The Author 2017. 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.

  14. Whole genome sequencing of 35 individuals provides insights into the genetic architecture of Korean population.

    Science.gov (United States)

    Zhang, Wenqian; Meehan, Joe; Su, Zhenqiang; Ng, Hui Wen; Shu, Mao; Luo, Heng; Ge, Weigong; Perkins, Roger; Tong, Weida; Hong, Huixiao

    2014-01-01

    Due to a significant decline in the costs associated with next-generation sequencing, it has become possible to decipher the genetic architecture of a population by sequencing a large number of individuals to a deep coverage. The Korean Personal Genomes Project (KPGP) recently sequenced 35 Korean genomes at high coverage using the Illumina Hiseq platform and made the deep sequencing data publicly available, providing the scientific community opportunities to decipher the genetic architecture of the Korean population. In this study, we used two single nucleotide variant (SNV) calling pipelines: mapping the raw reads obtained from whole genome sequencing of 35 Korean individuals in KPGP using BWA and SOAP2 followed by SNV calling using SAMtools and SOAPsnp, respectively. The consensus SNVs obtained from the two SNV pipelines were used to represent the SNVs of the Korean population. We compared these SNVs to those from 17 other populations provided by the HapMap consortium and the 1000 Genomes Project (1KGP) and identified SNVs that were only present in the Korean population. We studied the mutation spectrum and analyzed the genes of non-synonymous SNVs only detected in the Korean population. We detected a total of 8,555,726 SNVs in the 35 Korean individuals and identified 1,213,613 SNVs detected in at least one Korean individual (SNV-1) and 12,640 in all of 35 Korean individuals (SNV-35) but not in 17 other populations. In contrast with the SNVs common to other populations in HapMap and 1KGP, the Korean only SNVs had high percentages of non-silent variants, emphasizing the unique roles of these Korean only SNVs in the Korean population. Specifically, we identified 8,361 non-synonymous Korean only SNVs, of which 58 SNVs existed in all 35 Korean individuals. The 5,754 genes of non-synonymous Korean only SNVs were highly enriched in some metabolic pathways. We found adhesion is the top disease term associated with SNV-1 and Nelson syndrome is the only disease term

  15. Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms.

    Science.gov (United States)

    Immonen, Elina; Hämäläinen, Anni; Schuett, Wiebke; Tarka, Maja

    2018-01-01

    Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration.

  16. Genetic architecture of the marbled goby Pomatoschistus marmoratus (Perciformes, Gobiidae) in the Mediterranean Sea.

    Science.gov (United States)

    Mejri, Randa; Arculeo, Marco; Hassine, Oum Kalthoum Ben; Brutto, Sabrina Lo

    2011-02-01

    The marbled goby Pomatoschistus marmoratus, a species inhabiting coastal Mediterranean lagoons, has been studied by measuring its mitochondrial DNA variation. This analysis revealed a Mediterranean west vs east split and, subsequently, an eastern differentiation among the Libyan-Tunisian Gulf, the Adriatic Sea and the Aegean Sea. The high cohesion between the samples collected in the vast area of western Mediterranean contrasts with the genetic mosaic of the more sub-structured eastern Mediterranean. This western homogeneity can not yet be fully explained even if a human-mediated migratory flow, due to a maritime traffic, has been posited. The pattern in the eastern basin revealed a genetic architecture possibly due to the non-migratory habit of the gobid. Within this perspective, the role of the Mediterranean lagoon habitat should be related to how much it amplifies the effects of historical (e.g. past sea-level changes) and environmental (e.g. present-day hydrographic regime) processes as regards the genetic structure of the inhabiting species. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. A Mobile Asset Tracking System Architecture under Mobile-Stationary Co-Existing WSNs

    Science.gov (United States)

    Kim, Tae Hyon; Jo, Hyeong Gon; Lee, Jae Shin; Kang, Soon Ju

    2012-01-01

    The tracking of multiple wireless mobile nodes is not easy with current legacy WSN technologies, due to their inherent technical complexity, especially when heavy traffic and frequent movement of mobile nodes are encountered. To enable mobile asset tracking under these legacy WSN systems, it is necessary to design a specific system architecture that can manage numerous mobile nodes attached to mobile assets. In this paper, we present a practical system architecture including a communication protocol, a three-tier network, and server-side middleware for mobile asset tracking in legacy WSNs consisting of mobile-stationary co-existing infrastructures, and we prove the functionality of this architecture through careful evaluation in a test bed. Evaluation was carried out in a microwave anechoic chamber as well as on a straight road near our office. We evaluated communication mobility performance between mobile and stationary nodes, location-awareness performance, system stability under numerous mobile node conditions, and the successful packet transfer rate according to the speed of the mobile nodes. The results indicate that the proposed architecture is sufficiently robust for application in realistic mobile asset tracking services that require a large number of mobile nodes. PMID:23242277

  18. A common genetic factor underlies hypertension and other cardiovascular disorders

    Directory of Open Access Journals (Sweden)

    Spector Tim D

    2004-11-01

    Full Text Available Abstract Background Certain conditions characterised by blood vessel occlusion or vascular spasm have been found to cluster together in epidemiological studies. However the biological causes for these associations remain controversial. This study used a classical twin design to examine whether these conditions are linked through shared environmental exposures or by a common underlying genetic propensity to vasospasm. Methods We investigated the association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease in twins from a national register. Phenotype status was determined using a questionnaire and the genetic and environmental association between phenotypes was estimated through variance components analysis. Results Responses were obtained from 2,204 individuals comprising 525 monozygotic and 577 dizygotic pairs. There was a significant genetic contribution to all four traits with heritabilities ranging from 0.34 to 0.64. Multivariate model-fitting demonstrated that a single common genetic factor underlies the four conditions. Conclusions We have confirmed an association between hypertension, migraine, Raynaud's phenomenon and coronary artery disease, and shown that a single genetic factor underlies them. The demonstration of a shared genetic factor explains the association between them and adds weight to the theory of an inherited predisposition to vasospasm.

  19. Organic solar cells under the BHJ approach using conventional/inverted architectures

    Science.gov (United States)

    Salinas, J. F.; Salto, C.; Maldonado, J. L.; Ramos-Ortíz, G.; Rodríguez, M.; Meneses-Nava, M. A.; Barbosa-García, Oracio; Farfán, N.; Santillan, R.

    2011-08-01

    The search of clean and renewable energy sources is one of the most important challenges that mankind confronts. Recently there has been a notable interest to develop organic photovoltaic (OPV) technology as a mean of renewable energy source since it combines low-cost and easy fabrication. Most of the efforts have been directed to increase the efficiency, leaving aside the durability of the organic materials, however, a new architecture known as inverted solar cell might bring a never seen durability (years) that could make possible large scale applications of this technology. Here are presented the results we achieved using both, the conventional and inverted architectures employing as organic donor (D) the very well known semi-conducting polymer P3HT, in mixtures with the acceptor (A) fullerene PC61BM. The morphology of thin polymer films prepared by using the spin coating technique was analyzed by AFM. For the conventional architecture the cells were fabricated following the structure ITO/PEDOT:PSS/P3HT:PC61BM/Wood´s metal, where the Wood´s metal cathode is an alloy that melts at 75 °C. For the inverted architecture the structure ITO/ZnO/P3HT:PC61BM /PEDOT:PSS/(Ag, Cu or Silver paint) was used, where ITO worked as cathode by switching its work function through the introduction of ZnO nanoparticles. Under tests using Xenon lamp irradiation at 100 mW/cm2, the conventional and the inverted architectures produced efficiencies of 1.75 % and 0.5 %, respectively. For both architectures the chosen back-contact materials (Wood´s metal and silver paint) allowed us to easily make the OPVs cells without the need of vacuum steps.

  20. Optimising electrical system architecture using genetic algorithms; Optimierung der Bordnetzarchitektur mit Hilfe genetischer Algorithmen

    Energy Technology Data Exchange (ETDEWEB)

    Luebke, A. [Volkswagen AG, Wolfsburg (Germany). Fahrzeug-Elektrik/ -Elektronik Vorentwicklung; Reuss, H.C. [Technische Univ. Dresden (Germany). Inst. fuer Verbrennungsmotoren und Kraftfahrzeuge

    2000-06-01

    Control units in vehicles are increasingly being networked. Framework conditions, for example the cost of network nodes, change so rapidly that an optimised network rarely survives one model generation. This article describes the possible applications of a genetic algorithm which can be used to optimise the architecture of the datanet quickly and easily. (orig.) [German] Die Vernetzung der Steuergeraete im Kraftfahrzeug nimmt staendig zu. Dabei aendern sich die Randbedingungen, zum Beispiel die Kosten von Netzknoten, laufend, so dass eine einmal optimierte Architektur der Vernetzung schon fuer das naechste Fahrzeugmodell nicht mehr das Optimum darstellt. Der vorliegende Artikel beschreibt die Anwendungsmoeglichkeit eines genetischen Algorithmus, mit dessen Hilfe sich die Architektur des Datennetzes schnell und zuverlaessig optimieren laesst. (orig.)

  1. Genetic architecture of a feeding adaptation: garter snake (Thamnophis) resistance to tetrodotoxin bearing prey.

    Science.gov (United States)

    Feldman, Chris R; Brodie, Edmund D; Brodie, Edmund D; Pfrender, Michael E

    2010-11-07

    Detailing the genetic basis of adaptive variation in natural populations is a first step towards understanding the process of adaptive evolution, yet few ecologically relevant traits have been characterized at the genetic level in wild populations. Traits that mediate coevolutionary interactions between species are ideal for studying adaptation because of the intensity of selection and the well-characterized ecological context. We have previously described the ecological context, evolutionary history and partial genetic basis of tetrodotoxin (TTX) resistance in garter snakes (Thamnophis). Derived mutations in a voltage-gated sodium channel gene (Na(v)1.4) in three garter snake species are associated with resistance to TTX, the lethal neurotoxin found in their newt prey (Taricha). Here we evaluate the contribution of Na(v)1.4 alleles to TTX resistance in two of those species from central coastal California. We measured the phenotypes (TTX resistance) and genotypes (Na(v)1.4 and microsatellites) in a local sample of Thamnophis atratus and Thamnophis sirtalis. Allelic variation in Na(v)1.4 explains 23 per cent of the variation in TTX resistance in T. atratus while variation in a haphazard sample of the genome (neutral microsatellite markers) shows no association with the phenotype. Similarly, allelic variation in Na(v)1.4 correlates almost perfectly with TTX resistance in T. sirtalis, but neutral variation does not. These strong correlations suggest that Na(v)1.4 is a major effect locus. The simple genetic architecture of TTX resistance in garter snakes may significantly impact the dynamics of phenotypic coevolution. Fixation of a few alleles of major effect in some garter snake populations may have led to the evolution of extreme phenotypes and an 'escape' from the arms race with newts.

  2. Candidate genes and genetic architecture of symbiotic and agronomic traits revealed by whole-genome, sequence-based association genetics in Medicago truncatula.

    Directory of Open Access Journals (Sweden)

    John Stanton-Geddes

    Full Text Available Genome-wide association study (GWAS has revolutionized the search for the genetic basis of complex traits. To date, GWAS have generally relied on relatively sparse sampling of nucleotide diversity, which is likely to bias results by preferentially sampling high-frequency SNPs not in complete linkage disequilibrium (LD with causative SNPs. To avoid these limitations we conducted GWAS with >6 million SNPs identified by sequencing the genomes of 226 accessions of the model legume Medicago truncatula. We used these data to identify candidate genes and the genetic architecture underlying phenotypic variation in plant height, trichome density, flowering time, and nodulation. The characteristics of candidate SNPs differed among traits, with candidates for flowering time and trichome density in distinct clusters of high linkage disequilibrium (LD and the minor allele frequencies (MAF of candidates underlying variation in flowering time and height significantly greater than MAF of candidates underlying variation in other traits. Candidate SNPs tagged several characterized genes including nodulation related genes SERK2, MtnodGRP3, MtMMPL1, NFP, CaML3, MtnodGRP3A and flowering time gene MtFD as well as uncharacterized genes that become candidates for further molecular characterization. By comparing sequence-based candidates to candidates identified by in silico 250K SNP arrays, we provide an empirical example of how reliance on even high-density reduced representation genomic makers can bias GWAS results. Depending on the trait, only 30-70% of the top 20 in silico array candidates were within 1 kb of sequence-based candidates. Moreover, the sequence-based candidates tagged by array candidates were heavily biased towards common variants; these comparisons underscore the need for caution when interpreting results from GWAS conducted with sparsely covered genomes.

  3. River network architecture, genetic effective size and distributional patterns predict differences in genetic structure across species in a dryland stream fish community.

    Science.gov (United States)

    Pilger, Tyler J; Gido, Keith B; Propst, David L; Whitney, James E; Turner, Thomas F

    2017-05-01

    Dendritic ecological network (DEN) architecture can be a strong predictor of spatial genetic patterns in theoretical and simulation studies. Yet, interspecific differences in dispersal capabilities and distribution within the network may equally affect species' genetic structuring. We characterized patterns of genetic variation from up to ten microsatellite loci for nine numerically dominant members of the upper Gila River fish community, New Mexico, USA. Using comparative landscape genetics, we evaluated the role of network architecture for structuring populations within species (pairwise F ST ) while explicitly accounting for intraspecific demographic influences on effective population size (N e ). Five species exhibited patterns of connectivity and/or genetic diversity gradients that were predicted by network structure. These species were generally considered to be small-bodied or habitat specialists. Spatial variation of N e was a strong predictor of pairwise F ST for two species, suggesting patterns of connectivity may also be influenced by genetic drift independent of network properties. Finally, two study species exhibited genetic patterns that were unexplained by network properties and appeared to be related to nonequilibrium processes. Properties of DENs shape community-wide genetic structure but effects are modified by intrinsic traits and nonequilibrium processes. Further theoretical development of the DEN framework should account for such cases. © 2017 John Wiley & Sons Ltd.

  4. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M.; McLaughlin, Russell L.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; Vosa, Urmo; de Jong, Simone; Robinson, Matthew R.; Yang, Jian; Fogh, Isabella; van Doormaal, Perry T. C.; Tazelaar, Gijs H. P.; Koppers, Max; Blokhuis, Anna M.; Sproviero, William; Jones, Ashley R.; Kenna, Kevin P.; van Eijk, Kristel R.; Harschnitz, Oliver; Schellevis, Raymond D.; Brands, William J.; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavac, Metka; Koritnik, Blazi; Zidar, Janez; Leonardis, Lea; Groselj, Leja Dolenc; Millecamps, Stephanie; Salachas, Francois; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-Garcia, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A.; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, A. Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safaa; Duerr, Alexandra; Wood, Nicholas W.; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Noethen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-Francois; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M.; van der Kooi, Anneke J.; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P.; D'Alfonso, Sandra; Bertolin, Cinzia; Soraru, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P.; Fifita, Jennifer A.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Grosskreutz, Julian; Witte, Otto W.; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Huebner, Christian A.; Leigh, P. Nigel; Casale, Federico; Chio, Adrian; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H.; Brown, Robert H.; Glass, Jonathan D.; Landers, John E.; Hardiman, Orla; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R.; Visscher, Peter M.; de Bakker, Paul I. W.; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H.; Veldink, Jan H.

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  5. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M.; McLaughlin, Russell L.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R.; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H. P.; Koppers, Max; Blokhuis, Anna M.; Sproviero, William; Jones, Ashley R.; Kenna, Kevin P.; van Eijk, Kristel R.; Harschnitz, Oliver; Schellevis, Raymond D.; Brands, William J.; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A.; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, A. Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W.; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M.; van der Kooi, Anneke J.; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; del Bo, Roberto; Comi, Giacomo P.; D'alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P.; Fifita, Jennifer A.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Grosskreutz, Julian; Witte, Otto W.; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A.; Leigh, P. Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; van Damme, Philip; Franke, Lude; Pers, Tune H.; Brown, Robert H.; Glass, Jonathan D.; Landers, John E.; Hardiman, Orla; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R.; Visscher, Peter M.; de Bakker, Paul I. W.; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H.; Veldink, Jan H.

    2016-01-01

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  6. Barking up the right trees: the influence of forest fire on the genetic architecture of bark thickness in southeastern pines

    OpenAIRE

    Friedline, Christopher

    2016-01-01

    Using next-generation, high-throughput sequencing, we will dissect bark thickness as a complex and adaptive, quantitative trait across populations of four closely related species with the goal of uncovering shared genetic architecture at multiple evolutionary time scales. 

  7. eQTL Networks Reveal Complex Genetic Architecture in the Immature Soybean Seed

    Directory of Open Access Journals (Sweden)

    Yung-Tsi Bolon

    2014-03-01

    Full Text Available The complex network of regulatory factors and interactions involved in transcriptional regulation within the seed is not well understood. To evaluate gene expression regulation in the immature seed, we utilized a genetical genomics approach on a soybean [ (L. Merr.] recombinant inbred line (RIL population and produced a genome-wide expression quantitative trait loci (eQTL dataset. The validity of the dataset was confirmed by mapping the eQTL hotspot for flavonoid biosynthesis-related genes to a region containing repeats of chalcone synthase (CHS genes known to correspond to the soybean inhibitor locus that regulates seed color. We then identified eQTL for genes with seed-specific expression and discovered striking eQTL hotspots at distinct genomic intervals on chromosomes (Chr 20, 7, and 13. The main eQTL hotspot for transcriptional regulation of fatty acid biosynthesis genes also coincided with regulation of oleosin genes. Transcriptional upregulation of genesets from eQTL with opposite allelic effects were also found. Gene–eQTL networks were constructed and candidate regulatory genes were identified from these three key loci specific to seed expression and enriched in genes involved in seed oil accumulation. Our data provides new insight into the complex nature of gene networks in the immature soybean seed and the genetic architecture that contributes to seed development.

  8. Genetic architecture of hybrid male sterility in Drosophila: analysis of intraspecies variation for interspecies isolation.

    Directory of Open Access Journals (Sweden)

    Laura K Reed

    Full Text Available BACKGROUND: The genetic basis of postzygotic isolation is a central puzzle in evolutionary biology. Evolutionary forces causing hybrid sterility or inviability act on the responsible genes while they still are polymorphic, thus we have to study these traits as they arise, before isolation is complete. METHODOLOGY/PRINCIPAL FINDINGS: Isofemale strains of D. mojavensis vary significantly in their production of sterile F(1 sons when females are crossed to D. arizonae males. We took advantage of the intraspecific polymorphism, in a novel design, to perform quantitative trait locus (QTL mapping analyses directly on F(1 hybrid male sterility itself. We found that the genetic architecture of the polymorphism for hybrid male sterility (HMS in the F(1 is complex, involving multiple QTL, epistasis, and cytoplasmic effects. CONCLUSIONS/SIGNIFICANCE: The role of extensive intraspecific polymorphism, multiple QTL, and epistatic interactions in HMS in this young species pair shows that HMS is arising as a complex trait in this system. Directional selection alone would be unlikely to maintain polymorphism at multiple loci, thus we hypothesize that directional selection is unlikely to be the only evolutionary force influencing postzygotic isolation.

  9. Retrospective Binary-Trait Association Test Elucidates Genetic Architecture of Crohn Disease

    Science.gov (United States)

    Jiang, Duo; Zhong, Sheng; McPeek, Mary Sara

    2016-01-01

    In genetic association testing, failure to properly control for population structure can lead to severely inflated type 1 error and power loss. Meanwhile, adjustment for relevant covariates is often desirable and sometimes necessary to protect against spurious association and to improve power. Many recent methods to account for population structure and covariates are based on linear mixed models (LMMs), which are primarily designed for quantitative traits. For binary traits, however, LMM is a misspecified model and can lead to deteriorated performance. We propose CARAT, a binary-trait association testing approach based on a mixed-effects quasi-likelihood framework, which exploits the dichotomous nature of the trait and achieves computational efficiency through estimating equations. We show in simulation studies that CARAT consistently outperforms existing methods and maintains high power in a wide range of population structure settings and trait models. Furthermore, CARAT is based on a retrospective approach, which is robust to misspecification of the phenotype model. We apply our approach to a genome-wide analysis of Crohn disease, in which we replicate association with 17 previously identified regions. Moreover, our analysis on 5p13.1, an extensively reported region of association, shows evidence for the presence of multiple independent association signals in the region. This example shows how CARAT can leverage known disease risk factors to shed light on the genetic architecture of complex traits. PMID:26833331

  10. Hardware Genetic Algorithm Optimization by Critical Path Analysis using a Custom VLSI Architecture

    Directory of Open Access Journals (Sweden)

    Farouk Smith

    2015-07-01

    Full Text Available This paper propose a Virtual-Field Programmable Gate Array (V-FPGA architecture that allows direct access to its configuration bits to facilitate hardware evolution, thereby allowing any combinational or sequential digital circuit to be realized. By using the V-FPGA, this paper investigates two possible ways of making evolutionary hardware systems more scalable: by optimizing the system’s genetic algorithm (GA; and by decomposing the solution circuit into smaller, evolvable sub-circuits. GA optimization is done by: omitting a canonical GA’s crossover operator (i.e. by using a 1+λ algorithm; applying evolution constraints; and optimizing the fitness function. A noteworthy contribution this research has made is the in-depth analysis of the phenotypes’ CPs. Through analyzing the CPs, it has been shown that a great amount of insight can be gained into a phenotype’s fitness. We found that as the number of columns in the Cartesian Genetic Programming array increases, so the likelihood of an external output being placed in the column decreases. Furthermore, the number of used LEs per column also substantially decreases per added column. Finally, we demonstrated the evolution of a state-decomposed control circuit. It was shown that the evolution of each state’s sub-circuit was possible, and suggest that modular evolution can be a successful tool when dealing with scalability.

  11. The Evolving Neural and Genetic Architecture of Vertebrate Olfaction.

    Science.gov (United States)

    Bear, Daniel M; Lassance, Jean-Marc; Hoekstra, Hopi E; Datta, Sandeep Robert

    2016-10-24

    Evolution sculpts the olfactory nervous system in response to the unique sensory challenges facing each species. In vertebrates, dramatic and diverse adaptations to the chemical environment are possible because of the hierarchical structure of the olfactory receptor (OR) gene superfamily: expansion or contraction of OR subfamilies accompanies major changes in habitat and lifestyle; independent selection on OR subfamilies can permit local adaptation or conserved chemical communication; and genetic variation in single OR genes can alter odor percepts and behaviors driven by precise chemical cues. However, this genetic flexibility contrasts with the relatively fixed neural architecture of the vertebrate olfactory system, which requires that new olfactory receptors integrate into segregated and functionally distinct neural pathways. This organization allows evolution to couple critical chemical signals with selectively advantageous responses, but also constrains relationships between olfactory receptors and behavior. The coevolution of the OR repertoire and the olfactory system therefore reveals general principles of how the brain solves specific sensory problems and how it adapts to new ones. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Genome-wide association and epistasis studies unravel the genetic architecture of sudden death syndrome resistance in soybean.

    Science.gov (United States)

    Zhang, Jiaoping; Singh, Arti; Mueller, Daren S; Singh, Asheesh K

    2015-12-01

    Soybean [Glycine max (L.) Merr.] is an economically important crop that is grown worldwide. Sudden death syndrome (SDS), caused by Fusarium virguliforme, is one of the top yield-limiting diseases in soybean. However, the genetic basis of SDS resistance, especially with respect to epistatic interactions, is still unclear. To better understand the genetic architecture of soybean SDS resistance, genome-wide association and epistasis studies were performed using a population of 214 germplasm accessions and 31,914 SNPs from the SoySNP50K Illumina Infinium BeadChip. Twelve loci and 12 SNP-SNP interactions associated with SDS resistance were identified at various time points after inoculation. These additive and epistatic loci together explained 24-52% of the phenotypic variance. Disease-resistant, pathogenesis-related and chitin- and wound-responsive genes were identified in the proximity of peak SNPs, including stress-induced receptor-like kinase gene 1 (SIK1), which is pinpointed by a trait-associated SNP and encodes a leucine-rich repeat-containing protein. We report that the proportion of phenotypic variance explained by identified loci may be considerably improved by taking epistatic effects into account. This study shows the necessity of considering epistatic effects in soybean SDS resistance breeding using marker-assisted and genomic selection approaches. Based on our findings, we propose a model for soybean root defense against the SDS pathogen. Our results facilitate identification of the molecular mechanism underlying SDS resistance in soybean, and provide a genetic basis for improvement of soybean SDS resistance through breeding strategies based on additive and epistatic effects. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  13. Use of biological priors enhances understanding of genetic architecture and genomic prediction of complex traits within and between dairy cattle breeds

    DEFF Research Database (Denmark)

    Fang, Lingzhao; Sahana, Goutam; Ma, Peipei

    2017-01-01

    sequence variants in Holstein (HOL) and Jersey (JER) cattle were analysed. We first carried out a post-GWAS analysis in a HOL training population to assess the degree of enrichment of the association signals in the gene regions defined by each GO term. We then extended the genomic best linear unbiased......BACKGROUND: A better understanding of the genetic architecture underlying complex traits (e.g., the distribution of causal variants and their effects) may aid in the genomic prediction. Here, we hypothesized that the genomic variants of complex traits might be enriched in a subset of genomic...

  14. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Directory of Open Access Journals (Sweden)

    Chiao-Ling Lo

    2016-08-01

    Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  15. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Science.gov (United States)

    Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

    2016-08-01

    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  16. Family-assisted inference of the genetic architecture of major histocompatibility complex variation.

    Science.gov (United States)

    Gaigher, A; Burri, R; Gharib, W H; Taberlet, P; Roulin, A; Fumagalli, L

    2016-11-01

    With their direct link to individual fitness, genes of the major histocompatibility complex (MHC) are a popular system to study the evolution of adaptive genetic diversity. However, owing to the highly dynamic evolution of the MHC region, the isolation, characterization and genotyping of MHC genes remain a major challenge. While high-throughput sequencing technologies now provide unprecedented resolution of the high allelic diversity observed at the MHC, in many species, it remains unclear (i) how alleles are distributed among MHC loci, (ii) whether MHC loci are linked or segregate independently and (iii) how much copy number variation (CNV) can be observed for MHC genes in natural populations. Here, we show that the study of allele segregation patterns within families can provide significant insights in this context. We sequenced two MHC class I (MHC-I) loci in 1267 European barn owls (Tyto alba), including 590 offspring from 130 families using Illumina MiSeq technology. Coupled with a high per-individual sequencing coverage (~3000×), the study of allele segregation patterns within families provided information on three aspects of the architecture of MHC-I variation in barn owls: (i) extensive sharing of alleles among loci, (ii) strong linkage of MHC-I loci indicating tandem architecture and (iii) the presence of CNV in the barn owl MHC-I. We conclude that the additional information that can be gained from high-coverage amplicon sequencing by investigating allele segregation patterns in families not only helps improving the accuracy of MHC genotyping, but also contributes towards enhanced analyses in the context of MHC evolutionary ecology. © 2016 John Wiley & Sons Ltd.

  17. Genetic architecture and bottleneck analyses of Salem Black goat breed based on microsatellite markers

    Directory of Open Access Journals (Sweden)

    A. K. Thiruvenkadan

    2014-09-01

    Full Text Available Aim: The present study was undertaken in Salem Black goat population for genetic analysis at molecular level to exploit the breed for planning sustainable improvement, conservation and utilization, which subsequently can improve the livelihood of its stakeholders. Materials and Methods: Genomic DNA was isolated from blood samples of 50 unrelated Salem Black goats with typical phenotypic features in several villages in the breeding tract and the genetic characterization and bottleneck analysis in Salem Black goat was done using 25 microsatellite markers as recommended by the Food and Agricultural Organization, Rome, Italy. The basic measures of genetic variation were computed using bioinformatic software. To evaluate the Salem Black goats for mutation drift equilibrium, three tests were performed under three different mutation models, viz., infinite allele model (IAM, stepwise mutation model (SMM and two-phase model (TPM and the observed gene diversity (He and expected equilibrium gene diversity (Heq were estimated under different models of microsatellite evolution. Results: The study revealed that the observed number of alleles ranged from 4 (ETH10, ILSTS008 to 17 (BM64444 with a total of 213 alleles and mean of 10.14±0.83 alleles across loci. The overall observed heterozygosity, expected heterozygosity, inbreeding estimate and polymorphism information content values were 0.631±0.041, 0.820±0.024, 0.233±0.044 and 0.786±0.023 respectively indicating high genetic diversity. The average observed gene diversities (He pooled over different markers was 0.829±0.024 and the average expected gene diversities under IAM, TPM and SMM models were 0.769±0.026, 0.808±0.024 and 0.837±0.020 respectively. The number of loci found to exhibit gene diversity excess under IAM, TPM and SMM models were 18, 17 and 12 respectively. Conclusion: All the three statistical tests, viz., sign test, standardized differences test and Wilcoxon sign rank test, revealed

  18. Homogeneous genetic structure and variation in tree architecture of Larix kaempferi along altitudinal gradients on Mt. Fuji.

    Science.gov (United States)

    Nishimura, Masao; Setoguchi, Hiroaki

    2011-03-01

    Variations in tree architecture and in the genetic structure of Larix kaempferi on Mt. Fuji were surveyed along altitudinal gradients using 11 nSSR loci. In total, 249 individuals from six populations along three trails at altitudes ranging from approximately 1,300 to 2,700 m were investigated. Gradual changes in tree architecture with increasing elevation, from erect trees to flag trees and krummholz mats, were observed in the high-altitude populations (> 2,000 m) on all trails. These findings suggest that tree architecture is correlated with the severe environmental conditions associated with increasing elevation, such as strong winds. In contrast to obvious variations in tree architecture, the genetic diversity of populations along the trails was almost uniform (H (E) = 0.717-0.762) across the altitudinal range. The results of the AMOVA and STRUCTURE analyses, and the analysis for isolation by distance pattern, suggest homogeneous genetic structuring across all populations on Mt. Fuji, while the pairwise F (ST) showed barriers to gene flow between altitudinal populations that were demarcated as high- or low-altitude populations by Abies-Tsuga forest. Although the evergreen coniferous forests on the mountainside may hinder gene flow, this may be explained by the long-distance seed dispersal of the Japanese larch and/or a short population history resulting from eruptions or slush avalanches, although evergreen coniferous forests on the mountainside may hinder gene flow.

  19. Genetic Architecture of Vitamin B12 and Folate Levels Uncovered Applying Deeply Sequenced Large Datasets

    OpenAIRE

    Grarup, Niels; Sulem, Patrick; Sandholt, Camilla H.; Thorleifsson, Gudmar; Ahluwalia, Tarunveer S.; Steinthorsdottir, Valgerdur; Bjarnason, Helgi; Gudbjartsson, Daniel F.; Magnusson, Olafur T.; Spars?, Thomas; Albrechtsen, Anders; Kong, Augustine; Masson, Gisli; Tian, Geng; Cao, Hongzhi

    2013-01-01

    Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architectu...

  20. Shapes and geometries underlying the religious architecture in the 18th century

    Directory of Open Access Journals (Sweden)

    Sebastiano Giuliano

    2015-07-01

    of great renovation, known as the” Sicilian Baroque”.The second part of this research makes use of a very accurate graphic analysis aiming at understanding the sizing and proportioning methodologies which were used in the design phase.Sizes and proportions are essential to understand the work in its overall shape; they also make comparisons possible, regardless the sculptural and decorative apparatus and its architectural shape.The discovery  of the underlying geometrical and reference patterns allows the researchers to make some hypothesis on the proportions of the project, even if there are no drawings.; the main goal is to understand the origin of the project so as to identify the simple pattern to which all probable similarities or differences can be referred. Therefore the geometrical analysis is the way through which it is possible to study the design method of valuable works in Eastern Sicily.As altars are integral parts of churches, "actual architectures inside the architecture", expression of the complexity and the conformative dynamism of the baroque architecture, this research is based on these valuable elements, whose intermingling of shapes, functions and meanings, leads, from a figurative point of view, to some constructions which are very similar to facades.If the project design is a graphic-historical document telling about the geometrical apparatus of the architectural element in its formal and symbolic relationships, the survey carried out through advanced technologies is fundamental in the backwards survey.The comparison with the works of the age and the graphic analysis of the architectures on both small and big scales, tries to reveal and give back all those relationships which are at the origin of the design project and which have granted their conveyance to the different dimensional levels and their disclosure in  relatively distant areas.

  1. Poor Consumer Comprehension and Plan Selection Inconsistencies Under the 2016 Choice Architecture

    Directory of Open Access Journals (Sweden)

    Annabel Z. Wang BA

    2017-06-01

    Full Text Available Background: Many health policy experts have endorsed insurance competition as a way to reduce the cost and improve the quality of medical care. In line with this approach, health insurance exchanges, such as HealthCare.gov , allow consumers to compare insurance plans online. Since the 2013 rollout of HealthCare.gov , administrators have added features intended to help consumers better understand and compare insurance plans. Although well-intentioned, changes to exchange websites affect the context in which consumers view plans, or choice architecture, which may impede their ability to choose plans that best fit their needs at the lowest cost. Methods: By simulating the 2016 HealthCare.gov enrollment experience in an online sample of 374 American adults, we examined comprehension and choice of HealthCare.gov plans under its choice architecture. Results: We found room for improvement in plan comprehension, with higher rates of misunderstanding among participants with poor math skills ( P 0.9. Limitations: Participants were drawn from a general population sample. The study does not assess for all possible plan choice influencers, such as provider networks, brand recognition, or help from others. Conclusions: Our findings suggest two areas of improvement for exchanges: first, the remaining gap in consumer plan comprehension and, second, the apparent influence of sorting order—and likely other choice architecture elements—on plan choice. Our findings inform strategies for exchange administrators to help consumers understand and select plans that better fit their needs.

  2. Genetic and physiological controls of growth under water deficit.

    Science.gov (United States)

    Tardieu, François; Parent, Boris; Caldeira, Cecilio F; Welcker, Claude

    2014-04-01

    The sensitivity of expansive growth to water deficit has a large genetic variability, which is higher than that of photosynthesis. It is observed in several species, with some genotypes stopping growth in a relatively wet soil, whereas others continue growing until the lower limit of soil-available water. The responses of growth to soil water deficit and evaporative demand share an appreciable part of their genetic control through the colocation of quantitative trait loci as do the responses of the growth of different organs to water deficit. This result may be caused by common mechanisms of action discussed in this paper (particularly, plant hydraulic properties). We propose that expansive growth, putatively linked to hydraulic processes, determines the sink strength under water deficit, whereas photosynthesis determines source strength. These findings have large consequences for plant modeling under water deficit and for the design of breeding programs.

  3. Search for Genetic Variants Underlying Musical Aptitude and Related Traits

    OpenAIRE

    Ukkola-Vuoti, Liisa

    2013-01-01

    Music perception and practice represents complex cognitive functions of the brain. There is an abundance of data about the neurophysiological effects of music on the human brain, but heritability and especially molecular studies have been lacking. The development of genome technologies and bioinformatics has enabled the identification of genetic variants underlying complex human traits. These methods can be applied to normal human traits like music perception and performance. Prior to th...

  4. Sexually antagonistic selection on genetic variation underlying both male and female same-sex sexual behavior.

    Science.gov (United States)

    Berger, David; You, Tao; Minano, Maravillas R; Grieshop, Karl; Lind, Martin I; Arnqvist, Göran; Maklakov, Alexei A

    2016-05-13

    Intralocus sexual conflict, arising from selection for different alleles at the same locus in males and females, imposes a constraint on sex-specific adaptation. Intralocus sexual conflict can be alleviated by the evolution of sex-limited genetic architectures and phenotypic expression, but pleiotropic constraints may hinder this process. Here, we explored putative intralocus sexual conflict and genetic (co)variance in a poorly understood behavior with near male-limited expression. Same-sex sexual behaviors (SSBs) generally do not conform to classic evolutionary models of adaptation but are common in male animals and have been hypothesized to result from perception errors and selection for high male mating rates. However, perspectives incorporating sex-specific selection on genes shared by males and females to explain the expression and evolution of SSBs have largely been neglected. We performed two parallel sex-limited artificial selection experiments on SSB in male and female seed beetles, followed by sex-specific assays of locomotor activity and male sex recognition (two traits hypothesized to be functionally related to SSB) and adult reproductive success (allowing us to assess fitness consequences of genetic variance in SSB and its correlated components). Our experiments reveal both shared and sex-limited genetic variance for SSB. Strikingly, genetically correlated responses in locomotor activity and male sex-recognition were associated with sexually antagonistic fitness effects, but these effects differed qualitatively between male and female selection lines, implicating intralocus sexual conflict at both male- and female-specific genetic components underlying SSB. Our study provides experimental support for the hypothesis that widespread pleiotropy generates pervasive intralocus sexual conflict governing the expression of SSBs, suggesting that SSB in one sex can occur due to the expression of genes that carry benefits in the other sex.

  5. Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures

    Science.gov (United States)

    Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland

    1998-01-01

    Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.

  6. Genome-wide expression patterns and the genetic architecture of a fundamental social trait.

    Science.gov (United States)

    Wang, John; Ross, Kenneth G; Keller, Laurent

    2008-07-18

    Explaining how interactions between genes and the environment influence social behavior is a fundamental research goal, yet there is limited relevant information for species exhibiting natural variation in social organization. The fire ant Solenopsis invicta is characterized by a remarkable form of social polymorphism, with the presence of one or several queens per colony and the expression of other phenotypic and behavioral differences being completely associated with allelic variation at a single Mendelian factor marked by the gene Gp-9. Microarray analyses of adult workers revealed that differences in the Gp-9 genotype are associated with the differential expression of an unexpectedly small number of genes, many of which have predicted functions, implying a role in chemical communication relevant to the regulation of colony queen number. Even more surprisingly, worker gene expression profiles are more strongly influenced by indirect effects associated with the Gp-9 genotypic composition within their colony than by the direct effect of their own Gp-9 genotype. This constitutes an unusual example of an "extended phenotype" and suggests a complex genetic architecture with a single Mendelian factor, directly and indirectly influencing the individual behaviors that, in aggregate, produce an emergent colony-level phenotype.

  7. Genetic architecture of fusarium head blight resistance in four winter triticale populations.

    Science.gov (United States)

    Kalih, R; Maurer, H P; Miedaner, T

    2015-03-01

    Fusarium head blight (FHB) is a devastating disease that causes significant reductions in yield and quality in wheat, rye, and triticale. In triticale, knowledge of the genetic architecture of FHB resistance is missing but essential due to modern breeding requirements. In our study, four doubled-haploid triticale populations (N=120 to 200) were evaluated for resistance to FHB caused by artificial inoculation with Fusarium culmorum in four environments. DArT markers were used to genotype triticale populations. Seventeen quantitative trait loci (QTL) for FHB resistance were detected across all populations; six of them were derived from rye genome and located on chromosomes 4R, 5R, and 7R, which are here reported for the first time. The total cross-validated ratio of the explained phenotypic variance for all detected QTL in each population was 41 to 68%. In all, 17 QTL for plant height and 18 QTL for heading stage were also detected across all populations; 3 and 5 of them, respectively, were overlapping with QTL for FHB. In conclusion, FHB resistance in triticale is caused by a multitude of QTL, and pyramiding them contributes to higher resistance.

  8. Identifying the genetic components underlying the pathophysiology of movement disorders

    Directory of Open Access Journals (Sweden)

    Ezquerra M

    2011-06-01

    Full Text Available Mario Ezquerra, Yaroslau Compta, Maria J MartiParkinson’s Disease and Movement Disorders Unit, Service of Neurology, Institute of Clinical Neurosciences, Hospital Clinic of Barcelona, IDIBAPS, CIBERNED, SpainAbstract: Movement disorders are a heterogeneous group of neurological conditions, few of which have been classically described as bona fide hereditary illnesses (Huntington’s chorea, for instance. Most are considered to be either sporadic or to feature varying degrees of familial aggregation (parkinsonism and dystonia. In the late twentieth century, Mendelian monogenic mutations were found for movement disorders with a clear and consistent family history. Although important, these findings apply only to very rare forms of movement disorders. Already in the twenty-first century, and taking advantage of the modern developments in genetics and molecular biology, growing attention is being paid to the complex genetics of movement disorders. The search for risk genetic variants (polymorphisms in large cohorts and the identification of different risk variants across different populations and ethnic groups are under way, with the most relevant findings to date corresponding to recent genome wide association studies in Parkinson’s disease. These new approaches focusing on risk variants may enable the design of screening tests for early or even preclinical disease, and the identification of likely therapeutic targets.Keywords: genetics, movement disorders, Parkinson’s disease, parkinsonism, dystonia

  9. Architectural prototyping

    DEFF Research Database (Denmark)

    Bardram, Jakob Eyvind; Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2004-01-01

    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights...

  10. Architectural Prototyping

    DEFF Research Database (Denmark)

    Bardram, Jakob; Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2004-01-01

    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights...

  11. The genetic architecture of defence as resistance to and tolerance of bacterial infection in Drosophila melanogaster.

    Science.gov (United States)

    Howick, Virginia M; Lazzaro, Brian P

    2017-03-01

    Defence against pathogenic infection can take two forms: resistance and tolerance. Resistance is the ability of the host to limit a pathogen burden, whereas tolerance is the ability to limit the negative consequences of infection at a given level of infection intensity. Evolutionarily, a tolerance strategy that is independent of resistance could allow the host to avoid mounting a costly immune response and, theoretically, to avoid a co-evolutionary arms race between pathogen virulence and host resistance. Biomedically, understanding the mechanisms of tolerance and how they relate to resistance could potentially yield treatment strategies that focus on health improvement instead of pathogen elimination. To understand the impact of tolerance on host defence and identify genetic variants that determine host tolerance, we defined genetic variation in tolerance as the residual deviation from a binomial regression of fitness under infection against infection intensity. We then performed a genomewide association study to map the genetic basis of variation in resistance to and tolerance of infection by the bacterium Providencia rettgeri. We found a positive genetic correlation between resistance and tolerance, and we demonstrated that the level of resistance is highly predictive of tolerance. We identified 30 loci that predict tolerance, many of which are in genes involved in the regulation of immunity and metabolism. We used RNAi to confirm that a subset of mapped genes have a role in defence, including putative wound repair genes grainy head and debris buster. Our results indicate that tolerance is not an independent strategy from resistance, but that defence arises from a collection of physiological processes intertwined with canonical immunity and resistance. © 2017 John Wiley & Sons Ltd.

