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Sample records for genetical genomic determinants

  1. Genetical genomic determinants of alcohol consumption in rats and humans

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    Mangion Jonathan

    2009-10-01

    Full Text Available Abstract Background We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs. Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. Results In the HXB/BXH recombinant inbred (RI rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. Conclusion Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume

  2. Young Adults' Belief in Genetic Determinism, and Knowledge and Attitudes towards Modern Genetics and Genomics: The PUGGS Questionnaire.

    Science.gov (United States)

    Carver, Rebecca Bruu; Castéra, Jérémy; Gericke, Niklas; Evangelista, Neima Alice Menezes; El-Hani, Charbel N

    2017-01-01

    In this paper we present the development and validation a comprehensive questionnaire to assess college students' knowledge about modern genetics and genomics, their belief in genetic determinism, and their attitudes towards applications of modern genetics and genomic-based technologies. Written in everyday language with minimal jargon, the Public Understanding and Attitudes towards Genetics and Genomics (PUGGS) questionnaire is intended for use in research on science education and public understanding of science, as a means to investigate relationships between knowledge, determinism and attitudes about modern genetics, which are to date little understood. We developed a set of core ideas and initial items from reviewing the scientific literature on genetics and previous studies on public and student knowledge and attitudes about genetics. Seventeen international experts from different fields (e.g., genetics, education, philosophy of science) reviewed the initial items and their feedback was used to revise the questionnaire. We validated the questionnaire in two pilot tests with samples of university freshmen students. The final questionnaire contains 45 items, including both multiple choice and Likert scale response formats. Cronbach alpha showed good reliability for each section of the questionnaire. In conclusion, the PUGGS questionnaire is a reliable tool for investigating public understanding and attitudes towards modern genetics and genomic-based technologies.

  3. Young Adults’ Belief in Genetic Determinism, and Knowledge and Attitudes towards Modern Genetics and Genomics: The PUGGS Questionnaire

    Science.gov (United States)

    Carver, Rebecca Bruu; Castéra, Jérémy; Gericke, Niklas; Evangelista, Neima Alice Menezes

    2017-01-01

    In this paper we present the development and validation a comprehensive questionnaire to assess college students’ knowledge about modern genetics and genomics, their belief in genetic determinism, and their attitudes towards applications of modern genetics and genomic-based technologies. Written in everyday language with minimal jargon, the Public Understanding and Attitudes towards Genetics and Genomics (PUGGS) questionnaire is intended for use in research on science education and public understanding of science, as a means to investigate relationships between knowledge, determinism and attitudes about modern genetics, which are to date little understood. We developed a set of core ideas and initial items from reviewing the scientific literature on genetics and previous studies on public and student knowledge and attitudes about genetics. Seventeen international experts from different fields (e.g., genetics, education, philosophy of science) reviewed the initial items and their feedback was used to revise the questionnaire. We validated the questionnaire in two pilot tests with samples of university freshmen students. The final questionnaire contains 45 items, including both multiple choice and Likert scale response formats. Cronbach alpha showed good reliability for each section of the questionnaire. In conclusion, the PUGGS questionnaire is a reliable tool for investigating public understanding and attitudes towards modern genetics and genomic-based technologies. PMID:28114357

  4. A genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.

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    Anouk Georges

    Full Text Available A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree.

  5. A genome scan conducted in a multigenerational pedigree with convergent strabismus supports a complex genetic determinism.

    Science.gov (United States)

    Georges, Anouk; Cambisano, Nadine; Ahariz, Naïma; Karim, Latifa; Georges, Michel

    2013-01-01

    A genome-wide linkage scan was conducted in a Northern-European multigenerational pedigree with nine of 40 related members affected with concomitant strabismus. Twenty-seven members of the pedigree including all affected individuals were genotyped using a SNP array interrogating > 300,000 common SNPs. We conducted parametric and non-parametric linkage analyses assuming segregation of an autosomal dominant mutation, yet allowing for incomplete penetrance and phenocopies. We detected two chromosome regions with near-suggestive evidence for linkage, respectively on chromosomes 8 and 18. The chromosome 8 linkage implied a penetrance of 0.80 and a rate of phenocopy of 0.11, while the chromosome 18 linkage implied a penetrance of 0.64 and a rate of phenocopy of 0. Our analysis excludes a simple genetic determinism of strabismus in this pedigree.

  6. Genetic diversity of Streptococcus suis isolates as determined by comparative genome hybridization

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    Thi Hoa

    2011-07-01

    Full Text Available Abstract Background Streptococcus suis is a zoonotic pathogen that causes infections in young piglets. S. suis is a heterogeneous species. Thirty-three different capsular serotypes have been described, that differ in virulence between as well as within serotypes. Results In this study, the correlation between gene content, serotype, phenotype and virulence among 55 S. suis strains was studied using Comparative Genome Hybridization (CGH. Clustering of CGH data divided S. suis isolates into two clusters, A and B. Cluster A isolates could be discriminated from cluster B isolates based on the protein expression of extracellular factor (EF. Cluster A contained serotype 1 and 2 isolates that were correlated with virulence. Cluster B mainly contained serotype 7 and 9 isolates. Genetic similarity was observed between serotype 7 and serotype 2 isolates that do not express muramidase released protein (MRP and EF (MRP-EF-, suggesting these isolates originated from a common founder. Profiles of 25 putative virulence-associated genes of S. suis were determined among the 55 isolates. Presence of all 25 genes was shown for cluster A isolates, whereas cluster B isolates lacked one or more putative virulence genes. Divergence of S. suis isolates was further studied based on the presence of 39 regions of difference. Conservation of genes was evaluated by the definition of a core genome that contained 78% of all ORFs in P1/7. Conclusions In conclusion, we show that CGH is a valuable method to study distribution of genes or gene clusters among isolates in detail, yielding information on genetic similarity, and virulence traits of S. suis isolates.

  7. Genetics and Genomics

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    Good progress is being made on genetics and genomics of sugar beet, however it is in process and the tools are now being generated and some results are being analyzed. The GABI BeetSeq project released a first draft of the sugar beet genome of KWS2320, a dihaploid (see http://bvseq.molgen.mpg.de/Gen...

  8. Genome-wide identification of genetic determinants for the cytotoxicity of perifosine

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    Zhang Wei

    2008-09-01

    Full Text Available Abstract Perifosine belongs to the class of alkylphospholipid analogues, which act primarily at the cell membrane, thereby targeting signal transduction pathways. In phase I/II clinical trials, perifosine has induced tumour regression and caused disease stabilisation in a variety of tumour types. The genetic determinants responsible for its cytotoxicity have not been comprehensively studied, however. We performed a genome-wide analysis to identify genes whose expression levels or genotypic variation were correlated with the cytotoxicity of perifosine, using public databases on the US National Cancer Institute (NCI-60 human cancer cell lines. For demonstrating drug specificity, the NCI Standard Agent Database (including 171 drugs acting through a variety of mechanisms was used as a control. We identified agents with similar cytotoxicity profiles to that of perifosine in compounds used in the NCI drug screen. Furthermore, Gene Ontology and pathway analyses were carried out on genes more likely to be perifosine specific. The results suggested that genes correlated with perifosine cytotoxicity are connected by certain known pathways that lead to the mitogen-activated protein kinase signalling pathway and apoptosis. Biological processes such as 'response to stress', 'inflammatory response' and 'ubiquitin cycle' were enriched among these genes. Three single nucleotide polymorphisms (SNPs located in CACNA2DI and EXOC4 were found to be correlated with perifosine cytotoxicity. Our results provided a manageable list of genes whose expression levels or genotypic variation were strongly correlated with the cytotoxcity of perifosine. These genes could be targets for further studies using candidate-gene approaches. The results also provided insights into the pharmacodynamics of perifosine.