  12. Genome-wide association study identified genetic variations and candidate genes for plant architecture component traits in Chinese upland cotton.

    Science.gov (United States)

    Su, Junji; Li, Libei; Zhang, Chi; Wang, Caixiang; Gu, Lijiao; Wang, Hantao; Wei, Hengling; Liu, Qibao; Huang, Long; Yu, Shuxun

    2018-03-01

    Thirty significant associations between 22 SNPs and five plant architecture component traits in Chinese upland cotton were identified via GWAS. Four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits. A candidate gene, Gh_D03G0922, might be responsible for plant height in upland cotton. A compact plant architecture is increasingly required for mechanized harvesting processes in China. Therefore, cotton plant architecture is an important trait, and its components, such as plant height, fruit branch length and fruit branch angle, affect the suitability of a cultivar for mechanized harvesting. To determine the genetic basis of cotton plant architecture, a genome-wide association study (GWAS) was performed using a panel composed of 355 accessions and 93,250 single nucleotide polymorphisms (SNPs) identified using the specific-locus amplified fragment sequencing method. Thirty significant associations between 22 SNPs and five plant architecture component traits were identified via GWAS. Most importantly, four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits, and these SNPs were harbored in one linkage disequilibrium block. Furthermore, 21 candidate genes for plant architecture were predicted in a 0.95-Mb region including the four peak SNPs. One of these genes (Gh_D03G0922) was near the significant SNP D03_31584163 (8.40 kb), and its Arabidopsis homologs contain MADS-box domains that might be involved in plant growth and development. qRT-PCR showed that the expression of Gh_D03G0922 was upregulated in the apical buds and young leaves of the short and compact cotton varieties, and virus-induced gene silencing (VIGS) proved that the silenced plants exhibited increased PH. These results indicate that Gh_D03G0922 is likely the candidate gene for PH in cotton. The genetic variations and candidate genes identified in this study lay a foundation

  13. Genetic architecture of sensory exploitation: QTL mapping of female and male receiver traits in an acoustic moth.

    Science.gov (United States)

    Alem, S; Streiff, R; Courtois, B; Zenboudji, S; Limousin, D; Greenfield, M D

    2013-12-01

    The evolution of extravagant sexual traits by sensory exploitation occurs if males incidentally evolve features that stimulate females owing to a pre-existing environmental response that arose in the context of natural selection. The sensory exploitation process is thus expected to leave a specific genetic imprint, a pleiotropic control of the original environmental response and the novel sexual response in females. However, females may be subsequently selected to improve their discrimination of environmental and sexual stimuli. Accordingly, responses may have diverged and the original genetic architecture may have been modified. These possibilities may be considered by studying the genetic architecture of responses to male signals and to the environmental stimuli that were purportedly 'exploited' by those signals. However, no previous study has addressed the genetic control of sensory exploitation. We investigated this question in an acoustic pyralid moth, Achroia grisella, in which a male ultrasonic song attracts females and perception of ultrasound likely arose in the context of detecting predatory bats. We examined the genetic architecture of female response to bat echolocation signals and to male song via a cartographic study of quantitative trait loci (QTL) influencing these receiver traits. We found several QTL for both traits, but none of them were colocalized on the same chromosomes. These results indicate that - to the extent to which male A. grisella song originated by the process of sensory exploitation - some modification of the female responses occurred since the origin of the male signal. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  14. Invertebrate Trehalose-6-Phosphate Synthase Gene: Genetic Architecture, Biochemistry, Physiological Function, and Potential Applications

    Directory of Open Access Journals (Sweden)

    Bin Tang

    2018-01-01

    Full Text Available The non-reducing disaccharide trehalose is widely distributed among various organisms. It plays a crucial role as an instant source of energy, being the major blood sugar in insects. In addition, it helps countering abiotic stresses. Trehalose synthesis in insects and other invertebrates is thought to occur via the trehalose-6-phosphate synthase (TPS and trehalose-6-phosphate phosphatase (TPP pathways. In many insects, the TPP gene has not been identified, whereas multiple TPS genes that encode proteins harboring TPS/OtsA and TPP/OtsB conserved domains have been found and cloned in the same species. The function of the TPS gene in insects and other invertebrates has not been reviewed in depth, and the available information is quite fragmented. The present review discusses the current understanding of the trehalose synthesis pathway, TPS genetic architecture, biochemistry, physiological function, and potential sensitivity to insecticides. We note the variability in the number of TPS genes in different invertebrate species, consider whether trehalose synthesis may rely only on the TPS gene, and discuss the results of in vitro TPS overexpression experiment. Tissue expression profile and developmental characteristics of the TPS gene indicate that it is important in energy production, growth and development, metamorphosis, stress recovery, chitin synthesis, insect flight, and other biological processes. We highlight the molecular and biochemical properties of insect TPS that make it a suitable target of potential pest control inhibitors. The application of trehalose synthesis inhibitors is a promising direction in insect pest control because vertebrates do not synthesize trehalose; therefore, TPS inhibitors would be relatively safe for humans and higher animals, making them ideal insecticidal agents without off-target effects.

  15. Invertebrate Trehalose-6-Phosphate Synthase Gene: Genetic Architecture, Biochemistry, Physiological Function, and Potential Applications

    Science.gov (United States)

    Tang, Bin; Wang, Su; Wang, Shi-Gui; Wang, Hui-Juan; Zhang, Jia-Yong; Cui, Shuai-Ying

    2018-01-01

    The non-reducing disaccharide trehalose is widely distributed among various organisms. It plays a crucial role as an instant source of energy, being the major blood sugar in insects. In addition, it helps countering abiotic stresses. Trehalose synthesis in insects and other invertebrates is thought to occur via the trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP) pathways. In many insects, the TPP gene has not been identified, whereas multiple TPS genes that encode proteins harboring TPS/OtsA and TPP/OtsB conserved domains have been found and cloned in the same species. The function of the TPS gene in insects and other invertebrates has not been reviewed in depth, and the available information is quite fragmented. The present review discusses the current understanding of the trehalose synthesis pathway, TPS genetic architecture, biochemistry, physiological function, and potential sensitivity to insecticides. We note the variability in the number of TPS genes in different invertebrate species, consider whether trehalose synthesis may rely only on the TPS gene, and discuss the results of in vitro TPS overexpression experiment. Tissue expression profile and developmental characteristics of the TPS gene indicate that it is important in energy production, growth and development, metamorphosis, stress recovery, chitin synthesis, insect flight, and other biological processes. We highlight the molecular and biochemical properties of insect TPS that make it a suitable target of potential pest control inhibitors. The application of trehalose synthesis inhibitors is a promising direction in insect pest control because vertebrates do not synthesize trehalose; therefore, TPS inhibitors would be relatively safe for humans and higher animals, making them ideal insecticidal agents without off-target effects. PMID:29445344

  16. Unraveling the genetic architecture of environmental variance of somatic cell score using high-density single nucleotide polymorphism and cow data from experimental farms.

    Science.gov (United States)

    Mulder, H A; Crump, R E; Calus, M P L; Veerkamp, R F

    2013-01-01

    In recent years, it has been shown that not only is the phenotype under genetic control, but also the environmental variance. Very little, however, is known about the genetic architecture of environmental variance. The main objective of this study was to unravel the genetic architecture of the mean and environmental variance of somatic cell score (SCS) by identifying genome-wide associations for mean and environmental variance of SCS in dairy cows and by quantifying the accuracy of genome-wide breeding values. Somatic cell score was used because previous research has shown that the environmental variance of SCS is partly under genetic control and reduction of the variance of SCS by selection is desirable. In this study, we used 37,590 single nucleotide polymorphism (SNP) genotypes and 46,353 test-day records of 1,642 cows at experimental research farms in 4 countries in Europe. We used a genomic relationship matrix in a double hierarchical generalized linear model to estimate genome-wide breeding values and genetic parameters. The estimated mean and environmental variance per cow was used in a Bayesian multi-locus model to identify SNP associated with either the mean or the environmental variance of SCS. Based on the obtained accuracy of genome-wide breeding values, 985 and 541 independent chromosome segments affecting the mean and environmental variance of SCS, respectively, were identified. Using a genomic relationship matrix increased the accuracy of breeding values relative to using a pedigree relationship matrix. In total, 43 SNP were significantly associated with either the mean (22) or the environmental variance of SCS (21). The SNP with the highest Bayes factor was on chromosome 9 (Hapmap31053-BTA-111664) explaining approximately 3% of the genetic variance of the environmental variance of SCS. Other significant SNP explained less than 1% of the genetic variance. It can be concluded that fewer genomic regions affect the environmental variance of SCS than the

  17. Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease

    NARCIS (Netherlands)

    van der Harst, Pim; Verweij, Niek

    2018-01-01

    Rationale: Coronary artery disease (CAD) is a complex phenotype driven by genetic and environmental factors. Ninety-seven genetic risk loci have been identified to date, but the identification of additional susceptibility loci might be important to enhance our understanding of the genetic

  18. Genetic architecture of the F7 gene in a Spanish population: implication for mapping complex diseases and for functional assays.

    Science.gov (United States)

    Sabater-Lleal, M; Almasy, L; Martínez-Marchán, E; Martínez-Sánchez, E; Souto, R; Blangero, J; Souto, Jc; Fontcuberta, J; Soria, J M

    2006-05-01

    Delineating the genetic variability of loci coding for complex diseases helps to understand the individual variation in disease susceptibility and drug response. We present the allelic architecture of the F7 gene. This gene is the major determinant of FVII plasma levels, and these plasma levels constitute an important intermediate risk factor for cardiovascular disease. As part of the Genetic Analysis of Idiopathic Thrombophila Project, we completely re-sequenced the F7 locus (promoter, exons, introns, and 3'-untranslated region) in 40 unrelated individuals. We found 49 polymorphisms with only two amino acid changes suggesting that regulatory non-coding and intronic variants are responsible for the FVII variability. These results are important for mapping susceptibility alleles of complex diseases, because differences in pair-wise linkage disequilibrium patterns between DNA variants and haplotype frequency distributions may help to detect disease-associated alleles. In addition, we present the results of an in silico search that established genomic comparisons among different species. In conclusion, our study of the F7 DNA sequence variations is an example of a strategy for analyzing the genetic architecture of a quantitative trait locus. Furthermore, it provides a model for future analyses of genetic factors that contribute to the susceptibility of complex diseases in humans.

  19. Artificial selection on introduced Asian haplotypes shaped the genetic architecture in European commercial pigs.

    Science.gov (United States)

    Bosse, Mirte; Lopes, Marcos S; Madsen, Ole; Megens, Hendrik-Jan; Crooijmans, Richard P M A; Frantz, Laurent A F; Harlizius, Barbara; Bastiaansen, John W M; Groenen, Martien A M

    2015-12-22

    Early pig farmers in Europe imported Asian pigs to cross with their local breeds in order to improve traits of commercial interest. Current genomics techniques enabled genome-wide identification of these Asian introgressed haplotypes in modern European pig breeds. We propose that the Asian variants are still present because they affect phenotypes that were important for ancient traditional, as well as recent, commercial pig breeding. Genome-wide introgression levels were only weakly correlated with gene content and recombination frequency. However, regions with an excess or absence of Asian haplotypes (AS) contained genes that were previously identified as phenotypically important such as FASN, ME1, and KIT. Therefore, the Asian alleles are thought to have an effect on phenotypes that were historically under selection. We aimed to estimate the effect of AS in introgressed regions in Large White pigs on the traits of backfat (BF) and litter size. The majority of regions we tested that retained Asian deoxyribonucleic acid (DNA) showed significantly increased BF from the Asian alleles. Our results suggest that the introgression in Large White pigs has been strongly determined by the selective pressure acting upon the introgressed AS. We therefore conclude that human-driven hybridization and selection contributed to the genomic architecture of these commercial pigs. © 2015 The Author(s).

  20. [Men of the sugarcane fields and their hospitals: the architecture of health under the Estado Novo].

    Science.gov (United States)

    Monteiro, Marcia Rocha

    2011-12-01

    The article explores the emergence of an architectural heritage in the realm of healthcare assistance for workers in the sugarcane agroindustry in Brazil following enactment of the law known as the Estatuto da Lavoura Canavieira (1941), under the auspices of the Instituto do Açúcar e do Álcool and as part of Estado Novo policies (1937-1945). The institute proposed solutions based on surveys conducted at sugarcane mills in cane-producing states and on the medical and hospital system adopted by the institute's enlightened bureaucracy in the 1940s, which took the U.S. system as its model. Special focus is given to the central hospitals in Pernambuco and especially in Alagoas, which opposed institute guidelines.

  1. Influence of genetic architecture on contemporary local evolution in the soapberry bug, Jadera haematoloma: artificial selection on beak length.

    Science.gov (United States)

    Dingle, H; Carroll, S P; Famula, T R

    2009-10-01

    Little is known about the influence of genetic architecture on local adaptation. We investigated the genetic architecture of the rapid contemporary evolution of mouthparts, the flight polymorphism and life history traits in the soapberry bug Jadera haematoloma (Hemiptera) using laboratory selection. The mouthparts of these seed-feeding bugs have adapted in 40-50 years by decreasing in length following novel natural selection induced by a host switch to the seeds of an introduced tree with smaller fruits than those of the native host vine. Laboratory selection on beak length in both an ancestral population feeding on the native host and a derived population feeding on the introduced host reveals genetic variance allowing a rapid response (heritabilities of 0.51-0.87) to selection for either longer or shorter beaks. This selection resulted in reverse evolution by restoring long beaks in the derived population and forward evolution by re-creating short beaks in the ancestral bugs. There were strong genetic correlations (0.68-0.84) in both populations between beak lengths and the frequency of flight morphs, with short beaks associated with short wings. The results reveal a genetically interrelated set of adaptive multivariate traits including both beak length and flight morph. This suite of traits reflects host plant patchiness and seeding phenology. Weaker evidence suggests that egg mass and early egg production may be elements of the same suite. Reversible or forward evolution thus may occur in a broad set of genetically correlated multivariate traits undergoing rapid contemporary adaptation to altered local environments.

  2. Genetic architecture of rind penetrometer resistance in two maize recombinant inbred line populations.

    Science.gov (United States)

    Li, Kun; Yan, Jianbing; Li, Jiansheng; Yang, Xiaohong

    2014-06-03

    Maize (Zea Mays L.) is one of the most important cereal crops worldwide and provides food for billions of people. Stalk lodging can greatly undermine the standability of maize plants and therefore decrease crop yields. Rind penetrometer resistance is an effective and reliable method for evaluating maize stalk strength, which is highly correlated with stalk lodging resistance. In this study, two recombinant inbred line populations were constructed from crosses between the H127R and Chang7-2 lines, and between the B73 and By804 lines. We genotyped these two populations and their parents using 3,072 single nucleotide polymorphism markers and performed phenotypic assessment of rind penetrometer resistance in multiple environments to dissect the genetic architecture of rind penetrometer resistance in maize. Based on two linkage maps of 1,397.1 and 1,600.4 cM with average interval of 1.7 and 2.1 cM between adjacent makers, respectively, seven quantitative trait loci (QTL) for rind penetrometer resistance were detected in the two recombinant inbred line populations. These QTL were distributed in seven genomic regions, and each accounted for 4.4-18.9% of the rind penetrometer resistance variation. The QTL with the largest effect on rind penetrometer resistance, qRPR3-1, was located on chromosome 3 with the flanking markers PZE-103123325 and SYN23245. This locus was further narrowed down to a 3.1-Mb interval by haplotype analysis using high-density markers in the target region. Within this interval, four genes associated with the biosynthesis of cell wall components were considered as potential candidate genes for the rind penetrometer resistance effect. The inheritance of rind penetrometer resistance is rather complex. A few large-effect quantitative trait loci, together with a several minor-effect QTL, contributed to the phenotypic variation in rind penetrometer resistance in the two recombinant inbred line populations that were examined. A potential approach for

  3. Systems-level quantification of division timing reveals a common genetic architecture controlling asynchrony and fate asymmetry

    Science.gov (United States)

    Ho, Vincy Wing Sze; Wong, Ming-Kin; An, Xiaomeng; Guan, Daogang; Shao, Jiaofang; Ng, Hon Chun Kaoru; Ren, Xiaoliang; He, Kan; Liao, Jinyue; Ang, Yingjin; Chen, Long; Huang, Xiaotai; Yan, Bin; Xia, Yiji; Chan, Leanne Lai Hang; Chow, King Lau; Yan, Hong; Zhao, Zhongying

    2015-01-01

    Coordination of cell division timing is crucial for proper cell fate specification and tissue growth. However, the differential regulation of cell division timing across or within cell types during metazoan development remains poorly understood. To elucidate the systems-level genetic architecture coordinating division timing, we performed a high-content screening for genes whose depletion produced a significant reduction in the asynchrony of division between sister cells (ADS) compared to that of wild-type during Caenorhabditis elegans embryogenesis. We quantified division timing using 3D time-lapse imaging followed by computer-aided lineage analysis. A total of 822 genes were selected for perturbation based on their conservation and known roles in development. Surprisingly, we find that cell fate determinants are not only essential for establishing fate asymmetry, but also are imperative for setting the ADS regardless of cellular context, indicating a common genetic architecture used by both cellular processes. The fate determinants demonstrate either coupled or separate regulation between the two processes. The temporal coordination appears to facilitate cell migration during fate specification or tissue growth. Our quantitative dataset with cellular resolution provides a resource for future analyses of the genetic control of spatial and temporal coordination during metazoan development. PMID:26063786

  4. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases

    DEFF Research Database (Denmark)

    Ferrari, Raffaele; Wang, Yunpeng; Vandrovcova, Jana

    2017-01-01

    BACKGROUND: Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap betwee...

  5. Genetic variants in root architecture-related genes in a Glycine soja accession, a potential resource to improve cultivated soybean.

    Science.gov (United States)

    Prince, Silvas J; Song, Li; Qiu, Dan; Maldonado Dos Santos, Joao V; Chai, Chenglin; Joshi, Trupti; Patil, Gunvant; Valliyodan, Babu; Vuong, Tri D; Murphy, Mackensie; Krampis, Konstantinos; Tucker, Dominic M; Biyashev, Ruslan; Dorrance, Anne E; Maroof, M A Saghai; Xu, Dong; Shannon, J Grover; Nguyen, Henry T

    2015-02-25

    Root system architecture is important for water acquisition and nutrient acquisition for all crops. In soybean breeding programs, wild soybean alleles have been used successfully to enhance yield and seed composition traits, but have never been investigated to improve root system architecture. Therefore, in this study, high-density single-feature polymorphic markers and simple sequence repeats were used to map quantitative trait loci (QTLs) governing root system architecture in an inter-specific soybean mapping population developed from a cross between Glycine max and Glycine soja. Wild and cultivated soybean both contributed alleles towards significant additive large effect QTLs on chromosome 6 and 7 for a longer total root length and root distribution, respectively. Epistatic effect QTLs were also identified for taproot length, average diameter, and root distribution. These root traits will influence the water and nutrient uptake in soybean. Two cell division-related genes (D type cyclin and auxin efflux carrier protein) with insertion/deletion variations might contribute to the shorter root phenotypes observed in G. soja compared with cultivated soybean. Based on the location of the QTLs and sequence information from a second G. soja accession, three genes (slow anion channel associated 1 like, Auxin responsive NEDD8-activating complex and peroxidase), each with a non-synonymous single nucleotide polymorphism mutation were identified, which may also contribute to changes in root architecture in the cultivated soybean. In addition, Apoptosis inhibitor 5-like on chromosome 7 and slow anion channel associated 1-like on chromosome 15 had epistatic interactions for taproot length QTLs in soybean. Rare alleles from a G. soja accession are expected to enhance our understanding of the genetic components involved in root architecture traits, and could be combined to improve root system and drought adaptation in soybean.

  6. Preimplantation genetic diagnosis and rational choice under risk or uncertainty.

    Science.gov (United States)

    Zuradzki, Tomasz

    2014-11-01

    In this paper I present an argument in favour of a parental duty to use preimplantation genetic diagnosis (PGD). I argue that if embryos created in vitro were able to decide for themselves in a rational manner, they would sometimes choose PGD as a method of selection. Couples, therefore, should respect their hypothetical choices on a principle similar to that of patient autonomy. My thesis shows that no matter which moral doctrine couples subscribe to, they ought to conduct the PGD procedure in the situations when it is impossible to implant all of the created embryos and if there is a significant risk for giving birth to a child with a serious condition. 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.

  7. Genetic dissection of maize plant architecture with an ultra-high density bin map based on recombinant inbred lines.

    Science.gov (United States)

    Zhou, Zhiqiang; Zhang, Chaoshu; Zhou, Yu; Hao, Zhuanfang; Wang, Zhenhua; Zeng, Xing; Di, Hong; Li, Mingshun; Zhang, Degui; Yong, Hongjun; Zhang, Shihuang; Weng, Jianfeng; Li, Xinhai

    2016-03-03

    Plant architecture attributes, such as plant height, ear height, and internode number, have played an important role in the historical increases in grain yield, lodging resistance, and biomass in maize (Zea mays L.). Analyzing the genetic basis of variation in plant architecture using high density QTL mapping will be of benefit for the breeding of maize for many traits. However, the low density of molecular markers in existing genetic maps has limited the efficiency and accuracy of QTL mapping. Genotyping by sequencing (GBS) is an improved strategy for addressing a complex genome via next-generation sequencing technology. GBS has been a powerful tool for SNP discovery and high-density genetic map construction. The creation of ultra-high density genetic maps using large populations of advanced recombinant inbred lines (RILs) is an efficient way to identify QTL for complex agronomic traits. A set of 314 RILs derived from inbreds Ye478 and Qi319 were generated and subjected to GBS. A total of 137,699,000 reads with an average of 357,376 reads per individual RIL were generated, which is equivalent to approximately 0.07-fold coverage of the maize B73 RefGen_V3 genome for each individual RIL. A high-density genetic map was constructed using 4183 bin markers (100-Kb intervals with no recombination events). The total genetic distance covered by the linkage map was 1545.65 cM and the average distance between adjacent markers was 0.37 cM with a physical distance of about 0.51 Mb. Our results demonstrated a relatively high degree of collinearity between the genetic map and the B73 reference genome. The quality and accuracy of the bin map for QTL detection was verified by the mapping of a known gene, pericarp color 1 (P1), which controls the color of the cob, with a high LOD value of 80.78 on chromosome 1. Using this high-density bin map, 35 QTL affecting plant architecture, including 14 for plant height, 14 for ear height, and seven for internode number were detected

  8. A novel analytical framework for dissecting the genetic architecture of behavioral symptoms in neuropsychiatric disorders.

    Directory of Open Access Journals (Sweden)

    Anthony J Deo

    2010-03-01

    Full Text Available For diagnosis of neuropsychiatric disorders, a categorical classification system is often utilized as a simple way for conceptualizing an often complex clinical picture. This approach provides an unsatisfactory model of mental illness, since in practice patients do not conform to these prototypical diagnostic categories. Family studies show notable familial co-aggregation between schizophrenia and bipolar illness and between schizoaffective disorders and both bipolar disorder and schizophrenia, revealing that mental illness does not conform to such categorical models and is likely to follow a continuum encompassing a spectrum of behavioral symptoms.We introduce an analytic framework to dissect the phenotypic heterogeneity present in complex psychiatric disorders based on the conceptual paradigm of a continuum of psychosis. The approach identifies subgroups of behavioral symptoms that are likely to be phenotypically and genetically homogenous. We have evaluated this approach through analysis of simulated data with simulated behavioral traits and predisposing genetic factors. We also apply this approach to a psychiatric dataset of a genome scan for schizophrenia for which extensive behavioral information was collected for each individual patient and their families. With this approach, we identified significant evidence for linkage among depressed individuals with two distinct symptom profiles, that is individuals with sleep disturbance symptoms with linkage on chromosome 2q13 and also a mutually exclusive group of individuals with symptoms of concentration problems with linkage on chromosome 2q35. In addition we identified a subset of individuals with schizophrenia defined by language disturbances with linkage to chromosome 2p25.1 and a group of patients with a phenotype intermediate between those of schizophrenia and schizoaffective disorder with linkage to chromosome 2p21.The findings presented are novel and demonstrate the efficacy of this

  9. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

    Science.gov (United States)

    Morris, Andrew P; Voight, Benjamin F; Teslovich, Tanya M; Ferreira, Teresa; Segrè, Ayellet V; Steinthorsdottir, Valgerdur; Strawbridge, Rona J; Khan, Hassan; Grallert, Harald; Mahajan, Anubha; Prokopenko, Inga; Kang, Hyun Min; Dina, Christian; Esko, Tonu; Fraser, Ross M; Kanoni, Stavroula; Kumar, Ashish; Lagou, Vasiliki; Langenberg, Claudia; Luan, Jian'an; Lindgren, Cecilia M; Müller-Nurasyid, Martina; Pechlivanis, Sonali; Rayner, N William; Scott, Laura J; Wiltshire, Steven; Yengo, Loic; Kinnunen, Leena; Rossin, Elizabeth J; Raychaudhuri, Soumya; Johnson, Andrew D; Dimas, Antigone S; Loos, Ruth J F; Vedantam, Sailaja; Chen, Han; Florez, Jose C; Fox, Caroline; Liu, Ching-Ti; Rybin, Denis; Couper, David J; Kao, Wen Hong L; Li, Man; Cornelis, Marilyn C; Kraft, Peter; Sun, Qi; van Dam, Rob M; Stringham, Heather M; Chines, Peter S; Fischer, Krista; Fontanillas, Pierre; Holmen, Oddgeir L; Hunt, Sarah E; Jackson, Anne U; Kong, Augustine; Lawrence, Robert; Meyer, Julia; Perry, John RB; Platou, Carl GP; Potter, Simon; Rehnberg, Emil; Robertson, Neil; Sivapalaratnam, Suthesh; Stančáková, Alena; Stirrups, Kathleen; Thorleifsson, Gudmar; Tikkanen, Emmi; Wood, Andrew R; Almgren, Peter; Atalay, Mustafa; Benediktsson, Rafn; Bonnycastle, Lori L; Burtt, Noël; Carey, Jason; Charpentier, Guillaume; Crenshaw, Andrew T; Doney, Alex S F; Dorkhan, Mozhgan; Edkins, Sarah; Emilsson, Valur; Eury, Elodie; Forsen, Tom; Gertow, Karl; Gigante, Bruna; Grant, George B; Groves, Christopher J; Guiducci, Candace; Herder, Christian; Hreidarsson, Astradur B; Hui, Jennie; James, Alan; Jonsson, Anna; Rathmann, Wolfgang; Klopp, Norman; Kravic, Jasmina; Krjutškov, Kaarel; Langford, Cordelia; Leander, Karin; Lindholm, Eero; Lobbens, Stéphane; Männistö, Satu; Mirza, Ghazala; Mühleisen, Thomas W; Musk, Bill; Parkin, Melissa; Rallidis, Loukianos; Saramies, Jouko; Sennblad, Bengt; Shah, Sonia; Sigurðsson, Gunnar; Silveira, Angela; Steinbach, Gerald; Thorand, Barbara; Trakalo, Joseph; Veglia, Fabrizio; Wennauer, Roman; Winckler, Wendy; Zabaneh, Delilah; Campbell, Harry; van Duijn, Cornelia; Uitterlinden89-, Andre G; Hofman, Albert; Sijbrands, Eric; Abecasis, Goncalo R; Owen, Katharine R; Zeggini, Eleftheria; Trip, Mieke D; Forouhi, Nita G; Syvänen, Ann-Christine; Eriksson, Johan G; Peltonen, Leena; Nöthen, Markus M; Balkau, Beverley; Palmer, Colin N A; Lyssenko, Valeriya; Tuomi, Tiinamaija; Isomaa, Bo; Hunter, David J; Qi, Lu; Shuldiner, Alan R; Roden, Michael; Barroso, Ines; Wilsgaard, Tom; Beilby, John; Hovingh, Kees; Price, Jackie F; Wilson, James F; Rauramaa, Rainer; Lakka, Timo A; Lind, Lars; Dedoussis, George; Njølstad, Inger; Pedersen, Nancy L; Khaw, Kay-Tee; Wareham, Nicholas J; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Korpi-Hyövälti, Eeva; Saltevo, Juha; Laakso, Markku; Kuusisto, Johanna; Metspalu, Andres; Collins, Francis S; Mohlke, Karen L; Bergman, Richard N; Tuomilehto, Jaakko; Boehm, Bernhard O; Gieger, Christian; Hveem, Kristian; Cauchi, Stephane; Froguel, Philippe; Baldassarre, Damiano; Tremoli, Elena; Humphries, Steve E; Saleheen, Danish; Danesh, John; Ingelsson, Erik; Ripatti, Samuli; Salomaa, Veikko; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Peters, Annette; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Morris, Andrew D; Donnelly, Peter J; Frayling, Timothy M; Hattersley, Andrew T; Boerwinkle, Eric; Melander, Olle; Kathiresan, Sekar; Nilsson, Peter M; Deloukas, Panos; Thorsteinsdottir, Unnur; Groop, Leif C; Stefansson, Kari; Hu, Frank; Pankow, James S; Dupuis, Josée; Meigs, James B; Altshuler, David; Boehnke, Michael; McCarthy, Mark I

    2012-01-01

    To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis. PMID:22885922

  10. Genetic Architecture of Flowering Phenology in Cereals and Opportunities for Crop Improvement.

    Science.gov (United States)

    Hill, Camilla B; Li, Chengdao

    2016-01-01

    Cereal crop species including bread wheat ( Triticum aestivum L.), barley ( Hordeum vulgare L.), rice ( Oryza sativa L.), and maize ( Zea mays L.) provide the bulk of human nutrition and agricultural products for industrial use. These four cereals are central to meet future demands of food supply for an increasing world population under a changing climate. A prerequisite for cereal crop production is the transition from vegetative to reproductive and grain-filling phases starting with flower initiation, a key developmental switch tightly regulated in all flowering plants. Although studies in the dicotyledonous model plant Arabidopsis thaliana build the foundations of our current understanding of plant phenology genes and regulation, the availability of genome assemblies with high-confidence sequences for rice, maize, and more recently bread wheat and barley, now allow the identification of phenology-associated gene orthologs in monocots. Together with recent advances in next-generation sequencing technologies, QTL analysis, mutagenesis, complementation analysis, and RNA interference, many phenology genes have been functionally characterized in cereal crops and conserved as well as functionally divergent genes involved in flowering were found. Epigenetic and other molecular regulatory mechanisms that respond to environmental and endogenous triggers create an enormous plasticity in flowering behavior among cereal crops to ensure flowering is only induced under optimal conditions. In this review, we provide a summary of recent discoveries of flowering time regulators with an emphasis on four cereal crop species (bread wheat, barley, rice, and maize), in particular, crop-specific regulatory mechanisms and genes. In addition, pleiotropic effects on agronomically important traits such as grain yield, impact on adaptation to new growing environments and conditions, genetic sequence-based selection and targeted manipulation of phenology genes, as well as crop growth

  11. Aspects of Information Architecture involved in process mapping in Military Organizations under the semiotic perspective

    Directory of Open Access Journals (Sweden)

    Mac Amaral Cartaxo

    2016-04-01

    Full Text Available Introduction: The description of the processes to represent the activities in an organization has important call semiotic, It is the flowcharts of uses, management reports and the various forms of representation of the strategies used. The subsequent interpretation of the organization's employees involved in learning tasks and the symbols used to translate the meanings of management practices is essential role for the organization. Objective: The objective of this study was to identify evidence of conceptual and empirical, on aspects of information architecture involved in the mapping process carried out in military organizations under the semiotic perspective. Methodology: The research is characterized as qualitative, case study and the data collection technique was the semi-structured interview, applied to management advisors. Results: The main results indicate that management practices described with the use of pictorial symbols and different layouts have greater impact to explain the relevance of management practices and indicators. Conclusion: With regard to the semiotic appeal, it was found that the impact of a management report is significant due to the use of signs and layout that stimulate further reading by simplifying complex concepts in tables, diagrams summarizing lengthy descriptions.

  12. The Functional Architecture of the Brain Underlies Strategic Deception in Impression Management

    Directory of Open Access Journals (Sweden)

    Qiang Luo

    2017-11-01

    Full Text Available Impression management, as one of the most essential skills of social function, impacts one's survival and success in human societies. However, the neural architecture underpinning this social skill remains poorly understood. By employing a two-person bargaining game, we exposed three strategies involving distinct cognitive processes for social impression management with different levels of strategic deception. We utilized a novel adaptation of Granger causality accounting for signal-dependent noise (SDN, which captured the directional connectivity underlying the impression management during the bargaining game. We found that the sophisticated strategists engaged stronger directional connectivity from both dorsal anterior cingulate cortex and retrosplenial cortex to rostral prefrontal cortex, and the strengths of these directional influences were associated with higher level of deception during the game. Using the directional connectivity as a neural signature, we identified the strategic deception with 80% accuracy by a machine-learning classifier. These results suggest that different social strategies are supported by distinct patterns of directional connectivity among key brain regions for social cognition.

  13. When history repeats itself: exploring the genetic architecture of host-plant adaptation in two closely related lepidopteran species.

    Science.gov (United States)

    Alexandre, Hermine; Ponsard, Sergine; Bourguet, Denis; Vitalis, Renaud; Audiot, Philippe; Cros-Arteil, Sandrine; Streiff, Réjane

    2013-01-01

    The genus Ostrinia includes two allopatric maize pests across Eurasia, namely the European corn borer (ECB, O. nubilalis) and the Asian corn borer (ACB, O. furnacalis). A third species, the Adzuki bean borer (ABB, O. scapulalis), occurs in sympatry with both the ECB and the ACB. The ABB mostly feeds on native dicots, which probably correspond to the ancestral host plant type for the genus Ostrinia. This situation offers the opportunity to characterize the two presumably independent adaptations or preadaptations to maize that occurred in the ECB and ACB. In the present study, we aimed at deciphering the genetic architecture of these two adaptations to maize, a monocot host plant recently introduced into Eurasia. To this end, we performed a genome scan analysis based on 684 AFLP markers in 12 populations of ECB, ACB and ABB. We detected 2 outlier AFLP loci when comparing French populations of the ECB and ABB, and 9 outliers when comparing Chinese populations of the ACB and ABB. These outliers were different in both countries, and we found no evidence of linkage disequilibrium between any two of them. These results suggest that adaptation or preadaptation to maize relies on a different genetic architecture in the ECB and ACB. However, this conclusion must be considered in light of the constraints inherent to genome scan approaches and of the intricate evolution of adaptation and reproductive isolation in the Ostrinia spp. complex.

  14. Comparative linkage meta-analysis reveals regionally-distinct, disparate genetic architectures: application to bipolar disorder and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Brady Tang

    2011-04-01

    Full Text Available New high-throughput, population-based methods and next-generation sequencing capabilities hold great promise in the quest for common and rare variant discovery and in the search for "missing heritability." However, the optimal analytic strategies for approaching such data are still actively debated, representing the latest rate-limiting step in genetic progress. Since it is likely a majority of common variants of modest effect have been identified through the application of tagSNP-based microarray platforms (i.e., GWAS, alternative approaches robust to detection of low-frequency (1-5% MAF and rare (<1% variants are of great importance. Of direct relevance, we have available an accumulated wealth of linkage data collected through traditional genetic methods over several decades, the full value of which has not been exhausted. To that end, we compare results from two different linkage meta-analysis methods--GSMA and MSP--applied to the same set of 13 bipolar disorder and 16 schizophrenia GWLS datasets. Interestingly, we find that the two methods implicate distinct, largely non-overlapping, genomic regions. Furthermore, based on the statistical methods themselves and our contextualization of these results within the larger genetic literatures, our findings suggest, for each disorder, distinct genetic architectures may reside within disparate genomic regions. Thus, comparative linkage meta-analysis (CLMA may be used to optimize low-frequency and rare variant discovery in the modern genomic era.

  15. The genetic architecture of growth and fillet traits in farmed Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Tsai, Hsin Yuan; Hamilton, Alastair; Guy, Derrick R; Tinch, Alan E; Bishop, Stephen C; Houston, Ross D

    2015-05-19

    Performance and quality traits such as harvest weight, fillet weight and flesh color are of economic importance to the Atlantic salmon aquaculture industry. The genetic factors underlying these traits are of scientific and commercial interest. However, such traits are typically polygenic in nature, with the number and size of QTL likely to vary between studies and populations. The aim of this study was to investigate the genetic basis of several growth and fillet traits measured at harvest in a large farmed salmon population by using SNP markers. Due to the marked heterochiasmy in salmonids, an efficient two-stage mapping approach was applied whereby QTL were detected using a sire-based linkage analysis, a sparse SNP marker map and exploiting low rates of recombination, while a subsequent dam-based analysis focused on the significant chromosomes with a denser map to confirm QTL and estimate their position. The harvest traits all showed significant heritability, ranging from 0.05 for fillet yield up to 0.53 for the weight traits. In the sire-based analysis, 1695 offspring with trait records and their 20 sires were successfully genotyped for the SNPs on the sparse map. Chromosomes 13, 18, 19 and 20 were shown to harbor genome-wide significant QTL affecting several growth-related traits. The QTL on chr. 13, 18 and 20 were detected in the dam-based analysis using 512 offspring from 10 dams and explained approximately 6-7 % of the within-family variation in these traits. We have detected several QTL affecting economically important complex traits in a commercial salmon population. Overall, the results suggest that the traits are relatively polygenic and that QTL tend to be pleiotropic (affecting the weight of several components of the harvested fish). Comparison of QTL regions across studies suggests that harvest trait QTL tend to be relatively population-specific. Therefore, the application of marker or genomic selection for improvement in these traits is likely to be

  16. The genetic architecture of type 2 diabetes pharmacotherapy: the emerging genomic evidence.

    Science.gov (United States)

    Kavvoura, F K; Pappa, M; Evangelou, E; Ntzani, E E

    2014-01-01

    Response to anti-diabetic medications is not always predictable or favourable even in phenotypically similar type-2 diabetes (T2D) cases. This is not only due to patient's compliance and access to care but is also considered to be an effect of idiosyncratic differences among individuals, stemming from the combination of their unique genetic background and environmental exposures. In this systematic review, we aimed to summarise the available evidence on pharmacogenetic and pharmacogenomic studies of oral agents for T2D that are currently in the market and describe the agents studied, the targeted loci in regards to the efficacy and the toxicity profile of the agents included. We included 53 studies published between 2003-2012, which examined the following anti-diabetic classes: sulphonylureas, metformin, metiglinides and thiazolidenediones. There were no published studies on newer agents (e.g. incretin based treatments). Forty-nine studies (92.5%) examined the therapeutic response to oral antiglycaemic agents. Outcomes assessed included changes in metabolic markers (fasting or postprandial blood glucose, fasting or postprandial insulin, HbA1c), Homeostasis Assessment Model (HOMA)-Insulin Resistance (IR) or HOMA-B-cell function (HOMA-B), and time to monotherapy failure. Regarding side effects, hypoglycaemia and TZD-related oedema were the most commonly assessed. In the vast majority of the studies included (n=38, 71.7%), more than one outcomes (n=27, 50.9%) and/or more than one SNPs (n=21, 39.6%) were evaluated in the same publication, but most studies examined one drug (n=50, 94.3%). A considerable number of the proposed genes seem to be related to beta-cell development and function, but there are several genes whose underlying pathway linked to diabetes pharmacotherapy remains poorly understood. Pharmacogenomics are still not in pace with the wealth of information provided by GWAS in the genetics of T2D and related traits and the proposed associations need further

  17. The genetic architecture of coronary artery disease: current knowledge and future opportunities

    Science.gov (United States)

    Recent Findings Large-scale studies in human populations, coupled with rapid advances in genetic technologies over the last decade, have clearly established the association of common genetic variation with risk of CAD. However, the effect sizes of the susceptibility alleles are for the most part mod...

  18. A Realistic Model Under Which the Genetic Code is Optimal

    NARCIS (Netherlands)

    Buhrman, Harry; van der Gulik, Peter T. S.; Klau, Gunnar W.; Schaffner, Christian; Speijer, Dave; Stougie, Leen

    2013-01-01

    The genetic code has a high level of error robustness. Using values of hydrophobicity scales as a proxy for amino acid character, and the mean square measure as a function quantifying error robustness, a value can be obtained for a genetic code which reflects the error robustness of that code. By

  19. Coeliac disease : investigation of the genetic factors underlying coeliac disease

    NARCIS (Netherlands)

    Belzen, M.J. (Martine Juliana) van

    2003-01-01

    Coeliac disease is a common food intolerance with a complex genetic aetiology. It is caused by ingestion of gluten peptides from wheat and related proteins from barley and rye in genetically susceptible individuals. The disease affects the small intestine and leads to abnormalities ranging from the

  20. Genetic Circuit Performance under Conditions Relevant for Industrial Bioreactors

    NARCIS (Netherlands)

    Moser, Felix; Broers, Nicolette J.; Hartmans, Sybe; Tamsir, Alvin; Kerkman, Richard; Roubos, Johannes A.; Bovenberg, Roel; Voigt, Christopher A.

    2012-01-01

    Synthetic genetic programs promise to enable novel applications in industrial processes. For such applications, the genetic circuits that compose programs will require fidelity in varying and complex environments. In this work, we report the performance of two synthetic circuits in Escherichia coli

  1. A Realistic Model under which the Genetic Code is Optimal

    NARCIS (Netherlands)

    Buhrman, H.; van der Gulik, P.T.S.; Klau, G.W.; Schaffner, C.; Speijer, D.; Stougie, L.

    2013-01-01

    The genetic code has a high level of error robustness. Using values of hydrophobicity scales as a proxy for amino acid character, and the mean square measure as a function quantifying error robustness, a value can be obtained for a genetic code which reflects the error robustness of that code. By

  2. Genetic and Environmental Architecture of Changes in Episodic Memory from Middle to Late Middle Age

    Science.gov (United States)

    Panizzon, Matthew S.; Neale, Michael C.; Docherty, Anna R.; Franz, Carol E.; Jacobson, Kristen C.; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K.; McKenzie, Ruth M.; Lyons, Michael J.; Kremen, William S.

    2015-01-01

    Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined six measures from three episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints two of three test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for one test-specific factor (list learning). Mean change over time was nonsignificant for one test-level factor; one declined; one improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. PMID:25938244

  3. Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data.

    Science.gov (United States)

    Gibson, J; Russ, T C; Adams, M J; Clarke, T-K; Howard, D M; Hall, L S; Fernandez-Pujals, A M; Wigmore, E M; Hayward, C; Davies, G; Murray, A D; Smith, B H; Porteous, D J; Deary, I J; McIntosh, A M

    2017-04-18

    Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship. Using two complementary techniques, we found no evidence that the disorders are influenced by common genetic variants. Using linkage disequilibrium score regression with genome-wide association study (GWAS) summary statistics from the International Genomics of Alzheimer's Project, we report no significant genetic correlation between AD and MDD (r G =-0.103, P=0.59). Polygenic risk scores (PRS) generated using summary data from International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium were used to assess potential pleiotropy between the disorders. PRS for MDD were nominally associated with participant-recalled AD family history in GS:SFHS, although this association did not survive multiple comparison testing. AD PRS were not associated with depression status or late-onset depression, and a survival analysis showed no association between age of depression onset and genetic risk for AD. This study found no evidence to support a common polygenic structure for AD and MDD, suggesting that the comorbidity of these disorders is not explained by common genetic variants.

  4. Genetic architecture of a feeding adaptation: garter snake (Thamnophis) resistance to tetrodotoxin bearing prey

    OpenAIRE

    Feldman, Chris R.; Brodie, Edmund D.; Brodie, Edmund D.; Pfrender, Michael E.

    2010-01-01

    Detailing the genetic basis of adaptive variation in natural populations is a first step towards understanding the process of adaptive evolution, yet few ecologically relevant traits have been characterized at the genetic level in wild populations. Traits that mediate coevolutionary interactions between species are ideal for studying adaptation because of the intensity of selection and the well-characterized ecological context. We have previously described the ecological context, evolutionary...

  5. Organization of the Mammalian Locomotor CPG: Review of Computational Model and Circuit Architectures Based on Genetically Identified Spinal Interneurons

    Science.gov (United States)

    Dougherty, Kimberly J.; Shevtsova, Natalia A.

    2015-01-01

    Abstract The organization of neural circuits that form the locomotor central pattern generator (CPG) and provide flexor–extensor and left–right coordination of neuronal activity remains largely unknown. However, significant progress has been made in the molecular/genetic identification of several types of spinal interneurons, including V0 (V0D and V0V subtypes), V1, V2a, V2b, V3, and Shox2, among others. The possible functional roles of these interneurons can be suggested from changes in the locomotor pattern generated in mutant mice lacking particular neuron types. Computational modeling of spinal circuits may complement these studies by bringing together data from different experimental studies and proposing the possible connectivity of these interneurons that may define rhythm generation, flexor–extensor interactions on each side of the cord, and commissural interactions between left and right circuits. This review focuses on the analysis of potential architectures of spinal circuits that can reproduce recent results and suggest common explanations for a series of experimental data on genetically identified spinal interneurons, including the consequences of their genetic ablation, and provides important insights into the organization of the spinal CPG and neural control of locomotion. PMID:26478909

  6. Pollution breaks down the genetic architecture of life history traits in Caenorhabditis elegans.

    Science.gov (United States)

    Dutilleul, Morgan; Goussen, Benoit; Bonzom, Jean-Marc; Galas, Simon; Réale, Denis

    2015-01-01

    When pollution occurs in an environment, populations present suffer numerous negative and immediate effects on their life history traits. Their evolutionary potential to live in a highly stressful environment will depend on the selection pressure strengths and on the genetic structure, the trait heritability, and the genetic correlations between them. If expression of this structure changes in a stressful environment, it becomes necessary to quantify these changes to estimate the evolutionary potential of the population in this new environment. We studied the genetic structure for survival, fecundity, and early and late growth in isogenic lines of a Caenorhabditis elegans population subject to three different environments: a control environment, an environment polluted with uranium, and a high salt concentration environment. We found a heritability decrease in the polluted environments for fecundity and early growth, two traits that were the most heritable in the control environment. The genetic structure of the traits was particularly affected in the uranium polluted environment, probably due to generally low heritability in this environment. This could prevent selection from acting on traits despite the strong selection pressures exerted on them. Moreover, phenotypic traits were more strongly affected in the salt than in the uranium environment and the heritabilities were also lower in the latter environment. Consequently the decrease in heritability was not proportional to the population fitness reduction in the polluted environments. Our results suggest that pollution can alter the genetic structure of a C. elegans population, and thus modify its evolutionary potential.

  7. Pollution breaks down the genetic architecture of life history traits in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Morgan Dutilleul

    Full Text Available When pollution occurs in an environment, populations present suffer numerous negative and immediate effects on their life history traits. Their evolutionary potential to live in a highly stressful environment will depend on the selection pressure strengths and on the genetic structure, the trait heritability, and the genetic correlations between them. If expression of this structure changes in a stressful environment, it becomes necessary to quantify these changes to estimate the evolutionary potential of the population in this new environment. We studied the genetic structure for survival, fecundity, and early and late growth in isogenic lines of a Caenorhabditis elegans population subject to three different environments: a control environment, an environment polluted with uranium, and a high salt concentration environment. We found a heritability decrease in the polluted environments for fecundity and early growth, two traits that were the most heritable in the control environment. The genetic structure of the traits was particularly affected in the uranium polluted environment, probably due to generally low heritability in this environment. This could prevent selection from acting on traits despite the strong selection pressures exerted on them. Moreover, phenotypic traits were more strongly affected in the salt than in the uranium environment and the heritabilities were also lower in the latter environment. Consequently the decrease in heritability was not proportional to the population fitness reduction in the polluted environments. Our results suggest that pollution can alter the genetic structure of a C. elegans population, and thus modify its evolutionary potential.

  8. Exploration of genetic architecture through sib-ship reconstruction in advanced breeding population of Eucalyptus nitens.

    Directory of Open Access Journals (Sweden)

    Jaroslav Klápště

    Full Text Available Accurate inference of relatedness between individuals in breeding population contributes to the precision of genetic parameter estimates, effectiveness of inbreeding management and the amount of genetic progress delivered from breeding programs. Pedigree reconstruction has been proven to be an efficient tool to correct pedigree errors and recover hidden relatedness in open pollinated progeny tests but the method can be limited by the lack of parental genotypes and the high proportion of alien pollen from outside the breeding population. Our study investigates the efficiency of sib-ship reconstruction in an advanced breeding population of Eucalyptus nitens with only partially tracked pedigree. The sib-ship reconstruction allowed the identification of selfs (4% of the sample and the exploration of their potential effect on inbreeding depression in the traits studied. We detected signs of inbreeding depression in diameter at breast height and growth strain while no indications were observed in wood density, wood stiffness and tangential air-dry shrinkage. After the application of a corrected sib-ship relationship matrix, additive genetic variance and heritability were observed to increase where signs of inbreeding depression were initially detected. Conversely, the same genetic parameters for traits that appeared to be free of inbreeding depression decreased in size. It therefore appeared that greater genetic variance may be due, at least in part, to contributions from inbreeding in these studied populations rather than a removal of inbreeding as is traditionally thought.

  9. The genetic architecture of parallel armor plate reduction in threespine sticklebacks.

    Directory of Open Access Journals (Sweden)

    Pamela F Colosimo

    2004-05-01

    Full Text Available How many genetic changes control the evolution of new traits in natural populations? Are the same genetic changes seen in cases of parallel evolution? Despite long-standing interest in these questions, they have been difficult to address, particularly in vertebrates. We have analyzed the genetic basis of natural variation in three different aspects of the skeletal armor of threespine sticklebacks (Gasterosteus aculeatus: the pattern, number, and size of the bony lateral plates. A few chromosomal regions can account for variation in all three aspects of the lateral plates, with one major locus contributing to most of the variation in lateral plate pattern and number. Genetic mapping and allelic complementation experiments show that the same major locus is responsible for the parallel evolution of armor plate reduction in two widely separated populations. These results suggest that a small number of genetic changes can produce major skeletal alterations in natural populations and that the same major locus is used repeatedly when similar traits evolve in different locations.

  10. Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer.

    Science.gov (United States)

    Giessler, Klara M; Kleinheinz, Kortine; Huebschmann, Daniel; Balasubramanian, Gnana Prakash; Dubash, Taronish D; Dieter, Sebastian M; Siegl, Christine; Herbst, Friederike; Weber, Sarah; Hoffmann, Christopher M; Fronza, Raffaele; Buchhalter, Ivo; Paramasivam, Nagarajan; Eils, Roland; Schmidt, Manfred; von Kalle, Christof; Schneider, Martin; Ulrich, Alexis; Scholl, Claudia; Fröhling, Stefan; Weichert, Wilko; Brors, Benedikt; Schlesner, Matthias; Ball, Claudia R; Glimm, Hanno

    2017-07-03

    A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample. Long-term growth in serial xenografts and spheroids was driven by multiple genomic subclones with profoundly differing growth dynamics and hence different quantitative contributions over time. Strikingly, genetic barcoding demonstrated stable functional heterogeneity of CRC TcICs during serial xenografting despite near-complete changes in genomic subclone contribution. This demonstrates that functional heterogeneity is, at least frequently, present within genomic subclones and independent of mutational subclone differences. © 2017 Giessler et al.

  11. Exploring the genetic architecture of inflammatory bowel disease by whole genome sequencing identifies association at ADCY7

    Science.gov (United States)

    Jostins, Luke; Moutsianas, Loukas; Randall, Joshua; Kennedy, Nicholas A.; Lamb, Christopher A.; McCarthy, Shane; Ahmad, Tariq; Edwards, Cathryn; Serra, Eva Goncalves; Hart, Ailsa; Hawkey, Chris; Mansfield, John C.; Mowat, Craig; Newman, William G.; Nichols, Sam; Pollard, Martin; Satsangi, Jack; Simmons, Alison; Tremelling, Mark; Uhlig, Holm; Wilson, David C.; Lee, James C.; Prescott, Natalie J.; Lees, Charlie W.; Mathew, Christopher G.; Parkes, Miles; Barrett, Jeffrey C.; Anderson, Carl A.

    2016-01-01

    To further resolve the genetic architecture of the inflammatory bowel diseases, ulcerative colitis and Crohn’s disease, we sequenced the whole genomes of 4,280 patients at low coverage, and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing GWAS cohorts, and tested for association at ~12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants, and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn’s disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve our understanding of the biology of complex diseases. PMID:28067910

  12. Investigations on Genetic Architecture of Hairy Loci in Dairy Cattle by Using Single and Whole Genome Regression Approaches

    Directory of Open Access Journals (Sweden)

    B. Karacaören

    2016-07-01

    Full Text Available Development of body hair is an important physiological and cellular process that leads to better adaption in tropical environments for dairy cattle. Various studies suggested a major gene and, more recently, associated genes for hairy locus in dairy cattle. Main aim of this study was to i employ a variant of the discordant sib pair model, in which half sibs from the same sires are randomly sampled using their affection statues, ii use various single marker regression approaches, and iii use whole genome regression approaches to dissect genetic architecture of the hairy gene in the cattle. Whole and single genome regression approaches detected strong genomic signals from Chromosome 23. Although there is a major gene effect on hairy phenotype sourced from chromosome 23: whole genome regression approach also suggested polygenic component related with other parts of the genome. Such a result could not be obtained by any of the single marker approaches.

  13. Secondary Analysis and Integration of Existing Data to Elucidate the Genetic Architecture of Cancer Risk and Related Outcomes, R01 | Informatics Technology for Cancer Research (ITCR)

    Science.gov (United States)

    This funding opportunity announcement (FOA) encourages applications that propose to conduct secondary data analysis and integration of existing datasets and database resources, with the ultimate aim to elucidate the genetic architecture of cancer risk and related outcomes. The goal of this initiative is to address key scientific questions relevant to cancer epidemiology by supporting the analysis of existing genetic or genomic datasets, possibly in combination with environmental, outcomes, behavioral, lifestyle, and molecular profiles data.

  14. Secondary Analysis and Integration of Existing Data to Elucidate the Genetic Architecture of Cancer Risk and Related Outcomes, R21 | Informatics Technology for Cancer Research (ITCR)

    Science.gov (United States)

    This funding opportunity announcement (FOA) encourages applications that propose to conduct secondary data analysis and integration of existing datasets and database resources, with the ultimate aim to elucidate the genetic architecture of cancer risk and related outcomes. The goal of this initiative is to address key scientific questions relevant to cancer epidemiology by supporting the analysis of existing genetic or genomic datasets, possibly in combination with environmental, outcomes, behavioral, lifestyle, and molecular profiles data.

  15. The genetic architecture of body mass index from infancy to adulthood modified by parental education.

    Science.gov (United States)

    Silventoinen, Karri; Huppertz, Charlotte; van Beijsterveldt, Catharina E M; Bartels, Meike; Willemsen, Gonneke; Boomsma, Dorret I

    2016-09-01

    A higher prevalence of obesity in lower socioeconomic classes is common in Western societies. This study examined the role of gene-environment interactions in the association between parental education and body mass index (BMI) from infancy to the onset of adulthood. Parentally reported BMI from 1 to 13 and self-reported BMI from 14 to 20 years of age were collected in 16,646 complete Dutch twin pairs and analyzed by genetic twin modeling. At 7 to 8 years of age, children whose parents had middle or low educational levels had more excess weight than the children of more highly educated parents, and the difference increased until 18 to 20 years of age. The major part of the BMI variation was explained by additive genetic factors (a(2)  = 0.55-0.85), but environmental factors common for co-twins also played a significant role, especially from 3 to 7-8 years of age (c(2)  = 0.15-0.29). The genetic variation in BMI was higher in children whose parents had middle or low educational levels compared with children whose parents had a high educational level. The interaction between genetic factors and the childhood social environment may contribute to the formation of socioeconomic differences in obesity. © 2016 The Obesity Society.

  16. Genetic architecture of motives for leisure-time physical activity: a twin study.

    Science.gov (United States)

    Aaltonen, S; Kaprio, J; Vuoksimaa, E; Huppertz, C; Kujala, U M; Silventoinen, K

    2017-11-01

    The aim of this study was to estimate the contribution of genetic and environmental influences on motives for engaging in leisure-time physical activity. The participants were obtained from the FinnTwin16 study. A modified version of the Recreational Exercise Motivation Measure was used to assess the motives for leisure-time physical activity in 2542 twin individuals (mean age of 34.1 years). Linear structural equation modeling was used to investigate the genetic and environmental influences on motive dimensions. The highest heritability estimates were found for the motive dimensions of "enjoyment" [men 33% (95% CI 23-43%), women 53% (95% CI 45-60%)] and "affiliation" [men 39% (95% CI 0.28-0.49%), women 35% (95% CI 0.25-0.43%)]. The lowest heritability estimates were found for others' expectations [men 13% (95% CI 0.04-0.25%), women 15% (95% CI 0.07-0.24%)]. Unique environmental influences explained the remaining variances, which ranged from 47% to 87%. The heritability estimates for summary variables of intrinsic and extrinsic motives were 36% and 32% for men and 40% and 24% for women, respectively. In conclusion, genetic factors contribute to motives for leisure-time physical activity. However, the genetic effects are, at most, moderate, implying the greater relative role of environmental factors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer

    NARCIS (Netherlands)

    Timofeeva, Maria N.; Ben Kinnersley, [Unknown; Farrington, Susan M.; Whiffin, Nicola; Palles, Claire; Svinti, Victoria; Lloyd, Amy; Gorman, Maggie; Ooi, Li-Yin; Hosking, Fay; Barclay, Ella; Zgaga, Lina; Dobbins, Sara; Martin, Lynn; Theodoratou, Evropi; Broderick, Peter; Tenesa, Albert; Smillie, Claire; Grimes, Graeme; Hayward, Caroline; Campbell, Archie; Porteous, David; Deary, Ian J.; Harris, Sarah E.; Northwood, Emma L.; Barrett, Jennifer H.; Smith, Gillian; Wolf, Roland; Forman, David; Morreau, Hans; Ruano, Dina; Tops, Carli; Wijnen, Juul; Schrumpf, Melanie; Boot, Arnoud; Vasen, Hans F. A.; Hes, Frederik J.; van Wezel, Tom; Franke, Andre; Lieb, Wolgang; Schafmayer, Clemens; Hampe, Jochen; Buch, Stephan; Propping, Peter; Hemminki, Kari; Foersti, Asta; Westers, Helga; Hofstra, Robert; Pinheiro, Manuela; Pinto, Carla; Teixeira, Manuel; Ruiz-Ponte, Clara; Fernandez-Rozadilla, Ceres; Carracedo, Angel; Castells, Antoni; Castellvi-Bel, Sergi; Campbell, Harry; Bishop, D. Timothy; Tomlinson, Ian P. M.; Dunlop, Malcolm G.; Houlston, Richard S.

    2015-01-01

    Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and

  18. Genetic architecture and phenotypic plasticity of thermally-regulated traits in an eruptive species, Dendroctonus ponderosae

    Science.gov (United States)

    Barbara J. Bentz; Ryan B. Bracewell; Karen E. Mock; Michael E. Pfrender

    2011-01-01

    Phenotypic plasticity in thermally-regulated traits enables close tracking of changing environmental conditions, and can thereby enhance the potential for rapid population increase, a hallmark of outbreak insect species. In a changing climate, exposure to conditions that exceed the capacity of existing phenotypic plasticity may occur. Combining information on genetic...

  19. Genetic architecture and temporal patterns of biomass accumulation in spring barley revealed by image analysis.

    Science.gov (United States)

    Neumann, Kerstin; Zhao, Yusheng; Chu, Jianting; Keilwagen, Jens; Reif, Jochen C; Kilian, Benjamin; Graner, Andreas

    2017-08-10

    Genetic mapping of phenotypic traits generally focuses on a single time point, but biomass accumulates continuously during plant development. Resolution of the temporal dynamics that affect biomass recently became feasible using non-destructive imaging. With the aim to identify key genetic factors for vegetative biomass formation from the seedling stage to flowering, we explored growth over time in a diverse collection of two-rowed spring barley accessions. High heritabilities facilitated the temporal analysis of trait relationships and identification of quantitative trait loci (QTL). Biomass QTL tended to persist only a short period during early growth. More persistent QTL were detected around the booting stage. We identified seven major biomass QTL, which together explain 55% of the genetic variance at the seedling stage, and 43% at the booting stage. Three biomass QTL co-located with genes or QTL involved in phenology. The most important locus for biomass was independent from phenology and is located on chromosome 7HL at 141 cM. This locus explained ~20% of the genetic variance, was significant over a long period of time and co-located with HvDIM, a gene involved in brassinosteroid synthesis. Biomass is a dynamic trait and is therefore orchestrated by different QTL during early and late growth stages. Marker-assisted selection for high biomass at booting stage is most effective by also including favorable alleles from seedling biomass QTL. Selection for dynamic QTL may enhance genetic gain for complex traits such as biomass or, in the future, even grain yield.

  20. The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster.

    Science.gov (United States)

    Hunter, Chad M; Huang, Wen; Mackay, Trudy F C; Singh, Nadia D

    2016-04-01

    Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms. Despite this crucial function, rates of recombination are highly variable within and between taxa, and the genetic basis of this variation remains poorly understood. Here, we exploit natural variation in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) to map genetic variants affecting recombination rate. We used a two-step crossing scheme and visible markers to measure rates of recombination in a 33 cM interval on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP lines. Though we cannot exclude that some biases exist due to viability effects associated with the visible markers used in this study, we find ~2-fold variation in recombination rate among lines. Interestingly, we further find that recombination rates are uncorrelated between the two chromosomal intervals. We performed a genome-wide association study to identify genetic variants associated with recombination rate in each of the two intervals surveyed. We refined our list of candidate variants and genes associated with recombination rate variation and selected twenty genes for functional assessment. We present strong evidence that five genes are likely to contribute to natural variation in recombination rate in D. melanogaster; these genes lie outside the canonical meiotic recombination pathway. We also find a weak effect of Wolbachia infection on recombination rate and we confirm the interchromosomal effect. Our results highlight the magnitude of population variation in recombination rate present in D. melanogaster and implicate new genetic factors mediating natural variation in this quantitative trait.

  1. The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Chad M Hunter

    2016-04-01

    Full Text Available Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms. Despite this crucial function, rates of recombination are highly variable within and between taxa, and the genetic basis of this variation remains poorly understood. Here, we exploit natural variation in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP to map genetic variants affecting recombination rate. We used a two-step crossing scheme and visible markers to measure rates of recombination in a 33 cM interval on the X chromosome and in a 20.4 cM interval on chromosome 3R for 205 DGRP lines. Though we cannot exclude that some biases exist due to viability effects associated with the visible markers used in this study, we find ~2-fold variation in recombination rate among lines. Interestingly, we further find that recombination rates are uncorrelated between the two chromosomal intervals. We performed a genome-wide association study to identify genetic variants associated with recombination rate in each of the two intervals surveyed. We refined our list of candidate variants and genes associated with recombination rate variation and selected twenty genes for functional assessment. We present strong evidence that five genes are likely to contribute to natural variation in recombination rate in D. melanogaster; these genes lie outside the canonical meiotic recombination pathway. We also find a weak effect of Wolbachia infection on recombination rate and we confirm the interchromosomal effect. Our results highlight the magnitude of population variation in recombination rate present in D. melanogaster and implicate new genetic factors mediating natural variation in this quantitative trait.

  2. Genetic studies on leaf rolling and some root traits under drought ...

    African Journals Online (AJOL)

    Genetic studies on leaf rolling and some root traits under drought conditions in rice (Oryza sativa L.) AA Allah. Abstract. Crossing was made between three resistant and two susceptible parents to determine the genetic characteristics under drought conditions during 2002 and 2003 rice growing seasons. The resistant ...

  3. Catalyst Architecture

    DEFF Research Database (Denmark)

    ’Catalyst Architecture’ takes its point of departure in a broadened understanding of the role of architecture in relation to developmental problems in large cities. Architectural projects frame particular functions and via their form language, they can provide the user with an aesthetic experience....... The broadened understanding of architecture consists in that an architectural project, by virtue of its placement in the context and of its composition of programs, can have a mediating role in a positive or cultural development of the district in question. In this sense, we talk about architecture as catalyst...... cities on the planet have growing pains and social cohesiveness is under pressure from an increased difference between rich and poor, social segregation, ghettoes, immigration of guest workers and refugees, commercial mass tourism etc. In this context, it is important to ask which role architecture...

  4. Genetic architecture of natural variation in cuticular hydrocarbon composition in Drosophila melanogaster.

    Science.gov (United States)

    Dembeck, Lauren M; Böröczky, Katalin; Huang, Wen; Schal, Coby; Anholt, Robert R H; Mackay, Trudy F C

    2015-11-14

    Insect cuticular hydrocarbons (CHCs) prevent desiccation and serve as chemical signals that mediate social interactions. Drosophila melanogaster CHCs have been studied extensively, but the genetic basis for individual variation in CHC composition is largely unknown. We quantified variation in CHC profiles in the D. melanogaster Genetic Reference Panel (DGRP) and identified novel CHCs. We used principal component (PC) analysis to extract PCs that explain the majority of CHC variation and identified polymorphisms in or near 305 and 173 genes in females and males, respectively, associated with variation in these PCs. In addition, 17 DGRP lines contain the functional Desat2 allele characteristic of African and Caribbean D. melanogaster females (more 5,9-C27:2 and less 7,11-C27:2, female sex pheromone isomers). Disruption of expression of 24 candidate genes affected CHC composition in at least one sex. These genes are associated with fatty acid metabolism and represent mechanistic targets for individual variation in CHC composition.

  5. Genetic architecture of wood properties based on association analysis and co-expression networks in white spruce.

    Science.gov (United States)

    Lamara, Mebarek; Raherison, Elie; Lenz, Patrick; Beaulieu, Jean; Bousquet, Jean; MacKay, John

    2016-04-01

    Association studies are widely utilized to analyze complex traits but their ability to disclose genetic architectures is often limited by statistical constraints, and functional insights are usually minimal in nonmodel organisms like forest trees. We developed an approach to integrate association mapping results with co-expression networks. We tested single nucleotide polymorphisms (SNPs) in 2652 candidate genes for statistical associations with wood density, stiffness, microfibril angle and ring width in a population of 1694 white spruce trees (Picea glauca). Associations mapping identified 229-292 genes per wood trait using a statistical significance level of P wood associated genes and several known MYB and NAC regulators were identified as network hubs. The network revealed a link between the gene PgNAC8, wood stiffness and microfibril angle, as well as considerable within-season variation for both genetic control of wood traits and gene expression. Trait associations were distributed throughout the network suggesting complex interactions and pleiotropic effects. Our findings indicate that integration of association mapping and co-expression networks enhances our understanding of complex wood traits. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  6. Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

    Directory of Open Access Journals (Sweden)

    Rosemary C Challis

    Full Text Available We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII, a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found, similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

  7. Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

    Science.gov (United States)

    Challis, Rosemary C; Tian, Huikai; Yin, Wenbin; Ma, Minghong

    2016-01-01

    We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII), a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE) 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter) and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found), similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice) have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

  8. Dissecting the genetic architecture of F-1 hybrid sterility in house mice

    Czech Academy of Sciences Publication Activity Database

    Dzúr-Gejdošová, Mária; Šimeček, Petr; Gregorová, Soňa; Bhattacharyya, Tanmoy; Forejt, Jiří

    2012-01-01

    Roč. 66, č. 11 (2012), s. 3321-3335 ISSN 0014-3820 R&D Projects: GA MŠk(CZ) LD11079 Grant - others:AV ČR(CZ) Praemium Academiae Institutional research plan: CEZ:AV0Z50520514 Keywords : hybrid sterility * reproductive isolation * recombination hotspots * chromosome X * chromosome 17 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.864, year: 2012

  9. The genetic architecture of low-temperature adaptation in the wine yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    García-Ríos, Estéfani; Morard, Miguel; Parts, Leopold; Liti, Gianni; Guillamón, José M

    2017-02-14

    Low-temperature growth and fermentation of wine yeast can enhance wine aroma and make them highly desirable traits for the industry. Elucidating response to cold in Saccharomyces cerevisiae is, therefore, of paramount importance to select or genetically improve new wine strains. As most enological traits of industrial importance in yeasts, adaptation to low temperature is a polygenic trait regulated by many interacting loci. In order to unravel the genetic determinants of low-temperature fermentation, we mapped quantitative trait loci (QTLs) by bulk segregant analyses in the F13 offspring of two Saccharomyces cerevisiae industrial strains with divergent performance at low temperature. We detected four genomic regions involved in the adaptation at low temperature, three of them located in the subtelomeric regions (chromosomes XIII, XV and XVI) and one in the chromosome XIV. The QTL analysis revealed that subtelomeric regions play a key role in defining individual variation, which emphasizes the importance of these regions' adaptive nature. The reciprocal hemizygosity analysis (RHA), run to validate the genes involved in low-temperature fermentation, showed that genetic variation in mitochondrial proteins, maintenance of correct asymmetry and distribution of phospholipid in the plasma membrane are key determinants of low-temperature adaptation.

  10. Genetic Architecture of Capitate Glandular Trichome Density in Florets of Domesticated Sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Gao, Qing-Ming; Kane, Nolan C; Hulke, Brent S; Reinert, Stephan; Pogoda, Cloe S; Tittes, Silas; Prasifka, Jarrad R

    2017-01-01

    Capitate glandular trichomes (CGT), one type of glandular trichomes, are most common in Asteraceae species. CGT can produce various secondary metabolites such as sesquiterpene lactones (STLs) and provide durable resistance to insect pests. In sunflower, CGT-based host resistance is effective to combat the specialist pest, sunflower moth. However, the genetic basis of CGT density is not well understood in sunflower. In this study, we identified two major QTL controlling CGT density in sunflower florets by using a F 4 mapping population derived from the cross HA 300 × RHA 464 with a genetic linkage map constructed from genotyping-by-sequencing data and composed of 2121 SNP markers. One major QTL is located on chromosome 5, which explained 11.61% of the observed phenotypic variation, and the second QTL is located on chromosome 6, which explained 14.06% of the observed phenotypic variation. The QTL effects and the association between CGT density and QTL support interval were confirmed in a validation population which included 39 sunflower inbred lines with diverse genetic backgrounds. We also identified two strong candidate genes in the QTL support intervals, and the functions of their orthologs in other plant species suggested their potential roles in regulating capitate glandular trichome density in sunflower. Our results provide valuable information to sunflower breeding community for developing host resistance to sunflower insect pests.

  11. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    Cytoplasmic genetic male sterility (CGMS) resulting from nuclear-cytoplasmic interaction has been commercially exploited for the production of F1 hybrid seed in rice. The. CGMS system involves three lines, namely a cytoplasmic male sterile (CMS) line, a maintainer line and a restorer line where restorer line (R line) ...

  12. Genetic analysis of fertility restoration under CGMS system in rice ...

    Indian Academy of Sciences (India)

    Abstract. We studied the genetics of fertility restoration by producing three-way test cross (TWTC) hybrids involved different combi- nations of restorers, maintainers and partial restorers of rice. Pollen and spikelet fertility of 16 TWTC hybrids were studied. Six TWTC involving restorer/restorer combinations as male parents ...

  13. Adaptive genetic potential of coniferous forest tree species under climate change: implications for sustainable forest management

    Science.gov (United States)

    Mihai, Georgeta; Birsan, Marius-Victor; Teodosiu, Maria; Dumitrescu, Alexandru; Daia, Mihai; Mirancea, Ionel; Ivanov, Paula; Alin, Alexandru

    2017-04-01

    Mountain ecosystems are extremely vulnerable to climate change. The real potential for adaptation depends upon the existence of a wide genetic diversity in trees populations, upon the adaptive genetic variation, respectively. Genetic diversity offers the guarantee that forest species can survive, adapt and evolve under the influence of changing environmental conditions. The aim of this study is to evaluate the genetic diversity and adaptive genetic potential of two local species - Norway spruce and European silver fir - in the context of regional climate change. Based on data from a long-term provenance experiments network and climate variables spanning over more than 50 years, we have investigated the impact of climatic factors on growth performance and adaptation of tree species. Our results indicate that climatic and geographic factors significantly affect forest site productivity. Mean annual temperature and annual precipitation amount were found to be statistically significant explanatory variables. Combining the additive genetic model with the analysis of nuclear markers we obtained different images of the genetic structure of tree populations. As genetic indicators we used: gene frequencies, genetic diversity, genetic differentiation, genetic variance, plasticity. Spatial genetic analyses have allowed identifying the genetic centers holding high genetic diversity which will be valuable sources of gene able to buffer the negative effects of future climate change. Correlations between the marginal populations and in the optimal vegetation, between the level of genetic diversity and ecosystem stability, will allow the assessment of future risks arising from current genetic structure. Therefore, the strategies for sustainable forest management have to rely on the adaptive genetic variation and local adaptation of the valuable genetic resources. This work was realized within the framework of the project GENCLIM (Evaluating the adaptive potential of the main

  14. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.

    Science.gov (United States)

    Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa; Kabagambe, Edmond Kato; Hong, Jaeyoung; Ng, Maggie C Y; Hivert, Marie-France; Lu, Yingchang; An, Ping; Bentley, Amy R; Drolet, Anne M; Gaulton, Kyle J; Guo, Xiuqing; Armstrong, Loren L; Irvin, Marguerite R; Li, Man; Lipovich, Leonard; Rybin, Denis V; Taylor, Kent D; Agyemang, Charles; Palmer, Nicholette D; Cade, Brian E; Chen, Wei-Min; Dauriz, Marco; Delaney, Joseph A C; Edwards, Todd L; Evans, Daniel S; Evans, Michele K; Lange, Leslie A; Leong, Aaron; Liu, Jingmin; Liu, Yongmei; Nayak, Uma; Patel, Sanjay R; Porneala, Bianca C; Rasmussen-Torvik, Laura J; Snijder, Marieke B; Stallings, Sarah C; Tanaka, Toshiko; Yanek, Lisa R; Zhao, Wei; Becker, Diane M; Bielak, Lawrence F; Biggs, Mary L; Bottinger, Erwin P; Bowden, Donald W; Chen, Guanjie; Correa, Adolfo; Couper, David J; Crawford, Dana C; Cushman, Mary; Eicher, John D; Fornage, Myriam; Franceschini, Nora; Fu, Yi-Ping; Goodarzi, Mark O; Gottesman, Omri; Hara, Kazuo; Harris, Tamara B; Jensen, Richard A; Johnson, Andrew D; Jhun, Min A; Karter, Andrew J; Keller, Margaux F; Kho, Abel N; Kizer, Jorge R; Krauss, Ronald M; Langefeld, Carl D; Li, Xiaohui; Liang, Jingling; Liu, Simin; Lowe, William L; Mosley, Thomas H; North, Kari E; Pacheco, Jennifer A; Peyser, Patricia A; Patrick, Alan L; Rice, Kenneth M; Selvin, Elizabeth; Sims, Mario; Smith, Jennifer A; Tajuddin, Salman M; Vaidya, Dhananjay; Wren, Mary P; Yao, Jie; Zhu, Xiaofeng; Ziegler, Julie T; Zmuda, Joseph M; Zonderman, Alan B; Zwinderman, Aeilko H; Adeyemo, Adebowale; Boerwinkle, Eric; Ferrucci, Luigi; Hayes, M Geoffrey; Kardia, Sharon L R; Miljkovic, Iva; Pankow, James S; Rotimi, Charles N; Sale, Michele M; Wagenknecht, Lynne E; Arnett, Donna K; Chen, Yii-Der Ida; Nalls, Michael A; Province, Michael A; Kao, W H Linda; Siscovick, David S; Psaty, Bruce M; Wilson, James G; Loos, Ruth J F; Dupuis, Josée; Rich, Stephen S; Florez, Jose C; Rotter, Jerome I; Morris, Andrew P; Meigs, James B

    2016-07-07

    Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci. Copyright © 2016 American Society of Human Genetics. All rights reserved.

  15. A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection.

    Science.gov (United States)

    Siddle, Katherine J; Deschamps, Matthieu; Tailleux, Ludovic; Nédélec, Yohann; Pothlichet, Julien; Lugo-Villarino, Geanncarlo; Libri, Valentina; Gicquel, Brigitte; Neyrolles, Olivier; Laval, Guillaume; Patin, Etienne; Barreiro, Luis B; Quintana-Murci, Lluís

    2014-05-01

    MicroRNAs (miRNAs) are critical regulators of gene expression, and their role in a wide variety of biological processes, including host antimicrobial defense, is increasingly well described. Consistent with their diverse functional effects, miRNA expression is highly context dependent and shows marked changes upon cellular activation. However, the genetic control of miRNA expression in response to external stimuli and the impact of such perturbations on miRNA-mediated regulatory networks at the population level remain to be determined. Here we assessed changes in miRNA expression upon Mycobacterium tuberculosis infection and mapped expression quantitative trait loci (eQTL) in dendritic cells from a panel of healthy individuals. Genome-wide expression profiling revealed that ∼40% of miRNAs are differentially expressed upon infection. We find that the expression of 3% of miRNAs is controlled by proximate genetic factors, which are enriched in a promoter-specific histone modification associated with active transcription. Notably, we identify two infection-specific response eQTLs, for miR-326 and miR-1260, providing an initial assessment of the impact of genotype-environment interactions on miRNA molecular phenotypes. Furthermore, we show that infection coincides with a marked remodeling of the genome-wide relationships between miRNA and mRNA expression levels. This observation, supplemented by experimental data using the model of miR-29a, sheds light on the role of a set of miRNAs in cellular responses to infection. Collectively, this study increases our understanding of the genetic architecture of miRNA expression in response to infection, and highlights the wide-reaching impact of altering miRNA expression on the transcriptional landscape of a cell.

  16. Event-based home safety problem detection under the CPS home safety architecture

    OpenAIRE

    Yang, Zhengguo; Lim, Azman Osman; Tan, Yasuo

    2013-01-01

    This paper presents a CPS(Cyber-physical System) home safety architecture for home safety problem detection and reaction and shows some example cases. In order for home safety problem detection, there are three levels of events defined: elementary event, semantic event and entire event, which representing the meaning from parameter to single safety problem, and then the whole safety status of a house. For the relationship between these events and raw data, a Finite State Machine (FSM) based m...

  17. The Functional Architecture of the Brain Underlies Strategic Deception in Impression Management

    OpenAIRE

    Qiang Luo; Qiang Luo; Yina Ma; Yina Ma; Meghana A. Bhatt; Meghana A. Bhatt; P. Read Montague; P. Read Montague; P. Read Montague; Jianfeng Feng; Jianfeng Feng; Jianfeng Feng; Jianfeng Feng; Jianfeng Feng

    2017-01-01

    Impression management, as one of the most essential skills of social function, impacts one's survival and success in human societies. However, the neural architecture underpinning this social skill remains poorly understood. By employing a two-person bargaining game, we exposed three strategies involving distinct cognitive processes for social impression management with different levels of strategic deception. We utilized a novel adaptation of Granger causality accounting for signal-dependent...

  18. The evolutionary genetics of the genes underlying phenotypic associations for loblolly pine (Pinus taeda, Pinaceae).

    Science.gov (United States)

    Eckert, Andrew J; Wegrzyn, Jill L; Liechty, John D; Lee, Jennifer M; Cumbie, W Patrick; Davis, John M; Goldfarb, Barry; Loopstra, Carol A; Palle, Sreenath R; Quesada, Tania; Langley, Charles H; Neale, David B

    2013-12-01

    A primary goal of evolutionary genetics is to discover and explain the genetic basis of fitness-related traits and how this genetic basis evolves within natural populations. Unprecedented technological advances have fueled the discovery of genetic variants associated with ecologically relevant phenotypes in many different life forms, as well as the ability to scan genomes for deviations from selectively neutral models of evolution. Theoretically, the degree of overlap between lists of genomic regions identified using each approach is related to the genetic architecture of fitness-related traits and the strength and type of natural selection molding variation at these traits within natural populations. Here we address for the first time in a plant the degree of overlap between these lists, using patterns of nucleotide diversity and divergence for >7000 unique amplicons described from the extensive expressed sequence tag libraries generated for loblolly pine (Pinus taeda L.) in combination with the >1000 published genetic associations. We show that loci associated with phenotypic traits are distinct with regard to neutral expectations. Phenotypes measured at the whole plant level (e.g., disease resistance) exhibit an approximately twofold increase in the proportion of adaptive nonsynonymous substitutions over the genome-wide average. As expected for polygenic traits, these signals were apparent only when loci were considered at the level of functional sets. The ramifications of this result are discussed in light of the continued efforts to dissect the genetic basis of quantitative traits.

  19. Genetic architecture, inter-relationship and selection criteria for yield improvement in rice (Oryza sativa L.).

    Science.gov (United States)

    Yadav, S K; Pandey, P; Kumar, B; Suresh, B G

    2011-05-01

    This study has been conducted to determine the extent of genetic association between yield of Rice (Oryza sativa L.) and its components. The present experiment was carried out with 40 Rice (Oryza sativa L.) genotypes which were evaluated in a randomized block design with 3 replications during wet season of 2007 and 2008. Results showed that sufficient amount of variability was found in the entire gene pool for all traits studied. Higher magnitude of genotypic and phenotypic coefficients of variation was recorded for seed yield, harvest index, biological yield, number of spikelets per panicle, flag leaf length, plant height and number of tillers indicates that these characters are least influence by environment. High heritability coupled with high genetic advance as percent of mean was registered for seed yield, harvest index, number of spikelets per panicle, biological yield and flag leaf length, suggesting preponderance of additive gene action in the expression of these characters. Grain yield was significantly and positively associated with harvest index, number of tillers per hill, number of panicle per plant, panicle length, number of spikelet's per panicle and test weight at both genotypic and phenotypic levels. Path coefficient analysis revealed that harvest index, biological yield, number of tillers per hill, panicle length, number of spikelets per panicle, plant height and test weight had direct positive effect on seed yield, indicating these are the main contributors to yield. From this study it may be concluded that harvest index, number of tillers per hill, panicle length and number of spikelet per panicle and test weight are the most important characters that contributed directly to yield. Thus, these characters may serve selection criteria for improving genetic potential of rice.

  20. Genetic architecture of two red ruffed lemur (Varecia rubra) populations of Masoala national park.

    Science.gov (United States)

    Razakamaharavo, Vololoniaina R; McGuire, Susie M; Vasey, Natalie; Louis, Edward E; Brenneman, Rick A

    2010-01-01

    The current range of the red ruffed lemur (Varecia rubra) population is primarily restricted to forests of the Masoala Peninsula on the northeastern coast of Madagascar. Whereas much of the peninsula is protected as Masoala National Park, parts of the forest are at risk from anthropogenic pressures and habitat fragmentation. We sampled 32 individual red ruffed lemur from two sites: Ambatoledama (DAMA), a narrow forest corridor across an area of degraded habitat connecting larger blocks of forest in the northwestern reaches of the park, and Masiaposa (MAS) forest, a largely pristine forest on the lower western side of the peninsula. Population genetic parameters were estimated for these two populations employing 15 microsatellite loci derived from the V. variegata genome. We found that by exceeding the expected heterozygosity at mutation-drift equilibrium, the DAMA population has undergone a recent population bottleneck. Population structure analysis detected individuals harboring genotypic admixture of the DAMA genetic cluster in the MAS population, suggesting a possibility of unilateral gene flow or movement between these populations.