  9. Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis

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    Simeone, Ines; Anjum, Samreen; Mokrab, Younes; Bertucci, François; Finetti, Pascal; Curigliano, Giuseppe; Cerulo, Luigi; Tomei, Sara; Delogu, Lucia Gemma; Maccalli, Cristina; Miller, Lance D.; Ceccarelli, Michele

    2017-01-01

    ABSTRACT Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection. The T helper 1 (Th-1) phenotype (ICR4), which also displays upregulation of immune-regulatory transcripts such as PDL1, PD1, FOXP3, IDO1, and CTLA4, was associated with prolonged patients' survival. We validated these findings in an independent meta-cohort of 1,954 breast cancer gene expression data. Chromosome segment 4q21, which includes genes encoding for the Th-1 chemokines CXCL9-11, was significantly amplified only in the immune favorable phenotype (ICR4). The mutation and neoantigen load progressively decreased from ICR4 to ICR1 but could not fully explain immune phenotypic differences. Mutations of TP53 were enriched in the immune favorable phenotype (ICR4). Conversely, the presence of MAP3K1 and MAP2K4 mutations were tightly associated with an immune-unfavorable phenotype (ICR1). Using both the TCGA and the validation dataset, the degree of MAPK deregulation segregates breast tumors according to their immune disposition. These findings suggest that mutation-driven perturbations of MAPK pathways are linked to the negative regulation of intratumoral immune response in breast cancer. Modulations of MAPK pathways could be experimentally tested to enhance breast cancer immune sensitivity. PMID:28344865

  10. Transcription factor binding sites are genetic determinants of retroviral integration in the human genome.

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    Barbara Felice

    Full Text Available Gamma-retroviruses and lentiviruses integrate non-randomly in mammalian genomes, with specific preferences for active chromatin, promoters and regulatory regions. Gene transfer vectors derived from gamma-retroviruses target at high frequency genes involved in the control of growth, development and differentiation of the target cell, and may induce insertional tumors or pre-neoplastic clonal expansions in patients treated by gene therapy. The gene expression program of the target cell is apparently instrumental in directing gamma-retroviral integration, although the molecular basis of this phenomenon is poorly understood. We report a bioinformatic analysis of the distribution of transcription factor binding sites (TFBSs flanking >4,000 integrated proviruses in human hematopoietic and non-hematopoietic cells. We show that gamma-retroviral, but not lentiviral vectors, integrate in genomic regions enriched in cell-type specific subsets of TFBSs, independently from their relative position with respect to genes and transcription start sites. Analysis of sequences flanking the integration sites of Moloney leukemia virus (MLV- and human immunodeficiency virus (HIV-derived vectors carrying mutations in their long terminal repeats (LTRs, and of HIV vectors packaged with an MLV integrase, indicates that the MLV integrase and LTR enhancer are the viral determinants of the selection of TFBS-rich regions in the genome. This study identifies TFBSs as differential genomic determinants of retroviral target site selection in the human genome, and suggests that transcription factors binding the LTR enhancer may synergize with the integrase in tethering retroviral pre-integration complexes to transcriptionally active regulatory regions. Our data indicate that gamma-retroviruses and lentiviruses have evolved dramatically different strategies to interact with the host cell chromatin, and predict a higher risk in using gamma-retroviral vs. lentiviral vectors for human

  11. Genetic determinants of cardiovascular events among women with migraine: a genome-wide association study.

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    Markus Schürks

    Full Text Available BACKGROUND: Migraine is associated with an increased risk for cardiovascular disease (CVD. Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear. METHODS: We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women's Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR and 95% confidence intervals (CI and considered a genome-wide p-value <5×10(-8 as significant. RESULTS: Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10(-6. Among migraineurs with aura rs7698623 in MEPE (OR = 6.37; 95% CI 3.15-12.90; p = 2.7×10(-7 and rs4975709 in IRX4 (OR = 5.06; 95% CI 2.66-9.62; p = 7.7×10(-7 appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR = 3.05; 95% CI 1.98-4.69; p = 4.3×10(-7, and the intergenic rs1406961 with CVD death (OR = 12.33; 95% CI 4.62-32.87; p = 5.2×10(-7. Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR = 4.67; 95% CI 2.53-8.62; p = 8.0×10(-7. CONCLUSION: Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs

  12. Genetical Genomics for Evolutionary Studies

    NARCIS (Netherlands)

    Prins, J.C.P.; Smant, G.; Jansen, R.C.

    2012-01-01

    enetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome

  13. Streptococcus pneumoniae R6 interspecies transformation: genetic analysis of penicillin resistance determinants and genome-wide recombination events.

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    Sauerbier, Julia; Maurer, Patrick; Rieger, Martin; Hakenbeck, Regine

    2012-11-01

    Interspecies gene transfer has been implicated as the major driving force for the evolution of penicillin resistance in Streptococcus pneumoniae. Genomic alterations of S. pneumoniae R6 introduced during four successive transformations with DNA of the high-level penicillin-resistant Streptococcus mitis B6 with beta-lactam selection have now been determined and the contribution of genes to high resistance levels was analysed genetically. Essential for high level resistance to penicillins of the transformant CCCB was the combination of murM(B) (6) and the 3' region of pbp2b(B) (6) . Sequences of both genes were detected in clinical isolates of S. pneumoniae, confirming the participation of S. mitis in the global gene pool of beta-lactam resistance determinants. The S. mitis PBP1b gene which contains an authentic stop codon within the transpeptidase domain is now shown to contribute only marginal to resistance, but it is possible that the presence of its transglycosylase domain is important in the context of cognate PBPs. The genome sequence of CCCB revealed 36 recombination events, including deletion and acquisition of genes and repeat elements. A total of 78 genes were affected representing 67 kb or 3.3% of the genome, documenting extensive alterations scattered throughout the genome.

  14. Virulence determinants, drug resistance and mobile genetic elements of Laribacter hongkongensis: a genome-wide analysis

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    Lau Susanna KP

    2011-04-01

    Full Text Available Abstract Background Laribacter hongkongensis is associated with community-acquired gastroenteritis and traveler's diarrhea. In this study, we performed an in-depth annotation of the genes in its genome related to the various steps in the infective process, drug resistance and mobile genetic elements. Results For acid and bile resistance, L. hongkongensis possessed a urease gene cassette, two arc gene clusters and bile salt efflux systems. For intestinal colonization, it possessed a putative adhesin of the autotransporter family homologous to those of diffusely adherent Escherichia coli (E. coli and enterotoxigenic E. coli. To evade from host defense, it possessed superoxide dismutase and catalases. For lipopolysaccharide biosynthesis, it possessed the same set of genes that encode enzymes for synthesizing lipid A, two Kdo units and heptose units as E. coli, but different genes for its symmetrical acylation pattern, and nine genes for polysaccharide side chains biosynthesis. It contained a number of CDSs that encode putative cell surface acting (RTX toxin and hemolysins and intracellular cytotoxins (patatin-like proteins and enzymes for invasion (outer membrane phospholipase A. It contained a broad variety of antibiotic resistance-related genes, including genes related to β-lactam (n = 10 and multidrug efflux (n = 54. It also contained eight prophages, 17 other phage-related CDSs and 26 CDSs for transposases. Conclusions The L. hongkongensis genome possessed genes for acid and bile resistance, intestinal mucosa colonization, evasion of host defense and cytotoxicity and invasion. A broad variety of antibiotic resistance or multidrug resistance genes, a high number of prophages, other phage-related CDSs and CDSs for transposases, were also identified.

  15. A highly efficient strategy to determine genotypes of genetically-engineered mice using genomic DNA purified from hair roots.

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    Otaño-Rivera, Víctor; Boakye, Amma; Grobe, Nadja; Almutairi, Mohammed M; Kursan, Shams; Mattis, Lesan K; Castrop, Hayo; Gurley, Susan B; Elased, Khalid M; Boivin, Gregory P; Di Fulvio, Mauricio

    2017-04-01

    Genotyping of genetically-engineered mice is necessary for the effective design of breeding strategies and identification of mutant mice. This process relies on the identification of DNA markers introduced into genomic sequences of mice, a task usually performed using the polymerase chain reaction (PCR). Clearly, the limiting step in genotyping is isolating pure genomic DNA. Isolation of mouse DNA for genotyping typically involves painful procedures such as tail snip, digit removal, or ear punch. Although the harvesting of hair has previously been proposed as a source of genomic DNA, there has been a perceived complication and reluctance to use this non-painful technique because of low DNA yields and fear of contamination. In this study we developed a simple, economic, and efficient strategy using Chelex® resins to purify genomic DNA from hair roots of mice which are suitable for genotyping. Upon comparison with standard DNA purification methods using a commercially available kit, we demonstrate that Chelex® efficiently and consistently purifies high-quality DNA from hair roots, minimizing pain, shortening time and reducing costs associated with the determination of accurate genotypes. Therefore, the use of hair roots combined with Chelex® is a reliable and more humane alternative for DNA genotyping.

  16. Comparing genetic variants detected in the 1000 genomes project with SNPs determined by the International HapMap Consortium

    Indian Academy of Sciences (India)

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

    2015-12-01

    Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide a means for assessing concerns regarding SNP array-based GWAS findings as well as for realistically bounding expectations for next generation sequencing (NGS)-based GWAS. We calculated and compared base composition, transitions to transversions ratio, minor allele frequency and heterozygous rate for SNPs from HapMap and 1KGP for the 622 common individuals. We analysed the genotype discordance between HapMap and 1KGP to assess consistency in the SNPs from the two references. In 1KGP, 90.58% of 36,817,799 SNPs detected were not measured in HapMap. More SNPs with minor allele frequencies less than 0.01 were found in 1KGP than HapMap. The two references have low discordance (generally smaller than 0.02) in genotypes of common SNPs, with most discordance from heterozygous SNPs. Our study demonstrated that SNP array-based GWAS findings were reliable and useful, although only a small portion of genetic variances were explained. NGS can detect not only common but also rare variants, supporting the expectation that NGS-based GWAS will be able to incorporate a much larger portion of genetic variance than SNP arrays-based GWAS.

  17. Comparing genetic variants detected in the 1000 genomes project with SNPs determined by the International HapMap Consortium.

    Science.gov (United States)

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

    2015-12-01

    Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide a means for assessing concerns regarding SNP array-based GWAS findings as well as for realistically bounding expectations for next generation sequencing (NGS)-based GWAS. We calculated and compared base composition, transitions to transversions ratio, minor allele frequency and heterozygous rate for SNPs from HapMap and 1KGP for the 622 common individuals. We analysed the genotype discordance between HapMap and 1KGP to assess consistency in the SNPs from the two references. In 1KGP, 90.58% of 36,817,799 SNPs detected were not measured in HapMap. More SNPs with minor allele frequencies less than 0.01 were found in 1KGP than HapMap. The two references have low disc ordance (generally smaller than 0.02) in genotypes of common SNPs, with most discordance from heterozygous SNPs. Our study demonstrated that SNP array-based GWAS findings were reliable and useful, although only a small portion of genetic variances were explained. NGS can detect not only common but also rare variants, supporting the expectation that NGS-based GWAS will be able to incorporate a much larger portion of genetic variance than SNP arrays-based GWAS.

  18. Genetic modification and genetic determinism.

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    Resnik, David B; Vorhaus, Daniel B

    2006-06-26

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  19. Genetic modification and genetic determinism

    OpenAIRE

    Vorhaus Daniel B; Resnik David B

    2006-01-01

    Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound....

  20. Genome-wide mutagenesis of Xanthomonas axonopodis pv. citri reveals novel genetic determinants and regulation mechanisms of biofilm formation.

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    Jinyun Li

    Full Text Available Xanthomonas axonopodis pv. citri (Xac causes citrus canker disease, a major threat to citrus production worldwide. Accumulating evidence suggests that the formation of biofilms on citrus leaves plays an important role in the epiphytic survival of this pathogen prior to the development of canker disease. However, the process of Xac biofilm formation is poorly understood. Here, we report a genome-scale study of Xac biofilm formation in which we identified 92 genes, including 33 novel genes involved in biofilm formation and 7 previously characterized genes, colR, fhaB, fliC, galU, gumD, wxacO, and rbfC, known to be important for Xac biofilm formation. In addition, 52 other genes with defined or putative functions in biofilm formation were identified, even though they had not previously reported been to be associated with biofilm formation. The 92 genes were isolated from 292 biofilm-defective mutants following a screen of a transposon insertion library containing 22,000 Xac strain 306 mutants. Further analyses indicated that 16 of the novel genes are involved in the production of extracellular polysaccharide (EPS and/or lipopolysaccharide (LPS, 7 genes are involved in signaling and regulatory pathways, and 5 genes have unknown roles in biofilm formation. Furthermore, two novel genes, XAC0482, encoding a haloacid dehalogenase-like phosphatase, and XAC0494 (designated as rbfS, encoding a two-component sensor protein, were confirmed to be biofilm-related genes through complementation assays. Our data demonstrate that the formation of mature biofilm requires EPS, LPS, both flagellum-dependent and flagellum-independent cell motility, secreted proteins and extracellular DNA. Additionally, multiple signaling pathways are involved in Xac biofilm formation. This work is the first report on a genome-wide scale of the genetic processes of biofilm formation in plant pathogenic bacteria. The report provides significant new information about the genetic

  1. Genome-wide association study to identify the genetic determinants of otitis media susceptibility in childhood.

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    Marie S Rye

    Full Text Available BACKGROUND: Otitis media (OM is a common childhood disease characterised by middle ear inflammation and effusion. Susceptibility to recurrent acute OM (rAOM; ≥ 3 episodes of AOM in 6 months and chronic OM with effusion (COME; MEE ≥ 3 months is 40-70% heritable. Few underlying genes have been identified to date, and no genome-wide association study (GWAS of OM has been reported. METHODS AND FINDINGS: Data for 2,524,817 single nucleotide polymorphisms (SNPs; 535,544 quality-controlled SNPs genotyped by Illumina 660W-Quad; 1,989,273 by imputation were analysed for association with OM in 416 cases and 1,075 controls from the Western Australian Pregnancy Cohort (Raine Study. Logistic regression analyses under an additive model undertaken in GenABEL/ProbABEL adjusting for population substructure using principal components identified SNPs at CAPN14 (rs6755194: OR = 1.90; 95%CI 1.47-2.45; P(adj-PCA = 8.3 × 10(-7 on chromosome 2p23.1 as the top hit, with independent effects (rs1862981: OR = 1.60; 95%CI 1.29-1.99; P(adj-PCA = 2.2 × 10(-5 observed at the adjacent GALNT14 gene. In a gene-based analysis in VEGAS, BPIFA3 (P(Gene = 2 × 10(-5 and BPIFA1 (P(Gene = 1.07 × 10(-4 in the BPIFA gene cluster on chromosome 20q11.21 were the top hits. In all, 32 genomic regions show evidence of association (P(adj-PCA<10(-5 in this GWAS, with pathway analysis showing a connection between top candidates and the TGFβ pathway. However, top and tag-SNP analysis for seven selected candidate genes in this pathway did not replicate in 645 families (793 affected individuals from the Western Australian Family Study of Otitis Media (WAFSOM. Lack of replication may be explained by sample size, difference in OM disease severity between primary and replication cohorts or due to type I error in the primary GWAS. CONCLUSIONS: This first discovery GWAS for an OM phenotype has identified CAPN14 and GALNT14 on chromosome 2p23.1 and the BPIFA gene cluster on chromosome 20q11.21 as

  2. Genetic modification and genetic determinism

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    Vorhaus Daniel B

    2006-06-01

    Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  3. Genetic and pharmacogenetic determinants of cardiovascular disease

    NARCIS (Netherlands)

    Verschuren, Jeffrey Johan Willem

    2013-01-01

    This thesis, titled ‘Genetic and pharmacogenetic determinants of cardiovascular disease’ is divided in three sections. In section one the genetic determinants of coronary restenosis are explored. In the first genome-wide association study on this condition, in the GENetic DEterminants of Restenosis

  4. Genomics of sex determination.

    Science.gov (United States)

    Zhang, Jisen; Boualem, Adnane; Bendahmane, Abdelhafid; Ming, Ray

    2014-04-01

    Sex determination is a major switch in the evolutionary history of angiosperm, resulting 11% monoecious and dioecious species. The genomic sequences of papaya sex chromosomes unveiled the molecular basis of recombination suppression in the sex determination region, and candidate genes for sex determination. Identification and analyses of sex determination genes in cucurbits and maize demonstrated conservation of sex determination mechanism in one lineage and divergence between the two systems. Epigenetic control and hormonal influence of sex determination were elucidated in both plants and animals. Intensive investigation of potential sex determination genes in model species will improve our understanding of sex determination gene network. Such network will in turn accelerate the identification of sex determination genes in dioecious species with sex chromosomes, which are burdensome due to no recombination in sex determining regions. The sex determination genes in dioecious species are crucial for understanding the origin of dioecy and sex chromosomes, particularly in their early stage of evolution.

  5. Genetics, genomics and fertility

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    In order to enhance the sustainability of dairy businesses, new management tools are needed to increase the fertility of dairy cattle. Genomic selection has been successfully used by AI studs to screen potential sires and significantly decrease the generation interval of bulls. Buoyed by the success...

  6. Introduction to genetics and genomics in asthma: genetics of asthma.

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    Mathias, Rasika Ann

    2014-01-01

    While asthma is a heterogeneous disease, a strong genetic basis has been firmly established. Rather than being a single disease entity, asthma consists of related, overlapping syndromes [Barnes (Proc Am Thor Soc 8:143-148, 2011)] including three general domains: variable airway obstruction, airway hyper-responsiveness, and airway inflammation with a considerable proportion, but not all, of asthma being IgE-mediated further adding to its heterogeneity. This chapter reviews the approaches to the elucidation of genetics of asthma from the early evidence of familial clustering to the current state of knowledge with genome-wide approaches. The conclusion is that research efforts have led to a tremendous repository of genetic determinants of asthma, most of which fall into the above phenotypic domains of the syndrome. We now look to future integrative approaches of genetics, genomics (Chap. 10), and epigenetics (Chap. 11) to better understand the causal mechanism through which, these genetic loci act in manifesting asthma.