  1. AutDB: a platform to decode the genetic architecture of autism.

    Science.gov (United States)

    Pereanu, Wayne; Larsen, Eric C; Das, Ishita; Estévez, Marcel A; Sarkar, Anjali A; Spring-Pearson, Senanu; Kollu, Ravi; Basu, Saumyendra N; Banerjee-Basu, Sharmila

    2018-01-04

    AutDB is a deeply annotated resource for exploring the impact of genetic variations associated with autism spectrum disorders (ASD). First released in 2007, AutDB has evolved into a multi-modular resource of diverse types of genetic and functional evidence related to ASD. Current modules include: Human Gene, which annotates all ASD-linked genes and their variants; Animal Model, which catalogs behavioral, anatomical and physiological data from rodent models of ASD; Protein Interaction (PIN), which builds interactomes from direct relationships of protein products of ASD genes; and Copy Number Variant (CNV), which catalogs deletions and duplications of chromosomal loci identified in ASD. A multilevel data-integration strategy is utilized to connect the ASD genes to the components of the other modules. All information in this resource is manually curated by expert scientists from primary scientific publications and is referenced to source articles. AutDB is actively maintained with a rigorous quarterly data release schedule. As of June 2017, AutDB contains detailed annotations for 910 genes, 2197 CNV loci, 1060 rodent models and 38 296 PINs. With its widespread use by the research community, AutDB serves as a reference resource for analysis of large datasets, accelerating ASD research and potentially leading to targeted drug treatments. AutDB is available at http://autism.mindspec.org/autdb/Welcome.do. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

    Directory of Open Access Journals (Sweden)

    Riashna Sithaldeen

    Full Text Available Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp. supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

  3. Phytoplasmal infection derails genetically preprogrammed meristem fate and alters plant architecture.

    Science.gov (United States)

    Wei, Wei; Davis, Robert Edward; Nuss, Donald L; Zhao, Yan

    2013-11-19

    In the life cycle of higher plants, it is the fate of meristem cells that determines the pattern of growth and development, and therefore plant morphotype and fertility. Floral transition, the turning point from vegetative growth to reproductive development, is achieved via genetically programmed sequential changes in meristem fate from vegetative to inflorescence, and to floral, leading to flower formation and eventual seed production. The transition is rarely reversible once initiated. In this communication, we report that a bacterial infection can derail the genetically programmed fate of meristem cells, thereby drastically altering the growth pattern of the host plant. We identified four characteristic symptoms in tomato plants infected with a cell wall-less bacterium, phytoplasma. The symptoms are a manifestation of the pathogen-induced alterations of growth pattern, whereas each symptom corresponds to a distinct phase in the derailment of shoot apical meristem fate. The phases include premature floral meristem termination, suppressed floral meristem initiation, delayed conversion of vegetative meristem to inflorescence meristem, and repetitive initiation and outgrowth of lateral vegetative meristems. We further found that the pathogen-induced alterations of growth pattern were correlated with transcriptional reprogramming of key meristem switching genes. Our findings open an avenue toward understanding pathological alterations in patterns of plant growth and development, thus aiding identification of molecular targets for disease control and symptom alleviation. The findings also provide insights for understanding stem cell pluripotency and raise a tantalizing possibility for using phytoplasma as a tool to dissect the course of normal plant development and to modify plant morphogenesis by manipulating meristem fate.

  4. Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

    Science.gov (United States)

    Sithaldeen, Riashna; Ackermann, Rebecca Rogers; Bishop, Jacqueline M

    2015-01-01

    Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp.) supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef) through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

  5. A Comprehensive tRNA Deletion Library Unravels the Genetic Architecture of the tRNA Pool

    Science.gov (United States)

    Bloom-Ackermann, Zohar; Navon, Sivan; Gingold, Hila; Towers, Ruth; Pilpel, Yitzhak; Dahan, Orna

    2014-01-01

    Deciphering the architecture of the tRNA pool is a prime challenge in translation research, as tRNAs govern the efficiency and accuracy of the process. Towards this challenge, we created a systematic tRNA deletion library in Saccharomyces cerevisiae, aimed at dissecting the specific contribution of each tRNA gene to the tRNA pool and to the cell's fitness. By harnessing this resource, we observed that the majority of tRNA deletions show no appreciable phenotype in rich medium, yet under more challenging conditions, additional phenotypes were observed. Robustness to tRNA gene deletion was often facilitated through extensive backup compensation within and between tRNA families. Interestingly, we found that within tRNA families, genes carrying identical anti-codons can contribute differently to the cellular fitness, suggesting the importance of the genomic surrounding to tRNA expression. Characterization of the transcriptome response to deletions of tRNA genes exposed two disparate patterns: in single-copy families, deletions elicited a stress response; in deletions of genes from multi-copy families, expression of the translation machinery increased. Our results uncover the complex architecture of the tRNA pool and pave the way towards complete understanding of their role in cell physiology. PMID:24453985

  6. Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

    Science.gov (United States)

    Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

    2016-01-01

    Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).

  7. Legume genetic resources and transcriptome dynamics under abiotic stress conditions.

    Science.gov (United States)

    Abdelrahman, Mostafa; Jogaiah, Sudisha; Burritt, David J; Tran, Lam-Son Phan

    2018-01-04

    Grain legumes are an important source of nutrition and income for billions of consumers and farmers around the world. However, the low productivity of new legume varieties, due to the limited genetic diversity available for legume breeding programmes and poor policymaker support, combined with an increasingly unpredictable global climate is resulting in a large gap between current yields and the increasing demand for legumes as food. Hence, there is a need for novel approaches to develop new high-yielding legume cultivars that are able to cope with a range of environmental stressors. Next-generation technologies are providing the tools that could enable the more rapid and cost-effective genomic and transcriptomic studies for most major crops, allowing the identification of key functional and regulatory genes involved in abiotic stress resistance. In this review, we provide an overview of the recent achievements regarding abiotic stress resistance in a wide range of legume crops and highlight the transcriptomic and miRNA approaches that have been used. In addition, we critically evaluate the availability and importance of legume genetic resources with desirable abiotic stress resistance traits. © 2018 John Wiley & Sons Ltd.

  8. Comparative Hi-C Reveals that CTCF Underlies Evolution of Chromosomal Domain Architecture

    Directory of Open Access Journals (Sweden)

    Matteo Vietri Rudan

    2015-03-01

    Full Text Available Topological domains are key architectural building blocks of chromosomes, but their functional importance and evolutionary dynamics are not well defined. We performed comparative high-throughput chromosome conformation capture (Hi-C in four mammals and characterized the conservation and divergence of chromosomal contact insulation and the resulting domain architectures within distantly related genomes. We show that the modular organization of chromosomes is robustly conserved in syntenic regions and that this is compatible with conservation of the binding landscape of the insulator protein CTCF. Specifically, conserved CTCF sites are co-localized with cohesin, are enriched at strong topological domain borders, and bind to DNA motifs with orientations that define the directionality of CTCF’s long-range interactions. Conversely, divergent CTCF binding between species is correlated with divergence of internal domain structure, likely driven by local CTCF binding sequence changes, demonstrating how genome evolution can be linked to a continuous flux of local conformation changes. We also show that large-scale domains are reorganized during genome evolution as intact modules.

  9. Cuticular colour reflects underlying architecture and is affected by a limiting resource.

    Science.gov (United States)

    Evison, Sophie E F; Gallagher, Joe D; Thompson, John J W; Siva-Jothy, Michael T; Armitage, Sophie A O

    2017-04-01

    Central to the basis of ecological immunology are the ideas of costs and trade-offs between immunity and life history traits. As a physical barrier, the insect cuticle provides a key resistance trait, and Tenebrio molitor shows phenotypic variation in cuticular colour that correlates with resistance to the entomopathogenic fungus Metarhizium anisopliae. Here we first examined whether there is a relationship between cuticular colour variation and two aspects of cuticular architecture that we hypothesised may influence resistance to fungal invasion through the cuticle: its thickness and its porosity. Second, we tested the hypothesis that tyrosine, a semi-essential amino acid required for immune defence and cuticular melanisation and sclerotisation, can act as a limiting resource by supplementing the larval diet and subsequently examining adult cuticular colouration and thickness. We found that stock beetles and beetles artificially selected for extremes of cuticular colour had thicker less porous cuticles when they were darker, and thinner more porous cuticles when they were lighter, showing that colour co-varies with two architectural cuticular features. Experimental supplementation of the larval diet with tyrosine led to the development of darker adult cuticle and affected thickness in a sex-specific manner. However, it did not affect two immune traits. The results of this study provide a mechanism for maintenance of cuticular colour variation in this species of beetle; darker cuticles are thicker, but their production is potentially limited by resource constraints and differential investments in resistance mechanisms between the sexes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Genetic dissection of seed vigour traits in maize (Zea mays L.) under ...

    Indian Academy of Sciences (India)

    [Shi Y., Li G., Tian Z., Wang Z., Wang X., Zhu Y., Chen Y., Guo S., Qi J., Zhang X. and Ku L. 2016 Genetic dissection of seed vigour traits in maize (Zea mays L.) under low-temperature conditions. J. Genet. 95, 1017–1022]. Introduction. Seed vigour, an important factor governing the seed qual- ity, reflects potential seed ...

  11. Improving Genetic Algorithm with Fine-Tuned Crossover and Scaled Architecture

    Directory of Open Access Journals (Sweden)

    Ajay Shrestha

    2016-01-01

    Full Text Available Genetic Algorithm (GA is a metaheuristic used in solving combinatorial optimization problems. Inspired by evolutionary biology, GA uses selection, crossover, and mutation operators to efficiently traverse the solution search space. This paper proposes nature inspired fine-tuning to the crossover operator using the untapped idea of Mitochondrial DNA (mtDNA. mtDNA is a small subset of the overall DNA. It differentiates itself by inheriting entirely from the female, while the rest of the DNA is inherited equally from both parents. This unique characteristic of mtDNA can be an effective mechanism to identify members with similar genes and restrict crossover between them. It can reduce the rate of dilution of diversity and result in delayed convergence. In addition, we scale the well-known Island Model, where instances of GA are run independently and population members exchanged periodically, to a Continental Model. In this model, multiple web services are executed with each web service running an island model. We applied the concept of mtDNA in solving Traveling Salesman Problem and to train Neural Network for function approximation. Our implementation tests show that leveraging these new concepts of mtDNA and Continental Model results in relative improvement of the optimization quality of GA.

  12. Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

    Science.gov (United States)

    Neogi, Ujjwal; Sood, Vikas; Ronsard, Larence; Singh, Jyotsna; Lata, Sneh; Ramachandran, V G; Das, S; Wanchu, Ajay; Banerjea, Akhil C

    2011-12-01

    This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Myanmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

  13. The "unguarded-X" and the genetic architecture of lifespan: Inbreeding results in a potentially maladaptive sex-specific reduction of female lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Sultanova, Zahida; Andic, Muhammed; Carazo, Pau

    2018-03-01

    Sex differences in ageing and lifespan are ubiquitous in nature. The "unguarded-X" hypothesis (UXh) suggests they may be partly due to the expression of recessive mutations in the hemizygous sex chromosomes of the heterogametic sex, which could help explain sex-specific ageing in a broad array of taxa. A prediction central to the UX hypothesis is that inbreeding will decrease the lifespan of the homogametic sex more than the heterogametic sex, because only in the former does inbreeding increase the expression of recessive deleterious mutations. In this study, we test this prediction by examining the effects of inbreeding on the lifespan and fitness of male and female Drosophila melanogaster across different social environments. We found that, across social environments, inbreeding resulted in a greater reduction of female than male lifespan, and that inbreeding effects on fitness did not seem to counterbalance sex-specific effects on lifespan, suggesting the former are maladaptative. Inter- and intra-sexual correlation analyses also allowed us to identify evidence of an underlying joint genetic architecture for inbreeding effects on lifespan. We discuss these results in light of the UXh and other alternative explanations, and suggest that more attention should be paid to the possibility that the "unguarded-X" may play an important role in the evolution of sex-specific lifespan. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

  14. Effect of two non-synonymous ecto-5'-nucleotidase variants on the genetic architecture of inosine 5'-monophosphate (IMP) and its degradation products in Japanese Black beef.

    Science.gov (United States)

    Uemoto, Yoshinobu; Ohtake, Tsuyoshi; Sasago, Nanae; Takeda, Masayuki; Abe, Tsuyoshi; Sakuma, Hironori; Kojima, Takatoshi; Sasaki, Shinji

    2017-11-13

    Umami is a Japanese term for the fifth basic taste and is an important sensory property of beef palatability. Inosine 5'-monophosphate (IMP) contributes to umami taste in beef. Thus, the overall change in concentration of IMP and its degradation products can potentially affect the beef palatability. In this study, we investigated the genetic architecture of IMP and its degradation products in Japanese Black beef. First, we performed genome-wide association study (GWAS), candidate gene analysis, and functional analysis to detect the causal variants that affect IMP, inosine, and hypoxanthine. Second, we evaluated the allele frequencies in the different breeds, the contribution of genetic variance, and the effect on other economical traits using the detected variants. A total of 574 Japanese Black cattle were genotyped using the Illumina BovineSNP50 BeadChip and were then used for GWAS. The results of GWAS showed that the genome-wide significant single nucleotide polymorphisms (SNPs) on BTA9 were detected for IMP, inosine, and hypoxanthine. The ecto-5'-nucleotidase (NT5E) gene, which encodes the enzyme NT5E for the extracellular degradation of IMP to inosine, was located near the significant region on BTA9. The results of candidate gene analysis and functional analysis showed that two non-synonymous SNPs (c.1318C > T and c.1475 T > A) in NT5E affected the amount of IMP and its degradation products in beef by regulating the enzymatic activity of NT5E. The Q haplotype showed a positive effect on IMP and a negative effect on the enzymatic activity of NT5E in IMP degradation. The two SNPs were under perfect linkage disequilibrium in five different breeds, and different haplotype frequencies were seen among breeds. The two SNPs contribute to about half of the total genetic variance in IMP, and the results of genetic relationship between IMP and its degradation products showed that NT5E affected the overall concentration balance of IMP and its degradation products

  15. GENETIC ARCHITECTURE OF AMBULATORY BLOOD PRESSURE IN THE GENERAL POPULATION – INSIGHTS FROM CARDIOVASCULAR GENE-CENTRIC ARRAY

    Science.gov (United States)

    Tomaszewski, Maciej; Debiec, Radoslaw; Braund, Peter S; Nelson, Christopher P; Hardwick, Robert; Christofidou, Paraskevi; Denniff, Matthew; Codd, Veryan; Rafelt, Suzanne; van der Harst, Pim; Waterworth, Dawn; Song, Kijoung; Vollenweider, Peter; Waeber, Gerard; Zukowska-Szczechowska, Ewa; Burton, Paul R; Mooser, Vincent; Charchar, Fadi J; Thompson, John R; Tobin, Martin D; Samani, Nilesh J

    2010-01-01

    Genetic determinants of blood pressure are poorly defined. We undertook a large-scale gene-centric analysis to identify loci and pathways associated with ambulatory systolic and diastolic blood pressure. We measured 24-hour ambulatory BP in 2020 individuals from 520 white European nuclear families (the GRAPHIC Study) and genotyped their DNA using the Illumina HumanCVD BeadChip array which contains approximately 50000 single nucleotide polymorphisms in >2000 cardiovascular candidate loci. We found a strong association between rs13306560 polymorphism in the promoter region of MTHFR and CLCN6 and mean 24-hour diastolic blood pressure - each minor allele copy of rs13306560 was associated with 2.6 mmHg lower mean 24-hour diastolic blood pressure (P=1.2×10−8). rs13306560 was also associated with clinic diastolic blood pressure in a combined analysis of 8129 subjects from the GRAPHIC Study, the CoLaus Study and the Silesian Cardiovascular Study (P=5.4×10−6). Additional analysis of associations between variants in Gene Ontology-defined pathways and mean 24-hour blood pressure in the GRAPHIC Study showed that cell survival control signalling cascades could play a role in blood pressure regulation. There was also a significant over-representation of rare variants (minor allele frequency architecture of blood pressure. PMID:21060006

  16. Genetic Architecture of Dietary Fiber and Oligosaccharide Content in a Middle American Panel of Edible Dry Bean.

    Science.gov (United States)

    Moghaddam, Samira Mafi; Brick, Mark A; Echeverria, Dimas; Thompson, Henry J; Brick, Leslie A; Lee, Rian; Mamidi, Sujan; McClean, Phillip E

    2018-03-01

    Common bean ( L.) is the most consumed edible grain legume worldwide and contains a wide range of nutrients for human health including dietary fiber. Diets high in beans are associated with lower rates of chronic diseases such as obesity and type 2 diabetes, and the content of dietary fibers varies among different market classes of dry bean. In this study, we evaluated the dietary fiber content in a Middle American diversity panel (MDP) of common bean and evaluated the genetic architecture of the various dietary fiber components. The dietary fiber components included insoluble and soluble dietary fibers as well as the antinutritional raffinose family of oligosaccharides (RFOs; raffinose, stachyose, and verbascose). All variables measured differed among market classes and entries. Colored bean seeds had higher levels of insoluble dietary fibers with the black market class showing also the highest raffinose and stachyose content. Cultivars and lines released since 1997 had higher insoluble dietary fibers and RFO content in race Durango. Higher levels of RFOs were also observed in cultivars with type II growth habit that was a recent breeding target in Durango race germplasm. Candidate genes for dietary fiber traits, especially homologs to two main genes in the RFO biosynthesis pathway, were identified. The knowledge of diversity of dietary fibers in the MDP accompanied with the identification of candidate genes could effectively improve dietary fiber components in common bean. Copyright © 2018 Crop Science Society of America.

  17. Performance of diverse wheat genetic stocks under moisture stress condition

    International Nuclear Information System (INIS)

    Seher, M.; Shabbir, G.; Rasheed, A.

    2015-01-01

    This study was conducted to evaluate divergent wheat germplasm for their performance under drought and control conditions. The germplasm consists of wheat land races of Pakistan, advanced D-genome synthetic derivatives and high yielding varieties of Pakistan. This wide array of germplasm was selected to identify sources, which can be opted later by the wheat breeders while breeding for drought tolerance. The evaluation parameters involved some important physiochemical testing and morphological characteristics in the field under drought and control conditions. Based on these parameters, 13 wheat genotypes were selected on the basis of their best performance regarding morphological and physiological parameters. These genotypes exhibited higher yield under drought stress conditions and increased percentage of proline, sugar, SOD and protein content under laboratory conditions as compared to the susceptible genotypes. Correlation studies revealed that grains per spike (GPS) and thousand grain weight (TGW) had direct relationship with spike length (SL), proline and sugar content under both control and drought conditions. Thus, these parameters can be used as selection criteria for the identification of tolerant genotypes. (author)

  18. Genetic variation of loci potentially under selection confounds species-genetic diversity correlations in a fragmented habitat.

    Science.gov (United States)

    Bertin, Angeline; Gouin, Nicolas; Baumel, Alex; Gianoli, Ernesto; Serratosa, Juan; Osorio, Rodomiro; Manel, Stephanie

    2017-01-01

    Positive species-genetic diversity correlations (SGDCs) are often thought to result from the parallel influence of neutral processes on genetic and species diversity. Yet, confounding effects of non-neutral mechanisms have not been explored. Here, we investigate the impact of non-neutral genetic diversity on SGDCs in high Andean wetlands. We compare correlations between plant species diversity and genetic diversity (GD) calculated with and without loci potentially under selection (outlier loci). The study system includes 2188 specimens from five species (three common aquatic macroinvertebrate and two dominant plant species) that were genotyped for 396 amplified fragment length polymorphism loci. We also appraise the importance of neutral processes on SGDCs by investigating the influence of habitat fragmentation features. Significant positive SGDCs were detected for all five species (mean SGDC = 0.52 ± 0.05). While only a few outlier loci were detected in each species, they resulted in significant decreases in GD and in SGDCs. This supports the hypothesis that neutral processes drive species-genetic diversity relationships in high Andean wetlands. Unexpectedly, the effects on genetic diversity GD of the habitat fragmentation characteristics in this study increased with the presence of outlier loci in two species. Overall, our results reveal pitfalls in using habitat features to infer processes driving SGDCs and show that a few loci potentially under selection are enough to cause a significant downward bias in SGDC. Investigating confounding effects of outlier loci thus represents a useful approach to evidence the contribution of neutral processes on species-genetic diversity relationships. © 2016 John Wiley & Sons Ltd.

  19. Resistance to gray leaf spot of maize: genetic architecture and mechanisms elucidated through nested association mapping and near-isogenic line analysis.

    Science.gov (United States)

    Benson, Jacqueline M; Poland, Jesse A; Benson, Brent M; Stromberg, Erik L; Nelson, Rebecca J

    2015-03-01

    Gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is one of the most important diseases of maize worldwide. The pathogen has a necrotrophic lifestyle and no major genes are known for GLS. Quantitative resistance, although poorly understood, is important for GLS management. We used genetic mapping to refine understanding of the genetic architecture of GLS resistance and to develop hypotheses regarding the mechanisms underlying quantitative disease resistance (QDR) loci. Nested association mapping (NAM) was used to identify 16 quantitative trait loci (QTL) for QDR to GLS, including seven novel QTL, each of which demonstrated allelic series with significant effects above and below the magnitude of the B73 reference allele. Alleles at three QTL, qGLS1.04, qGLS2.09, and qGLS4.05, conferred disease reductions of greater than 10%. Interactions between loci were detected for three pairs of loci, including an interaction between iqGLS4.05 and qGLS7.03. Near-isogenic lines (NILs) were developed to confirm and fine-map three of the 16 QTL, and to develop hypotheses regarding mechanisms of resistance. qGLS1.04 was fine-mapped from an interval of 27.0 Mb to two intervals of 6.5 Mb and 5.2 Mb, consistent with the hypothesis that multiple genes underlie highly significant QTL identified by NAM. qGLS2.09, which was also associated with maturity (days to anthesis) and with resistance to southern leaf blight, was narrowed to a 4-Mb interval. The distance between major leaf veins was strongly associated with resistance to GLS at qGLS4.05. NILs for qGLS1.04 were treated with the C. zeae-maydis toxin cercosporin to test the role of host-specific toxin in QDR. Cercosporin exposure increased expression of a putative flavin-monooxygenase (FMO) gene, a candidate detoxification-related gene underlying qGLS1.04. This integrated approach to confirming QTL and characterizing the potential underlying mechanisms advances the understanding of QDR and will facilitate the

  20. Resistance to gray leaf spot of maize: genetic architecture and mechanisms elucidated through nested association mapping and near-isogenic line analysis.

    Directory of Open Access Journals (Sweden)

    Jacqueline M Benson

    2015-03-01

    Full Text Available Gray leaf spot (GLS, caused by Cercospora zeae-maydis and Cercospora zeina, is one of the most important diseases of maize worldwide. The pathogen has a necrotrophic lifestyle and no major genes are known for GLS. Quantitative resistance, although poorly understood, is important for GLS management. We used genetic mapping to refine understanding of the genetic architecture of GLS resistance and to develop hypotheses regarding the mechanisms underlying quantitative disease resistance (QDR loci. Nested association mapping (NAM was used to identify 16 quantitative trait loci (QTL for QDR to GLS, including seven novel QTL, each of which demonstrated allelic series with significant effects above and below the magnitude of the B73 reference allele. Alleles at three QTL, qGLS1.04, qGLS2.09, and qGLS4.05, conferred disease reductions of greater than 10%. Interactions between loci were detected for three pairs of loci, including an interaction between iqGLS4.05 and qGLS7.03. Near-isogenic lines (NILs were developed to confirm and fine-map three of the 16 QTL, and to develop hypotheses regarding mechanisms of resistance. qGLS1.04 was fine-mapped from an interval of 27.0 Mb to two intervals of 6.5 Mb and 5.2 Mb, consistent with the hypothesis that multiple genes underlie highly significant QTL identified by NAM. qGLS2.09, which was also associated with maturity (days to anthesis and with resistance to southern leaf blight, was narrowed to a 4-Mb interval. The distance between major leaf veins was strongly associated with resistance to GLS at qGLS4.05. NILs for qGLS1.04 were treated with the C. zeae-maydis toxin cercosporin to test the role of host-specific toxin in QDR. Cercosporin exposure increased expression of a putative flavin-monooxygenase (FMO gene, a candidate detoxification-related gene underlying qGLS1.04. This integrated approach to confirming QTL and characterizing the potential underlying mechanisms advances the understanding of QDR and will

  1. Genetic architecture of pollination syndrome transition between hummingbird-specialist and generalist species in the genus Rhytidophyllum (Gesneriaceae

    Directory of Open Access Journals (Sweden)

    Hermine Alexandre

    2015-06-01

    Full Text Available Adaptation to pollinators is a key factor of diversification in angiosperms. The Caribbean sister genera Rhytidophyllum and Gesneria present an important diversification of floral characters. Most of their species can be divided in two major pollination syndromes. Large-open flowers with pale colours and great amount of nectar represent the generalist syndrome, while the hummingbird-specialist syndrome corresponds to red tubular flowers with a less important nectar volume. Repeated convergent evolution toward the generalist syndrome in this group suggests that such transitions rely on few genes of moderate to large effect. To test this hypothesis, we built a linkage map and performed a QTL detection for divergent pollination syndrome traits by crossing one specimen of the generalist species Rhytidophyllum auriculatum with one specimen of the hummingbird pollinated R. rupincola. Using geometric morphometrics and univariate traits measurements, we found that floral shape among the second-generation hybrids is correlated with morphological variation observed between generalist and hummingbird-specialist species at the genus level. The QTL analysis showed that colour and nectar volume variation between syndromes involve each one major QTL while floral shape has a more complex genetic basis and rely on few genes of moderate effect. Finally, we did not detect any genetic linkage between the QTLs underlying those traits. This genetic independence of traits could have facilitated evolution toward optimal syndromes.

  2. The genetic architecture of oral language, reading fluency, and reading comprehension: A twin study from 7 to 16 years.

    Science.gov (United States)

    Tosto, Maria G; Hayiou-Thomas, Marianna E; Harlaar, Nicole; Prom-Wormley, Elizabeth; Dale, Philip S; Plomin, Robert

    2017-06-01

    This study examines the genetic and environmental etiology underlying the development of oral language and reading skills, and the relationship between them, over a long period of developmental time spanning middle childhood and adolescence. It focuses particularly on the differential relationship between language and two different aspects of reading: reading fluency and reading comprehension. Structural equation models were applied to language and reading data at 7, 12, and 16 years from the large-scale TEDS twin study. A series of multivariate twin models show a clear patterning of oral language with reading comprehension, as distinct from reading fluency: significant but moderate genetic overlap between oral language and reading fluency (genetic correlation r g = .46-.58 at 7, 12, and 16) contrasts with very substantial genetic overlap between oral language and reading comprehension (r g = .81-.87, at 12 and 16). This pattern is even clearer in a latent factors model, fit to the data aggregated across ages, in which a single factor representing oral language and reading comprehension is correlated with-but distinct from-a second factor representing reading fluency. A distinction between oral language and reading fluency is also apparent in different developmental trajectories: While the heritability of oral language increases over the period from 7 to 12 to 16 years (from h² = .27 to .47 to .55), the heritability of reading fluency is high and largely stable over the same period of time (h² = .73 to .71 to .64). (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  3. Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elizabeth G Holliday

    Full Text Available Genetic factors explain a majority of risk variance for age-related macular degeneration (AMD. While genome-wide association studies (GWAS for late AMD implicate genes in complement, inflammatory and lipid pathways, the genetic architecture of early AMD has been relatively under studied. We conducted a GWAS meta-analysis of early AMD, including 4,089 individuals with prevalent signs of early AMD (soft drusen and/or retinal pigment epithelial changes and 20,453 individuals without these signs. For various published late AMD risk loci, we also compared effect sizes between early and late AMD using an additional 484 individuals with prevalent late AMD. GWAS meta-analysis confirmed previously reported association of variants at the complement factor H (CFH (peak P = 1.5×10(-31 and age-related maculopathy susceptibility 2 (ARMS2 (P = 4.3×10(-24 loci, and suggested Apolipoprotein E (ApoE polymorphisms (rs2075650; P = 1.1×10(-6 associated with early AMD. Other possible loci that did not reach GWAS significance included variants in the zinc finger protein gene GLI3 (rs2049622; P = 8.9×10(-6 and upstream of GLI2 (rs6721654; P = 6.5×10(-6, encoding retinal Sonic hedgehog signalling regulators, and in the tyrosinase (TYR gene (rs621313; P = 3.5×10(-6, involved in melanin biosynthesis. For a range of published, late AMD risk loci, estimated effect sizes were significantly lower for early than late AMD. This study confirms the involvement of multiple established AMD risk variants in early AMD, but suggests weaker genetic effects on the risk of early AMD relative to late AMD. Several biological processes were suggested to be potentially specific for early AMD, including pathways regulating RPE cell melanin content and signalling pathways potentially involved in retinal regeneration, generating hypotheses for further investigation.

  4. Histological Architecture Underlying Brain-Immune Cell-Cell Interactions and the Cerebral Response to Systemic Inflammation.

    Science.gov (United States)

    Shimada, Atsuyoshi; Hasegawa-Ishii, Sanae

    2017-01-01

    Although the brain is now known to actively interact with the immune system under non-inflammatory conditions, the site of cell-cell interactions between brain parenchymal cells and immune cells has been an open question until recently. Studies by our and other groups have indicated that brain structures such as the leptomeninges, choroid plexus stroma and epithelium, attachments of choroid plexus, vascular endothelial cells, cells of the perivascular space, circumventricular organs, and astrocytic endfeet construct the histological architecture that provides a location for intercellular interactions between bone marrow-derived myeloid lineage cells and brain parenchymal cells under non-inflammatory conditions. This architecture also functions as the interface between the brain and the immune system, through which systemic inflammation-induced molecular events can be relayed to the brain parenchyma at early stages of systemic inflammation during which the blood-brain barrier is relatively preserved. Although brain microglia are well known to be activated by systemic inflammation, the mechanism by which systemic inflammatory challenge and microglial activation are connected has not been well documented. Perturbed brain-immune interaction underlies a wide variety of neurological and psychiatric disorders including ischemic brain injury, status epilepticus, repeated social defeat, and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Proinflammatory status associated with cytokine imbalance is involved in autism spectrum disorders, schizophrenia, and depression. In this article, we propose a mechanism connecting systemic inflammation, brain-immune interface cells, and brain parenchymal cells and discuss the relevance of basic studies of the mechanism to neurological disorders with a special emphasis on sepsis-associated encephalopathy and preterm brain injury.

  5. Genetic architecture of contemporary adaptation to biotic invasions: quantitative trait locus mapping of beak reduction in soapberry bugs.

    Science.gov (United States)

    Yu, Y; Andrés, Jose A

    2014-02-19

    Biological invasions can result in new selection pressures driven by the establishment of new biotic interactions. The response of exotic and native species to selection depends critically on the genetic architecture of ecologically relevant traits. In the Florida peninsula, the soapberry bug (Jadera haematoloma) has colonized the recently introduced Chinese flametree, Koelreuteria elegans, as a host plant. Driven by feeding efficiency, the populations associated with this new host have differentiated into a new bug ecomorph characterized by short beaks more appropriate for feeding on the flattened pods of the Chinese flametree. In this study, we have generated a three-generation pedigree from crossing the long-beaked and short-beaked ecomorphs to construct a de novo linkage map and to locate putative quantitative trait locus (QTL) controlling beak length and body size in J. haematoloma. Using amplified fragment-length polymorphism markers and a two-way pseudo-testcross design, we have produced two parental maps in six linkage groups, covering the known number of chromosomes. QTL analysis revealed one significant QTL for beak length on a maternal linkage group and the corresponding paternal linkage group. Three QTL were found for body size. Through single marker regression analysis, nine single markers that could not be placed on the map were also found to be significantly associated with one or both of the two traits. Interestingly, the most significant body size QTL co-localized with the beak length QTL, suggesting linkage disequilibrium or pleiotropic effects of related traits. Our results suggest an oligogenic control of beak length.

  6. Genetic variation and reproductive timing: African American women from the Population Architecture using Genomics and Epidemiology (PAGE Study.

    Directory of Open Access Journals (Sweden)

    Kylee L Spencer

    Full Text Available Age at menarche (AM and age at natural menopause (ANM define the boundaries of the reproductive lifespan in women. Their timing is associated with various diseases, including cancer and cardiovascular disease. Genome-wide association studies have identified several genetic variants associated with either AM or ANM in populations of largely European or Asian descent women. The extent to which these associations generalize to diverse populations remains unknown. Therefore, we sought to replicate previously reported AM and ANM findings and to identify novel AM and ANM variants using the Metabochip (n = 161,098 SNPs in 4,159 and 1,860 African American women, respectively, in the Women's Health Initiative (WHI and Atherosclerosis Risk in Communities (ARIC studies, as part of the Population Architecture using Genomics and Epidemiology (PAGE Study. We replicated or generalized one previously identified variant for AM, rs1361108/CENPW, and two variants for ANM, rs897798/BRSK1 and rs769450/APOE, to our African American cohort. Overall, generalization of the majority of previously-identified variants for AM and ANM, including LIN28B and MCM8, was not observed in this African American sample. We identified three novel loci associated with ANM that reached significance after multiple testing correction (LDLR rs189596789, p = 5×10⁻⁰⁸; KCNQ1 rs79972789, p = 1.9×10⁻⁰⁷; COL4A3BP rs181686584, p = 2.9×10⁻⁰⁷. Our most significant AM association was upstream of RSF1, a gene implicated in ovarian and breast cancers (rs11604207, p = 1.6×10⁻⁰⁶. While most associations were identified in either AM or ANM, we did identify genes suggestively associated with both: PHACTR1 and ARHGAP42. The lack of generalization coupled with the potentially novel associations identified here emphasize the need for additional genetic discovery efforts for AM and ANM in diverse populations.

  7. Transitions in Land Use Architecture under Multiple Human Driving Forces in a Semi-Arid Zone

    Directory of Open Access Journals (Sweden)

    Issa Ouedraogo

    2015-07-01

    Full Text Available The present study aimed to detect the main shifts in land-use architecture and assess the factors behind the changes in typical tropical semi-arid land in Burkina Faso. Three sets of time-series LANDSAT data over a 23-year period were used to detect land use changes and their underpinning drivers in multifunctional but vulnerable ecologies. Group discussions in selected villages were organized for mapping output interpretation and collection of essential drivers of change as perceived by local populations. Results revealed profound changes and transitions during the study period. During the last decade, shrub and wood savannahs exhibited high net changes (39% and −37% respectively with a weak net positive change for cropland (only 2%, while cropland and shrub savannah exhibited high swap (8% and 16%. This suggests that the area of cropland remained almost unchanged but was subject to relocation, wood savannah decreased drastically, and shrub savannah increased exponentially. Cropland exhibited a null net persistence while shrub and wood savannahs exhibited positive and negative net persistence (1.91 and −10.24, respectively, indicating that there is movement toward agricultural intensification and wood savannah tended to disappear to the benefit of shrub savannah. Local people are aware of the changes that have occurred and support the idea that illegal wood cutting and farming are inappropriate farming practices associated with immigration; absence of alternative cash generation sources, overgrazing and increasing demand for wood energy are driving the changes in their ecosystems. Policies that integrate restoration and conservation of natural ecosystems and promote sustainable agroforestry practices in the study zone are highly recommended.

  8. Epileptic Encephalopathy in Childhood: A Stepwise Approach for Identification of Underlying Genetic Causes.

    Science.gov (United States)

    Patel, Jaina; Mercimek-Mahmutoglu, Saadet

    2016-10-01

    Epilepsy is one of the most common neurological disorders in childhood. Epilepsy associated with global developmental delay and cognitive dysfunction is defined as epileptic encephalopathy. Certain inherited metabolic disorders presenting with epileptic encephalopathy can be treated with disease specific diet, vitamin, amino acid or cofactor supplementations. In those disorders, disease specific therapy is successful to achieve good seizure control and improve long-term neurodevelopmental outcome. For this reason, intractable epilepsy with global developmental delay or history of developmental regression warrants detailed metabolic investigations for the possibility of an underlying treatable inherited metabolic disorder, which should be undertaken as first line investigations. An underlying genetic etiology in epileptic encephalopathy has been supported by recent studies such as array comparative genomic hybridization, targeted next generation sequencing panels, whole exome and whole genome sequencing. These studies report a diagnostic yield up to 70%, depending on the applied genetic testing as well as number of patients enrolled. In patients with epileptic encephalopathy, a stepwise approach for diagnostic work-up will help to diagnose treatable inherited metabolic disorders quickly. Application of detailed genetic investigations such as targeted next generation sequencing as second line and whole exome sequencing as third line testing will diagnose underlying genetic disease which will help for genetic counseling as well as guide for prenatal diagnosis. Knowledge of underlying genetic cause will provide novel insights into the pathogenesis of epileptic encephalopathy and pave the ground towards the development of targeted neuroprotective treatment strategies to improve the health outcome of children with epileptic encephalopathy.

  9. Virus-host co-evolution under a modified nuclear genetic code

    Directory of Open Access Journals (Sweden)

    Derek J. Taylor

    2013-03-01

    Full Text Available Among eukaryotes with modified nuclear genetic codes, viruses are unknown. However, here we provide evidence of an RNA virus that infects a fungal host (Scheffersomyces segobiensis with a derived nuclear genetic code where CUG codes for serine. The genomic architecture and phylogeny are consistent with infection by a double-stranded RNA virus of the genus Totivirus. We provide evidence of past or present infection with totiviruses in five species of yeasts with modified genetic codes. All but one of the CUG codons in the viral genome have been eliminated, suggesting that avoidance of the modified codon was important to viral adaptation. Our mass spectroscopy analysis indicates that a congener of the host species has co-opted and expresses a capsid gene from totiviruses as a cellular protein. Viral avoidance of the host’s modified codon and host co-option of a protein from totiviruses suggest that RNA viruses co-evolved with yeasts that underwent a major evolutionary transition from the standard genetic code.

  10. The genetic basis of alcoholism: multiple phenotypes, many genes, complex networks

    Science.gov (United States)

    2012-01-01

    Alcoholism is a significant public health problem. A picture of the genetic architecture underlying alcohol-related phenotypes is emerging from genome-wide association studies and work on genetically tractable model organisms. PMID:22348705

  11. Genetic variation underlying psychosis-inducing effects of cannabis: critical review and future directions.

    Science.gov (United States)

    Decoster, Jeroen; van Os, Jim; Myin-Germeys, Inez; De Hert, Marc; van Winkel, Ruud

    2012-01-01

    Cannabis use is associated with an increased risk for psychotic disorder, yet most cannabis users do not develop psychosis, suggesting that other factors are also involved. This paper reviews the available evidence suggesting that differential sensitivity to the psychosis-inducing effects of cannabis may be related to underlying genetic liability. There is robust evidence that persons at psychometric risk for psychosis are most vulnerable to display psychotic symptoms subsequent to the use of cannabis. Multiple studies have also found that persons at familial risk for psychosis have an increased sensitivity to the effects of cannabis. Together, these findings support the concept of a biological interaction between cannabis use and one's underlying genetic vulnerability. At the molecular-genetic level, however, few (if any) interactions have been consistently replicated, although a reported interaction with variation in AKT1 is promising and deserves further follow-up. The apparent lack of consistent replication can be ascribed to problems of initial gene selection, statistical power, a bias towards positive results and insufficient attempts at true replication, leading to the conclusion that increased sample sizes, greater density of genetic markers and a stronger focus on true replication are necessary. The major challenge for molecular-genetic gene-environment interaction research will be to combine the agnostic detection of disorder-associated genetic variants from genome-wide studies with the hypothesis-based approach from epidemiological and neurobiological studies. Possible strategies for future cannabis interaction studies are discussed.

  12. Changes in cell wall architecture of wheat coleoptiles grown under continuous hypergravity conditions

    Science.gov (United States)

    Wakabayashi, K.; Soga, K.; Kamisaka, S.; Hoson, T.

    Modifications of cell wall structure of wheat coleoptiles in response to continuous hypergravity (300 g) treatment were investigated. Length of coleoptiles exposed to hypergravity for 2-4 days from germination stage was 60-70% of that of 1 g control. The net amounts of cell wall polysaccharides, such as hemicellulose and cellulose, of hypergravity-treated coleoptiles increased as much as those of 1 g control coleoptiles during the incubation period. As a result, the levels of cell wall polysaccharides per unit length of coleoptile, which mean the thickness of cell walls, largely increased under hypergravity conditions. Particularly, the amounts of hemicellulosic polymers with middle molecular mass (0.2-1 MDa) largely increased from day 2 to 3 under hypergravity conditions. The major sugar components of the hemicellulose fraction are arabinose, xylose and glucose. The ratios of arabinose and xylose to glucose were higher in hypergravity-treated coleoptiles than in control coleoptiles. The fractionation of hemicellulosic polymers into the neutral and acidic polymers by the anion-exchange column showed that the levels of acidic polymers (mainly composed of arabinoxylans) in cell walls of hypergravity-treated coleoptiles were higher than those of control coleoptiles. In addition to wall polysaccharides, the amounts of cell wall-bound phenolics, such as ferulic acid and diferulic acid, substantially increased during the incubation period both in 1 g control and hypergravity-treated coleoptiles. Especially, the levels of diferulic acid which cross-links hemicellulosic polymers were higher in hypergravity-treated coleoptiles than in control coleoptiles during the incubation period. These results suggest that hypergravity stimuli from the germination stage bias the type of synthesized hemicellulosic polysaccharides, although they do not restrict the net synthesis of cell wall constituents in wheat coleoptiles. The stimulation of the synthesis of arabinoxylans and of the

  13. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Maggie C Y Ng

    2014-08-01

    Full Text Available Type 2 diabetes (T2D is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1 and two novel loci (HLA-B and INS-IGF2 at genome-wide significance (4.15 × 10(-94

  14. Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating.