  7. GENETICS AND GENOMICS OF PLANT GENETIC RESOURCES

    Directory of Open Access Journals (Sweden)

    Börner A.

    2012-08-01

    Full Text Available Plant genetic resources play a major role for global food security. The most significant and widespread mean of conserving plant genetic resources is ex situ conservation. Most conserved accessions are kept in specialized facilities known as genebanks maintained by public or private institutions. World-wide 7.4 million accessions are stored in about 1,500 ex situ genebanks.In addition, series of genetic stocks including chromosome substitution lines, alloplasmic lines, single chromosome recombinant lines, introgression lines, etc. have been created. Analysing these genetic stocks many qualitative and quantitative inherited traits were associated to certain chromosomes, chromosome arms or introgressed segments. Today, genetic stocks are supplemented by a huge number of genotyped mapping populations. Beside progenies of bi-parental crosses (doubled haploid lines, recombinant inbred lines, etc. panels for association mapping were created recently.In our presentation we give examples for the successful utilisation of genebank accessions and genetic stocks for genetic and genomic studies. Using both segregation and association mapping approaches, data on mapping of loci/marker trait associations for a range of different traits are presented.

  8. Genetic determinants of plasma triglycerides

    Science.gov (United States)

    Johansen, Christopher T.; Kathiresan, Sekar; Hegele, Robert A.

    2011-01-01

    Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ∼10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. PMID:21041806

  9. Genetics, genomes and cloning the biotechnology revolution

    CERN Document Server

    CERN. Geneva

    1999-01-01

    As this century draws to a close, spectacular advances in the fields of genomics and genetics are opening up dramatic new horizons for medicine. For much of the 20th century, genetic research has focused on rare diseases caused by mutations in a particular gene. However, more recently it has been realised that common genetic variations (polymorphisms), interacting with the environment, can influence an individual's susceptibility to diseases widely represented in our populations (e.g. mental illness and asthma), redefining the term "genetic disease". Officially starting in 1990, the Human Genome Project was a $3-billion, 15-year program to find the estimated 80,000 human genes and determine the sequence of the 3 billion DNA building blocks that underlie all of human biology and its diversity. The resulting boom in genetic information and technologies, not only from humans, but from many other organisms, means that we now have new tools to understand and treat normal and disease states. This information is bei...

  10. Salmon and steelhead genetics and genomics - Epigenetic and genomic variation in salmon and steelhead

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Conduct analyses of epigenetic and genomic variation in Chinook salmon and steelhead to determine influence on phenotypic expression of life history traits. Genetic,...

  11. Genomic Relatedness Strengthens Genetic Connectedness Across Management Units.

    Science.gov (United States)

    Yu, Haipeng; Spangler, Matthew L; Lewis, Ronald M; Morota, Gota

    2017-08-31

    Genetic connectedness refers to a measure of genetic relatedness across management units (e.g., herds and flocks). With the presence of high genetic connectedness in management units, best linear unbiased prediction (BLUP) is known to provide reliable comparisons between genetic values. Genetic connectedness has been studied for pedigree-based BLUP; however, relatively little attention has been paid to using genomic information to measure connectedness. In this study, we assessed genome-based connectedness across management units by applying prediction error variance of difference (PEVD), coefficient of determination (CD), and prediction error correlation (r) to a combination of computer simulation and real data (mice and cattle). We found that genomic information (G) increased the estimate of connectedness among individuals from different management units compared to that based on pedigree (A). A disconnected design benefited the most. In both datasets, PEVD and CD statistics inferred increased connectedness across units when using G- rather than A-based relatedness suggesting stronger connectedness. With r once using allele frequencies equal to one-half or scaling G to values between 0 and 2, which is intrinsic to A, connectedness also increased with genomic information. However, PEVD occasionally increased, and r decreased when obtained using the alternative form of G, instead suggesting less connectedness. Such inconsistencies were not found with CD. We contend that genomic relatedness strengthens measures of genetic connectedness across units and has the potential to aid genomic evaluation of livestock species. Copyright © 2017, G3: Genes, Genomes, Genetics.

  12. Genetic diversity for Russian wheat aphid resistance as determined by genome-wide association mapping and inheritance in progeny

    Science.gov (United States)

    Russian wheat aphid (RWA) is an increasing problem on barley throughout the world. Genetic resistance has been identified and used to create barley germplasm and cultivars adapted to the US. Several mapping studies have been conducted to identify loci associated with resistance, but questions remain...

  13. Genomics and the future of conservation genetics.

    Science.gov (United States)

    Allendorf, Fred W; Hohenlohe, Paul A; Luikart, Gordon

    2010-10-01

    We will soon have complete genome sequences from thousands of species, as well as from many individuals within species. This coming explosion of information will transform our understanding of the amount, distribution and functional significance of genetic variation in natural populations. Now is a crucial time to explore the potential implications of this information revolution for conservation genetics and to recognize limitations in applying genomic tools to conservation issues. We identify and discuss those problems for which genomics will be most valuable for curbing the accelerating worldwide loss of biodiversity. We also provide guidance on which genomics tools and approaches will be most appropriate to use for different aspects of conservation.

  14. Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE study.

    Directory of Open Access Journals (Sweden)

    Logan Dumitrescu

    2011-06-01

    Full Text Available For the past five years, genome-wide association studies (GWAS have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C, and triglyceride (TG levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE study was established in 2008 to characterize GWAS-identified variants in diverse population-based studies. We genotyped 49 GWAS-identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG levels in self-identified European American (~20,000, African American (~9,000, American Indian (~6,000, Mexican American/Hispanic (~2,500, Japanese/East Asian (~690, and Pacific Islander/Native Hawaiian (~175 adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92% SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05 and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG in European Americans generalized to African Americans (48%, 61%, and 57%, American Indians (45%, 64%, and 77%, and Mexican Americans/Hispanics (57%, 56%, and 86%. Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits.

  15. Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

    NARCIS (Netherlands)

    Q. Li (Qing); R. Wojciechowski (Robert); C.L. Simpson (Claire); P.G. Hysi (Pirro); V.J.M. Verhoeven (Virginie); M.K. Ikram (Kamran); R. Höhn (René); V. Vitart (Veronique); A.W. Hewit (Alex); K. Oexle (Konrad); K.M. Makela (Kari Matti); S. MacGregor (Stuart); M. Pirastu (Mario); Q. Fan (Qiao); C-Y. Cheng (Ching-Yu); B. St Pourcain (Beate); G. Mcmahon (George); J.P. Kemp (John); K. Northstone (Kate); J.S. Rahi (Jugnoo); P. Cumberland (Phillippa); N.G. Martin (Nicholas); P.G. Sanfilippo (Paul G.); Y. Lu (Yi); Y. Wang (Ying); C. Hayward (Caroline); O. Polasek (Ozren); H. Campbell (Harry); G. Bencic (Goran); A. Wright (Alan); J. Wedenoja (Juho); T. Zeller (Tanja); A. Schillert (Arne); A. Mirshahi (Alireza); K.J. Lackner (Karl); S.P. Yip (Shea Ping); M.K.H. Yap (Maurice K. H.); J.S. Ried (Janina); C. Gieger (Christian); D. Murgia (Daniela); J.F. Wilson (James F); B.W. Fleck (Brian W.); S. Yazar (Seyhan); J.R. Vingerling (Hans); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); N. Amin (Najaf); L.C. Karssen (Lennart); B.A. Oostra (Ben); X. Zhou (Xin); Y.Y. Teo (Yik Ying); E.S. Tai (Shyong); E.N. Vithana (Eranga); V.A. Barathi (Veluchamy); Y. Zheng (Yingfeng); R. Siantar (Rosalynn); K. Neelam (Kumari); Y. Shin (Youchan); J. Lam (Janice); E. Yonova-Doing (Ekaterina); C. Venturini (Cristina); S.M. Hosseini (S Mohsen); H.-S. Wong (Hoi-Suen); T. Lehtimäki (Terho); M. Kähönen (Mika); O. Raitakari (Olli); N. Timpson (Nicholas); D.M. Evans (David M.); C.C. Khor; T. Aung (Tin); T.L. Young (Terri); P. Mitchell (Paul); B.E.K. Klein (Barbara); C.M. van Duijn (Cock); T. Meitinger (Thomas); J.B. Jonas (Jost B.); P.N. Baird (Paul); D.A. Mackey (David); T.Y. Wong (Tien); S-M. Saw (Seang-Mei); O. Pärssinen (Olavi); D.E. Stambolian (Dwight); C.J. Hammond (Christopher); C.C.W. Klaver (Caroline); C. Williams (Cathy); A.D. Paterson (Andrew); J.E. Bailey-Wilson (Joan E.); J. Guggenheim (Jean)

    2015-01-01

    textabstractTo identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295

  16. Primary care and genetics and genomics.

    Science.gov (United States)

    Scott, Joan; Trotter, Tracy

    2013-12-01

    With the recent expansion of genetic science, its evolving translation to clinical medicine, and the growing number of available resources for genomics in primary care, the primary care provider must increasingly integrate genetics and genomics into daily practice. Because primary care medicine combines the treatment of acute illness with disease prevention and anticipatory guidance, the primary care provider is in an ideal position to evaluate and treat patients for genetic disease. The notion that genetic knowledge is only rarely needed will have to be replaced with a comprehensive approach that integrates "genetic thinking" into every patient encounter. Genomic competencies will need to be added to the primary care provider's repertoire; such competencies include prevention, assessment, evaluation, and diagnosis of genetic conditions; the ordering and interpreting of genetic tests; communication with families; appropriate referrals; and the management or comanagement of care. The process of deciding when to order genetic tests, what tests to order, and how to interpret the results is complex, and the tests and their results have specific risks and benefits, especially for pediatric patients. The longitudinal nature of primary pediatric care provides the opportunity to obtain and continually update the family history, which is the most powerful initial genetic "test." The ongoing provider-family relationship, coupled with the astounding number of advances in genetic and genomic testing, also necessitates a constant re-evaluation of past diagnosis or nondiagnosis.