    Science.gov (United States)

    Kirkpatrick, Stacey L; Goldberg, Lisa R; Yazdani, Neema; Babbs, R Keith; Wu, Jiayi; Reed, Eric R; Jenkins, David F; Bolgioni, Amanda F; Landaverde, Kelsey I; Luttik, Kimberly P; Mitchell, Karen S; Kumar, Vivek; Johnson, W Evan; Mulligan, Megan K; Cottone, Pietro; Bryant, Camron D

    2017-05-01

    Eating disorders are lethal and heritable; however, the underlying genetic factors are unknown. Binge eating is a highly heritable trait associated with eating disorders that is comorbid with mood and substance use disorders. Therefore, understanding its genetic basis will inform therapeutic development that could improve several comorbid neuropsychiatric conditions. We assessed binge eating in closely related C57BL/6 mouse substrains and in an F 2 cross to identify quantitative trait loci associated with binge eating. We used gene targeting to validate candidate genetic factors. Finally, we used transcriptome analysis of the striatum via messenger RNA sequencing to identify the premorbid transcriptome and the binge-induced transcriptome to inform molecular mechanisms mediating binge eating susceptibility and establishment. C57BL/6NJ but not C57BL/6J mice showed rapid and robust escalation in palatable food consumption. We mapped a single genome-wide significant quantitative trait locus on chromosome 11 (logarithm of the odds = 7.4) to a missense mutation in cytoplasmic FMR1-interacting protein 2 (Cyfip2). We validated Cyfip2 as a major genetic factor underlying binge eating in heterozygous knockout mice on a C57BL/6N background that showed reduced binge eating toward a wild-type C57BL/6J-like level. Transcriptome analysis of premorbid genetic risk identified the enrichment terms morphine addiction and retrograde endocannabinoid signaling, whereas binge eating resulted in the downregulation of a gene set enriched for decreased myelination, oligodendrocyte differentiation, and expression. We identified Cyfip2 as a major significant genetic factor underlying binge eating and provide a behavioral paradigm for future genome-wide association studies in populations with increased genetic complexity. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. GENETIC VARIABILITY OF CULTURED PLANT TISSUES UNDER NORMAL CONDITIONS AND UNDER STRESS

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    Dolgikh Yu.I.

    2012-08-01

    Full Text Available The genetic variability induced by in vitro conditions known as somaclonal variation is of practical interest due to its potential uses in plant breeding but, on the other hand, if clonal propagation or transformation is main goal, it becomes an unwelcome phenomenon. Thus, it is important to know frequency, the genomic distribution, the mechanisms and factors influencing somaclonal variation. We studied variability of PCR-based DNA markers of cultured tissues and regenerated plants of maize and bread wheat. The original A188 line of maize and the somaclones obtained were tested using 38 RAPD and 10 ISSR primers. None of the A188 plants showed variation in the RAPD and ISSR spectra for any of the primers used. However, the PCR spectra obtained from the somaclones demonstrated some variations, i.e., 22 RAPD primers and 6 ISSR primers differentiated at least one somaclonal variant from the progenitor line. Six SCAR markers were developed based on several RAPD and ISSR fragments. The inheritance of these SCAR markers was verified in the selfing progeny of each somaclone in the R1–R4 generations and in the hybrids, with A188 as the parental line in the F1 and F2 generations. These markers were sequenced and bioinformatic searches were performed to understand the molecular events that may underlie the variability observed in the somaclones. All changes were found in noncoding sequences and were induced by different molecular events, such as the insertion of long terminal repeat transposon, precise miniature inverted repeat transposable element (MITE excision, microdeletion, recombination, and a change in the pool of mitochondrial DNA. In two groups of independently produced somaclones, the same features (morphological, molecular were variable, which confirms the theory of ‘hot spots’ occurring in the genome. The presence of the same molecular markers in the somaclones and in different non-somaclonal maize variants suggests that in some cases

  16. Cognitive mechanisms underlying disorganization of thought in a genetic syndrome (47,XXY)

    NARCIS (Netherlands)

    Van Rijn, Sophie; Aleman, Andre; De Sonneville, Leo; Swaab, Hanna

    Because of the risk for development of psychopathology such as psychotic symptoms, it has been suggested that studying men with the XXY karyotype may help in the search for underlying cognitive, neural and genetic mechanisms. The aim of this study was to identify cognitive mechanisms that may

  17. Genetic influence on blood pressure measured in the office, under laboratory stress and during real life

    NARCIS (Netherlands)

    Wang, Xiaoling; Ding, Xiuhua; Su, Shaoyong; Harshfield, Gregory; Treiber, Frank; Snieder, Harold

    To determine to what extent the genetic influences on blood pressure (BP) measured in the office, under psychologically stressful conditions in the laboratory and during real life are different from each other. Office BP, BP during a video game challenge and a social stressor interview, and 24-h

  18. A genetic analysis of relative growth rate and underlying components in Hordeum spontaneum

    NARCIS (Netherlands)

    Poorter, H.; Van Rijn, C.P.E.; Vanhala, T.K.; Verhoeven, K.J.F.; de Jong, Y.E.M.; Stams, A.J.M.; Lambers, H.

    2005-01-01

    Species from productive and unproductive habitats differ inherently in their relative growth rate (RGR) and a wide range of correlated quantitative traits. We investigated the genetic basis of this trait complex, and specifically assessed whether it is under the control of just one or a few genes

  19. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes

    DEFF Research Database (Denmark)

    Ng, Maggie C Y; Shriner, Daniel; Chen, Brian H

    2014-01-01

    Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry...... of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting....... In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs...

  20. The genetic architecture of reproductive isolation during speciation-with-gene-flow in lake whitefish species pairs assessed by RAD sequencing.

    Science.gov (United States)

    Gagnaire, Pierre-Alexandre; Pavey, Scott A; Normandeau, Eric; Bernatchez, Louis

    2013-09-01

    During speciation-with-gene-flow, effective migration varies across the genome as a function of several factors, including proximity of selected loci, recombination rate, strength of selection, and number of selected loci. Genome scans may provide better empirical understanding of the genome-wide patterns of genetic differentiation, especially if the variance due to the previously mentioned factors is partitioned. In North American lake whitefish (Coregonus clupeaformis), glacial lineages that diverged in allopatry about 60,000 years ago and came into contact 12,000 years ago have independently evolved in several lakes into two sympatric species pairs (a normal benthic and a dwarf limnetic). Variable degrees of reproductive isolation between species pairs across lakes offer a continuum of genetic and phenotypic divergence associated with adaptation to distinct ecological niches. To disentangle the complex array of genetically based barriers that locally reduce the effective migration rate between whitefish species pairs, we compared genome-wide patterns of divergence across five lakes distributed along this divergence continuum. Using restriction site associated DNA (RAD) sequencing, we combined genetic mapping and population genetics approaches to identify genomic regions resistant to introgression and derive empirical measures of the barrier strength as a function of recombination distance. We found that the size of the genomic islands of differentiation was influenced by the joint effects of linkage disequilibrium maintained by selection on many loci, the strength of ecological niche divergence, as well as demographic characteristics unique to each lake. Partial parallelism in divergent genomic regions likely reflected the combined effects of polygenic adaptation from standing variation and independent changes in the genetic architecture of postzygotic isolation. This study illustrates how integrating genetic mapping and population genomics of multiple sympatric

  1. Nash Bargaining Game-Theoretic Framework for Power Control in Distributed Multiple-Radar Architecture Underlying Wireless Communication System

    Directory of Open Access Journals (Sweden)

    Chenguang Shi

    2018-04-01

    Full Text Available This paper presents a novel Nash bargaining solution (NBS-based cooperative game-theoretic framework for power control in a distributed multiple-radar architecture underlying a wireless communication system. Our primary objective is to minimize the total power consumption of the distributed multiple-radar system (DMRS with the protection of wireless communication user’s transmission, while guaranteeing each radar’s target detection requirement. A unified cooperative game-theoretic framework is proposed for the optimization problem, where interference power constraints (IPCs are imposed to protect the communication user’s transmission, and a minimum signal-to-interference-plus-noise ratio (SINR requirement is employed to provide reliable target detection for each radar. The existence, uniqueness and fairness of the NBS to this cooperative game are proven. An iterative Nash bargaining power control algorithm with low computational complexity and fast convergence is developed and is shown to converge to a Pareto-optimal equilibrium for the cooperative game model. Numerical simulations and analyses are further presented to highlight the advantages and testify to the efficiency of our proposed cooperative game algorithm. It is demonstrated that the distributed algorithm is effective for power control and could protect the communication system with limited implementation overhead.

  2. Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.

    Science.gov (United States)

    Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja

    2017-01-17

    Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10 -6 , MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

  3. Phase and Microstructure Evolution and Toughening Mechanism of a Hierarchical Architectured Al2O3-Y2O3 Coating under High Temperature

    Science.gov (United States)

    Rong, Jian; Yang, Kai; Zhuang, Yin; Ni, Jinxing; Zhao, Huayu; Tao, Shunyan; Zhong, Xinghua; Ding, Chuanxian

    2018-02-01

    In recent years, numerous techniques have been developed to mimic nacre-like hierarchical architectures in order to improve the damage tolerance of materials. We present herein a simple strategy to fabricate such a hierarchical architectured Al2O3-Y2O3 composite coating via atmospheric plasma spraying. The evolution of the phase and microstructure of the Al2O3-Y2O3 composite coating were characterized under conditions of high-temperature exposure in air at 800-1350 °C. The hardness and porosity of several typical coatings were determined. In situ formation of dense hierarchical architectured Al2O3-YAG composite coating with improved hardness was achieved after heat treatment at 1350 °C. Compared with Al2O3 coating, elevated toughness was found for the hierarchical architectured Al2O3-YAG composite coating, which can be ascribed to the distribution of YAG phase that contributed to crack termination and deflection, and microbridging. After thermal aging treatment at 1350 °C, the hierarchical architectured Al2O3-YAG composite coating was quite stable after 100 h of thermal exposure. Furthermore, the Al2O3-Y2O3 composite coating exhibited superior sintering resistance compared with the Al2O3 coating.

  4. AFLPs reveal different population genetic structure under contrasting environments in the marine snail Nucella lapillus L.

    Directory of Open Access Journals (Sweden)

    Belén Carro

    Full Text Available Dispersal has received growing attention in marine ecology, particularly since evidence obtained with up-to-date techniques challenged the traditional view. The dogwhelk Nucella lapillus L., a sedentary gastropod with direct development, is a good example: dispersal was traditionally assumed to be limited until studies with microsatellites disputed this idea. To shed some light on this controversy, the genetic structure of dogwhelk populations in northwest Spain was investigated with highly polymorphic AFLP markers giving special attention to the influence of hydrodynamic stress. In agreement with the expectations for a poor disperser, our results show a significant genetic structure at regional (<200 km and areal scales (<15 km. However, the spatial genetic structure varied with wave-exposure in the present case study: IBD was evident under sheltered conditions but absent from the exposed area where genetic differentiation was stronger. Our results provide evidence that differences in wave-exposure can exert a detectable influence on the genetic structure of coastal organisms, even in species without a planktonic larva.

  5. Genetic Adaptation to Growth Under Laboratory Conditions in Escherichia coli and Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Anna Knöppel

    2018-04-01

    Full Text Available Experimental evolution under controlled laboratory conditions is becoming increasingly important to address various evolutionary questions, including, for example, the dynamics and mechanisms of genetic adaptation to different growth and stress conditions. In such experiments, mutations typically appear that increase the fitness under the conditions tested (medium adaptation, but that are not necessarily of interest for the specific research question. Here, we have identified mutations that appeared during serial passage of E. coli and S. enterica in four different and commonly used laboratory media and measured the relative competitive fitness and maximum growth rate of 111 genetically re-constituted strains, carrying different single and multiple mutations. Little overlap was found between the mutations that were selected in the two species and the different media, implying that adaptation occurs via different genetic pathways. Furthermore, we show that commonly occurring adaptive mutations can generate undesired genetic variation in a population and reduce the accuracy of competition experiments. However, by introducing media adaptation mutations with large effects into the parental strain that was used for the evolution experiment, the variation (standard deviation was decreased 10-fold, and it was possible to measure fitness differences between two competitors as small as |s| < 0.001.

  6. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    This paper will discuss the challenges faced by architectural education today. It takes as its starting point the double commitment of any school of architecture: on the one hand the task of preserving the particular knowledge that belongs to the discipline of architecture, and on the other hand...... the obligation to prepare students to perform in a profession that is largely defined by forces outside that discipline. It will be proposed that the autonomy of architecture can be understood as a unique kind of information: as architecture’s self-reliance or knowledge-about itself. A knowledge...... that is not scientific or academic but is more like a latent body of data that we find embedded in existing works of architecture. This information, it is argued, is not limited by the historical context of the work. It can be thought of as a virtual capacity – a reservoir of spatial configurations that can...

  7. Genetic architecture of aluminum tolerance in rice (Oryza sativa determined through genome-wide association analysis and QTL mapping.

    Directory of Open Access Journals (Sweden)

    Adam N Famoso

    2011-08-01

    Full Text Available Aluminum (Al toxicity is a primary limitation to crop productivity on acid soils, and rice has been demonstrated to be significantly more Al tolerant than other cereal crops. However, the mechanisms of rice Al tolerance are largely unknown, and no genes underlying natural variation have been reported. We screened 383 diverse rice accessions, conducted a genome-wide association (GWA study, and conducted QTL mapping in two bi-parental populations using three estimates of Al tolerance based on root growth. Subpopulation structure explained 57% of the phenotypic variation, and the mean Al tolerance in Japonica was twice that of Indica. Forty-eight regions associated with Al tolerance were identified by GWA analysis, most of which were subpopulation-specific. Four of these regions co-localized with a priori candidate genes, and two highly significant regions co-localized with previously identified QTLs. Three regions corresponding to induced Al-sensitive rice mutants (ART1, STAR2, Nrat1 were identified through bi-parental QTL mapping or GWA to be involved in natural variation for Al tolerance. Haplotype analysis around the Nrat1 gene identified susceptible and tolerant haplotypes explaining 40% of the Al tolerance variation within the aus subpopulation, and sequence analysis of Nrat1 identified a trio of non-synonymous mutations predictive of Al sensitivity in our diversity panel. GWA analysis discovered more phenotype-genotype associations and provided higher resolution, but QTL mapping identified critical rare and/or subpopulation-specific alleles not detected by GWA analysis. Mapping using Indica/Japonica populations identified QTLs associated with transgressive variation where alleles from a susceptible aus or indica parent enhanced Al tolerance in a tolerant Japonica background. This work supports the hypothesis that selectively introgressing alleles across subpopulations is an efficient approach for trait enhancement in plant breeding programs

  8. Genetic Variation of Morphological Traits and Transpiration in an Apple Core Collection under Well-Watered Conditions: Towards the Identification of Morphotypes with High Water Use Efficiency.

    Directory of Open Access Journals (Sweden)

    Gerardo Lopez

    Full Text Available Water use efficiency (WUE is a quantitative measurement which improvement is a major issue in the context of global warming and restrictions in water availability for agriculture. In this study, we aimed at studying the variation and genetic control of WUE and the respective role of its components (plant biomass and transpiration in a perennial fruit crop. We explored an INRA apple core collection grown in a phenotyping platform to screen one-year-old scions for their accumulated biomass, transpiration and WUE under optimal growing conditions. Plant biomass was decompose into morphological components related to either growth or organ expansion. For each trait, nine mixed models were evaluated to account for the genetic effect and spatial heterogeneity inside the platform. The Best Linear Unbiased Predictors of genetic values were estimated after model selection. Mean broad-sense heritabilities were calculated from variance estimates. Heritability values indicated that biomass (0.76 and WUE (0.73 were under genetic control. This genetic control was lower in plant transpiration with an heritability of 0.54. Across the collection, biomass accounted for 70% of the WUE variability. A Hierarchical Ascendant Classification of the core collection indicated the existence of six groups of genotypes with contrasting morphology and WUE. Differences between morphotypes were interpreted as resulting from differences in the main processes responsible for plant growth: cell division leading to the generation of new organs and cell elongation leading to organ dimension. Although further studies will be necessary on mature trees with more complex architecture and multiple sinks such as fruits, this study is a first step for improving apple plant material for the use of water.

  9. CoaSim: A Flexible Environment for Simulating Genetic Data under Coalescent Models

    DEFF Research Database (Denmark)

    Mailund; Schierup, Mikkel Heide; Pedersen, Christian Nørgaard Storm

    2005-01-01

    Background Coalescent simulations are playing a large role in interpreting large scale intra- polymorphism surveys and for planning and evaluating association studies. Coalescent of data sets under different models can be compared to the actual data to test different evolutionary factors and thus...... get insight into these. Results We have created the CoaSim application as a flexible environment for Monte various types of genetic data under equilibrium and non-equilibrium coalescent variety of applications. Interaction with the tool is through the Guile version scripting language. Scheme scripts...

  10. The Prosocial Personality and its Facets: Genetic and Environmental Architecture of Mother-reported Behavior of 7-year old Twins

    Directory of Open Access Journals (Sweden)

    Ariel eKnafo-Noam

    2015-02-01

    Full Text Available Children vary markedly in their tendency to behave prosocially, and recent research has implicated both genetic and environmental factors in this variability. Yet, little is known about the extent to which different aspects of prosociality constitute a single dimension (the prosocial personality, and to the extent they are intercorrelated, whether these aspects share their genetic and environmental origins. As part of the Longitudinal Israeli Study of Twins (LIST, mothers of 183 monozygotic (MZ and dizygotic (DZ 7-year old twins (51% male reported regarding their children's prosociality using questionnaires. Five prosociality facets (sharing, social concern, kindness, helping, and empathic concern were identified. All five facets intercorrelated positively (r>.39 suggesting a single-factor structure to the data, consistent with the theoretical idea of a single prosociality trait. Higher MZ than DZ twin correlations indicated genetic contributions to each prosociality facet. A common-factor-common-pathway multivariate model estimated high (69% heritability for the common prosociality factor, with the non-shared environment and error accounting for the remaining variance. For each facet, unique genetic and environmental contributions were identified as well. The results point to the presence of a broad prosociality phenotype, largely affected by genetics; whereas additional genetic and environmental factors contribute to different aspects of prosociality, such as helping and sharing.

  11. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    Science.gov (United States)

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991

  12. Comparative proteomic analysis of genetically modified maize grown under different agroecosystems conditions in Brazil

    Science.gov (United States)

    2013-01-01

    Background Profiling technologies allow the simultaneous measurement and comparison of thousands of cell components without prior knowledge of their identity. In the present study, we used two-dimensional gel electrophoresis combined with mass spectrometry to evaluate protein expression of Brazilian genetically modified maize hybrid grown under different agroecosystems conditions. To this effect, leaf samples were subjected to comparative analysis using the near-isogenic non-GM hybrid as the comparator. Results In the first stage of the analysis, the main sources of variation in the dataset were identified by using Principal Components Analysis which correlated most of the variation to the different agroecosystems conditions. Comparative analysis within each field revealed a total of thirty two differentially expressed proteins between GM and non-GM samples that were identified and their molecular functions were mainly assigned to carbohydrate and energy metabolism, genetic information processing and stress response. Conclusions To the best of our knowledge this study represents the first evidence of protein identities with differentially expressed isoforms in Brazilian MON810 genetic background hybrid grown under field conditions. As global databases on outputs from “omics” analysis become available, these could provide a highly desirable benchmark for safety assessments. PMID:24304660

  13. Seasonality shows evidence for polygenic architecture and genetic correlation with schizophrenia and bipolar disorder – a meta-analysis of genetic studies

    Science.gov (United States)

    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

  14. Managing genetic tests, surveillance, and preventive medicine under a public health insurance system.

    Science.gov (United States)

    Filipova-Neumann, Lilia; Hoy, Michael

    2014-03-01

    There is a prospect in the medium to long term future of substantial advancements in the understanding of the relationship between disease and genetics. We consider the implications of increased information from genetic tests about predisposition to diseases from the perspective of managing health care provision under a public health insurance scheme. In particular, we consider how such information may potentially improve the targeting of medical surveillance (or prevention) activities to improve the chances of early detection of disease onset. We show that the moral hazard implications inherent in surveillance and prevention decisions that are chosen to be privately rather than socially optimal may be exacerbated by increased information about person-specific predisposition to disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Exploring the genetics underlying autoimmune diseases with network analysis and link prediction

    KAUST Repository

    Alanis Lobato, Gregorio

    2014-02-01

    Ever since the first Genome Wide Association Study (GWAS) was carried out we have seen an important number of discoveries of biological and clinical relevance. However, there are some scientists that consider that these research outcomes and their utility are far from what was expected from this experimental design. We instead believe that the thousands of genetic variants associated with complex disorders by means of GWASs are an extremely valuable source of information that needs to be mined in a different way. Based on this philosophy, we followed a holistic perspective to analyze GWAS data and explored the structural properties of the network representation of one of these datasets with the aim to advance our understanding of the genetic intricacies underlying autoimmune human diseases. The simplicity, computational efficiency and precision of the tools proposed in this paper represent a new means to address GWAS data and contribute to the better exploitation of these rich sources of information. © 2014 IEEE.

  16. The joint regulation of genetic gain and inbreeding under mate selection.

    Science.gov (United States)

    Klieve, H M; Kinghorn, B P; Barwick, S A

    1994-01-12

    Stochastic simulation was used to evaluate a range of selection strategies with respect to both additive genetic response and inbreeding. Strategies involving selection on BLUP ebvs or individual phenotype, followed by random mating, were compared with mate selection strategies which used portfolio analysis to give joint consideration to genetic merit and inbreeding. An adapted Mean Of Total Absolute Deviations (MOTAD) method was used in a mate selection model to define optimal matings with regard to aggregate genetic merit and inbreeding for a base population h(2) of 0.2. Compared with random mating following selection on BLUP ebvs, inbreeding levels after 10 years of selection were able to be reduced under BLUP plus mate selection from ∼.23 to as little as .11. Additive genetic gain was either little compromised or increased. The results suggest that information linking expected levels of genetic merit and inbreeding can be used to find the preferred selection strategy. ZUSAMMENFASSUNG: Gemeinsame Kontrolle von Zuchtfortschritt und Inzucht bei Partnerselektion Es wurde stochastische Simulation zur Auswertung einer Reihe von Selektionsstrategien hinsichtlich Zuchtwertzuwachs und Inzucht verwendet. Strategien mit Selektion auf der Basis von BLUP ebvs oder individuellem Phänotyp mit nachfolgender Zufallspaarung wurden mit Partnerselektionsstrategien verglichen, die Portfolioanalyse zur gemeinsamen Beachtung von Zuchtwert und Inzucht verwendeten. Eine Methode adaptierter MITTELWERTE TOTALER ABSOLUTER ABWEICHUNGEN (MOTAD) Methode wurde beim Partnerselektionsmodell zur Definition optimaler Paarungen in Hinblick auf Gesamtzuchtwert und Inzucht bei einer Populationsheritabilität von 0,2 verwendet. Verglichen mit Zufallspaarung nach Selektion auf BLUP ebvs waren die Inzuchtgrade nach 10 Selektionsjahren von 0,23 auf 0,11 reduziert und additiver Zuchtfortschritt war dabei wenig beeinträchtigt oder nahm sogar zu. Die Ergebnisse weisen darauf hin, daß Information, die

  17. Genetic Parameter Estimates of Carcass Traits under National Scale Breeding Scheme for Beef Cattle

    Directory of Open Access Journals (Sweden)

    ChangHee Do

    2016-08-01

    productivity and carcass quality could be obtained under the national scale breeding scheme of Korea for Hanwoo and that continuous efforts to improve the breeding scheme should be made to increase genetic progress.

  18. Delimiting genetic units in Neotropical toads under incomplete lineage sorting and hybridization

    Directory of Open Access Journals (Sweden)

    Thomé Maria Tereza C

    2012-12-01

    Full Text Available Abstract Background Delimiting genetic units is useful to enhance taxonomic discovery and is often the first step toward understanding evolutionary mechanisms generating diversification. The six species within the Rhinella crucifer group of toads were defined under morphological criteria alone. Previous data suggest limited correspondence of these species to mitochondrial lineages, and morphological intergradation at transitions between forms suggests hybridization. Here we extensively sampled populations throughout the geographic distribution of the group and analyzed mitochondrial and nuclear sequence data to delimit genetic units using tree–based and allele frequency–based approaches. Results These approaches yielded complementary results, with allele frequency-based methods performing unexpectedly well given the limited number of loci examined. Both mitochondrial and nuclear markers supported a genetic structure of five units within the group, with three of the inferred units distributed within its main range, while two other units occur in separate isolates. The inferred units are mostly discordant with currently described forms: unequivocal association exists for only two of the six species in the group. Genetic evidence for hybridization exists for two pairs of units, with clear cyto–nuclear allele mixing observed in one case. Conclusions Our results confirmed that current taxonomy does not represent evolutionary units in the Rhinella crucifer group. Correspondence between genetically distinguishable units and the currently recognized species is only possible for Rhinella henseli and R. inopina. The recognition of other species relies on the reassessment of the geographic range of R. crucifer, the examination of the type series of R. ornata for hybrids, and on the use of additional markers to verify the genetic distinctiveness of R. abei. We state that R. pombali should not remain a valid species since its description appears to be

  19. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

    NARCIS (Netherlands)

    Mahajan, Anubha; Go, Min Jin; Zhang, Weihua; Below, Jennifer E.; Gaulton, Kyle J.; Ferreira, Teresa; Horikoshi, Momoko; Johnson, Andrew D.; Ng, Maggie C. Y.; Prokopenko, Inga; Saleheen, Danish; Wang, Xu; Zeggini, Eleftheria; Abecasis, Goncalo R.; Adair, Linda S.; Almgren, Peter; Atalay, Mustafa; Aung, Tin; Baldassarre, Damiano; Balkau, Beverley; Bao, Yuqian; Barnett, Anthony H.; Barroso, Ines; Basit, Abdul; Been, Latonya F.; Beilby, John; Bell, Graeme I.; Benediktsson, Rafn; Bergman, Richard N.; Boehm, Bernhard O.; Boerwinkle, Eric; Bonnycastle, Lori L.; Burtt, Noël; Cai, Qiuyin; Campbell, Harry; Carey, Jason; Cauchi, Stephane; Caulfield, Mark; Chan, Juliana C. N.; Chang, Li-Ching; Chang, Tien-Jyun; Chang, Yi-Cheng; Charpentier, Guillaume; Chen, Chien-Hsiun; Chen, Han; Chen, Yuan-Tsong; Chia, Kee-Seng; Chidambaram, Manickam; Chines, Peter S.; Cho, Nam H.; Cho, Young Min; Chuang, Lee-Ming; Collins, Francis S.; Cornelis, Marilyn C.; Couper, David J.; Crenshaw, Andrew T.; van Dam, Rob M.; Danesh, John; Das, Debashish; de Faire, Ulf; Dedoussis, George; Deloukas, Panos; Dimas, Antigone S.; Dina, Christian; Doney, Alex S. F.; Donnelly, Peter J.; Dorkhan, Mozhgan; van Duijn, Cornelia; Dupuis, Josée; Edkins, Sarah; Elliott, Paul; Emilsson, Valur; Erbel, Raimund; Eriksson, Johan G.; Escobedo, Jorge; Esko, Tonu; Eury, Elodie; Florez, Jose C.; Fontanillas, Pierre; Forouhi, Nita G.; Forsen, Tom; Fox, Caroline; Fraser, Ross M.; Frayling, Timothy M.; Froguel, Philippe; Frossard, Philippe; Gao, Yutang; Gertow, Karl; Gieger, Christian; Gigante, Bruna; Grallert, Harald; Grant, George B.; Groop, Leif C.; Groves, Christopher J.; Grundberg, Elin; Guiducci, Candace; Hamsten, Anders; Han, Bok-Ghee; Hara, Kazuo; Hassanali, Neelam; Hattersley, Andrew T.; Hayward, Caroline; Hedman, Asa K.; Herder, Christian; Hofman, Albert; Holmen, Oddgeir L.; Hovingh, Kees; Hreidarsson, Astradur B.; Hu, Cheng; Hu, Frank B.; Hui, Jennie; Humphries, Steve E.; Hunt, Sarah E.; Hunter, David J.; Hveem, Kristian; Hydrie, Zafar I.; Ikegami, Hiroshi; Illig, Thomas; Ingelsson, Erik; Islam, Muhammed; Isomaa, Bo; Jackson, Anne U.; Jafar, Tazeen; James, Alan; Jia, Weiping; Jöckel, Karl-Heinz; Jonsson, Anna; Jowett, Jeremy B. M.; Kadowaki, Takashi; Kang, Hyun Min; Kanoni, Stavroula; Kao, Wen Hong L.; Kathiresan, Sekar; Kato, Norihiro; Katulanda, Prasad; Keinanen-Kiukaanniemi, Sirkka M.; Kelly, Ann M.; Khan, Hassan; Khaw, Kay-Tee; Khor, Chiea-Chuen; Kim, Hyung-Lae; Kim, Sangsoo; Kim, Young Jin; Kinnunen, Leena; Klopp, Norman; Kong, Augustine; Korpi-Hyövälti, Eeva; Kowlessur, Sudhir; Kraft, Peter; Kravic, Jasmina; Kristensen, Malene M.; Krithika, S.; Kumar, Ashish; Kumate, Jesus; Kuusisto, Johanna; Kwak, Soo Heon; Laakso, Markku; Lagou, Vasiliki; Lakka, Timo A.; Langenberg, Claudia; Langford, Cordelia; Lawrence, Robert; Leander, Karin; Lee, Jen-Mai; Lee, Nanette R.; Li, Man; Li, Xinzhong; Li, Yun; Liang, Junbin; Liju, Samuel; Lim, Wei-Yen; Lind, Lars; Lindgren, Cecilia M.; Lindholm, Eero; Liu, Ching-Ti; Liu, Jian Jun; Lobbens, Stéphane; Long, Jirong; Loos, Ruth J. F.; Lu, Wei; Luan, Jian'an; Lyssenko, Valeriya; Ma, Ronald C. W.; Maeda, Shiro; Mägi, Reedik; Männistö, Satu; Matthews, David R.; Meigs, James B.; Melander, Olle; Metspalu, Andres; Meyer, Julia; Mirza, Ghazala; Mihailov, Evelin; Moebus, Susanne; Mohan, Viswanathan; Mohlke, Karen L.; Morris, Andrew D.; Mühleisen, Thomas W.; Müller-Nurasyid, Martina; Musk, Bill; Nakamura, Jiro; Nakashima, Eitaro; Navarro, Pau; Ng, Peng-Keat; Nica, Alexandra C.; Nilsson, Peter M.; Njølstad, Inger; Nöthen, Markus M.; Ohnaka, Keizo; Ong, Twee Hee; Owen, Katharine R.; Palmer, Colin N. A.; Pankow, James S.; Park, Kyong Soo; Parkin, Melissa; Pechlivanis, Sonali; Pedersen, Nancy L.; Peltonen, Leena; Perry, John R. B.; Peters, Annette; Pinidiyapathirage, Janani M.; Platou, Carl G. P.; Potter, Simon; Price, Jackie F.; Qi, Lu; Radha, Venkatesan; Rallidis, Loukianos; Rasheed, Asif; Rathmann, Wolfgang; Rauramaa, Rainer; Raychaudhuri, Soumya; Rayner, N. William; Rees, Simon D.; Rehnberg, Emil; Ripatti, Samuli; Robertson, Neil; Roden, Michael; Rossin, Elizabeth J.; Rudan, Igor; Rybin, Denis; Saaristo, Timo E.; Salomaa, Veikko; Saltevo, Juha; Samuel, Maria; Sanghera, Dharambir K.; Saramies, Jouko; Scott, James; Scott, Laura J.; Scott, Robert A.; Segrè, Ayellet V.; Sehmi, Joban; Sennblad, Bengt; Shah, Nabi; Shah, Sonia; Shera, A. Samad; Shu, Xiao Ou; Shuldiner, Alan R.; Sigurðsson, Gunnar; Sijbrands, Eric; Silveira, Angela; Sim, Xueling; Sivapalaratnam, Suthesh; Small, Kerrin S.; So, Wing Yee; Stančáková, Alena; Stefansson, Kari; Steinbach, Gerald; Steinthorsdottir, Valgerdur; Stirrups, Kathleen; Strawbridge, Rona J.; Stringham, Heather M.; Sun, Qi; Suo, Chen; Syvänen, Ann-Christine; Takayanagi, Ryoichi; Takeuchi, Fumihiko; Tay, Wan Ting; Teslovich, Tanya M.; Thorand, Barbara; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Trakalo, Joseph; Tremoli, Elena; Trip, Mieke D.; Tsai, Fuu Jen; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Uitterlinden, Andre G.; Valladares-Salgado, Adan; Vedantam, Sailaja; Veglia, Fabrizio; Voight, Benjamin F.; Wang, Congrong; Wareham, Nicholas J.; Wennauer, Roman; Wickremasinghe, Ananda R.; Wilsgaard, Tom; Wilson, James F.; Wiltshire, Steven; Winckler, Wendy; Wong, Tien Yin; Wood, Andrew R.; Wu, Jer-Yuarn; Wu, Ying; Yamamoto, Ken; Yamauchi, Toshimasa; Yang, Mingyu; Yengo, Loic; Yokota, Mitsuhiro; Young, Robin; Zabaneh, Delilah; Zhang, Fan; Zhang, Rong; Zheng, Wei; Zimmet, Paul Z.; Altshuler, David; Bowden, Donald W.; Cho, Yoon Shin; Cox, Nancy J.; Cruz, Miguel; Hanis, Craig L.; Kooner, Jaspal; Lee, Jong-Young; Seielstad, Mark; teo, Yik Ying; Boehnke, Michael; Parra, Esteban J.; Chambers, John C.; Tai, E. Shyong; McCarthy, Mark I.; Morris, Andrew P.

    2014-01-01

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We

  20. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

    NARCIS (Netherlands)

    Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa; Kabagambe, Edmond Kato; Hong, Jaeyoung; Ng, Maggie C. Y.; Hivert, Marie-France; Lu, Yingchang; An, Ping; Bentley, Amy R.; Drolet, Anne M.; Gaulton, Kyle J.; Guo, Xiuqing; Armstrong, Loren L.; Irvin, Marguerite R.; Li, Man; Lipovich, Leonard; Rybin, Denis V.; Taylor, Kent D.; Agyemang, Charles; Palmer, Nicholette D.; Cade, Brian E.; Chen, Wei-Min; Dauriz, Marco; Delaney, Joseph A. C.; Edwards, Todd L.; Evans, Daniel S.; Evans, Michele K.; Lange, Leslie A.; Leong, Aaron; Liu, Jingmin; Liu, Yongmei; Nayak, Uma; Patel, Sanjay R.; Porneala, Bianca C.; Rasmussen-Torvik, Laura J.; Snijder, Marieke B.; Stallings, Sarah C.; Tanaka, Toshiko; Yanek, Lisa R.; Zhao, Wei; Becker, Diane M.; Bielak, Lawrence F.; Biggs, Mary L.; Bottinger, Erwin P.; Bowden, Donald W.; Chen, Guanjie; Correa, Adolfo; Couper, David J.; Crawford, Dana C.; Cushman, Mary; Eicher, John D.; Fornage, Myriam; Franceschini, Nora; Fu, Yi-Ping; Goodarzi, Mark O.; Gottesman, Omri; Hara, Kazuo; Harris, Tamara B.; Jensen, Richard A.; Johnson, Andrew D.; Jhun, Min A.; Karter, Andrew J.; Keller, Margaux F.; Kho, Abel N.; Kizer, Jorge R.; Krauss, Ronald M.; Langefeld, Carl D.; Li, Xiaohui; Liang, Jingling; Liu, Simin; Lowe, William L.; Mosley, Thomas H.; North, Kari E.; Pacheco, Jennifer A.; Peyser, Patricia A.; Patrick, Alan L.; Rice, Kenneth M.; Selvin, Elizabeth; Sims, Mario; Smith, Jennifer A.; Tajuddin, Salman M.; Vaidya, Dhananjay; Wren, Mary P.; Yao, Jie; Zhu, Xiaofeng; Ziegler, Julie T.; Zmuda, Joseph M.; Zonderman, Alan B.; Zwinderman, Aeilko H.; Adeyemo, Adebowale; Boerwinkle, Eric; Ferrucci, Luigi; Hayes, M. Geoffrey; Kardia, Sharon L. R.; Miljkovic, Iva; Pankow, James S.; Rotimi, Charles N.; Sale, Michele M.; Wagenknecht, Lynne E.; Arnett, Donna K.; Chen, Yii-Der Ida; Nalls, Michael A.; Province, Michael A.; Kao, W. H. Linda; Siscovick, David S.; Psaty, Bruce M.; Wilson, James G.; Loos, Ruth J. F.; Dupuis, Josée; Rich, Stephen S.; Florez, Jose C.; Rotter, Jerome I.; Morris, Andrew P.; Meigs, James B.

    2016-01-01

    Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA)

  1. Architectural slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

    Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context...

  2. Genetic variability of garlic accessions as revealed by agro-morphological traits evaluated under different environments.

    Science.gov (United States)

    Hoogerheide, E S S; Azevedo Filho, J A; Vencovsky, R; Zucchi, M I; Zago, B W; Pinheiro, J B

    2017-05-31

    The cultivated garlic (Allium sativum L.) displays a wide phenotypic diversity, which is derived from natural mutations and phenotypic plasticity, due to dependence on soil type, moisture, latitude, altitude and cultural practices, leading to a large number of cultivars. This study aimed to evaluate the genetic variability shown by 63 garlic accessions belonging to Instituto Agronômico de Campinas and the Escola Superior de Agricultura "Luiz de Queiroz" germplasm collections. We evaluated ten quantitative characters in experimental trials conducted under two localities of the State of São Paulo: Monte Alegre do Sul and Piracicaba, during the agricultural year of 2007, in a randomized blocks design with five replications. The Mahalanobis distance was used to measure genetic dissimilarities. The UPGMA method and Tocher's method were used as clustering procedures. Results indicated significant variation among accessions (P < 0.01) for all evaluated characters, except for the percentage of secondary bulb growth in MAS, indicating the existence of genetic variation for bulb production, and germplasm evaluation considering different environments is more reliable for the characterization of the genotypic variability among garlic accessions, since it diminishes the environmental effects in the clustering of genotypes.

  3. Novel genetic loci underlying human intracranial volume identified through genome-wide association.

    Science.gov (United States)

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-12-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  4. Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children.

    Science.gov (United States)

    Skeide, Michael A; Kirsten, Holger; Kraft, Indra; Schaadt, Gesa; Müller, Bent; Neef, Nicole; Brauer, Jens; Wilcke, Arndt; Emmrich, Frank; Boltze, Johannes; Friederici, Angela D

    2015-09-01

    Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Sardinians genetic background explained by runs of homozygosity and genomic regions under positive selection.

    Science.gov (United States)

    Di Gaetano, Cornelia; Fiorito, Giovanni; Ortu, Maria Francesca; Rosa, Fabio; Guarrera, Simonetta; Pardini, Barbara; Cusi, Daniele; Frau, Francesca; Barlassina, Cristina; Troffa, Chiara; Argiolas, Giuseppe; Zaninello, Roberta; Fresu, Giovanni; Glorioso, Nicola; Piazza, Alberto; Matullo, Giuseppe

    2014-01-01

    The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5)) when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.

  6. Multi-objective optimization of design and testing of safety instrumented systems with MooN voting architectures using a genetic algorithm

    International Nuclear Information System (INIS)

    Torres-Echeverría, A.C.; Martorell, S.; Thompson, H.A.

    2012-01-01

    This paper presents the optimization of design and test policies of safety instrumented systems using MooN voting redundancies by a multi-objective genetic algorithm. The objectives to optimize are the Average Probability of Dangerous Failure on Demand, which represents the system safety integrity, the Spurious Trip Rate and the Lifecycle Cost. In this way safety, reliability and cost are included. This is done by using novel models of time-dependent probability of failure on demand and spurious trip rate, recently published by the authors. These models are capable of delivering the level of modeling detail required by the standard IEC 61508. Modeling includes common cause failure and diagnostic coverage. The Probability of Failure on Demand model also permits to quantify results with changing testing strategies. The optimization is performed using the multi-objective Genetic Algorithm NSGA-II. This allows weighting of the trade-offs between the three objectives and, thus, implementation of safety systems that keep a good balance between safety, reliability and cost. The complete methodology is applied to two separate case studies, one for optimization of system design with redundancy allocation and component selection and another for optimization of testing policies. Both optimization cases are performed for both systems with MooN redundancies and systems with only parallel redundancies. Their results are compared, demonstrating how introducing MooN architectures presents a significant improvement for the optimization process.

  7. The flowering repressor SVP underlies a novel Arabidopsis thaliana QTL interacting with the genetic background.

    Science.gov (United States)

    Méndez-Vigo, Belén; Martínez-Zapater, José M; Alonso-Blanco, Carlos

    2013-01-01

    The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression lines from the Japanese accession Fuk, which was selected based on the substantial transgression observed in an F(2) population with the reference strain Ler. Analysis of an early flowering line carrying a single Fuk introgression identified Flowering Arabidopsis QTL1 (FAQ1). We fine-mapped FAQ1 in an 11 kb genomic region containing the MADS transcription factor gene SHORT VEGETATIVE PHASE (SVP). Complementation of the early flowering phenotype of FAQ1-Fuk with a SVP-Ler transgen demonstrated that FAQ1 is SVP. We further proved by directed mutagenesis and transgenesis that a single amino acid substitution in SVP causes the loss-of-function and early flowering of Fuk allele. Analysis of a worldwide collection of accessions detected FAQ1/SVP-Fuk allele only in Asia, with the highest frequency appearing in Japan, where we could also detect a potential ancestral genotype of FAQ1/SVP-Fuk. In addition, we evaluated allelic and epistatic interactions of SVP natural alleles by analysing more than one hundred transgenic lines carrying Ler or Fuk SVP alleles in five genetic backgrounds. Quantitative analyses of these lines showed that FAQ1/SVP effects vary from large to small depending on the genetic background. These results support that the flowering repressor SVP has been recently selected in A. thaliana as a target for early flowering, and evidence the relevance of genetic interactions for the intraspecific evolution of FAQ1/SVP and flowering time.