  17. Genetic Determinants of Lipid Traits in Diverse Populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study

    Science.gov (United States)

    Dumitrescu, Logan; Carty, Cara L.; Taylor, Kira; Schumacher, Fredrick R.; Hindorff, Lucia A.; Ambite, José L.; Anderson, Garnet; Best, Lyle G.; Brown-Gentry, Kristin; Bůžková, Petra; Carlson, Christopher S.; Cochran, Barbara; Cole, Shelley A.; Devereux, Richard B.; Duggan, Dave; Eaton, Charles B.; Fornage, Myriam; Franceschini, Nora; Haessler, Jeff; Howard, Barbara V.; Johnson, Karen C.; Laston, Sandra; Kolonel, Laurence N.; Lee, Elisa T.; MacCluer, Jean W.; Manolio, Teri A.; Pendergrass, Sarah A.; Quibrera, Miguel; Shohet, Ralph V.; Wilkens, Lynne R.; Haiman, Christopher A.; Le Marchand, Loïc; Buyske, Steven; Kooperberg, Charles; North, Kari E.; Crawford, Dana C.

    2011-01-01

    For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS–identified variants in diverse population-based studies. We genotyped 49 GWAS–identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (∼20,000), African American (∼9,000), American Indian (∼6,000), Mexican American/Hispanic (∼2,500), Japanese/East Asian (∼690), and Pacific Islander/Native Hawaiian (∼175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits. PMID:21738485

  18. Genome and Phenotype Microarray Analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7: Genetic Determinants and Metabolic Abilities with Environmental Relevance

    Science.gov (United States)

    D’Ursi, Pasqualina; Milanesi, Luciano; Di Canito, Alessandra; Zampolli, Jessica; Collina, Elena; Decorosi, Francesca; Viti, Carlo; Fedi, Stefano; Presentato, Alessandro; Zannoni, Davide; Di Gennaro, Patrizia

    2015-01-01

    In this paper comparative genome and phenotype microarray analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7 were performed. Rhodococcus sp. BCP1 was selected for its ability to grow on short-chain n-alkanes and R. opacus R7 was isolated for its ability to grow on naphthalene and on o-xylene. Results of genome comparison, including BCP1, R7, along with other Rhodococcus reference strains, showed that at least 30% of the genome of each strain presented unique sequences and only 50% of the predicted proteome was shared. To associate genomic features with metabolic capabilities of BCP1 and R7 strains, hundreds of different growth conditions were tested through Phenotype Microarray, by using Biolog plates and plates manually prepared with additional xenobiotic compounds. Around one-third of the surveyed carbon sources was utilized by both strains although R7 generally showed higher metabolic activity values compared to BCP1. Moreover, R7 showed broader range of nitrogen and sulphur sources. Phenotype Microarray data were combined with genomic analysis to genetically support the metabolic features of the two strains. The genome analysis allowed to identify some gene clusters involved in the metabolism of the main tested xenobiotic compounds. Results show that R7 contains multiple genes for the degradation of a large set of aromatic and PAHs compounds, while a lower variability in terms of genes predicted to be involved in aromatic degradation was found in BCP1. This genetic feature can be related to the strong genetic pressure exerted by the two different environment from which the two strains were isolated. According to this, in the BCP1 genome the smo gene cluster involved in the short-chain n-alkanes degradation, is included in one of the unique regions and it is not conserved in the Rhodococcus strains compared in this work. Data obtained underline the great potential of these two Rhodococcus spp. strains for biodegradation and environmental decontamination

  19. Genome and Phenotype Microarray Analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7: Genetic Determinants and Metabolic Abilities with Environmental Relevance.

    Science.gov (United States)

    Orro, Alessandro; Cappelletti, Martina; D'Ursi, Pasqualina; Milanesi, Luciano; Di Canito, Alessandra; Zampolli, Jessica; Collina, Elena; Decorosi, Francesca; Viti, Carlo; Fedi, Stefano; Presentato, Alessandro; Zannoni, Davide; Di Gennaro, Patrizia

    2015-01-01

    In this paper comparative genome and phenotype microarray analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7 were performed. Rhodococcus sp. BCP1 was selected for its ability to grow on short-chain n-alkanes and R. opacus R7 was isolated for its ability to grow on naphthalene and on o-xylene. Results of genome comparison, including BCP1, R7, along with other Rhodococcus reference strains, showed that at least 30% of the genome of each strain presented unique sequences and only 50% of the predicted proteome was shared. To associate genomic features with metabolic capabilities of BCP1 and R7 strains, hundreds of different growth conditions were tested through Phenotype Microarray, by using Biolog plates and plates manually prepared with additional xenobiotic compounds. Around one-third of the surveyed carbon sources was utilized by both strains although R7 generally showed higher metabolic activity values compared to BCP1. Moreover, R7 showed broader range of nitrogen and sulphur sources. Phenotype Microarray data were combined with genomic analysis to genetically support the metabolic features of the two strains. The genome analysis allowed to identify some gene clusters involved in the metabolism of the main tested xenobiotic compounds. Results show that R7 contains multiple genes for the degradation of a large set of aromatic and PAHs compounds, while a lower variability in terms of genes predicted to be involved in aromatic degradation was found in BCP1. This genetic feature can be related to the strong genetic pressure exerted by the two different environment from which the two strains were isolated. According to this, in the BCP1 genome the smo gene cluster involved in the short-chain n-alkanes degradation, is included in one of the unique regions and it is not conserved in the Rhodococcus strains compared in this work. Data obtained underline the great potential of these two Rhodococcus spp. strains for biodegradation and environmental decontamination

  20. Clinical implications of genomics for cancer risk genetics.

    Science.gov (United States)

    Thomas, David M; James, Paul A; Ballinger, Mandy L

    2015-06-01

    The study of human genetics has provided substantial insight into cancer biology. With an increase in sequencing capacity and a reduction in sequencing costs, genomics will probably transform clinical cancer genetics. A heritable basis for many cancers is accepted, but so far less than half the genetic drivers have been identified. Genomics will increasingly be applied to populations irrespective of family history, which will change the framework of phenotype-directed genetic testing. Panel testing and whole genome sequencing will identify novel, polygenic, and de-novo determinants of cancer risk, often with lower penetrance, which will challenge present binary clinical classification systems and management algorithms. In the future, genotype-stratified public screening and prevention programmes could form part of tailored population risk management. The integration of research with clinical practice will result in so-called discovery cohorts that will help identify clinically significant genetic variation.

  1. Machine learning in genetics and genomics

    Science.gov (United States)

    Libbrecht, Maxwell W.; Noble, William Stafford

    2016-01-01

    The field of machine learning promises to enable computers to assist humans in making sense of large, complex data sets. In this review, we outline some of the main applications of machine learning to genetic and genomic data. In the process, we identify some recurrent challenges associated with this type of analysis and provide general guidelines to assist in the practical application of machine learning to real genetic and genomic data. PMID:25948244

  2. Genetic determinants of common epilepsies

    DEFF Research Database (Denmark)

    2014-01-01

    and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). METHODS: We combined genome-wide association data from 12 cohorts of individuals with epilepsy...... and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different...... genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance...

  3. Whole genome approaches to quantitative genetics.

    Science.gov (United States)

    Visscher, Peter M

    2009-06-01

    Apart from parent-offspring pairs and clones, relative pairs vary in the proportion of the genome that they share identical by descent. In the past, quantitative geneticists have used the expected value of sharing genes by descent to estimate genetic parameters and predict breeding values. With the possibility to genotype individuals for many markers across the genome it is now possible to empirically estimate the actual relationship between relatives. We review some of the theory underlying the variation in genetic identity, show applications to estimating genetic variance for height in humans and discuss other applications.

  4. Genomics, proteomics, and genetics of leptospira.

    Science.gov (United States)

    Picardeau, Mathieu

    2015-01-01

    Recent advances in molecular genetics, such as the ability to construct defined mutants, have allowed the study of virulence factors and more generally the biology in Leptospira. However, pathogenic leptospires remain much less easily transformable than the saprophyte L. biflexa and further development and improvement of genetic tools are required. Here, we review tools that have been used to genetically manipulate Leptospira. We also describe the major advances achieved in both genomics and postgenomics technologies, including transcriptomics and proteomics.

  5. Genetic and genomic approaches to understanding macrophage identity and function.

    Science.gov (United States)

    Glass, Christopher K

    2015-04-01

    A major goal of our laboratory is to understand the molecular mechanisms that underlie the development and functions of diverse macrophage phenotypes in health and disease. Recent studies using genetic and genomic approaches suggest a relatively simple model of collaborative and hierarchical interactions between lineage-determining and signal-dependent transcription factors that enable selection and activation of transcriptional enhancers that specify macrophage identity and function. In addition, we have found that it is possible to use natural genetic variation as a powerful tool for advancing our understanding of how the macrophage deciphers the information encoded by the genome to attain specific phenotypes in a context-dependent manner. Here, I will describe our recent efforts to extend genetic and genomic approaches to investigate the roles of distinct tissue environments in determining the phenotypes of different resident populations of macrophages.

  6. Genome and Phenotype Microarray Analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7: Genetic Determinants and Metabolic Abilities with Environmental Relevance.

    Directory of Open Access Journals (Sweden)

    Alessandro Orro

    Full Text Available In this paper comparative genome and phenotype microarray analyses of Rhodococcus sp. BCP1 and Rhodococcus opacus R7 were performed. Rhodococcus sp. BCP1 was selected for its ability to grow on short-chain n-alkanes and R. opacus R7 was isolated for its ability to grow on naphthalene and on o-xylene. Results of genome comparison, including BCP1, R7, along with other Rhodococcus reference strains, showed that at least 30% of the genome of each strain presented unique sequences and only 50% of the predicted proteome was shared. To associate genomic features with metabolic capabilities of BCP1 and R7 strains, hundreds of different growth conditions were tested through Phenotype Microarray, by using Biolog plates and plates manually prepared with additional xenobiotic compounds. Around one-third of the surveyed carbon sources was utilized by both strains although R7 generally showed higher metabolic activity values compared to BCP1. Moreover, R7 showed broader range of nitrogen and sulphur sources. Phenotype Microarray data were combined with genomic analysis to genetically support the metabolic features of the two strains. The genome analysis allowed to identify some gene clusters involved in the metabolism of the main tested xenobiotic compounds. Results show that R7 contains multiple genes for the degradation of a large set of aromatic and PAHs compounds, while a lower variability in terms of genes predicted to be involved in aromatic degradation was found in BCP1. This genetic feature can be related to the strong genetic pressure exerted by the two different environment from which the two strains were isolated. According to this, in the BCP1 genome the smo gene cluster involved in the short-chain n-alkanes degradation, is included in one of the unique regions and it is not conserved in the Rhodococcus strains compared in this work. Data obtained underline the great potential of these two Rhodococcus spp. strains for biodegradation and

  7. Genetic Determinants of Depression

    NARCIS (Netherlands)

    S. López León (Sandra)

    2008-01-01

    textabstractThe aim of the studies in this genetic epidemiological thesis was to investigate candidate genes that play a role in the etiology of depression and to obtain new insights about biological pathways that may be involved in this disorder. The introduction of the thesis presents a review of

  8. Genetics and genomics: impact on perinatal nursing.

    Science.gov (United States)

    Lewis, Judith A

    2011-01-01

    In 1953, Watson and Crick first described the structure of the DNA molecule, an event that led to a new understanding of the nature of heredity. Just 50 years later, a conference was held in Bethesda, Maryland to announce the completion of the sequencing of the human genome. The era of genomic healthcare has begun, and it has profound implications for nursing education, nursing practice, and nursing research. This article will highlight some important areas in perinatal and neonatal nursing that have been affected by genetics and genomics, as well as some emerging areas of research that will be relevant to perinatal and neonatal nursing.

  9. From Genetics to Genomics of Epilepsy

    Directory of Open Access Journals (Sweden)

    Silvio Garofalo

    2012-01-01

    Full Text Available The introduction of DNA microarrays and DNA sequencing technologies in medical genetics and diagnostics has been a challenge that has significantly transformed medical practice and patient management. Because of the great advancements in molecular genetics and the development of simple laboratory technology to identify the mutations in the causative genes, also the diagnostic approach to epilepsy has significantly changed. However, the clinical use of molecular cytogenetics and high-throughput DNA sequencing technologies, which are able to test an entire genome for genetic variants that are associated with the disease, is preparing a further revolution in the near future. Molecular Karyotype and Next-Generation Sequencing have the potential to identify causative genes or loci also in sporadic or non-familial epilepsy cases and may well represent the transition from a genetic to a genomic approach to epilepsy.

  10. Identifying genetics and genomics nursing competencies common among published recommendations.

    Science.gov (United States)

    Greco, Karen E; Salveson, Catherine

    2009-10-01

    The purpose of this article is to identify published recommendations for genetics and genomics competencies or curriculum for nurses in the United States and to summarize genetic and genomic nursing competencies based on common themes among these documents. A review of the literature between January 1998 and June 2008 was conducted. Efforts were also made to access the gray literature. Five consensus documents describing recommendations for genetics and genomics competencies for nurses meeting inclusion criteria were analyzed. Twelve genetics and genomics competencies were created based on common themes among the recommendations. These competencies include: demonstrate an understanding of basic genetic and genomic concepts, provide and explain genetic and genomic information, refer to appropriate genetics professionals and services, and identify the limits of one's own genetics and genomics expertise. The competencies represent fundamental genetics and genomics competencies for nurses on the basis of common themes among several consensus recommendations identified in the literature.

  11. genomic and transcriptomic approaches towards the genetic ...

    African Journals Online (AJOL)

    USER

    to the complex nature of these stresses, and the genotype x environment interaction (GxE). .... collection (Azam-Ali et al., 2001); (vi) biological .... Integrative platform to study gene function and gene evolution in legumes ..... a powerful dissection of the genetic control of ... complemented by a new approach called genomic.

  12. Advances in Genetical Genomics of Plants

    NARCIS (Netherlands)

    Joosen, R.V.L.; Ligterink, W.; Hilhorst, H.W.M.; Keurentjes, J.J.B.

    2009-01-01

    Natural variation provides a valuable resource to study the genetic regulation of quantitative traits. In quantitative trait locus (QTL) analyses this variation, captured in segregating mapping populations, is used to identify the genomic regions affecting these traits. The identification of the cau

  13. GENETIC DETERMINATIONS OF MENTALITY

    Directory of Open Access Journals (Sweden)

    L. V. Osadcha

    2015-12-01

    Full Text Available Purpose. The article is devoted to clarifying the role of physicality and psycho-physical characteristics of a person as a preconditions of the mentality forming. It is conducted a retrospective analysis of discourse on the mentality, the history of the concept, its temporal characteristics and collective conditioning. The concept of mentality has been widely studied in various fields of socio-humanities such as: history, psychology, and even marginal context of scientific discourses, including the esoteric. This study attempted to analyse the mentality phenomenon through the prism of the concept of experience. Methodology. The concept of experience was acquired by essential justification through the representatives of the phenomenological approach - the late Edmund Husserl, Maurice Merleau-Ponty, Bernhard Valdenfels. On the other hand the concept of mentality as a form of collective unconscious experience was entered to the scientific vocabulary by the representatives of the French historical science - M. Bloch, L. Febvre, J. Le Goff and others. At the intersection of these two methods, historical and phenomenological, the genetic method has been established – as a history of coverage and experience of internalization. Thanks to the application of genetic method the transition of phenomenon into the concept was examined. Novelty. The problem of change dynamics of mental phenomenon, in particular psycho-physical nature of a person, which has been only mentioned in F. Braudel works but has not received the adequate theoretical coverage, is analysed. To explain the practices of physicality and causality of this factor the action component of the cultural the overview of developments of such authors as V. Rozin (2005, M. Epstein (2005, N. Brunov (2003, A. Soares, M. Farhangmehr, A. Shoham (2007, D. Vaskul, F. Vannini Hospital (2012 was committed. Conclusions. The transition to paradoxical behaviour that is oriented on sign, and not on signalling

  14. Genetics and genomics of pulmonary arterial hypertension.

    Science.gov (United States)

    Soubrier, Florent; Chung, Wendy K; Machado, Rajiv; Grünig, Ekkehard; Aldred, Micheala; Geraci, Mark; Loyd, James E; Elliott, C Gregory; Trembath, Richard C; Newman, John H; Humbert, Marc

    2013-12-24

    Major discoveries have been obtained within the last decade in the field of hereditary predisposition to pulmonary arterial hypertension (PAH). Among them, the identification of bone morphogenetic protein receptor type 2 (BMPR2) as the major predisposing gene and activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) as the major gene when PAH is associated with hereditary hemorrhagic telangiectasia. The mutation detection rate for the known genes is approximately 75% in familial PAH, but the mutation shortfall remains unexplained even after careful molecular investigation of these genes. To identify additional genetic variants predisposing to PAH, investigators harnessed the power of next-generation sequencing to successfully identify additional genes that will be described in this report. Furthermore, common genetic predisposing factors for PAH can be identified by genome-wide association studies and are detailed in this paper. The careful study of families and routine genetic diagnosis facilitated natural history studies based on large registries of PAH patients to be set up in different countries. These longitudinal or cross-sectional studies permitted the clinical characterization of PAH in mutation carriers to be accurately described. The availability of molecular genetic diagnosis has opened up a new field for patient care, including genetic counseling for a severe disease, taking into account that the major predisposing gene has a highly variable penetrance between families. Molecular information can be drawn from the genomic study of affected tissues in PAH, in particular, pulmonary vascular tissues and cells, to gain insight into the mechanisms leading to the development of the disease. High-throughput genomic techniques, on the basis of next-generation sequencing, now allow the accurate quantification and analysis of ribonucleic acid, species, including micro-ribonucleic acids, and allow for a genome-wide investigation of epigenetic or

  15. Advances in faba bean genetics and genomics

    Directory of Open Access Journals (Sweden)

    Donal Martin O'Sullivan

    2016-08-01

    Full Text Available Vicia faba L, is a globally important grain legume whose main centres of diversity are the Fertile Crescent and Mediterranean basin. Because of its small number (six of exceptionally large and easily observed chromosomes it became a model species for plant cytogenetics the 70s and 80s. It is somewhat ironic therefore, that the emergence of more genomically tractable model plant species such as Arabidopsis and Medicago coincided with a marked decline in genome research on the formerly favoured plant cytogenetic model. Thus, as ever higher density molecular marker coverage and dense genetic and even complete genome sequence maps of key crop and model species emerged through the 1990s and early 2000s, genetic and genome knowledge of Vicia faba lagged far behind other grain legumes such as soybean, common bean and pea.However, cheap sequencing technologies have stimulated the production of deep transcriptome coverage from several tissue types and numerous distinct cultivars in recent years. This has permitted the reconstruction of the faba bean meta-transcriptome and has fuelled development of extensive sets of Simple Sequence Repeat and Single Nucleotide Polymorphism (SNP markers. Genetics of faba bean stretches back to the 1930s, but it was not until 1993 that DNA markers were used to construct genetic maps. A series of Random Amplified Polymorphic DNA-based genetic studies mainly targeted at quantitative loci underlying resistance to a series of biotic and abiotic stresses were conducted during the 1990’s and early 2000s. More recently, SNP-based genetic maps have permitted chromosome intervals of interest to be aligned to collinear segments of sequenced legume genomes such as the model legume Medicago truncatula, which in turn opens up the possibility for hypotheses on gene content, order and function to be translated from model to crop. Some examples of where knowledge of gene content and function have already been productively exploited are

  16. Determination of Genetic Structure and Signatures of Selection in Three Strains of Tanzania Shorthorn Zebu, Boran and Friesian Cattle by Genome-Wide SNP Analyses

    Science.gov (United States)

    Msalya, George; Kim, Eui-Soo; Laisser, Emmanuel L. K.; Kipanyula, Maulilio J.; Karimuribo, Esron D.; Kusiluka, Lughano J. M.; Chenyambuga, Sebastian W.; Rothschild, Max F.

    2017-01-01

    Background More than 90 percent of cattle in Tanzania belong to the indigenous Tanzania Short Horn Zebu (TSZ) population which has been classified into 12 strains based on historical evidence, morphological characteristics, and geographic distribution. However, specific genetic information of each TSZ population has been lacking and has caused difficulties in designing programs such as selection, crossbreeding, breed improvement or conservation. This study was designed to evaluate the genetic structure, assess genetic relationships, and to identify signatures of selection among cattle of Tanzania with the main goal of understanding genetic relationship, variation and uniqueness among them. Methodology/Principal findings The Illumina Bos indicus SNP 80K BeadChip was used to genotype genome wide SNPs in 168 DNA samples obtained from three strains of TSZ cattle namely Maasai, Tarime and Sukuma as well as two comparative breeds; Boran and Friesian. Population structure and signatures of selection were examined using principal component analysis (PCA), admixture analysis, pairwise distances (FST), integrated haplotype score (iHS), identical by state (IBS) and runs of homozygosity (ROH). There was a low level of inbreeding (F~0.01) in the TSZ population compared to the Boran and Friesian breeds. The analyses of FST, IBS and admixture identified no considerable differentiation between TSZ trains. Importantly, common ancestry in Boran and TSZ were revealed based on admixture and IBD, implying gene flow between two populations. In addition, Friesian ancestry was found in Boran. A few common significant iHS were detected, which may reflect influence of recent selection in each breed or strain. Conclusions Population admixture and selection signatures could be applied to develop conservation plan of TSZ cattle as well as future breeding programs in East African cattle. PMID:28129396

  17. Genome-wide association study of swine farrowing traits. Part I: genetic and genomic parameter estimates.

    Science.gov (United States)

    Schneider, J F; Rempel, L A; Rohrer, G A

    2012-10-01

    The primary objective of this study was to determine genetic and genomic parameters among swine (Sus scrofa) farrowing traits. Genetic parameters were obtained using MTDFREML. Genomic parameters were obtained using GENSEL. Genetic and residual variances obtained from MTDFREML were used as priors for the Bayes C analysis of GENSEL. Farrowing traits included total number born (TNB), number born alive (NBA), number born dead (NBD), number stillborn (NSB), number of mummies (MUM), litter birth weight (LBW), and average piglet birth weight (ABW). Statistically significant heritabilities included TNB (0.09, P = 0.048), NBA (0.09, P = 0.041), LBW (0.20, P = 0.002), and ABW (0.26, P ABW (0.63, P ABW (0.31). Limited information is available in the literature about genomic parameters. Only the GP estimate for NSB is significantly lower than what has been published. The GP estimate for ABW is greater than the estimate for heritability found in this study. Other traits with significant heritability had GP estimates half the value of heritability. This research indicates that significant genetic markers will be found for TNB, NBA, LBW, and ABW that will have either immediate use in industry or provide a roadmap to further research with fine mapping or sequencing of areas of significance. Furthermore, these results indicate that genomic selection implemented at an early age would have similar annual progress as traditional selection, and could be incorporated along with traditional selection procedures to improve genetic progress of litter traits.

  18. Genetics and Genomics of Pathogens: Fighting Infections with Genome-Sequencing Technology.

    Science.gov (United States)

    Plavskin, Alexandra

    2016-01-01

    Discussions of clinical genetics and genomics often focus on screening for disease-causing genes in humans and the promise of targeted therapies. Another important area of research is analysis of pathogen genomes. Genetics and genomics-based approaches, such as population genomics and phylogenetics, provide insight into mechanisms of resistance, sources of infections, and pathogen transmission routes.

  19. Determination of epigenetic inheritance, genetic inheritance, and estimation of genome DNA methylation in a full-sib family of Cupressus sempervirens L.

    Science.gov (United States)

    Avramidou, Evangelia V; Doulis, Andreas G; Aravanopoulos, Filippos A

    2015-05-15

    Genetic inheritance and epigenetic inheritance are significant determinants of plant evolution, adaptation and plasticity. We studied inheritance of restriction site polymorphisms by the f-AFLP method and epigenetic DNA cytosine methylation inheritance by the f-MSAP technique. The study involved parents and 190 progeny of a Cupressus sempervirens L. full-sib family. Results from AFLP genetic data revealed that 71.8% of the fragments studied are under Mendelian genetic control, whereas faithful Mendelian inheritance for the MSAP fragments was low (4.29%). Further, MSAP fragment analysis showed that total methylation presented a mean of 28.2%, which was higher than the midparent value, while maternal inheritance was higher (5.65%) than paternal (3.01%). Interestingly de novo methylation in the progeny was high (19.65%) compared to parental methylation. Genetic and epigenetic distances for parents and offspring were not correlated (R(2)=0.0005). Furthermore, we studied correlation of total relative methylation and CG methylation with growth (height, diameter). We found CG/CNG methylation (N: A, C, T) to be positively correlated with height and diameter, while total relative methylation and CG methylation were positively correlated with height. Results are discussed in light of further research needed and of their potential application in breeding.