  8. The flowering repressor SVP underlies a novel Arabidopsis thaliana QTL interacting with the genetic background.

    Directory of Open Access Journals (Sweden)

    Belén Méndez-Vigo

    Full Text Available The timing of flowering initiation is a fundamental trait for the adaptation of annual plants to different environments. Large amounts of intraspecific quantitative variation have been described for it among natural accessions of many species, but the molecular and evolutionary mechanisms underlying this genetic variation are mainly being determined in the model plant Arabidopsis thaliana. To find novel A. thaliana flowering QTL, we developed introgression lines from the Japanese accession Fuk, which was selected based on the substantial transgression observed in an F(2 population with the reference strain Ler. Analysis of an early flowering line carrying a single Fuk introgression identified Flowering Arabidopsis QTL1 (FAQ1. We fine-mapped FAQ1 in an 11 kb genomic region containing the MADS transcription factor gene SHORT VEGETATIVE PHASE (SVP. Complementation of the early flowering phenotype of FAQ1-Fuk with a SVP-Ler transgen demonstrated that FAQ1 is SVP. We further proved by directed mutagenesis and transgenesis that a single amino acid substitution in SVP causes the loss-of-function and early flowering of Fuk allele. Analysis of a worldwide collection of accessions detected FAQ1/SVP-Fuk allele only in Asia, with the highest frequency appearing in Japan, where we could also detect a potential ancestral genotype of FAQ1/SVP-Fuk. In addition, we evaluated allelic and epistatic interactions of SVP natural alleles by analysing more than one hundred transgenic lines carrying Ler or Fuk SVP alleles in five genetic backgrounds. Quantitative analyses of these lines showed that FAQ1/SVP effects vary from large to small depending on the genetic background. These results support that the flowering repressor SVP has been recently selected in A. thaliana as a target for early flowering, and evidence the relevance of genetic interactions for the intraspecific evolution of FAQ1/SVP and flowering time.

  9. Genetic architecture of lipid traits changes over time and differs by race: Princeton Lipid Follow-up Study

    Science.gov (United States)

    Woo, Jessica G.; Morrison, John A.; Stroop, Davis M.; Aronson Friedman, Lisa; Martin, Lisa J.

    2014-01-01

    Dyslipidemia is a major risk factor for CVD. Previous studies on lipid heritability have largely focused on white populations assessed after the obesity epidemic. Given secular trends and racial differences in lipid levels, this study explored whether lipid heritability is consistent across time and between races. African American and white nuclear families had fasting lipids measured in the 1970s and 22–30 years later. Heritability was estimated, and bivariate analyses between visits were conducted by race using variance components analysis. A total of 1,454 individuals (age 14.1/40.6 for offspring/parents at baseline; 39.6/66.5 at follow-up) in 373 families (286 white, 87 African American) were included. Lipid trait heritabilities were typically stronger during the 1970s than the 2000s. At baseline, additive genetic variation for LDL was significantly lower in African Americans than whites (P = 0.015). Shared genetic contribution to lipid variability over time was significant in both whites (all P specific approaches are needed to clarify the genetic etiology of lipids. PMID:24859784

  10. Unfolding an under-determined neutron spectrum using genetic algorithm based Monte Carlo

    International Nuclear Information System (INIS)

    Suman, V.; Sarkar, P.K.

    2011-01-01

    Spallation in addition to the other photon-neutron reactions in target materials and different components in accelerators may result in production of huge amount of energetic protons which further leads to the production of neutron and contributes to the main component of the total dose. For dosimetric purposes in accelerator facilities the detector measurements doesn't provide directly the actual neutron flux values but a cumulative picture. To obtain Neutron spectrum from the measured data, response functions of the measuring instrument together with the measurements are used into many unfolding techniques which are frequently used for unfolding the hidden spectral information. Here we discuss a genetic algorithm based unfolding technique which is in the process of development. Genetic Algorithm is a stochastic method based on natural selection, which mimics Darwinian theory of survival of the best. The above said method has been tested to unfold the neutron spectra obtained from a reaction carried out at an accelerator facility, with energetic carbon ions on thick silver target along with its respective neutron response of BC501A liquid scintillation detector. The problem dealt here is under-determined where the number of measurements is less than the required energy bin information. The results so obtained were compared with those obtained using the established unfolding code FERDOR, which unfolds data for completely determined problems. It is seen that the genetic algorithm based solution has a reasonable match with the results of FERDOR, when smoothening carried out by Monte Carlo is taken into consideration. This method appears to be a promising candidate for unfolding neutron spectrum in cases of under-determined and over-determined, where measurements are more. The method also has advantages of flexibility, computational simplicity and works well without need of any initial guess spectrum. (author)

  11. Sugarcane production under smallholder farming systems: Farmers preferred traits, constraints and genetic resources

    Directory of Open Access Journals (Sweden)

    Esayas Tena

    2016-05-01

    Full Text Available Smallholder sugarcane production sector is under researched and underdeveloped with limited industrial link and support. The objectives of this study were to assess the current state of sugarcane production, farmers’ perceived production constraints and preferred traits, and to collect germplasm grown by smallholder farmers in southern Ethiopia for strategic breeding and conservation. The study was conducted across 16 administrative zones, 28 districts and 56 peasant associations involving 560 smallholder sugarcane growers in southern Ethiopia using a participatory rural appraisal (PRA approach. Sugarcane genetic resources were collected through structured sampling. Findings from this study indicated that monocropping was identified as the predominant sugarcane farming system. Respondent farmers prioritized drought tolerance (21%, increased cane yield (20%, early maturity (18%, marketability (17%, and high biomass (14% as the top preferred traits of sugarcane. Ninety diverse sugarcane landraces were collected from homesteads of smallholder farmers. Findings from this study would serve as baseline information towards sugarcane research and development emphasising the constraints and preferences of smallholder sugarcane growers in Ethiopia or similar agro-ecologies. This is the first study to report farmers preferred traits and constraints, and genetic resources of sugarcane under smallholder farming systems in Ethiopia.

  12. Bacterial Genetic Architecture of Ecological Interactions in Co-culture by GWAS-Taking Escherichia coli and Staphylococcus aureus as an Example.

    Science.gov (United States)

    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.

  13. Genetics of dispersal

    Science.gov (United States)

    Bocedi, Greta; Cote, Julien; Legrand, Delphine; Guillaume, Frédéric; Wheat, Christopher W.; Fronhofer, Emanuel A.; Garcia, Cristina; Henry, Roslyn; Husby, Arild; Baguette, Michel; Bonte, Dries; Coulon, Aurélie; Kokko, Hanna; Matthysen, Erik; Niitepõld, Kristjan; Nonaka, Etsuko; Stevens, Virginie M.; Travis, Justin M. J.; Donohue, Kathleen; Bullock, James M.; del Mar Delgado, Maria

    2017-01-01

    ABSTRACT Dispersal is a process of central importance for the ecological and evolutionary dynamics of populations and communities, because of its diverse consequences for gene flow and demography. It is subject to evolutionary change, which begs the question, what is the genetic basis of this potentially complex trait? To address this question, we (i) review the empirical literature on the genetic basis of dispersal, (ii) explore how theoretical investigations of the evolution of dispersal have represented the genetics of dispersal, and (iii) discuss how the genetic basis of dispersal influences theoretical predictions of the evolution of dispersal and potential consequences. Dispersal has a detectable genetic basis in many organisms, from bacteria to plants and animals. Generally, there is evidence for significant genetic variation for dispersal or dispersal‐related phenotypes or evidence for the micro‐evolution of dispersal in natural populations. Dispersal is typically the outcome of several interacting traits, and this complexity is reflected in its genetic architecture: while some genes of moderate to large effect can influence certain aspects of dispersal, dispersal traits are typically polygenic. Correlations among dispersal traits as well as between dispersal traits and other traits under selection are common, and the genetic basis of dispersal can be highly environment‐dependent. By contrast, models have historically considered a highly simplified genetic architecture of dispersal. It is only recently that models have started to consider multiple loci influencing dispersal, as well as non‐additive effects such as dominance and epistasis, showing that the genetic basis of dispersal can influence evolutionary rates and outcomes, especially under non‐equilibrium conditions. For example, the number of loci controlling dispersal can influence projected rates of dispersal evolution during range shifts and corresponding demographic impacts

  14. ANTHOCYANIN PIGMENTATION IN TRITICUM AESTIVUM L.: GENETIC BASIS AND ROLE UNDER ABIOTIC STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Tereshchenko O.Yu.

    2012-08-01

    Full Text Available Anthocyanins are secondary metabolites of plants. They have a wide range of biological activity such as antioxidant, photoprotection, osmoregulation, heavy metal ions chelation, antimicrobial and antifungal activities, which help plants to survive under different stress conditions. Bread wheat (T. aestivum L. can have purple pigmentation provided by anthocyanin compounds in different organs, such as grain pericarp, coleoptile, culm, leaf blades, leaf sheaths, glumes and anthers. However, the genetic mechanisms underlying formation of these traits as well as contribution of the pigmentation to stress tolerance have not been widely studied in wheat. The aim of the current study was to investigate molecular-genetic mechanisms underlying anthocyanin pigmentation in different wheat organs and to estimate the role of the pigmentation under different abiotic stress conditions in wheat seedlings. In the current study, near-isogenic lines (NILs: cv. ‘Saratovskaya 29’ (‘S29’ and lines i:S29Pp1Pp2PF and i:S29Pp1Pp3P developed on the ‘S29’ background but having grain pericarp coloration (genes Pp and more intense coleoptile (Rc, culm (Pc, leaf blade (Plb, leaf sheath (Pls pigmentation in comparison with ‘S29’, were used. Comparative transcriptional analysis of the five structural genes Chs, Chi, F3h, Dfr, Ans, encoding enzymes participating in the anthocyanin biosynthesis, was performed in different organs of NILs. It was shown that the presence of the Rc, Pc, Plb, Pls and Pp alleles conferring strong anthocyanin pigmentation induced more intense transcription of the structural genes, suggesting the genes Rc, Pc, Plb, Pls and Pp to play a regulatory role in anthocyanin biosynthesis network. To evaluate the role of anthocyanins in stress response at the seedling stage, growth ability of the NILs and anthocyanin content in their coleoptiles were assessed after treatments with NaCl (100 and 200 mM, CdCl2 (25 and 50 μM and 15% PEG 6000

  15. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

    OpenAIRE

    Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa; Kabagambe, Edmond Kato; Hong, Jaeyoung; Ng, Maggie C.Y.; Hivert, Marie-France; Lu, Yingchang; An, Ping; Bentley, Amy R.; Drolet, Anne M.; Gaulton, Kyle J.; Guo, Xiuqing; Armstrong, Loren L.; Irvin, Marguerite R.

    2016-01-01

    Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) m...

  16. A Bow-Tie Genetic Architecture for Morphogenesis Suggested by a Genome-Wide RNAi Screen in Caenorhabditis elegans

    Science.gov (United States)

    Nelson, Matthew D.; Zhou, Elinor; Kiontke, Karin; Fradin, Hélène; Maldonado, Grayson; Martin, Daniel; Shah, Khushbu; Fitch, David H. A.

    2011-01-01

    During animal development, cellular morphogenesis plays a fundamental role in determining the shape and function of tissues and organs. Identifying the components that regulate and drive morphogenesis is thus a major goal of developmental biology. The four-celled tip of the Caenorhabditis elegans male tail is a simple but powerful model for studying the mechanism of morphogenesis and its spatiotemporal regulation. Here, through a genome-wide post-embryonic RNAi-feeding screen, we identified 212 components that regulate or participate in male tail tip morphogenesis. We constructed a working hypothesis for a gene regulatory network of tail tip morphogenesis. We found regulatory roles for the posterior Hox genes nob-1 and php-3, the TGF-β pathway, nuclear hormone receptors (e.g. nhr-25), the heterochronic gene blmp-1, and the GATA transcription factors egl-18 and elt-6. The majority of the pathways converge at dmd-3 and mab-3. In addition, nhr-25 and dmd-3/mab-3 regulate each others' expression, thus placing these three genes at the center of a complex regulatory network. We also show that dmd-3 and mab-3 negatively regulate other signaling pathways and affect downstream cellular processes such as vesicular trafficking (e.g. arl-1, rme-8) and rearrangement of the cytoskeleton (e.g. cdc-42, nmy-1, and nmy-2). Based on these data, we suggest that male tail tip morphogenesis is governed by a gene regulatory network with a bow-tie architecture. PMID:21408209

  17. Dissection of Genetic Factors underlying Wheat Kernel Shape and Size in an Elite × Nonadapted Cross using a High Density SNP Linkage Map

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2016-03-01

    Full Text Available Wheat kernel shape and size has been under selection since early domestication. Kernel morphology is a major consideration in wheat breeding, as it impacts grain yield and quality. A population of 160 recombinant inbred lines (RIL, developed using an elite (ND 705 and a nonadapted genotype (PI 414566, was extensively phenotyped in replicated field trials and genotyped using Infinium iSelect 90K assay to gain insight into the genetic architecture of kernel shape and size. A high density genetic map consisting of 10,172 single nucleotide polymorphism (SNP markers, with an average marker density of 0.39 cM/marker, identified a total of 29 genomic regions associated with six grain shape and size traits; ∼80% of these regions were associated with multiple traits. The analyses showed that kernel length (KL and width (KW are genetically independent, while a large number (∼59% of the quantitative trait loci (QTL for kernel shape traits were in common with genomic regions associated with kernel size traits. The most significant QTL was identified on chromosome 4B, and could be an ortholog of major rice grain size and shape gene or . Major and stable loci also were identified on the homeologous regions of Group 5 chromosomes, and in the regions of (6A and (7A genes. Both parental genotypes contributed equivalent positive QTL alleles, suggesting that the nonadapted germplasm has a great potential for enhancing the gene pool for grain shape and size. This study provides new knowledge on the genetic dissection of kernel morphology, with a much higher resolution, which may aid further improvement in wheat yield and quality using genomic tools.

  18. Improvement of Wear Performance of Nano-Multilayer PVD Coatings under Dry Hard End Milling Conditions Based on Their Architectural Development

    Directory of Open Access Journals (Sweden)

    Shahereen Chowdhury

    2018-02-01

    Full Text Available The TiAlCrSiYN-based family of PVD (physical vapor deposition hard coatings was specially designed for extreme conditions involving the dry ultra-performance machining of hardened tool steels. However, there is a strong potential for further advances in the wear performance of the coatings through improvements in their architecture. A few different coating architectures (monolayer, multilayer, bi-multilayer, bi-multilayer with increased number of alternating nano-layers were studied in relation to cutting-tool life. Comprehensive characterization of the structure and properties of the coatings has been performed using XRD, SEM, TEM, micro-mechanical studies and tool-life evaluation. The wear performance was then related to the ability of the coating layer to exhibit minimal surface damage under operation, which is directly associated with the various micro-mechanical characteristics (such as hardness, elastic modulus and related characteristics; nano-impact; scratch test-based characteristics. The results presented exhibited that a substantial increase in tool life as well as improvement of the mechanical properties could be achieved through the architectural development of the coatings.

  19. New developments on the neurobiological and pharmaco-genetic mechanisms underlying internet and videogame addiction.

    Science.gov (United States)

    Weinstein, Aviv; Lejoyeux, Michel

    2015-03-01

    There is emerging evidence that the psychobiological mechanisms underlying behavioral addictions such as internet and videogame addiction resemble those of addiction for substances of abuse. Review of brain imaging, treatment and genetic studies on videogame and internet addiction. Literature search of published articles between 2009 and 2013 in Pubmed using "internet addiction" and "videogame addiction" as the search word. Twenty-nine studies have been selected and evaluated under the criteria of brain imaging, treatment, and genetics. Brain imaging studies of the resting state have shown that long-term internet game playing affected brain regions responsible for reward, impulse control and sensory-motor coordination. Brain activation studies have shown that videogame playing involved changes in reward and loss of control and that gaming pictures have activated regions similarly to those activated by cue-exposure to drugs. Structural studies have shown alterations in the volume of the ventral striatum possible as result of changes in reward. Furthermore, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and that there were faulty inhibitory control and reward mechanisms videogame addicted individuals. Finally, treatment studies using fMRI have shown reduction in craving for videogames and reduced associated brain activity. Videogame playing may be supported by similar neural mechanisms underlying drug abuse. Similar to drug and alcohol abuse, internet addiction results in sub-sensitivity of dopamine reward mechanisms. Given the fact that this research is in its early stage it is premature to conclude that internet addiction is equivalent to substance addictions. © American Academy of Addiction Psychiatry.

  20. Genetic Parameters And Selection Response For Yield Traits In Bread Wheat Under Irrigated And Rainfed Environments

    Science.gov (United States)

    Khalil, Iftikhar Hussain; at-ur-Rahman, Hiday; Khan, Imran

    2008-01-01

    A set of 22 F5:7 experimental wheat lines along with four check cultivars (Dera-98, Fakhr-e-Sarhad, Ghaznavi-98 and Tatara) were evaluated as independent experiments under irrigated and rainfed environments using a randomized complete block design at NWFP Agricultural University, Peshawar during 2004-05. The two environments were statistically different for days to heading and spike length only. Highly significant genetic variability existed among the wheat lines (P<0.01) in the combined analysis across environments for all traits. Genotype×environment interactions were non-significant for all traits except 1000-grain weight indicating consistent performance of wheat genotypes across the two environments. Wheat lines and check cultivars were 2 to 5 days early in heading under rainfed environment compared to the irrigated. Plant height, spike length, 1000-grain weight, biological and grain yields were generally reduced under rainfed environment. Genetic variances were of greater magnitude than environmental variances for most of the traits in both environments. The heritability estimates were of higher magnitude (0.74 to 0.96) for days to heading, plant height, spike length, biological and grain yield, while medium (0.31 to 0.51) for 1000-grain weight. Selection differentials were negative for heading (-7.3 days in irrigated vs -9.4 days in rainfed) and plant height (-9.0 cm in irrigated vs -8.7 cm in rainfed) indicating possibility of selecting wheat genotypes with early heading and short plant stature. Positive selection differentials of 1.3 vs 1.6 cm for spike length, 3.8 vs 3.4 g for 1000-grain weight, 2488.2 vs 3139.7 kg ha-1 for biological yield and 691.6 vs 565.4 kg ha-1 for grain yield at 20% selection intensity were observed under irrigated and rainfed environments, respectively. Expected selection responses were 7.98 vs 8.91 days for heading, 8.20 vs 9.52 cm for plant height, 1.01 vs 1.61 cm for spike length, 2.12 vs 1.15 g for 1000-grain weight, 1655

  1. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Mahajan, Anubha; Go, Min Jin; Zhang, Weihua

    2014-01-01

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We...... observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls...... of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery...

  2. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

    Science.gov (United States)

    Berndt, Sonja I.; Gustafsson, Stefan; Mägi, Reedik; Ganna, Andrea; Wheeler, Eleanor; Feitosa, Mary F.; Justice, Anne E.; Monda, Keri L.; Croteau-Chonka, Damien C.; Day, Felix R.; Esko, Tõnu; Fall, Tove; Ferreira, Teresa; Gentilini, Davide; Jackson, Anne U.; Luan, Jian’an; Randall, Joshua C.; Vedantam, Sailaja; Willer, Cristen J.; Winkler, Thomas W.; Wood, Andrew R.; Workalemahu, Tsegaselassie; Hu, Yi-Juan; Lee, Sang Hong; Liang, Liming; Lin, Dan-Yu; Min, Josine L.; Neale, Benjamin M.; Thorleifsson, Gudmar; Yang, Jian; Albrecht, Eva; Amin, Najaf; Bragg-Gresham, Jennifer L.; Cadby, Gemma; den Heijer, Martin; Eklund, Niina; Fischer, Krista; Goel, Anuj; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jarick, Ivonne; Johansson, Åsa; Johnson, Toby; Kanoni, Stavroula; Kleber, Marcus E.; König, Inke R.; Kristiansson, Kati; Kutalik, Zoltán; Lamina, Claudia; Lecoeur, Cecile; Li, Guo; Mangino, Massimo; McArdle, Wendy L.; Medina-Gomez, Carolina; Müller-Nurasyid, Martina; Ngwa, Julius S.; Nolte, Ilja M.; Paternoster, Lavinia; Pechlivanis, Sonali; Perola, Markus; Peters, Marjolein J.; Preuss, Michael; Rose, Lynda M.; Shi, Jianxin; Shungin, Dmitry; Smith, Albert Vernon; Strawbridge, Rona J.; Surakka, Ida; Teumer, Alexander; Trip, Mieke D.; Tyrer, Jonathan; Van Vliet-Ostaptchouk, Jana V.; Vandenput, Liesbeth; Waite, Lindsay L.; Zhao, Jing Hua; Absher, Devin; Asselbergs, Folkert W.; Atalay, Mustafa; Attwood, Antony P.; Balmforth, Anthony J.; Basart, Hanneke; Beilby, John; Bonnycastle, Lori L.; Brambilla, Paolo; Bruinenberg, Marcel; Campbell, Harry; Chasman, Daniel I.; Chines, Peter S.; Collins, Francis S.; Connell, John M.; Cookson, William; de Faire, Ulf; de Vegt, Femmie; Dei, Mariano; Dimitriou, Maria; Edkins, Sarah; Estrada, Karol; Evans, David M.; Farrall, Martin; Ferrario, Marco M.; Ferrières, Jean; Franke, Lude; Frau, Francesca; Gejman, Pablo V.; Grallert, Harald; Grönberg, Henrik; Gudnason, Vilmundur; Hall, Alistair S.; Hall, Per; Hartikainen, Anna-Liisa; Hayward, Caroline; Heard-Costa, Nancy L.; Heath, Andrew C.; Hebebrand, Johannes; Homuth, Georg; Hu, Frank B.; Hunt, Sarah E.; Hyppönen, Elina; Iribarren, Carlos; Jacobs, Kevin B.; Jansson, John-Olov; Jula, Antti; Kähönen, Mika; Kathiresan, Sekar; Kee, Frank; Khaw, Kay-Tee; Kivimaki, Mika; Koenig, Wolfgang; Kraja, Aldi T.; Kumari, Meena; Kuulasmaa, Kari; Kuusisto, Johanna; Laitinen, Jaana H.; Lakka, Timo A.; Langenberg, Claudia; Launer, Lenore J.; Lind, Lars; Lindström, Jaana; Liu, Jianjun; Liuzzi, Antonio; Lokki, Marja-Liisa; Lorentzon, Mattias; Madden, Pamela A.; Magnusson, Patrik K.; Manunta, Paolo; Marek, Diana; März, Winfried; Mateo Leach, Irene; McKnight, Barbara; Medland, Sarah E.; Mihailov, Evelin; Milani, Lili; Montgomery, Grant W.; Mooser, Vincent; Mühleisen, Thomas W.; Munroe, Patricia B.; Musk, Arthur W.; Narisu, Narisu; Navis, Gerjan; Nicholson, George; Nohr, Ellen A.; Ong, Ken K.; Oostra, Ben A.; Palmer, Colin N.A.; Palotie, Aarno; Peden, John F.; Pedersen, Nancy; Peters, Annette; Polasek, Ozren; Pouta, Anneli; Pramstaller, Peter P.; Prokopenko, Inga; Pütter, Carolin; Radhakrishnan, Aparna; Raitakari, Olli; Rendon, Augusto; Rivadeneira, Fernando; Rudan, Igor; Saaristo, Timo E.; Sambrook, Jennifer G.; Sanders, Alan R.; Sanna, Serena; Saramies, Jouko; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Shin, So-Youn; Signorini, Stefano; Sinisalo, Juha; Skrobek, Boris; Soranzo, Nicole; Stančáková, Alena; Stark, Klaus; Stephens, Jonathan C.; Stirrups, Kathleen; Stolk, Ronald P.; Stumvoll, Michael; Swift, Amy J.; Theodoraki, Eirini V.; Thorand, Barbara; Tregouet, David-Alexandre; Tremoli, Elena; Van der Klauw, Melanie M.; van Meurs, Joyce B.J.; Vermeulen, Sita H.; Viikari, Jorma; Virtamo, Jarmo; Vitart, Veronique; Waeber, Gérard; Wang, Zhaoming; Widén, Elisabeth; Wild, Sarah H.; Willemsen, Gonneke; Winkelmann, Bernhard R.; Witteman, Jacqueline C.M.; Wolffenbuttel, Bruce H.R.; Wong, Andrew; Wright, Alan F.; Zillikens, M. Carola; Amouyel, Philippe; Boehm, Bernhard O.; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Cupples, L. Adrienne; Cusi, Daniele; Dedoussis, George V.; Erdmann, Jeanette; Eriksson, Johan G.; Franks, Paul W.; Froguel, Philippe; Gieger, Christian; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hengstenberg, Christian; Hicks, Andrew A.; Hingorani, Aroon; Hinney, Anke; Hofman, Albert; Hovingh, Kees G.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Keinanen-Kiukaanniemi, Sirkka M.; Kiemeney, Lambertus A.; Kuh, Diana; Laakso, Markku; Lehtimäki, Terho; Levinson, Douglas F.; Martin, Nicholas G.; Metspalu, Andres; Morris, Andrew D.; Nieminen, Markku S.; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Ouwehand, Willem H.; Palmer, Lyle J.; Penninx, Brenda; Power, Chris; Province, Michael A.; Psaty, Bruce M.; Qi, Lu; Rauramaa, Rainer; Ridker, Paul M.; Ripatti, Samuli; Salomaa, Veikko; Samani, Nilesh J.; Snieder, Harold; Sørensen, Thorkild I.A.; Spector, Timothy D.; Stefansson, Kari; Tönjes, Anke; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; van der Harst, Pim; Vollenweider, Peter; Wallaschofski, Henri; Wareham, Nicholas J.; Watkins, Hugh; Wichmann, H.-Erich; Wilson, James F.; Abecasis, Goncalo R.; Assimes, Themistocles L.; Barroso, Inês; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Frayling, Timothy; Groop, Leif C.; Haritunian, Talin; Heid, Iris M.; Hunter, David; Kaplan, Robert C.; Karpe, Fredrik; Moffatt, Miriam; Mohlke, Karen L.; O’Connell, Jeffrey R.; Pawitan, Yudi; Schadt, Eric E.; Schlessinger, David; Steinthorsdottir, Valgerdur; Strachan, David P.; Thorsteinsdottir, Unnur; van Duijn, Cornelia M.; Visscher, Peter M.; Di Blasio, Anna Maria; Hirschhorn, Joel N.; Lindgren, Cecilia M.; Morris, Andrew P.; Meyre, David; Scherag, André; McCarthy, Mark I.; Speliotes, Elizabeth K.; North, Kari E.; Loos, Ruth J.F.; Ingelsson, Erik

    2014-01-01

    Approaches exploiting extremes of the trait distribution may reveal novel loci for common traits, but it is unknown whether such loci are generalizable to the general population. In a genome-wide search for loci associated with upper vs. lower 5th percentiles of body mass index, height and waist-hip ratio, as well as clinical classes of obesity including up to 263,407 European individuals, we identified four new loci (IGFBP4, H6PD, RSRC1, PPP2R2A) influencing height detected in the tails and seven new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3, ZZZ3) for clinical classes of obesity. Further, we show that there is large overlap in terms of genetic structure and distribution of variants between traits based on extremes and the general population and little etiologic heterogeneity between obesity subgroups. PMID:23563607

  3. Grid Architecture 2

    Energy Technology Data Exchange (ETDEWEB)

    Taft, Jeffrey D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-01-01

    The report describes work done on Grid Architecture under the auspices of the Department of Electricity Office of Electricity Delivery and Reliability in 2015. As described in the first Grid Architecture report, the primary purpose of this work is to provide stakeholder insight about grid issues so as to enable superior decision making on their part. Doing this requires the creation of various work products, including oft-times complex diagrams, analyses, and explanations. This report provides architectural insights into several important grid topics and also describes work done to advance the science of Grid Architecture as well.

  4. Genetic engineering of Trypanosoma (Dutonella vivax and in vitro differentiation under axenic conditions.

    Directory of Open Access Journals (Sweden)

    Simon D'Archivio

    2011-12-01

    Full Text Available Trypanosoma vivax is one of the most common parasites responsible for animal trypanosomosis, and although this disease is widespread in Africa and Latin America, very few studies have been conducted on the parasite's biology. This is in part due to the fact that no reproducible experimental methods had been developed to maintain the different evolutive forms of this trypanosome under laboratory conditions. Appropriate protocols were developed in the 1990s for the axenic maintenance of three major animal Trypanosoma species: T. b. brucei, T. congolense and T. vivax. These pioneer studies rapidly led to the successful genetic manipulation of T. b. brucei and T. congolense. Advances were made in the understanding of these parasites' biology and virulence, and new drug targets were identified. By contrast, challenging in vitro conditions have been developed for T. vivax in the past, and this per se has contributed to defer both its genetic manipulation and subsequent gene function studies. Here we report on the optimization of non-infective T. vivax epimastigote axenic cultures and on the process of parasite in vitro differentiation into metacyclic infective forms. We have also constructed the first T. vivax specific expression vector that drives constitutive expression of the luciferase reporter gene. This vector was then used to establish and optimize epimastigote transfection. We then developed highly reproducible conditions that can be used to obtain and select stably transfected mutants that continue metacyclogenesis and are infectious in immunocompetent rodents.

  5. A genetic-algorithm-aided stochastic optimization model for regional air quality management under uncertainty.

    Science.gov (United States)

    Qin, Xiaosheng; Huang, Guohe; Liu, Lei

    2010-01-01

    A genetic-algorithm-aided stochastic optimization (GASO) model was developed in this study for supporting regional air quality management under uncertainty. The model incorporated genetic algorithm (GA) and Monte Carlo simulation techniques into a general stochastic chance-constrained programming (CCP) framework and allowed uncertainties in simulation and optimization model parameters to be considered explicitly in the design of least-cost strategies. GA was used to seek the optimal solution of the management model by progressively evaluating the performances of individual solutions. Monte Carlo simulation was used to check the feasibility of each solution. A management problem in terms of regional air pollution control was studied to demonstrate the applicability of the proposed method. Results of the case study indicated the proposed model could effectively communicate uncertainties into the optimization process and generate solutions that contained a spectrum of potential air pollutant treatment options with risk and cost information. Decision alternatives could be obtained by analyzing tradeoffs between the overall pollutant treatment cost and the system-failure risk due to inherent uncertainties.

  6. Effects of trawl selectivity and genetic parameters on fish body length under long-term trawling

    Science.gov (United States)

    Yu, Yang; Sun, Peng; Cui, He; Sheng, Huaxiang; Zhao, Fenfang; Tang, Yanli; Chen, Zelin

    2015-10-01

    Long-term fishing pressure affects the biological characteristics of exploited fish stocks. The biological characteristics of hairtail ( Trichiurus lepturus) in the East China Sea are unable to recover because of long-term trawling. Fishing induces evolutionary effects on the fish's biological characteristics. Evidence of these changes includes small size at age, a shift to earlier age structure, and early maturation. Natural and artificial selection usually affect the fish's life history. Selection can induce different chances of reproduction, and individual fish can give a different genetic contribution to the next generation. In this study, analysis of time-dependent probability of significance and test of sensitivity were used to explore the effects of fish exploitation rate, mesh size, and heritability with long-term trawling. Results showed that fishing parameters were important drivers to exploited fish population. However, genetic traits altered by fishing were slow, and the changes in biological characteristics were weaker than those caused by fishing selection. Exploitation rate and mesh size exhibited similar evolutionary trend tendency under long-term fishing. The time-dependent probability of significance trend showed a gradual growth and tended to be stable. Therefore, the direction of fishing-induced evolution and successful management of fish species require considerable attention to contribute to sustainable fisheries in China.

  7. Genetic Algorithm for Multiuser Discrete Network Design Problem under Demand Uncertainty

    Directory of Open Access Journals (Sweden)

    Wu Juan

    2012-01-01

    Full Text Available Discrete network design is an important part of urban transportation planning. The purpose of this paper is to present a bilevel model for discrete network design. The upper-level model aims to minimize the total travel time under a stochastic demand to design a discrete network. In the lower-level model, demands are assigned to the network through a multiuser traffic equilibrium assignment. Generally, discrete network could affect path selections of demands, while the results of the multiuser traffic equilibrium assignment need to reconstruct a new discrete network. An iterative approach including an improved genetic algorithm and Frank-Wolfe algorithm is used to solve the bi-level model. The numerical results on Nguyen Dupuis network show that the model and the related algorithms were effective for discrete network design.

  8. Population genetics inference for longitudinally-sampled mutants under strong selection.

    Science.gov (United States)

    Lacerda, Miguel; Seoighe, Cathal

    2014-11-01

    Longitudinal allele frequency data are becoming increasingly prevalent. Such samples permit statistical inference of the population genetics parameters that influence the fate of mutant variants. To infer these parameters by maximum likelihood, the mutant frequency is often assumed to evolve according to the Wright-Fisher model. For computational reasons, this discrete model is commonly approximated by a diffusion process that requires the assumption that the forces of natural selection and mutation are weak. This assumption is not always appropriate. For example, mutations that impart drug resistance in pathogens may evolve under strong selective pressure. Here, we present an alternative approximation to the mutant-frequency distribution that does not make any assumptions about the magnitude of selection or mutation and is much more computationally efficient than the standard diffusion approximation. Simulation studies are used to compare the performance of our method to that of the Wright-Fisher and Gaussian diffusion approximations. For large populations, our method is found to provide a much better approximation to the mutant-frequency distribution when selection is strong, while all three methods perform comparably when selection is weak. Importantly, maximum-likelihood estimates of the selection coefficient are severely attenuated when selection is strong under the two diffusion models, but not when our method is used. This is further demonstrated with an application to mutant-frequency data from an experimental study of bacteriophage evolution. We therefore recommend our method for estimating the selection coefficient when the effective population size is too large to utilize the discrete Wright-Fisher model. Copyright © 2014 by the Genetics Society of America.

  9. Scanning the landscape of genome architecture of non-O1 and non-O139 Vibrio cholerae by whole genome mapping reveals extensive population genetic diversity.

    Science.gov (United States)

    Chapman, Carol; Henry, Matthew; Bishop-Lilly, Kimberly A; Awosika, Joy; Briska, Adam; Ptashkin, Ryan N; Wagner, Trevor; Rajanna, Chythanya; Tsang, Hsinyi; Johnson, Shannon L; Mokashi, Vishwesh P; Chain, Patrick S G; Sozhamannan, Shanmuga

    2015-01-01

    Historically, cholera outbreaks have been linked to V. cholerae O1 serogroup strains or its derivatives of the O37 and O139 serogroups. A genomic study on the 2010 Haiti cholera outbreak strains highlighted the putative role of non O1/non-O139 V. cholerae in causing cholera and the lack of genomic sequences of such strains from around the world. Here we address these gaps by scanning a global collection of V. cholerae strains as a first step towards understanding the population genetic diversity and epidemic potential of non O1/non-O139 strains. Whole Genome Mapping (Optical Mapping) based bar coding produces a high resolution, ordered restriction map, depicting a complete view of the unique chromosomal architecture of an organism. To assess the genomic diversity of non-O1/non-O139 V. cholerae, we applied a Whole Genome Mapping strategy on a well-defined and geographically and temporally diverse strain collection, the Sakazaki serogroup type strains. Whole Genome Map data on 91 of the 206 serogroup type strains support the hypothesis that V. cholerae has an unprecedented genetic and genomic structural diversity. Interestingly, we discovered chromosomal fusions in two unusual strains that possess a single chromosome instead of the two chromosomes usually found in V. cholerae. We also found pervasive chromosomal rearrangements such as duplications and indels in many strains. The majority of Vibrio genome sequences currently in public databases are unfinished draft sequences. The Whole Genome Mapping approach presented here enables rapid screening of large strain collections to capture genomic complexities that would not have been otherwise revealed by unfinished draft genome sequencing and thus aids in assembling and finishing draft sequences of complex genomes. Furthermore, Whole Genome Mapping allows for prediction of novel V. cholerae non-O1/non-O139 strains that may have the potential to cause future cholera outbreaks.

  10. The iPSYCH2012 case–cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders

    Science.gov (United States)

    Pedersen, C B; Bybjerg-Grauholm, J; Pedersen, M G; Grove, J; Agerbo, E; Bækvad-Hansen, M; Poulsen, J B; Hansen, C S; McGrath, J J; Als, T D; Goldstein, J I; Neale, B M; Daly, M J; Hougaard, D M; Mors, O; Nordentoft, M; Børglum, A D; Werge, T; Mortensen, P B

    2018-01-01

    The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case–Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30 000). Within the sample of 86 189 individuals, a total of 57 377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information, and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders. PMID:28924187

  11. Recyclable magnetic photocatalysts of Fe2+/TiO2 hierarchical architecture with effective removal of Cr(VI) under UV light from water

    International Nuclear Information System (INIS)

    Xu, S.C.; Zhang, Y.X.; Pan, S.S.; Ding, H.L.; Li, G.H.

    2011-01-01

    Highlights: ► Fe 2+ /TiO 2 catalyst has a three-level hierarchical architecture. ► With a removal effectiveness of 99.3% at Cr(VI) concentration of 10 mg L −1 . ► Two-step reduction: TiO 2 photoreduces Fe 2+ to Fe and Fe reduces Cr(VI) to Cr(III). ► Hierarchical architecture serves as both photocatalytic reactor and absorbent. ► Fe 2+ /TiO 2 catalyst can be magnetically separated from wastewater and recycled. - Abstract: We report the synthesis and photocatalytic removal of Cr(VI) from water of hierarchical micro/nanostructured Fe 2+ /TiO 2 tubes. The TiO 2 tubes fabricated by a facile solvothermal approach show a three-level hierarchical architecture assembled from dense nanosheets nearly vertically standing on the surface of TiO 2 microtube. The nanosheets with a thickness of about 20 nm are composed of numerous TiO 2 nanocrystals with size in the range of 15–20 nm. Ferrous ions are doped into the hierarchical architecture by a reduction route. The Fe 2+ /TiO 2 catalyst demonstrates an effective removal of Cr(VI) from water under UV light and the removal effectiveness reaches 99.3% at the initial Cr(VI) concentration of 10 mg L −1 . The ferrous ion in the catalyst serves not as the photo-electron trap but as an intermedium of a two-step reduction. The TiO 2 photoreduces the Fe 2+ ions to Fe atoms firstly, then the Fe atoms reduce the Cr(VI) to Cr(III), and the later is removed by adsorption. The hierarchical architecture of the catalyst serves as a reactor for the photocatalytic reaction of Cr(VI) ions and an effective absorbent for the removal of Cr(III) ions. The catalyst can be easily magnetically separated from the wastewater after photocatalytic reaction and recycled after acid treatment.

  12. Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations

    DEFF Research Database (Denmark)

    Stein, Evan A; Dann, Eldad J; Wiegman, Albert

    2017-01-01

    BACKGROUND: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been f...... and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).......BACKGROUND: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been...... formally evaluated in, or approved for, HoFH children. OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations. METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin...

  13. Genetics of aggression.

    Science.gov (United States)

    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.

  14. Influence of ethnic traditional cultures on genetic diversity of rice landraces under on-farm conservation in southwest China.

    Science.gov (United States)

    Wang, Yanjie; Wang, Yanli; Sun, Xiaodong; Caiji, Zhuoma; Yang, Jingbiao; Cui, Di; Cao, Guilan; Ma, Xiaoding; Han, Bing; Xue, Dayuan; Han, Longzhi

    2016-10-27

    Crop genetic resources are important components of biodiversity. However, with the large-scale promotion of mono-cropping, genetic diversity has largely been lost. Ex-situ conservation approaches were widely used to protect traditional crop varieties worldwide. However, this method fails to maintain the dynamic evolutionary processes of crop genetic resources in their original habitats, leading to genetic diversity reduction and even loss of the capacity of resistance to new diseases and pests. Therefore, on-farm conservation has been considered a crucial complement to ex-situ conservation. This study aimed at clarifying the genetic diversity differences between ex-situ conservation and on-farm conservation and to exploring the influence of traditional cultures on genetic diversity of rice landraces under on-farm conservation. The conservation status of rice landrace varieties, including Indica and Japonica, non-glutinous rice (Oryza sativa) and glutinous rice (Oryza sativa var. glutinosa Matsum), was obtained through ethno-biology investigation method in 12 villages of ethnic groups from Guizhou, Yunnan and Guangxi provinces of China. The genetic diversity between 24 pairs of the same rice landraces from different times were compared using simple sequence repeat (SSR) molecular markers technology. The landrace paris studied were collected in 1980 and maintained ex-situ, while 2014 samples were collected on-farm in southwest of China. The results showed that many varieties of rice landraces have been preserved on-farm by local farmers for hundreds or thousands of years. The number of alleles (Na), effective number of alleles (Ne), Nei genetic diversity index (He) and Shannon information index (I) of rice landraces were significantly higher by 12.3-30.4 % under on-farm conservation than under ex-situ conservation. Compared with the ex-situ conservation approach, rice landraces under on-farm conservation programs had more alleles and higher genetic diversity. In

  15. Genetics

    Science.gov (United States)

    ... Likelihood of getting certain diseases Mental abilities Natural talents An abnormal trait (anomaly) that is passed down ... one of them has a genetic disorder. Information Human beings have cells with 46 chromosomes . These consist ...

  16. Transcriptomes Reveal Genetic Signatures Underlying Physiological Variations Imposed by Different Fermentation Conditions in Lactobacillus plantarum

    Science.gov (United States)

    Bongers, Roger S.; van Bokhorst-van de Veen, Hermien; Wiersma, Anne; Overmars, Lex; Marco, Maria L.; Kleerebezem, Michiel

    2012-01-01

    Lactic acid bacteria (LAB) are utilized widely for the fermentation of foods. In the current post-genomic era, tools have been developed that explore genetic diversity among LAB strains aiming to link these variations to differential phenotypes observed in the strains investigated. However, these genotype-phenotype matching approaches fail to assess the role of conserved genes in the determination of physiological characteristics of cultures by environmental conditions. This manuscript describes a complementary approach in which Lactobacillus plantarum WCFS1 was fermented under a variety of conditions that differ in temperature, pH, as well as NaCl, amino acid, and O2 levels. Samples derived from these fermentations were analyzed by full-genome transcriptomics, paralleled by the assessment of physiological characteristics, e.g., maximum growth rate, yield, and organic acid profiles. A data-storage and -mining suite designated FermDB was constructed and exploited to identify correlations between fermentation conditions and industrially relevant physiological characteristics of L. plantarum, as well as the associated transcriptome signatures. Finally, integration of the specific fermentation variables with the transcriptomes enabled the reconstruction of the gene-regulatory networks involved. The fermentation-genomics platform presented here is a valuable complementary approach to earlier described genotype-phenotype matching strategies which allows the identification of transcriptome signatures underlying physiological variations imposed by different fermentation conditions. PMID:22802930

  17. Concrete Mix Design for Service Life of RC Structures under Carbonation Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Seung-Jun Kwon

    2014-01-01

    Full Text Available Steel corrosion in reinforced concrete (RC structure is such a critical problem to structural safety that many researches have been performed for maintaining required performance during intended service life. This paper is for a numerical technique for obtaining optimum concrete mix proportions through genetic algorithm (GA for RC structures under carbonation which is considered as a serious deterioration in underground sites and big cities. For this study, mix proportions and CO2 diffusion coefficients are analyzed through the previous studies, and then the fitness function of CO2 diffusion coefficient is derived through regression analysis. The fitness function from 69 test results includes 5 variables of mix proportions such as w/c (water to cement ratio, cement content, sand content percentage, coarse aggregate content, and R.H. (relative humidity. Through GA technique, simulated mix proportions are obtained for 12 cases of verification and they show reasonable results with average relative error of 4.6%. Assuming intended service life and design parameters, intended CO2 diffusion coefficients and cement contents are determined and then related mix proportions are simulated. The proposed technique can provide initial concrete mix proportions which satisfy service life under carbonation.

  18. Communication of IT-Architecture

    NARCIS (Netherlands)

    Koning, H.

    2008-01-01

    This PhD thesis contains the results of various research activities that fall under the topic ‘communication of IT-architecture’. The term IT-architecture defines the various types of architecture that can be found in the domain of Information Technology (software architecture, enterprise

  19. Robotic architectures

    CSIR Research Space (South Africa)

    Mtshali, M

    2010-01-01

    Full Text Available In the development of mobile robotic systems, a robotic architecture plays a crucial role in interconnecting all the sub-systems and controlling the system. The design of robotic architectures for mobile autonomous robots is a challenging...

  20. Genetic Loci Governing Grain Yield and Root Development under Variable Rice Cultivation Conditions

    Directory of Open Access Journals (Sweden)

    Margaret Catolos

    2017-10-01

    Full Text Available Drought is the major abiotic stress to rice grain yield under unpredictable changing climatic scenarios. The widely grown, high yielding but drought susceptible rice varieties need to be improved by unraveling the genomic regions controlling traits enhancing drought tolerance. The present study was conducted with the aim to identify quantitative trait loci (QTLs for grain yield and root development traits under irrigated non-stress and reproductive-stage drought stress in both lowland and upland situations. A mapping population consisting of 480 lines derived from a cross between Dular (drought-tolerant and IR64-21 (drought susceptible was used. QTL analysis revealed three major consistent-effect QTLs for grain yield (qDTY1.1, qDTY1.3, and qDTY8.1 under non-stress and reproductive-stage drought stress conditions, and 2 QTLs for root traits (qRT9.1 for root-growth angle and qRT5.1 for multiple root traits, i.e., seedling-stage root length, root dry weight and crown root number. The genetic locus qDTY1.1 was identified as hotspot for grain yield and yield-related agronomic and root traits. The study identified significant positive correlations among numbers of crown roots and mesocotyl length at the seedling stage and root length and root dry weight at depth at later stages with grain yield and yield-related traits. Under reproductive stage drought stress, the grain yield advantage of the lines with QTLs ranged from 24.1 to 108.9% under upland and 3.0–22.7% under lowland conditions over the lines without QTLs. The lines with QTL combinations qDTY1.3+qDTY8.1 showed the highest mean grain yield advantage followed by lines having qDTY1.1+qDTY8.1 and qDTY1.1+qDTY8.1+qDTY1.3, across upland/lowland reproductive-stage drought stress. The identified QTLs for root traits, mesocotyl length, grain yield and yield-related traits can be immediately deployed in marker-assisted breeding to develop drought tolerant high yielding rice varieties.

  1. Solid-State (13)C NMR Delineates the Architectural Design of Biopolymers in Native and Genetically Altered Tomato Fruit Cuticles.

    Science.gov (United States)

    Chatterjee, Subhasish; Matas, Antonio J; Isaacson, Tal; Kehlet, Cindie; Rose, Jocelyn K C; Stark, Ruth E

    2016-01-11

    Plant cuticles on outer fruit and leaf surfaces are natural macromolecular composites of waxes and polyesters that ensure mechanical integrity and mitigate environmental challenges. They also provide renewable raw materials for cosmetics, packaging, and coatings. To delineate the structural framework and flexibility underlying the versatile functions of cutin biopolymers associated with polysaccharide-rich cell-wall matrices, solid-state NMR spectra and spin relaxation times were measured in a tomato fruit model system, including different developmental stages and surface phenotypes. The hydrophilic-hydrophobic balance of the cutin ensures compatibility with the underlying polysaccharide cell walls; the hydroxy fatty acid structures of outer epidermal cutin also support deposition of hydrophobic waxes and aromatic moieties while promoting the formation of cell-wall cross-links that rigidify and strengthen the cuticle composite during fruit development. Fruit cutin-deficient tomato mutants with compromised microbial resistance exhibit less efficient local and collective biopolymer motions, stiffening their cuticular surfaces and increasing their susceptibility to fracture.

  2. Genetically modified parthenocarpic eggplants: improved fruit productivity under both greenhouse and open field cultivation.

    Directory of Open Access Journals (Sweden)

    Pandolfini Tiziana

    2002-04-01

    Full Text Available Abstract Background Parthenocarpy, or fruit development in the absence of fertilization, has been genetically engineered in eggplant and in other horticultural species by using the DefH9-iaaM gene. The iaaM gene codes for tryptophan monoxygenase and confers auxin synthesis, while the DefH9 controlling regions drive expression of the gene specifically in the ovules and placenta. A previous greenhouse trial for winter production of genetically engineered (GM parthenocarpic eggplants demonstrated a significant increase (an average of 33% increase in fruit production concomitant with a reduction in cultivation costs. Results GM parthenocarpic eggplants have been evaluated in three field trials. Two greenhouse spring trials have shown that these plants outyielded the corresponding untransformed genotypes, while a summer trial has shown that improved fruit productivity in GM eggplants can also be achieved in open field cultivation. Since the fruits were always seedless, the quality of GM eggplant fruits was improved as well. RT-PCR analysis demonstrated that the DefH9-iaaM gene is expressed during late stages of fruit development. Conclusions The DefH9-iaaM parthenocarpic gene is a biotechnological tool that enhances the agronomic value of all eggplant genotypes tested. The main advantages of DefH9-iaaM eggplants are: i improved fruit productivity (at least 30–35% under both greenhouse and open field cultivation; ii production of good quality (marketable fruits during different types of cultivation; iii seedless fruit with improved quality. Such advantages have been achieved without the use of either male or female sterility genes.

  3. VLSI architecture

    Energy Technology Data Exchange (ETDEWEB)

    Randell, B.; Treleaven, P.C.

    1983-01-01

    This book is a collection of course papers which discusses the latest (1982) milestone of electronic building blocks and its effect on computer architecture. Contributions range from selecting a VLSI process technology to Japan's Fifth Generation Computer Architecture. Contents, abridged: VLSI and machine architecture. Graphic design aids: HED and FATFREDDY. On the LUCIFER system. Clocking of VLSI circuits. Decentralised computer architectures for VLSI. Index.

  4. Genetic and agronomic assessment of cob traits in corn under low and normal nitrogen management conditions.

    Science.gov (United States)

    Jansen, Constantin; Zhang, Yongzhong; Liu, Hongjun; Gonzalez-Portilla, Pedro J; Lauter, Nick; Kumar, Bharath; Trucillo-Silva, Ignacio; Martin, Juan Pablo San; Lee, Michael; Simcox, Kevin; Schussler, Jeff; Dhugga, Kanwarpal; Lübberstedt, Thomas

    2015-07-01

    Exploring and understanding the genetic basis of cob biomass in relation to grain yield under varying nitrogen management regimes will help breeders to develop dual-purpose maize. With rising energy demands and costs for fossil fuels, alternative energy from renewable sources such as maize cobs will become competitive. Maize cobs have beneficial characteristics for utilization as feedstock including compact tissue, high cellulose content, and low ash and nitrogen content. Nitrogen is quantitatively the most important nutrient for plant growth. However, the influence of nitrogen fertilization on maize cob production is unclear. In this study, quantitative trait loci (QTL) have been analyzed for cob morphological traits such as cob weight, volume, length, diameter and cob tissue density, and grain yield under normal and low nitrogen regimes. 213 doubled-haploid lines of the intermated B73 × Mo17 (IBM) Syn10 population have been resequenced for 8575 bins, based on SNP markers. A total of 138 QTL were found for six traits across six trials using composite interval mapping with ten cofactors and empirical comparison-wise thresholds (P = 0.001). Despite moderate to high repeatabilities across trials, few QTL were consistent across trials and overall levels of explained phenotypic variance were lower than expected some of the cob trait × trial combinations (R (2) = 7.3-43.1 %). Variation for cob traits was less affected by nitrogen conditions than by grain yield. Thus, the economics of cob usage under low nitrogen regimes is promising.

  5. Architecture & Environment

    Science.gov (United States)

    Erickson, Mary; Delahunt, Michael

    2010-01-01

    Most art teachers would agree that architecture is an important form of visual art, but they do not always include it in their curriculums. In this article, the authors share core ideas from "Architecture and Environment," a teaching resource that they developed out of a long-term interest in teaching architecture and their fascination with the…

  6. Differential SPL gene expression patterns reveal candidate genes underlying flowering time and architectural differences in Mimulus and Arabidopsis.

    Science.gov (United States)

    Jorgensen, Stacy A; Preston, Jill C

    2014-04-01

    Evolutionary transitions in growth habit and flowering time responses to variable environmental signals have occurred multiple times independently across angiosperms and have major impacts on plant fitness. Proteins in the SPL family of transcription factors collectively regulate flowering time genes that have been implicated in interspecific shifts in annuality/perenniality. However, their potential importance in the evolution of angiosperm growth habit has not been extensively investigated. Here we identify orthologs representative of the major SPL gene clades in annual Arabidopsis thaliana and Mimulus guttatus IM767, and perennial A. lyrata and M. guttatus PR, and characterize their expression. Spatio-temporal expression patterns are complex across both diverse tissues of the same taxa and comparable tissues of different taxa, consistent with genic sub- or neo-functionalization. However, our data are consistent with a general role for several SPL genes in the promotion of juvenile to adult phase change and/or flowering time in Mimulus and Arabidopsis. Furthermore, several candidate genes were identified for future study whose differential expression correlates with growth habit and architectural variation in annual versus perennial taxa. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Joint genetic and network analyses identify loci associated with root growth under NaCl stress in Arabidopsis thaliana.

    Science.gov (United States)

    Kobayashi, Yuriko; Sadhukhan, Ayan; Tazib, Tanveer; Nakano, Yuki; Kusunoki, Kazutaka; Kamara, Mohamed; Chaffai, Radhouane; Iuchi, Satoshi; Sahoo, Lingaraj; Kobayashi, Masatomo; Hoekenga, Owen A; Koyama, Hiroyuki

    2016-04-01

    Plants have evolved a series of tolerance mechanisms to saline stress, which perturbs physiological processes throughout the plant. To identify genetic mechanisms associated with salinity tolerance, we performed linkage analysis and genome-wide association study (GWAS) on maintenance of root growth of Arabidopsis thaliana in hydroponic culture with weak and severe NaCl toxicity. The top 200 single-nucleotide polymorphisms (SNPs) determined by GWAS could cumulatively explain approximately 70% of the variation observed at each stress level. The most significant SNPs were linked to the genes of ATP-binding cassette B10 and vacuolar proton ATPase A2. Several known salinity tolerance genes such as potassium channel KAT1 and calcium sensor SOS3 were also linked to SNPs in the top 200. In parallel, we constructed a gene co-expression network to independently verify that particular groups of genes work together to a common purpose. We identify molecular mechanisms to confer salt tolerance from both predictable and novel physiological sources and validate the utility of combined genetic and network analysis. Additionally, our study indicates that the genetic architecture of salt tolerance is responsive to the severity of stress. These gene datasets are a significant information resource for a following exploration of gene function. © 2015 John Wiley & Sons Ltd.

  8. Genetics

    International Nuclear Information System (INIS)

    Hubitschek, H.E.

    1975-01-01

    Progress is reported on the following research projects: genetic effects of high LET radiations; genetic regulation, alteration, and repair; chromosome replication and the division cycle of Escherichia coli; effects of radioisotope decay in the DNA of microorganisms; initiation and termination of DNA replication in Bacillus subtilis; mutagenesis in mouse myeloma cells; lethal and mutagenic effects of near-uv radiation; effect of 8-methoxypsoralen on photodynamic lethality and mutagenicity in Escherichia coli; DNA repair of the lethal effects of far-uv; and near uv irradiation of bacterial cells

  9. Impact of Scaffold Micro and Macro Architecture on Schwann Cell Proliferation under Dynamic Conditions in a Rotating Wall Vessel Bioreactor.

    Science.gov (United States)

    Valmikinathan, Chandra M; Hoffman, John; Yu, Xiaojun

    2011-01-01

    Over the last decade tissue engineering has emerged as a powerful alternative to regenerate lost tissues owing to trauma or tumor. Evidence shows that Schwann cell containing scaffolds have improved performance in vivo as compared to scaffolds that depend on cellularization post implantation. However, owing to limited supply of cells from the patients themselves, several approaches have been taken to enhance cell proliferation rates to produce complete and uniform cellularization of scaffolds. The most common approach is the application of a bioreactor to enhance cell proliferation rate and therefore reduce the time needed to obtain sufficiently significant number of glial cells, prior to implantation.In this study, we show the application of a rotating wall bioreactor system for studying Schwann cell proliferation on nanofibrous spiral shaped scaffolds, prepared by solvent casting and salt leaching techniques. The scaffolds were fabricated from polycaprolactone (PCL), which has ideal mechanical properties and upon degradation does not produce acidic byproducts. The spiral scaffolds were coated with aligned or random nanofibers, produced by electrospinning, to provide a substrate that mimics the native extracellular matrix and the essential contact guidance cues.At the 4 day time point, an enhanced rate of cell proliferation was observed on the open structured nanofibrous spiral scaffolds in a rotating wall bioreactor, as compared to static culture conditions. However, the cell proliferation rate on the other contemporary scaffolds architectures such as the tubular and cylindrical scaffolds show reduced cell proliferation in the bioreactor as compared to static conditions, at the same time point. Moreover, the rotating wall bioreactor does not alter the orientation or the phenotype of the Schwann cells on the aligned nanofiber containing scaffolds, wherein, the cells remain aligned along the length of the scaffolds. Therefore, these open structured spiral scaffolds

  10. Relational Architecture

    DEFF Research Database (Denmark)

    Reeh, Henrik

    2018-01-01

    The present study of PhD education and its impact on architectural research singles out three layers of relational architecture. A first layer of relationality appears in a graphic model in which an intimate link between PhD education and architectural research is outlined. The model reflects...... in a scholarly institution (element #3), as well as the certified PhD scholar (element #4) and the architectural profession, notably its labour market (element #5). This first layer outlines the contemporary context which allows architectural research to take place in a dynamic relationship to doctoral education....... A second layer of relational architecture is revealed when one examines the conception of architecture generated in selected PhD dissertations. Focusing on six dissertations with which the author of the present article was involved as a supervisor, the analysis lays bare a series of dynamic...

  11. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

    Directory of Open Access Journals (Sweden)

    Maleeha Maria

    Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

  12. Simultaneous Estimation of Mixing Rates and Genetic Drift Under Successive Sampling of Genetic Markers With Application to the Mud Crab (Scylla paramamosain) in Japan

    OpenAIRE

    Kitakado, Toshihide; Kitada, Shuichi; Obata, Yasuhiro; Kishino, Hirohisa

    2006-01-01

    In stock enhancement programs, it is important to assess mixing rates of released individuals in stocks. For this purpose, genetic stock identification has been applied. The allele frequencies in a composite population are expressed as a mixture of the allele frequencies in the natural and released populations. The estimation of mixing rates is possible, under successive sampling from the composite population, on the basis of temporal changes in allele frequencies. The allele frequencies in t...

  13. Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians' skin.

    Science.gov (United States)

    Fan, Wenqiao; Jiang, Yusong; Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Sun, Hanchang; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan

    2017-01-01

    Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians.

  14. Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians’ skin

    Science.gov (United States)

    Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan

    2017-01-01

    Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians. PMID:29267366

  15. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  16. The underlying mechanisms of genetic innovation and speciation in the family Corynebacteriaceae: A phylogenomics approach.

    Science.gov (United States)

    Zhi, Xiao-Yang; Jiang, Zhao; Yang, Ling-Ling; Huang, Ying

    2017-02-01

    The pangenome of a bacterial species population is formed by genetic reduction and genetic expansion over the long course of evolution. Gene loss is a pervasive source of genetic reduction, and (exogenous and endogenous) gene gain is the main driver of genetic expansion. To understand the genetic innovation and speciation of the family Corynebacteriaceae, which cause a wide range of serious infections in humans and animals, we analyzed the pangenome of this family, and reconstructed its phylogeny using a phylogenomics approach. Genetic variations have occurred throughout the whole evolutionary history of the Corynebacteriaceae. Gene loss has been the primary force causing genetic changes, not only in terms of the number of protein families affected, but also because of its continuity on the time series. The variation in metabolism caused by these genetic changes mainly occurred for membrane transporters, two-component systems, and metabolism related to amino acids and carbohydrates. Interestingly, horizontal gene transfer (HGT) not only caused changes related to pathogenicity, but also triggered the acquisition of antimicrobial resistance. The Darwinian theory of evolution did not adequately explain the effects of dispersive HGT and/or gene loss in the evolution of the Corynebacteriaceae. These findings provide new insight into the evolution and speciation of Corynebacteriaceae and advance our understanding of the genetic innovation in microbial populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Modelled in vivo HIV fitness under drug selective pressure and estimated genetic barrier towards resistance are predictive for virological response

    DEFF Research Database (Denmark)

    Deforche, Koen; Cozzi-Lepri, Alessandro; Theys, Kristof

    2008-01-01

    BACKGROUND: A method has been developed to estimate a fitness landscape experienced by HIV-1 under treatment selective pressure as a function of the genotypic sequence thereby also estimating the genetic barrier to resistance. METHODS: We evaluated the performance of two estimated fitness landsca...

  18. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan

    NARCIS (Netherlands)

    Maria, M.; Ajmal, M.; Azam, M.; Waheed, N.K.; Siddiqui, S.N.; Mustafa, B.; Ayub, H.; Ali, L.; Ahmad, S.; Micheal, S.; Hussain, A.; Shah, S.T.; Ali, S.H.; Ahmed, W.; Khan, Y.M.; Hollander, A.I. den; Haer-Wigman, L.; Collin, R.W.J.; Khan, M.I.; Qamar, R.; Cremers, F.P.M.

    2015-01-01

    BACKGROUND: Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective

  19. 75 FR 68911 - Regulations Under the Genetic Information Nondiscrimination Act of 2008

    Science.gov (United States)

    2010-11-09

    ... covered entities, however, might engage in conduct that could cause an employer to discriminate. For... disease or disorder. But just as the number of genetic tests increases, so do the concerns of the general... efforts to develop new medicines and treatments for genetic diseases and disorders would be slowed or...

  20. Fractal Geometry of Architecture

    Science.gov (United States)

    Lorenz, Wolfgang E.

    In Fractals smaller parts and the whole are linked together. Fractals are self-similar, as those parts are, at least approximately, scaled-down copies of the rough whole. In architecture, such a concept has also been known for a long time. Not only architects of the twentieth century called for an overall idea that is mirrored in every single detail, but also Gothic cathedrals and Indian temples offer self-similarity. This study mainly focuses upon the question whether this concept of self-similarity makes architecture with fractal properties more diverse and interesting than Euclidean Modern architecture. The first part gives an introduction and explains Fractal properties in various natural and architectural objects, presenting the underlying structure by computer programmed renderings. In this connection, differences between the fractal, architectural concept and true, mathematical Fractals are worked out to become aware of limits. This is the basis for dealing with the problem whether fractal-like architecture, particularly facades, can be measured so that different designs can be compared with each other under the aspect of fractal properties. Finally the usability of the Box-Counting Method, an easy-to-use measurement method of Fractal Dimension is analyzed with regard to architecture.

  1. Computer architecture technology trends

    CERN Document Server

    1991-01-01

    Please note this is a Short Discount publication. This year's edition of Computer Architecture Technology Trends analyses the trends which are taking place in the architecture of computing systems today. Due to the sheer number of different applications to which computers are being applied, there seems no end to the different adoptions which proliferate. There are, however, some underlying trends which appear. Decision makers should be aware of these trends when specifying architectures, particularly for future applications. This report is fully revised and updated and provides insight in

  2. Osteoporotic vertebral fractures during pregnancy: be aware of a potential underlying genetic cause.

    Science.gov (United States)

    Campos-Obando, Natalia; Oei, Ling; Hoefsloot, Lies H; Kiewiet, Rosalie M; Klaver, Caroline C W; Simon, Marleen E H; Zillikens, M Carola

    2014-04-01

    Although the baby growing in its mother's womb needs calcium for skeletal development, osteoporosis and fractures very rarely occur during pregnancy. A 27-year-old woman in the seventh month of her first pregnancy contracted midthoracic back pain after lifting an object. The pain was attributed to her pregnancy, but it remained postpartum. Her past medical history was uneventful, except for severely reduced vision of her left eye since birth. Family history revealed that her maternal grandmother had postmenopausal osteoporosis and her half-brother had three fractures during childhood after minor trauma. Her height was 1.58 m; she had no blue sclerae or joint hyperlaxity. Laboratory examination including serum calcium, phosphate, alkaline phosphatase, creatinine, β-carboxyterminal cross-linking telopeptide of type I collagen, 25-hydroxyvitamin D, and TSH was normal. Multiple thoracic vertebral fractures were diagnosed on x-ray examination, and dual-energy x-ray absorptiometry scanning showed severe osteoporosis (Z-scores: L2-L4, -5.6 SD; femur neck, -3.9 SD). DNA analyses revealed two compound heterozygous missense mutations in LRP5. The patient's mother carried one of the LRP5 mutations and was diagnosed with osteoporosis. Her half-brother, treated with cabergoline for a microprolactinoma, also had osteoporosis of the lumbar spine on dual-energy x-ray absorptiometry and carried the same LRP5 mutation. The patient was treated with risedronate for 2.5 years. Bone mineral density and back pain improved. She stopped bisphosphonate use 6 months before planning a second pregnancy. Our patient was diagnosed with osteoporosis pseudoglioma syndrome/familial exudative vitreoretinopathy. Potential underlying genetic causes should be considered in pregnancy-associated osteoporosis with implications for patients and relatives. More studies regarding osteoporosis treatment preceding conception are desirable.

  3. Likelihood for transcriptions in a genetic regulatory system under asymmetric stable Lévy noise

    Science.gov (United States)

    Wang, Hui; Cheng, Xiujun; Duan, Jinqiao; Kurths, Jürgen; Li, Xiaofan

    2018-01-01

    This work is devoted to investigating the evolution of concentration in a genetic regulation system, when the synthesis reaction rate is under additive and multiplicative asymmetric stable Lévy fluctuations. By focusing on the impact of skewness (i.e., non-symmetry) in the probability distributions of noise, we find that via examining the mean first exit time (MFET) and the first escape probability (FEP), the asymmetric fluctuations, interacting with nonlinearity in the system, lead to peculiar likelihood for transcription. This includes, in the additive noise case, realizing higher likelihood of transcription for larger positive skewness (i.e., asymmetry) index β, causing a stochastic bifurcation at the non-Gaussianity index value α = 1 (i.e., it is a separating point or line for the likelihood for transcription), and achieving a turning point at the threshold value β≈-0.5 (i.e., beyond which the likelihood for transcription suddenly reversed for α values). The stochastic bifurcation and turning point phenomena do not occur in the symmetric noise case (β = 0). While in the multiplicative noise case, non-Gaussianity index value α = 1 is a separating point or line for both the MFET and the FEP. We also investigate the noise enhanced stability phenomenon. Additionally, we are able to specify the regions in the whole parameter space for the asymmetric noise, in which we attain desired likelihood for transcription. We have conducted a series of numerical experiments in "regulating" the likelihood of gene transcription by tuning asymmetric stable Lévy noise indexes. This work offers insights for possible ways of achieving gene regulation in experimental research.

  4. Catalyst Architecture

    DEFF Research Database (Denmark)

    Kiib, Hans; Marling, Gitte; Hansen, Peter Mandal

    2014-01-01

    How can architecture promote the enriching experiences of the tolerant, the democratic, and the learning city - a city worth living in, worth supporting and worth investing in? Catalyst Architecture comprises architectural projects, which, by virtue of their location, context and their combination...... of programs, have a role in mediating positive social and/or cultural development. In this sense, we talk about architecture as a catalyst for: sustainable adaptation of the city’s infrastructure appropriate renovation of dilapidated urban districts strengthening of social cohesiveness in the city development...

  5. Genetic diversity of Vietnamese lowland rice germplasms as revealed by SSR markers in relation to seedling vigour under submergence

    Directory of Open Access Journals (Sweden)

    Hien Thi Thu Vu

    2016-01-01

    Full Text Available In the direct-seeding rice cultivation system, seedling vigour is one of the most important traits for stable stand establishment during early seedling stages, particularly under submergence that is caused by temporal flash flood. We studied the genetic diversity in a set of 40 Vietnamese lowland rice varieties using 30 simple sequence repeat (SSR markers covering all rice chromosomes. A total of 111 alleles were detected, with a mean of 3.7 alleles per locus. The number of polymorphic alleles detected by each SSR marker ranged from 2 to 6. The fragment size of a given SSR locus varied between 85 and 650 bp and the frequency of a major allele at each locus ranged from 32.5% to 76.9%. Polymorphism information content value varied from 0.355 to 0.774 with an average of 0.594. The genetic similarity calculated between pairs of rice varieties ranged from 0.03 to 0.97 with an average of 0.27. According to a constructed dendrogram of unweighted pair group method with arithmetic mean based on the SSR marker analysis, the tested rice varieties were clustered into two major groups consisting of five subgroups. Significant correlations existed between the mean genetic similarity and the mean seedling vigour estimated by shoot length under submergence among the tested varieties. Our results suggested usefulness of the SSR marker system to assess genetic diversity in Vietnamese rice germplasms in relation to their seedling vigour under submergence.

  6. Application of the distributed genetic algorithm for in-core fuel optimization problems under parallel computational environment

    International Nuclear Information System (INIS)

    Yamamoto, Akio; Hashimoto, Hiroshi

    2002-01-01

    The distributed genetic algorithm (DGA) is applied for loading pattern optimization problems of the pressurized water reactors. A basic concept of DGA follows that of the conventional genetic algorithm (GA). However, DGA equally distributes candidates of solutions (i.e. loading patterns) to several independent ''islands'' and evolves them in each island. Communications between islands, i.e. migrations of some candidates between islands are performed with a certain period. Since candidates of solutions independently evolve in each island while accepting different genes of migrants, premature convergence in the conventional GA can be prevented. Because many candidate loading patterns should be evaluated in GA or DGA, the parallelization is efficient to reduce turn around time. Parallel efficiency of DGA was measured using our optimization code and good efficiency was attained even in a heterogeneous cluster environment due to dynamic distribution of the calculation load. The optimization code is based on the client/server architecture with the TCP/IP native socket and a client (optimization) module and calculation server modules communicate the objects of loading patterns each other. Throughout the sensitivity study on optimization parameters of DGA, a suitable set of the parameters for a test problem was identified. Finally, optimization capability of DGA and the conventional GA was compared in the test problem and DGA provided better optimization results than the conventional GA. (author)

  7. Effect on Bone Architecture of Marginal Grooves in Dental Implants Under Occlusal Loaded Conditions in Beagle Dogs.

    Science.gov (United States)

    Kato, Hatsumi; Kuroshima, Shinichiro; Inaba, Nao; Uto, Yusuke; Sawase, Takashi

    2018-02-01

    The aim of this study was to clarify whether marginal grooves on dental implants affect osseointegration, bone structure, and the alignment of collagen fibers to determine bone quality under loaded conditions. Anodized Ti-6Al-4V alloy dental implants, with and without marginal grooves (test and control implants, respectively), were used (3.7 × 8.0 mm). Fourth premolars and first molars of 6 beagle mandibles were extracted. Two control and test implants were placed in randomly selected healed sites at 12 weeks after tooth extraction. Screw-retained single crowns for first molars were fabricated. Euthanasia was performed at 8 weeks after the application of occlusal forces. Implant marginal bone level, bone to implant contact (BIC), bone structure around dental implants, and the alignment of collagen fibers determining bone quality were analyzed. The marginal bone level in test implants was significantly higher than that in control implants. Occlusal forces significantly increased BIC in test implants ( P = .007), whereas BIC did not change in control implants, irrespective of occlusal forces ( P = .303). Moreover, occlusal forces significantly increased BIC in test implants compared with control implants ( P = .032). Additionally, occlusal forces preferentially aligned collagen fibers in test implants, but not control implants. Hence, marginal grooves on dental implants have positive effects on increased osseointegration and adapted bone quality based on the preferential alignment of collagen fibers around dental implants under loaded conditions.

  8. Genetic Interaction between Arabidopsis Qpm3.1 Locus and Bacterial Effector Gene hopW1-1 Underlies Natural Variation in Quantitative Disease Resistance to Pseudomonas Infection

    Science.gov (United States)

    Luo, Qi; Liu, Wei-Wei; Pan, Ke-Di; Peng, You-Liang; Fan, Jun

    2017-01-01

    Wide quantitative variation in plant disease resistance across Arabidopsis wild populations has been documented and the underlying mechanisms remain largely unknown. To investigate the genetic and molecular basis of this variation, Arabidopsis recombinant inbred lines (RILs) derived from Aa-0 × Col-0 and Gie-0 × Col-0 crosses were constructed and used for inoculation with Pseudomonas syringae pathovars maculicola ES4326 (ES4326) and tomato DC3000 (DC3000). Bacterial growth assays revealed continuous distribution across the large differences between the most and the least susceptible lines in the RILs. Quantitative trait locus (QTL) mapping analyses identified a number of QTLs underpinning the variance in disease resistance, among which Qpm3.1, a major QTL on chromosome III from both Aa-0 and Gie-0 accessions, preferentially restricted the growth of ES4326. A genetic screen for the ES4326 gene selectively leading to bacterial growth inhibition on accession Aa-0 uncovered the effector gene hopW1-1. Further QTL analysis of disease in RILs inoculated with DC3000 carrying hopW1-1 showed that the genetic interaction between Qpm3.1 and hopW1-1 determined Arabidopsis resistance to bacterial infection. These findings illustrate the complexity of Arabidopsis-Pseudomonas interaction and highlight the importance of pathogen effectors in delineating genetic architectures of quantitative variation in plant disease resistance. PMID:28523008

  9. Genome-wide association mapping reveals a rich genetic architecture of stripe rust resistance loci in emmer wheat (Triticum turgidum ssp. dicoccum).

    Science.gov (United States)

    Liu, Weizhen; Maccaferri, Marco; Chen, Xianming; Laghetti, Gaetano; Pignone, Domenico; Pumphrey, Michael; Tuberosa, Roberto

    2017-11-01

    SNP-based genome scanning in worldwide domesticated emmer germplasm showed high genetic diversity, rapid linkage disequilibrium decay and 51 loci for stripe rust resistance, a large proportion of which were novel. Cultivated emmer wheat (Triticum turgidum ssp. dicoccum), one of the oldest domesticated crops in the world, is a potentially rich reservoir of variation for improvement of resistance/tolerance to biotic and abiotic stresses in wheat. Resistance to stripe rust (Puccinia striiformis f. sp. tritici) in emmer wheat has been under-investigated. Here, we employed genome-wide association (GWAS) mapping with a mixed linear model to dissect effective stripe rust resistance loci in a worldwide collection of 176 cultivated emmer wheat accessions. Adult plants were tested in six environments and seedlings were evaluated with five races from the United States and one from Italy under greenhouse conditions. Five accessions were resistant across all experiments. The panel was genotyped with the wheat 90,000 Illumina iSelect single nucleotide polymorphism (SNP) array and 5106 polymorphic SNP markers with mapped positions were obtained. A high level of genetic diversity and fast linkage disequilibrium decay were observed. In total, we identified 14 loci associated with field resistance in multiple environments. Thirty-seven loci were significantly associated with all-stage (seedling) resistance and six of them were effective against multiple races. Of the 51 total loci, 29 were mapped distantly from previously reported stripe rust resistance genes or quantitative trait loci and represent newly discovered resistance loci. Our results suggest that GWAS is an effective method for characterizing genes in cultivated emmer wheat and confirm that emmer wheat is a rich source of stripe rust resistance loci that can be used for wheat improvement.

  10. Architectural Contestation

    NARCIS (Netherlands)

    Merle, J.

    2012-01-01

    This dissertation addresses the reductive reading of Georges Bataille's work done within the field of architectural criticism and theory which tends to set aside the fundamental ‘broken’ totality of Bataille's oeuvre and also to narrowly interpret it as a mere critique of architectural form,

  11. Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.

    Science.gov (United States)

    Mallett, Andrew J; McCarthy, Hugh J; Ho, Gladys; Holman, Katherine; Farnsworth, Elizabeth; Patel, Chirag; Fletcher, Jeffery T; Mallawaarachchi, Amali; Quinlan, Catherine; Bennetts, Bruce; Alexander, Stephen I

    2017-12-01

    Inherited kidney disease encompasses a broad range of disorders, with both multiple genes contributing to specific phenotypes and single gene defects having multiple clinical presentations. Advances in sequencing capacity may allow a genetic diagnosis for familial renal disease, by testing the increasing number of known causative genes. However, there has been limited translation of research findings of causative genes into clinical settings. Here, we report the results of a national accredited diagnostic genetic service for familial renal disease. An expert multidisciplinary team developed a targeted exomic sequencing approach with ten curated multigene panels (207 genes) and variant assessment individualized to the patient's phenotype. A genetic diagnosis (pathogenic genetic variant[s]) was identified in 58 of 135 families referred in two years. The genetic diagnosis rate was similar between families with a pediatric versus adult proband (46% vs 40%), although significant differences were found in certain panels such as atypical hemolytic uremic syndrome (88% vs 17%). High diagnostic rates were found for Alport syndrome (22 of 27) and tubular disorders (8 of 10), whereas the monogenic diagnostic rate for congenital anomalies of the kidney and urinary tract was one of 13. Quality reporting was aided by a strong clinical renal and genetic multidisciplinary committee review. Importantly, for a diagnostic service, few variants of uncertain significance were found with this targeted, phenotype-based approach. Thus, use of targeted massively parallel sequencing approaches in inherited kidney disease has a significant capacity to diagnose the underlying genetic disorder across most renal phenotypes. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  12. Systemic Architecture

    DEFF Research Database (Denmark)

    Poletto, Marco; Pasquero, Claudia

    This is a manual investigating the subject of urban ecology and systemic development from the perspective of architectural design. It sets out to explore two main goals: to discuss the contemporary relevance of a systemic practice to architectural design, and to share a toolbox of informational...... design protocols developed to describe the city as a territory of self-organization. Collecting together nearly a decade of design experiments by the authors and their practice, ecoLogicStudio, the book discusses key disciplinary definitions such as ecologic urbanism, algorithmic architecture, bottom......-up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto...

  13. Architectural Creation of Light

    DEFF Research Database (Denmark)

    Bülow, Katja

    2015-01-01

    Bidraget "Architectural Creation of Light" indgår sammen med 108 andre bidrag i bogen "You Say Light, I Think Shadow". Bogens indhold undersøger: "Hvad er lys". I dette bidrag besvares spørgsmålet gennem iagttagelser af arkitektstuderendes undersøgelser af lyset i deres arbejdsmodeller i...

  14. A Shared Genetic Propensity Underlies Experiences of Bullying Victimization in Late Childhood and Self-Rated Paranoid Thinking in Adolescence

    Science.gov (United States)

    Shakoor, Sania; McGuire, Phillip; Cardno, Alastair G.; Freeman, Daniel; Plomin, Robert; Ronald, Angelica

    2015-01-01

    Background: Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Method: Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Results: Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). Conclusion: In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms. PMID:25323579

  15. A shared genetic propensity underlies experiences of bullying victimization in late childhood and self-rated paranoid thinking in adolescence.

    Science.gov (United States)

    Shakoor, Sania; McGuire, Phillip; Cardno, Alastair G; Freeman, Daniel; Plomin, Robert; Ronald, Angelica

    2015-05-01

    Bullying is a risk factor for developing psychotic experiences (PEs). Whether bullying is associated with particular PEs, and the extent to which genes and environments influence the association, are unknown. This study investigated which specific PEs in adolescence are associated with earlier bullying victimization and the genetic and environmental contributions underlying their association. Participants were 4826 twin pairs from a longitudinal community-based twin study in England and Wales who reported on their bullying victimization at the age of 12 years. Measures of specific PEs (self-rated Paranoia, Hallucinations, Cognitive disorganization, Grandiosity, Anhedonia, and parent-rated Negative Symptoms) were recorded at age of 16 years. Childhood bullying victimization was most strongly associated with Paranoia in adolescence (r = .26; P bullying victimization and Paranoia were both heritable (35% and 52%, respectively) with unique environmental influences (39% and 48%, respectively), and bullying victimization showed common environmental influences (26%). The association between bullying victimization and Paranoia operated almost entirely via genetic influences (bivariate heritability = 93%), with considerable genetic overlap (genetic correlation = .55). In contrast to the assumed role of bullying victimization as an environmental trigger, these data suggest that bullying victimization in late childhood is particularly linked to self-rated Paranoia in adolescence via a shared genetic propensity. Clinically, individuals with a history of bullying victimization are predicted to be particularly susceptible to paranoid symptoms. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  16. Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection.

    Science.gov (United States)

    Müller, Dominik; Schopp, Pascal; Melchinger, Albrecht E

    2017-03-10

    Recurrent selection (RS) has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents [Formula: see text] but little is known about how [Formula: see text] affects genomic selection (GS) in RS, especially the persistency of prediction accuracy ([Formula: see text]) and genetic gain. Synthetics were simulated by intermating [Formula: see text]= 2-32 parent lines from an ancestral population with short- or long-range linkage disequilibrium ([Formula: see text]) and subjected to multiple cycles of GS. We determined [Formula: see text] and genetic gain across 30 cycles for different training set ( TS ) sizes, marker densities, and generations of recombination before model training. Contributions to [Formula: see text] and genetic gain from pedigree relationships, as well as from cosegregation and [Formula: see text] between QTL and markers, were analyzed via four scenarios differing in (i) the relatedness between TS and selection candidates and (ii) whether selection was based on markers or pedigree records. Persistency of [Formula: see text] was high for small [Formula: see text] where predominantly cosegregation contributed to [Formula: see text], but also for large [Formula: see text] where [Formula: see text] replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing [Formula: see text] > 4, given long-range LD A in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to [Formula: see text] for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size ([Formula: see text]) and higher marker density improved persistency of

  17. Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection

    Directory of Open Access Journals (Sweden)

    Dominik Müller

    2017-03-01

    Full Text Available Recurrent selection (RS has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents ( Np , but little is known about how Np affects genomic selection (GS in RS, especially the persistency of prediction accuracy (rg , g ^ and genetic gain. Synthetics were simulated by intermating Np= 2–32 parent lines from an ancestral population with short- or long-range linkage disequilibrium (LDA and subjected to multiple cycles of GS. We determined rg , g ^ and genetic gain across 30 cycles for different training set (TS sizes, marker densities, and generations of recombination before model training. Contributions to rg , g ^ and genetic gain from pedigree relationships, as well as from cosegregation and LDA between QTL and markers, were analyzed via four scenarios differing in (i the relatedness between TS and selection candidates and (ii whether selection was based on markers or pedigree records. Persistency of rg , g ^ was high for small Np , where predominantly cosegregation contributed to rg , g ^ , but also for large Np , where LDA replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing Np > 4, given long-range LDA in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to rg , g ^ for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size (NTS and higher marker density improved persistency of rg , g ^ and hence genetic gain, but additional recombinations could not increase genetic gain.