  20. Comparative and functional genomics reveals genetic diversity and determinants of host specificity among reference strains and a large collection of Chinese isolates of the phytopathogen Xanthomonas campestris pv. campestris

    OpenAIRE

    He, Yong-Qiang; Zhang, Liang; Jiang, Bo-Le; Zhang, Zheng-Chun; Xu, Rong-Qi; Tang, Dong-Jie; Qin, Jing; Jiang, Wei; Zhang, Xia; LIAO, JIE; Cao, Jin-Ru; Zhang, Sui-Sheng; Wei, Mei-Liang; Liang, Xiao-Xia; Lu, Guang-Tao

    2007-01-01

    Background Xanthomonas campestris pathovar campestris (Xcc) is the causal agent of black rot disease of crucifers worldwide. The molecular genetic diversity and host specificity of Xcc are poorly understood. Results We constructed a microarray based on the complete genome sequence of Xcc strain 8004 and investigated the genetic diversity and host specificity of Xcc by array-based comparative genome hybridization analyses of 18 virulent strains. The results demonstrate that a genetic core comp...

  1. Analysis of genome-wide association studies of Alzheimer disease and of Parkinson disease to determine if these 2 diseases share a common genetic risk.

    Science.gov (United States)

    Moskvina, Valentina; Harold, Denise; Russo, GianCarlo; Vedernikov, Alexey; Sharma, Manu; Saad, Mohamed; Holmans, Peter; Bras, Jose M; Bettella, Francesco; Keller, Margaux F; Nicolaou, Nayia; Simón-Sánchez, Javier; Gibbs, J Raphael; Schulte, Claudia; Durr, Alexandra; Guerreiro, Rita; Hernandez, Dena; Brice, Alexis; Stefánsson, Hreinn; Majamaa, Kari; Gasser, Thomas; Heutink, Peter; Wood, Nick; Martinez, Maria; Singleton, Andrew B; Nalls, Michael A; Hardy, John; Owen, Michael J; O'Donovan, Michael C; Williams, Julie; Morris, Huw R; Williams, Nigel M

    2013-10-01

    Despite Alzheimer disease (AD) and Parkinson disease (PD) being clinically distinct entities, there is a possibility of a pathological overlap, with some genome-wide association (GWA) studies suggesting that the 2 diseases represent a biological continuum. The application of GWA studies to idiopathic forms of AD and PD have identified a number of loci that contain genetic variants that increase the risk of these disorders. To assess the genetic overlap between PD and AD by testing for the presence of potentially pleiotropic loci in 2 recent GWA studies of PD and AD. Combined GWA analysis. Data sets from the United Kingdom, Germany, France, and the United States. Thousands of patients with AD or PD and their controls. Meta-analysis of GWA studies of AD and PD. To identify evidence for potentially pleiotropic alleles that increased the risk for both PD and AD, we performed a combined PD-AD meta-analysis and compared the results with those obtained in the primary GWA studies.We also tested for a net effect of potentially polygenic alleles that were shared by both disorders by performing a polygenic score analysis. Finally, we also performed a gene-based association analysis that was aimed at detecting genes that harbor multiple disease-causing single-nucleotide polymorphisms, some of which confer a risk of PD and some a risk of AD. Detailed interrogation of the single-nucleotide polymorphism, polygenic, and gene-based analyses resulted in no significant evidence that supported the presence of loci that increase the risk of both PD and AD. Our findings therefore imply that loci that increase the risk of both PD and AD are not widespread and that the pathological overlap could instead be “downstream” of the primary susceptibility genes that increase the risk of each disease.

  2. Online genetic databases informing human genome epidemiology

    Directory of Open Access Journals (Sweden)

    Higgins Julian PT

    2007-07-01

    Full Text Available Abstract Background With the advent of high throughput genotyping technology and the information available via projects such as the human genome sequencing and the HapMap project, more and more data relevant to the study of genetics and disease risk will be produced. Systematic reviews and meta-analyses of human genome epidemiology studies rely on the ability to identify relevant studies and to obtain suitable data from these studies. A first port of call for most such reviews is a search of MEDLINE. We examined whether this could be usefully supplemented by identifying databases on the World Wide Web that contain genetic epidemiological information. Methods We conducted a systematic search for online databases containing genetic epidemiological information on gene prevalence or gene-disease association. In those containing information on genetic association studies, we examined what additional information could be obtained to supplement a MEDLINE literature search. Results We identified 111 databases containing prevalence data, 67 databases specific to a single gene and only 13 that contained information on gene-disease associations. Most of the latter 13 databases were linked to MEDLINE, although five contained information that may not be available from other sources. Conclusion There is no single resource of structured data from genetic association studies covering multiple diseases, and in relation to the number of studies being conducted there is very little information specific to gene-disease association studies currently available on the World Wide Web. Until comprehensive data repositories are created and utilized regularly, new data will remain largely inaccessible to many systematic review authors and meta-analysts.

  3. Genetics and genomics of ankylosing spondylitis.

    Science.gov (United States)

    Thomas, Gethin P; Brown, Matthew A

    2010-01-01

    Ankylosing spondylitis (AS) is a common, highly heritable arthropathy, the pathogenesis of which is poorly understood. The mechanism by which the main gene for the disease, HLA-B27, leads to AS is unknown. Genetic and genomic studies have demonstrated involvement of the interleukin-23 (IL-23) signaling pathway in AS, a finding which has stimulated much new research into the disease and has led to therapeutic trials. Several other genes and genetic regions, including further major histocompatibility complex (MHC) and non-MHC loci, have been shown to be involved in the disease, but it is not clear yet how they actually induce the condition. These findings have shown that there is a strong genetic overlap between AS and Crohn's disease in particular, although there are also major differences in the genes involved in the two conditions, presumably explaining their different presentations. Genomic and proteomic studies are in an early phase but have potential both as diagnostic/prognostic tools and as a further hypothesis-free tool to investigate AS pathogenesis. Given the slow progress in studying the mechanism of association of HLA-B27 with AS, these may prove to be more fruitful approaches to investigating the pathogenesis of the disease.

  4. Applied Genetics and Genomics in Alfalfa Breeding

    Directory of Open Access Journals (Sweden)

    E. Charles Brummer

    2012-03-01

    Full Text Available Alfalfa (Medicago sativa L., a perennial and outcrossing species, is a widely planted forage legume for hay, pasture and silage throughout the world. Currently, alfalfa breeding relies on recurrent phenotypic selection, but alternatives incorporating molecular marker assisted breeding could enhance genetic gain per unit time and per unit cost, and accelerate alfalfa improvement. Many major quantitative trait loci (QTL related to agronomic traits have been identified by family-based QTL mapping, but in relatively large genomic regions. Candidate genes elucidated from model species have helped to identify some potential causal loci in alfalfa mapping and breeding population for specific traits. Recently, high throughput sequencing technologies, coupled with advanced bioinformatics tools, have been used to identify large numbers of single nucleotide polymorphisms (SNP in alfalfa, which are being developed into markers. These markers will facilitate fine mapping of quantitative traits and genome wide association mapping of agronomic traits and further advanced breeding strategies for alfalfa, such as marker-assisted selection and genomic selection. Based on ideas from the literature, we suggest several ways to improve selection in alfalfa including (1 diversity selection and paternity testing, (2 introgression of QTL and (3 genomic selection.

  5. Where Next for Genetics and Genomics?

    Science.gov (United States)

    Tyler-Smith, Chris; Yang, Huanming; Landweber, Laura F; Dunham, Ian; Knoppers, Bartha M; Donnelly, Peter; Mardis, Elaine R; Snyder, Michael; McVean, Gil

    2015-07-01

    The last few decades have utterly transformed genetics and genomics, but what might the next ten years bring? PLOS Biology asked eight leaders spanning a range of related areas to give us their predictions. Without exception, the predictions are for more data on a massive scale and of more diverse types. All are optimistic and predict enormous positive impact on scientific understanding, while a recurring theme is the benefit of such data for the transformation and personalization of medicine. Several also point out that the biggest changes will very likely be those that we don't foresee, even now.

  6. Predicting human genetic interactions from cancer genome evolution.

    Directory of Open Access Journals (Sweden)

    Xiaowen Lu

    Full Text Available Synthetic Lethal (SL genetic interactions play a key role in various types of biological research, ranging from understanding genotype-phenotype relationships to identifying drug-targets against cancer. Despite recent advances in empirical measuring SL interactions in human