  18. Mapping QTL for Seed Germinability under Low Temperature Using a New High-Density Genetic Map of Rice

    Directory of Open Access Journals (Sweden)

    Ningfei Jiang

    2017-07-01

    Full Text Available Mapping major quantitative trait loci (QTL responsible for rice seed germinability under low temperature (GULT can provide valuable genetic source for improving cold tolerance in rice breeding. In this study, 124 rice backcross recombinant inbred lines (BRILs derived from a cross indica cv. Changhui 891 and japonica cv. 02428 were genotyped through re-sequencing technology. A bin map was generated which includes 3057 bins covering distance of 1266.5 cM with an average of 0.41 cM between markers. On the basis of newly constructed high-density genetic map, six QTL were detected ranging from 40 to 140 kb on Nipponbare genome. Among these, two QTL qCGR8 and qGRR11 alleles shared by 02428 could increase GULT and seed germination recovery rate after cold stress, respectively. However, qNGR1 and qNGR4 may be two major QTL affecting indica Changhui 891germination under normal condition. QTL qGRR1 and qGRR8 affected the seed germination recovery rate after cold stress and the alleles with increasing effects were shared by the Changhui 891 could improve seed germination rate after cold stress dramatically. These QTL could be a highly valuable genetic factors for cold tolerance improvement in rice lines. Moreover, the BRILs developed in this study will serve as an appropriate choice for mapping and studying genetic basis of rice complex traits.

  19. Temporal evolution of brain reorganization under cross-modal training: insights into the functional architecture of encoding and retrieval networks

    Science.gov (United States)

    Likova, Lora T.

    2015-03-01

    This study is based on the recent discovery of massive and well-structured cross-modal memory activation generated in the primary visual cortex (V1) of totally blind people as a result of novel training in drawing without any vision (Likova, 2012). This unexpected functional reorganization of primary visual cortex was obtained after undergoing only a week of training by the novel Cognitive-Kinesthetic Method, and was consistent across pilot groups of different categories of visual deprivation: congenitally blind, late-onset blind and blindfolded (Likova, 2014). These findings led us to implicate V1 as the implementation of the theoretical visuo-spatial 'sketchpad' for working memory in the human brain. Since neither the source nor the subsequent 'recipient' of this non-visual memory information in V1 is known, these results raise a number of important questions about the underlying functional organization of the respective encoding and retrieval networks in the brain. To address these questions, an individual totally blind from birth was given a week of Cognitive-Kinesthetic training, accompanied by functional magnetic resonance imaging (fMRI) both before and just after training, and again after a two-month consolidation period. The results revealed a remarkable temporal sequence of training-based response reorganization in both the hippocampal complex and the temporal-lobe object processing hierarchy over the prolonged consolidation period. In particular, a pattern of profound learning-based transformations in the hippocampus was strongly reflected in V1, with the retrieval function showing massive growth as result of the Cognitive-Kinesthetic memory training and consolidation, while the initially strong hippocampal response during tactile exploration and encoding became non-existent. Furthermore, after training, an alternating patch structure in the form of a cascade of discrete ventral regions underwent radical transformations to reach complete functional

  20. COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians.

    Directory of Open Access Journals (Sweden)

    Martis W Cowles

    2014-10-01

    Full Text Available Members of the COE family of transcription factors are required for central nervous system (CNS development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals.

  1. COE loss-of-function analysis reveals a genetic program underlying maintenance and regeneration of the nervous system in planarians.

    Science.gov (United States)

    Cowles, Martis W; Omuro, Kerilyn C; Stanley, Brianna N; Quintanilla, Carlo G; Zayas, Ricardo M

    2014-10-01

    Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured) planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals.

  2. Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes.

    Science.gov (United States)

    Dooley, James; Tian, Lei; Schonefeldt, Susann; Delghingaro-Augusto, Viviane; Garcia-Perez, Josselyn E; Pasciuto, Emanuela; Di Marino, Daniele; Carr, Edward J; Oskolkov, Nikolay; Lyssenko, Valeriya; Franckaert, Dean; Lagou, Vasiliki; Overbergh, Lut; Vandenbussche, Jonathan; Allemeersch, Joke; Chabot-Roy, Genevieve; Dahlstrom, Jane E; Laybutt, D Ross; Petrovsky, Nikolai; Socha, Luis; Gevaert, Kris; Jetten, Anton M; Lambrechts, Diether; Linterman, Michelle A; Goodnow, Chris C; Nolan, Christopher J; Lesage, Sylvie; Schlenner, Susan M; Liston, Adrian

    2016-05-01

    Type 1 (T1D) and type 2 (T2D) diabetes share pathophysiological characteristics, yet mechanistic links have remained elusive. T1D results from autoimmune destruction of pancreatic beta cells, whereas beta cell failure in T2D is delayed and progressive. Here we find a new genetic component of diabetes susceptibility in T1D non-obese diabetic (NOD) mice, identifying immune-independent beta cell fragility. Genetic variation in Xrcc4 and Glis3 alters the response of NOD beta cells to unfolded protein stress, enhancing the apoptotic and senescent fates. The same transcriptional relationships were observed in human islets, demonstrating the role of beta cell fragility in genetic predisposition to diabetes.

  3. DSP Architecture Design Essentials

    CERN Document Server

    Marković, Dejan

    2012-01-01

    In DSP Architecture Design Essentials, authors Dejan Marković and Robert W. Brodersen cover a key subject for the successful realization of DSP algorithms for communications, multimedia, and healthcare applications. The book addresses the need for DSP architecture design that maps advanced DSP algorithms to hardware in the most power- and area-efficient way. The key feature of this text is a design methodology based on a high-level design model that leads to hardware implementation with minimum power and area. The methodology includes algorithm-level considerations such as automated word-length reduction and intrinsic data properties that can be leveraged to reduce hardware complexity. From a high-level data-flow graph model, an architecture exploration methodology based on linear programming is used to create an array of architectural solutions tailored to the underlying hardware technology. The book is supplemented with online material: bibliography, design examples, CAD tutorials and custom software.

  4. Genetic variation underlying resistance to infectious hematopoietic necrosis virus in a steelhead trout (Oncorhynchus mykiss) population

    Science.gov (United States)

    Brieuc, Marine S. O.; Purcell, Maureen K.; Palmer, Alexander D.; Naish, Kerry A.

    2015-01-01

    Understanding the mechanisms of host resistance to pathogens will allow insights into the response of wild populations to the emergence of new pathogens. Infectious hematopoietic necrosis virus (IHNV) is endemic to the Pacific Northwest and infectious to Pacific salmon and trout (Oncorhynchus spp.). Emergence of the M genogroup of IHNV in steelhead trout O. mykiss in the coastal streams of Washington State, between 2007 and 2011, was geographically heterogeneous. Differences in host resistance due to genetic change were hypothesized to be a factor influencing the IHNV emergence patterns. For example, juvenile steelhead trout losses at the Quinault National Fish Hatchery (QNFH) were much lower than those at a nearby facility that cultures a stock originally derived from the same source population. Using a classical quantitative genetic approach, we determined the potential for the QNFH steelhead trout population to respond to selection caused by the pathogen, by estimating the heritability for 2 traits indicative of IHNV resistance, mortality (h2 = 0.377 (0.226 - 0.550)) and days to death (h2 = 0.093 (0.018 - 0.203)). These results confirm that there is a genetic basis for resistance and that this population has the potential to adapt to IHNV. Additionally, genetic correlation between days to death and fish length suggests a correlated response in these traits to selection. Reduction of genetic variation, as well as the presence or absence of resistant alleles, could affect the ability of populations to adapt to the pathogen. Identification of the genetic basis for IHNV resistance could allow the assessment of the susceptibility of other steelhead populations.

  5. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    This PhD thesis is motived by a personal interest in the theoretical, practical and creative qualities of architecture. But also a wonder and curiosity about the cultural and social relations architecture represents through its occupation with both the sciences and the arts. Inspired by present i...... with the material appearance of objects, but also the imaginary world of dreams and memories which are concealed with the communicative significance of intentions when designing the future super hospitals....... initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture......, is the current building of a series of Danish ‘super hospitals’ and an increased focus among architectural practices on research-based knowledge produced with the architectural sub-disciplines Healing Architecture and Evidence-Based Design. The problem is that this research does not focus on patient eating...

  6. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  7. Healing Architecture

    DEFF Research Database (Denmark)

    Folmer, Mette Blicher; Mullins, Michael; Frandsen, Anne Kathrine

    2012-01-01

    The project examines how architecture and design of space in the intensive unit promotes or hinders interaction between relatives and patients. The primary starting point is the relatives. Relatives’ support and interaction with their loved ones is important in order to promote the patients healing...... process. Therefore knowledge on how space can support interaction is fundamental for the architect, in order to make the best design solutions. Several scientific studies document that the hospital's architecture and design are important for human healing processes, including how the physical environment...... architectural and design solutions in order to improve quality of interaction between relative and patient in the hospital's intensive unit....

  8. Architectural technology

    DEFF Research Database (Denmark)

    2005-01-01

    The booklet offers an overall introduction to the Institute of Architectural Technology and its projects and activities, and an invitation to the reader to contact the institute or the individual researcher for further information. The research, which takes place at the Institute of Architectural...... Technology at the Roayl Danish Academy of Fine Arts, School of Architecture, reflects a spread between strategic, goal-oriented pilot projects, commissioned by a ministry, a fund or a private company, and on the other hand projects which originate from strong personal interests and enthusiasm of individual...

  9. Brief Communication: Quantitative- and molecular-genetic differentiation in humans and chimpanzees: implications for the evolutionary processes underlying cranial diversification.

    Science.gov (United States)

    Weaver, Timothy D

    2014-08-01

    Estimates of the amount of genetic differentiation in humans among major geographic regions (e.g., Eastern Asia vs. Europe) from quantitative-genetic analyses of cranial measurements closely match those from classical- and molecular-genetic markers. Typically, among-region differences account for ∼10% of the total variation. This correspondence is generally interpreted as evidence for the importance of neutral evolutionary processes (e.g., genetic drift) in generating among-region differences in human cranial form, but it was initially surprising because human cranial diversity was frequently assumed to show a strong signature of natural selection. Is the human degree of similarity of cranial and DNA-sequence estimates of among-region genetic differentiation unusual? How do comparisons with other taxa illuminate the evolutionary processes underlying cranial diversification? Chimpanzees provide a useful starting point for placing the human results in a broader comparative context, because common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the extant species most closely related to humans. To address these questions, I used 27 cranial measurements collected on a sample of 861 humans and 263 chimpanzees to estimate the amount of genetic differentiation between pairs of groups (between regions for humans and between species or subspecies for chimpanzees). Consistent with previous results, the human cranial estimates are quite similar to published DNA-sequence estimates. In contrast, the chimpanzee cranial estimates are much smaller than published DNA-sequence estimates. It appears that cranial differentiation has been limited in chimpanzees relative to humans. © 2014 Wiley Periodicals, Inc.

  10. Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations

    NARCIS (Netherlands)

    Stein, Evan A.; Dann, Eldad J.; Wiegman, Albert; Skovby, Flemming; Gaudet, Daniel; Sokal, Etienne; Charng, Min-Ji; Mohamed, Mafauzy; Luirink, Ilse; Raichlen, Joel S.; Sundén, Mattias; Carlsson, Stefan C.; Raal, Frederick J.; Kastelein, John J. P.

    2017-01-01

    BACKGROUND Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been

  11. Genetic Factors Underlying the Risk of Thalidomide-Related Neuropathy in Patients With Multiple Myeloma

    NARCIS (Netherlands)

    Johnson, David C.; Corthals, Sophie L.; Walker, Brian A.; Ross, Fiona M.; Gregory, Walter M.; Dickens, Nicholas J.; Lokhorst, Henk M.; Goldschmidt, Hartmut; Davies, Faith E.; Durie, Brian G. M.; Van Ness, Brian; Child, J. Anthony; Sonneveld, Pieter; Morgan, Gareth J.

    2011-01-01

    Purpose To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN). Patients and Methods We analyzed DNA from 1,495 patients with multiple myeloma. Using a custom-built single nucleotide polymorphism (SNP) array, we tested the

  12. Genetic and environmental contributions underlying stability in Childhood Obsessive-Compulsive Behavior.

    NARCIS (Netherlands)

    van Grootheest, D.S.; Bartels, M.; Cath, D.C.; Beekman, A.T.F.; Hudziak, J.; Boomsma, D.I.

    2007-01-01

    Background: Little is known about the stability of obsessive-compulsive (OC) behavior during childhood. The objective of this study is to determine the developmental stability of pediatric OC behavior and the genetic and environmental influences on stability in a large population-based twin sample.

  13. How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

    Science.gov (United States)

    Fox, Sharon E.; Levitt, Pat; Nelson, Charles A., III.

    2010-01-01

    Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this study a conceptual framework is provided for considering how the structure of early experience gets "under the skin." The study begins with a description of the genetic framework that lays the foundation for brain…

  14. Architectured Nanomembranes

    Energy Technology Data Exchange (ETDEWEB)

    Sturgeon, Matthew R. [Former ORNL postdoc; Hu, Michael Z. [ORNL

    2017-07-01

    This paper has reviewed the frontier field of “architectured membranes” that contains anisotropic oriented porous nanostructures of inorganic materials. Three example types of architectured membranes were discussed with some relevant results from our own research: (1) anodized thin-layer titania membranes on porous anodized aluminum oxide (AAO) substrates of different pore sizes, (2) porous glass membranes on alumina substrate, and (3) guest-host membranes based on infiltration of yttrium-stabilized zirconia inside the pore channels of AAO matrices.

  15. A novel Brassica–rhizotron system to unravel the dynamic changes in root system architecture of oilseed rape under phosphorus deficiency

    Science.gov (United States)

    Yuan, Pan; Ding, Guang-Da; Cai, Hong-Mei; Jin, Ke-Mo; Broadley, Martin Roger; Xu, Fang-Sen; Shi, Lei

    2016-01-01

    Background and Aims An important adaptation of plants to phosphorus (P) deficiency is to alter root system architecture (RSA) to increase P acquisition from the soil, but soil-based observations of RSA are technically challenging, especially in mature plants. The aim of this study was to investigate the root development and RSA of oilseed rape (Brassica napus L.) under low and high soil P conditions during an entire growth cycle. Methods A new large Brassica–rhizotron system (approx. 118-litre volume) was developed to study the RSA dynamics of B. napus ‘Zhongshuang11’ in soils, using top-soils supplemented with low P (LP) or high P (HP) for a full plant growth period. Total root length (TRL), root tip number (RTN), root length density (RLD), biomass and seed yield traits were measured. Key Results TRL and RTN increased more rapidly in HP than LP plants from seedling to flowering stages. Both traits declined from flowering to silique stages, and then increased slightly in HP plants; in contrast, root senescence was observed in LP plants. RSA parameters measured from the polycarbonate plates were empirically consistent with analyses of excavated roots. Seed yield and shoot dry weights were closely associated positively with root dry weights, TRL, RLD and RTN at both HP and LP. Conclusions The Brassica–rhizotron system is an effective method for soil-based root phenotyping across an entire growth cycle. Given that root senescence is likely to occur earlier under low P conditions, crop P deficiency is likely to affect late water and nitrogen uptake, which is critical for efficient resource use and optimal crop yields. PMID:27279575

  16. A novel Brassica-rhizotron system to unravel the dynamic changes in root system architecture of oilseed rape under phosphorus deficiency.

    Science.gov (United States)

    Yuan, Pan; Ding, Guang-Da; Cai, Hong-Mei; Jin, Ke-Mo; Broadley, Martin Roger; Xu, Fang-Sen; Shi, Lei

    2016-08-01

    An important adaptation of plants to phosphorus (P) deficiency is to alter root system architecture (RSA) to increase P acquisition from the soil, but soil-based observations of RSA are technically challenging, especially in mature plants. The aim of this study was to investigate the root development and RSA of oilseed rape (Brassica napus L.) under low and high soil P conditions during an entire growth cycle. A new large Brassica-rhizotron system (approx. 118-litre volume) was developed to study the RSA dynamics of B. napus 'Zhongshuang11' in soils, using top-soils supplemented with low P (LP) or high P (HP) for a full plant growth period. Total root length (TRL), root tip number (RTN), root length density (RLD), biomass and seed yield traits were measured. TRL and RTN increased more rapidly in HP than LP plants from seedling to flowering stages. Both traits declined from flowering to silique stages, and then increased slightly in HP plants; in contrast, root senescence was observed in LP plants. RSA parameters measured from the polycarbonate plates were empirically consistent with analyses of excavated roots. Seed yield and shoot dry weights were closely associated positively with root dry weights, TRL, RLD and RTN at both HP and LP. The Brassica-rhizotron system is an effective method for soil-based root phenotyping across an entire growth cycle. Given that root senescence is likely to occur earlier under low P conditions, crop P deficiency is likely to affect late water and nitrogen uptake, which is critical for efficient resource use and optimal crop yields. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Large-Scale Association Study Confirms Genetic Complexity Underlying Type 2 Diabetes

    OpenAIRE

    Barroso, Inês; Luan, Jian'an; Middelberg, Rita P. S; Harding, Anne-Helen; Franks, Paul W; Jakes, Rupert W; Clayton, David; Schafer, Alan J; O'Rahilly, Stephen; Wareham, Nicholas J

    2003-01-01

    Type 2 diabetes is an increasingly common, serious metabolic disorder with a substantial inherited component. It is characterised by defects in both insulin secretion and action. Progress in identification of specific genetic variants predisposing to the disease has been limited. To complement ongoing positional cloning efforts, we have undertaken a large-scale candidate gene association study. We examined 152 SNPs in 71 candidate genes for association with diabetes status and related phenoty...

  18. Architectural freedom and industrialized architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    to explain that architecture can be thought as a complex and diverse design through customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performing expression in direct relation to the given context. Through the last couple of years we have...... expression in the specific housing area. It is the aim of this article to expand the different design strategies which architects can use – to give the individual project attitudes and designs with architectural quality. Through the customized component production it is possible to choose different...... for retrofit design. If we add the question of the installations e.g. ventilation to this systematic thinking of building technique we get a diverse and functional architecture, thereby creating a new and clearer story telling about new and smart system based thinking behind architectural expression....

  19. Architectural freedom and industrialised architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    Architectural freedom and industrialized architecture. Inge Vestergaard, Associate Professor, Cand. Arch. Aarhus School of Architecture, Denmark Noerreport 20, 8000 Aarhus C Telephone +45 89 36 0000 E-mai l inge.vestergaard@aarch.dk Based on the repetitive architecture from the "building boom" 1960...... customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performed expression in direct relation to the given context. Through the last couple of years we have in Denmark been focusing a more sustainable and low energy building technique, which also include...... to the building physic problems a new industrialized period has started based on light weight elements basically made of wooden structures, faced with different suitable materials meant for individual expression for the specific housing area. It is the purpose of this article to widen up the different design...

  20. Architectural freedom and industrialized architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    Based on the repetitive architecture from the “building boom” from 1960 to 1973, it is discussed how architects can handle these Danish element and montage buildings through the transformation to upgraded aesthetical, functional and energy efficient architecture. The method used is analysis...... of cases, parallels to literature studies and client and producer interviews. The analysis compares best practice in Denmark and best practice in Austria. Modern architects accepted the fact that industrialized architecture told the storey of repetition and monotony as basic condition. This article aims...... to explain that architecture can be thought as a complex and diverse design through customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performing expression in direct relation to the given context. Through the last couple of years we have...

  1. Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.

    Science.gov (United States)

    Imhann, Floris; Vich Vila, Arnau; Bonder, Marc Jan; Fu, Jingyuan; Gevers, Dirk; Visschedijk, Marijn C; Spekhorst, Lieke M; Alberts, Rudi; Franke, Lude; van Dullemen, Hendrik M; Ter Steege, Rinze W F; Huttenhower, Curtis; Dijkstra, Gerard; Xavier, Ramnik J; Festen, Eleonora A M; Wijmenga, Cisca; Zhernakova, Alexandra; Weersma, Rinse K

    2018-01-01

    Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2 , CARD9 , ATG16L1 , IRGM and FUT2 . Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10 -13 ). We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. PICNIC Architecture.

    Science.gov (United States)

    Saranummi, Niilo

    2005-01-01

    The PICNIC architecture aims at supporting inter-enterprise integration and the facilitation of collaboration between healthcare organisations. The concept of a Regional Health Economy (RHE) is introduced to illustrate the varying nature of inter-enterprise collaboration between healthcare organisations collaborating in providing health services to citizens and patients in a regional setting. The PICNIC architecture comprises a number of PICNIC IT Services, the interfaces between them and presents a way to assemble these into a functioning Regional Health Care Network meeting the needs and concerns of its stakeholders. The PICNIC architecture is presented through a number of views relevant to different stakeholder groups. The stakeholders of the first view are national and regional health authorities and policy makers. The view describes how the architecture enables the implementation of national and regional health policies, strategies and organisational structures. The stakeholders of the second view, the service viewpoint, are the care providers, health professionals, patients and citizens. The view describes how the architecture supports and enables regional care delivery and process management including continuity of care (shared care) and citizen-centred health services. The stakeholders of the third view, the engineering view, are those that design, build and implement the RHCN. The view comprises four sub views: software engineering, IT services engineering, security and data. The proposed architecture is founded into the main stream of how distributed computing environments are evolving. The architecture is realised using the web services approach. A number of well established technology platforms and generic standards exist that can be used to implement the software components. The software components that are specified in PICNIC are implemented in Open Source.

  3. Architectural freedom and industrialised architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    to the building physic problems a new industrialized period has started based on light weight elements basically made of wooden structures, faced with different suitable materials meant for individual expression for the specific housing area. It is the purpose of this article to widen up the different design...... to this systematic thinking of the building technique we get a diverse and functional architecture. Creating a new and clearer story telling about new and smart system based thinking behind the architectural expression....

  4. Genetic Analysis for Some of Morphological Traits in Bread Wheat under Drought Stress Condition Using Generations Mean Analysis

    Directory of Open Access Journals (Sweden)

    Jamileh Abedi

    2015-06-01

    Full Text Available Perception of genes action controlling of quantitative traits is very important in genetic breeding methods the plant populations. to study and estimate the parameters of genetic and appointment the best genetically model for justification the genetic changing some of traits the bread wheat under drought stress condition, parents (P1 & P2 and F3, F4, F5 generations together the four control cultivars (Kharchia, Gaspard, Moghan and Mahuti were evaluated by generation mean analysis using a agoment design including six blocks. Generation mean analysis was performed for all traits with Mather and Jinks model using joint scaling test. Three parameter model [m d h] provided the best fit for all traits expect harvest index, main spike grain weight, number of grain per plant, Total spike weight of plant with significant at 5% and 1% levels . Though additive and dominance effect both had interfered in controlling often the traits but with attention to difference effects and variety component was determined that dominance is more impressive than additive effect for traits of number of tiller, main spike weight, grain yield and grain number of main spike. Therefore will benefit using of these traits in the collection and to improve these traits hybridization would be much efficient than the selection strategies. In this study additive Ч additive epistasis effect only observed for traits of Total spike weight of plant, number of grain per plant, main spike grain weight and harvest index and other traits hadn’t any epistasis effect that it was demonstration lack of existence the genes reciprocal effect in the inheritance studied traits. Therefore we can suggest that the selection strategies perform in terminal generations and additive Ч additive epistasis effect would be confirmed in selection under self-pollination condition.

  5. Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD.

    Science.gov (United States)

    Chen, Hongbo; Kankel, Mark W; Su, Susan C; Han, Steve W S; Ofengeim, Dimitry

    2018-03-01

    Although amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, was first described in 1874, a flurry of genetic discoveries in the last 10 years has markedly increased our understanding of this disease. These findings have not only enhanced our knowledge of mechanisms leading to ALS, but also have revealed that ALS shares many genetic causes with another neurodegenerative disease, frontotemporal lobar dementia (FTLD). In this review, we survey how recent genetic studies have bridged our mechanistic understanding of these two related diseases and how the genetics behind ALS and FTLD point to complex disorders, implicating non-neuronal cell types in disease pathophysiology. The involvement of non-neuronal cell types is consistent with a non-cell autonomous component in these diseases. This is further supported by studies that identified a critical role of immune-associated genes within ALS/FTLD and other neurodegenerative disorders. The molecular functions of these genes support an emerging concept that various non-autonomous functions are involved in neurodegeneration. Further insights into such a mechanism(s) will ultimately lead to a better understanding of potential routes of therapeutic intervention. Facts ALS and FTLD are severe neurodegenerative disorders on the same disease spectrum. Multiple cellular processes including dysregulation of RNA homeostasis, imbalance of proteostasis, contribute to ALS/FTLD pathogenesis. Aberrant function in non-neuronal cell types, including microglia, contributes to ALS/FTLD. Strong neuroimmune and neuroinflammatory components are associated with ALS/FTLD patients. Open Questions Why can patients with similar mutations have different disease manifestations, i.e., why do C9ORF72 mutations lead to motor neuron loss in some patients while others exhibit loss of neurons in the frontotemporal lobe? Do ALS causal mutations result in microglial dysfunction and contribute to ALS/FTLD pathology? How do microglia

  6. Architectural geometry

    KAUST Repository

    Pottmann, Helmut

    2014-11-26

    Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural geometry, meanwhile contains a great wealth of individual contributions which are relevant in various fields. For mathematicians, the relation to discrete differential geometry is significant, in particular the integrable system viewpoint. Besides, new application contexts have become available for quite some old-established concepts. Regarding graphics and geometry processing, architectural geometry yields interesting new questions but also new objects, e.g. replacing meshes by other combinatorial arrangements. Numerical optimization plays a major role but in itself would be powerless without geometric understanding. Summing up, architectural geometry has become a rewarding field of study. We here survey the main directions which have been pursued, we show real projects where geometric considerations have played a role, and we outline open problems which we think are significant for the future development of both theory and practice of architectural geometry.

  7. Architectural Prototyping in Industrial Practice

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2008-01-01

    Architectural prototyping is the process of using executable code to investigate stakeholders’ software architecture concerns with respect to a system under development. Previous work has established this as a useful and cost-effective way of exploration and learning of the design space of a system......, in addressing issues regarding quality attributes, in addressing architectural risks, and in addressing the problem of knowledge transfer and conformance. Little work has been reported so far on the actual industrial use of architectural prototyping. In this paper, we report from an ethnographical study...... prototypes include end-user or business related functionality rather than purely architectural functionality. Based on these observations we provide recommendations for effective industrial architectural prototyping....

  8. DGAT1 underlies large genetic variation in milk-fat composition of dairy cows.

    Science.gov (United States)

    Schennink, A; Stoop, W M; Visker, M H P W; Heck, J M L; Bovenhuis, H; van der Poel, J J; van Valenberg, H J F; van Arendonk, J A M

    2007-10-01

    Dietary fat may play a role in the aetiology of many chronic diseases. Milk and milk-derived foods contribute substantially to dietary fat, but have a fat composition that is not optimal for human health. We measured the fat composition of milk samples in 1918 Dutch Holstein Friesian cows in their first lactation and estimated genetic parameters for fatty acids. Substantial genetic variation in milk-fat composition was found: heritabilities were high for short- and medium-chain fatty acids (C4:0-C16:0) and moderate for long-chain fatty acids (saturated and unsaturated C18). We genotyped 1762 cows for the DGAT1 K232A polymorphism, which is known to affect milk-fat percentage, to study the effect of the polymorphism on milk-fat composition. We found that the DGAT1 K232A polymorphism has a clear influence on milk-fat composition. The DGAT1 allele that encodes lysine (K) at position 232 (232K) is associated with more saturated fat; a larger fraction of C16:0; and smaller fractions of C14:0, unsaturated C18 and conjugated linoleic acid (P < 0.001). We conclude that selective breeding can make a significant contribution to change the fat composition of cow's milk.

  9. BAYESIAN PREDICTION OF GENETIC PARAMETERS IN Eucalyptus globulus CLONES UNDER WATER SUPPLY CONDITIONS

    Directory of Open Access Journals (Sweden)

    Freddy Mora

    2013-06-01

    Full Text Available http://dx.doi.org/10.5902/198050989297A Bayesian analysis of genetic parameters for growth traits at twelve months after planting was carried out in twenty nine Eucalyptus globulus clones in southern Chile. Two different environmental conditions were considered: 1 Non-irrigation and; 2 Plants were irrigated with a localized irrigation system. The Bayesian approach was performed using Gibbs sampling algorithm in a clone-environment interaction model. Inheritability values ​​were high in the water supply condition (posterior mode: H2=0.41, 0.36 and 0.39 for height, diameter and sectional area, respectively, while in the environment without irrigation, the inheritabilities were significantly lower, which was confirmed by the Bayesian credible intervals (95% probability. The posterior mode of the genetic correlation between sites was positive and high for all traits (r=0.7, 0.65 and 0.8, for height, diameter and sectional area, respectively and according to the credible interval, it was statistically different from zero, indicating a non-significant interaction.

  10. Assessment of Genetics Understanding. Under What Conditions Do Situational Features Have an Impact on Measures?

    Science.gov (United States)

    Schmiemann, Philipp; Nehm, Ross H.; Tornabene, Robyn E.

    2017-12-01

    Understanding how situational features of assessment tasks impact reasoning is important for many educational pursuits, notably the selection of curricular examples to illustrate phenomena, the design of formative and summative assessment items, and determination of whether instruction has fostered the development of abstract schemas divorced from particular instances. The goal of our study was to employ an experimental research design to quantify the degree to which situational features impact inferences about participants' understanding of Mendelian genetics. Two participant samples from different educational levels and cultural backgrounds (high school, n = 480; university, n = 444; Germany and USA) were used to test for context effects. A multi-matrix test design was employed, and item packets differing in situational features (e.g., plant, animal, human, fictitious) were randomly distributed to participants in the two samples. Rasch analyses of participant scores from both samples produced good item fit, person reliability, and item reliability and indicated that the university sample displayed stronger performance on the items compared to the high school sample. We found, surprisingly, that in both samples, no significant differences in performance occurred among the animal, plant, and human item contexts, or between the fictitious and "real" item contexts. In the university sample, we were also able to test for differences in performance between genders, among ethnic groups, and by prior biology coursework. None of these factors had a meaningful impact upon performance or context effects. Thus some, but not all, types of genetics problem solving or item formats are impacted by situational features.

  11. Structural comparison of tRNA m1A58 methyltransferases revealed different molecular strategies to maintain their oligomeric architecture under extreme conditions

    Directory of Open Access Journals (Sweden)

    Guelorget Amandine

    2011-12-01

    Full Text Available Abstract Background tRNA m1A58 methyltransferases (TrmI catalyze the transfer of a methyl group from S-adenosyl-L-methionine to nitrogen 1 of adenine 58 in the T-loop of tRNAs from all three domains of life. The m1A58 modification has been shown to be essential for cell growth in yeast and for adaptation to high temperatures in thermophilic organisms. These enzymes were shown to be active as tetramers. The crystal structures of five TrmIs from hyperthermophilic archaea and thermophilic or mesophilic bacteria have previously been determined, the optimal growth temperature of these organisms ranging from 37°C to 100°C. All TrmIs are assembled as tetramers formed by dimers of tightly assembled dimers. Results In this study, we present a comparative structural analysis of these TrmIs, which highlights factors that allow them to function over a large range of temperature. The monomers of the five enzymes are structurally highly similar, but the inter-monomer contacts differ strongly. Our analysis shows that bacterial enzymes from thermophilic organisms display additional intermolecular ionic interactions across the dimer interfaces, whereas hyperthermophilic enzymes present additional hydrophobic contacts. Moreover, as an alternative to two bidentate ionic interactions that stabilize the tetrameric interface in all other TrmI proteins, the tetramer of the archaeal P. abyssi enzyme is strengthened by four intersubunit disulfide bridges. Conclusions The availability of crystal structures of TrmIs from mesophilic, thermophilic or hyperthermophilic organisms allows a detailed analysis of the architecture of this protein family. Our structural comparisons provide insight into the different molecular strategies used to achieve the tetrameric organization in order to maintain the enzyme activity under extreme conditions.

  12. Architectural Engineers

    DEFF Research Database (Denmark)

    Petersen, Rikke Premer

    engineering is addresses from two perspectives – as an educational response and an occupational constellation. Architecture and engineering are two of the traditional design professions and they frequently meet in the occupational setting, but at educational institutions they remain largely estranged....... The paper builds on a multi-sited study of an architectural engineering program at the Technical University of Denmark and an architectural engineering team within an international engineering consultancy based on Denmark. They are both responding to new tendencies within the building industry where...... the role of engineers and architects increasingly overlap during the design process, but their approaches reflect different perceptions of the consequences. The paper discusses some of the challenges that design education, not only within engineering, is facing today: young designers must be equipped...

  13. Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    collaboration: How can qualitative anthropological approaches contribute to contemporary architecture? And just as importantly: What can anthropologists learn from architects’ understanding of spatial and material surroundings? Recent theoretical developments in anthropology stress the role of materials......Architecture and anthropology have always had a common focus on dwelling, housing, urban life and spatial organisation. Current developments in both disciplines make it even more relevant to explore their boundaries and overlaps. Architects are inspired by anthropological insights and methods......, while recent material and spatial turns in anthropology have also brought an increasing interest in design, architecture and the built environment. Understanding the relationship between the social and the physical is at the heart of both disciplines, and they can obviously benefit from further...

  14. Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    Architecture and anthropology have always had a common focus on dwelling, housing, urban life and spatial organisation. Current developments in both disciplines make it even more relevant to explore their boundaries and overlaps. Architects are inspired by anthropological insights and methods......, while recent material and spatial turns in anthropology have also brought an increasing interest in design, architecture and the built environment. Understanding the relationship between the social and the physical is at the heart of both disciplines, and they can obviously benefit from further...... collaboration: How can qualitative anthropological approaches contribute to contemporary architecture? And just as importantly: What can anthropologists learn from architects’ understanding of spatial and material surroundings? Recent theoretical developments in anthropology stress the role of materials...

  15. Architectural Narratives

    DEFF Research Database (Denmark)

    Kiib, Hans

    2010-01-01

    a functional framework for these concepts, but tries increasingly to endow the main idea of the cultural project with a spatially aesthetic expression - a shift towards “experience architecture.” A great number of these projects typically recycle and reinterpret narratives related to historical buildings......In this essay, I focus on the combination of programs and the architecture of cultural projects that have emerged within the last few years. These projects are characterized as “hybrid cultural projects,” because they intend to combine experience with entertainment, play, and learning. This essay...... identifies new rationales related to this development, and it argues that “cultural planning” has increasingly shifted its focus from a cultural institutional approach to a more market-oriented strategy that integrates art and business. The role of architecture has changed, too. It not only provides...

  16. Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    anthropology. On the one hand, there are obviously good reasons for developing architecture based on anthropological insights in local contexts and anthropologically inspired techniques for ‘collaborative formation of issues’. Houses and built environments are huge investments, their life expectancy...... and other spaces that architects are preoccupied with. On the other hand, the distinction between architecture and design is not merely one of scale. Design and architecture represent – at least in Denmark – also quite different disciplinary traditions and methods. Where designers develop prototypes......, architects tend to work with models and plans that are not easily understood by lay people. Further, many architects are themselves sceptical towards notions of user-involvement and collaborative design. They fear that the imagination of citizens and users is restricted to what they are already familiar with...

  17. Reframing Architecture

    DEFF Research Database (Denmark)

    Riis, Søren

    2013-01-01

    I would like to thank Prof. Stephen Read (2011) and Prof. Andrew Benjamin (2011) for both giving inspiring and elaborate comments on my article “Dwelling in-between walls: the architectural surround”. As I will try to demonstrate below, their two different responses not only supplement my article...... focuses on how the absence of an initial distinction might threaten the endeavour of my paper. In my reply to Read and Benjamin, I will discuss their suggestions and arguments, while at the same time hopefully clarifying the postphenomenological approach to architecture....

  18. From green architecture to architectural green

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    of green architecture. The paper argues that this greenification of facades is insufficient. The green is only a skin cladding the exterior envelope without having a spatial significance. Through the paper it is proposed to flip the order of words from green architecture to architectural green...... that describes the architectural exclusivity of this particular architecture genre. The adjective green expresses architectural qualities differentiating green architecture from none-green architecture. Currently, adding trees and vegetation to the building’s facade is the main architectural characteristics...

  19. New Energy Architecture. Myanmar

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-06-15

    A global transition towards a new energy architecture is under way, driven by countries' need to respond to the changing dynamics of economic growth, environmental sustainability and energy security. The World Economic Forum, in collaboration with Accenture, has created the New Energy Architecture Initiative to address and accelerate this transition. The Initiative supports the development of national strategies and policy frameworks as countries seek to achieve the combined goals of energy security and access, sustainability, and economic growth and development. The World Economic Forum has formed a partnership with the Ministry of Energy of Myanmar to help apply the Initiative's approach to this developing and resource-rich nation. The Asian Development Bank and the World Economic Forum's Project Adviser, Accenture, have collaborated with the Forum on this consultation process, and have been supported by relevant government, industry and civil society stakeholders. The consultation process aims to understand the nation's current energy architecture challenges and provide an overview of a path to a New Energy Architecture through a series of insights. These insights could form the basis for a long-term multistakeholder roadmap to build Myanmar's energy sector in a way that is secure and sustainable, and promotes economic growth as the country makes its democratic transition. While not all recommendations can be implemented in the near term, they do provide options for creating a prioritized roadmap for Myanmar's energy transition. This report is the culmination of a nine-month multistakeholder process investigating Myanmar's energy architecture. Over the course of many visits to the country, the team has conducted numerous interviews, multistakeholder workshops, and learning and data-gathering exercises to ensure a comprehensive range of information and views. The team has also engaged with a variety of stakeholders to better

  20. Genetic and Molecular Mechanisms Underlying Symbiotic Specificity in Legume-Rhizobium Interactions

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2018-03-01

    Full Text Available Legumes are able to form a symbiotic relationship with nitrogen-fixing soil bacteria called rhizobia. The result of this symbiosis is to form nodules on the plant root, within which the bacteria can convert atmospheric nitrogen into ammonia that can be used by the plant. Establishment of a successful symbiosis requires the two symbiotic partners to be compatible with each other throughout the process of symbiotic development. However, incompatibility frequently occurs, such that a bacterial strain is unable to nodulate a particular host plant or forms nodules that are incapable of fixing nitrogen. Genetic and molecular mechanisms that regulate symbiotic specificity are diverse, involving a wide range of host and bacterial genes/signals with various modes of action. In this review, we will provide an update on our current knowledge of how the recognition specificity has evolved in the context of symbiosis signaling and plant immunity.

  1. Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence.

    Science.gov (United States)

    Martin, Elizabeth M; Stýblo, Miroslav; Fry, Rebecca C

    2017-05-01

    Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic β-cell damage, pancreatic β-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.

  2. Genetic subdivision and candidate genes under selection in North American grey wolves.

    Science.gov (United States)

    Schweizer, Rena M; vonHoldt, Bridgett M; Harrigan, Ryan; Knowles, James C; Musiani, Marco; Coltman, David; Novembre, John; Wayne, Robert K

    2016-01-01

    Previous genetic studies of the highly mobile grey wolf (Canis lupus) found population structure that coincides with habitat and phenotype differences. We hypothesized that these ecologically distinct populations (ecotypes) should exhibit signatures of selection in genes related to morphology, coat colour and metabolism. To test these predictions, we quantified population structure related to habitat using a genotyping array to assess variation in 42 036 single-nucleotide polymorphisms (SNPs) in 111 North American grey wolves. Using these SNP data and individual-level measurements of 12 environmental variables, we identified six ecotypes: West Forest, Boreal Forest, Arctic, High Arctic, British Columbia and Atlantic Forest. Next, we explored signals of selection across these wolf ecotypes through the use of three complementary methods to detect selection: FST /haplotype homozygosity bivariate percentilae, bayescan, and environmentally correlated directional selection with bayenv. Across all methods, we found consistent signals of selection on genes related to morphology, coat coloration, metabolism, as predicted, as well as vision and hearing. In several high-ranking candidate genes, including LEPR, TYR and SLC14A2, we found variation in allele frequencies that follow environmental changes in temperature and precipitation, a result that is consistent with local adaptation rather than genetic drift. Our findings show that local adaptation can occur despite gene flow in a highly mobile species and can be detected through a moderately dense genomic scan. These patterns of local adaptation revealed by SNP genotyping likely reflect high fidelity to natal habitats of dispersing wolves, strong ecological divergence among habitats, and moderate levels of linkage in the wolf genome. © 2015 John Wiley & Sons Ltd.

  3. Architecture and communication

    Directory of Open Access Journals (Sweden)

    Špela Hudnik

    2003-01-01

    Full Text Available The article presents effects of technology, science and capital strategies on changes in traditional forms and definitions of space, architecture and bodies. It confronts us with new processes of thinking and living that are constantly being transformed into new dynamic time and spatial contexts. Space is becoming the information filter, communication network. A cross-section of three landscapes: landscape of megastructures, nomadic landscapes and psychedelic landscapes, theory contributes to understanding of media and space-age technology, information technology and electronical language. It offers designs of various megastructures, media surfaces and envelopes of contemporary information society: the anthropological module, hyper- and infra-bodies, bio-electronical bodies and population genetics bodies. It presents the architecture of communication.

  4. Architecture Analysis

    NARCIS (Netherlands)

    Iacob, Maria-Eugenia; Jonkers, Henk; van der Torre, Leon; de Boer, Frank S.; Bonsangue, Marcello; Stam, Andries W.; Lankhorst, Marc M.; Quartel, Dick A.C.; Aldea, Adina; Lankhorst, Marc

    2017-01-01

    This chapter also explains what the added value of enterprise architecture analysis techniques is in addition to existing, more detailed, and domain-specific ones for business processes or software, for example. Analogous to the idea of using the ArchiMate enterprise modelling language to integrate

  5. Metabolistic Architecture

    DEFF Research Database (Denmark)

    2013-01-01

    Textile Spaces presents different approaches to using textile as a spatial definer and artistic medium. The publication collages images and text, art and architecture, science, philosophy and literature, process and product, past, present and future. It forms an insight into soft materials...

  6. Textile Architecture

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen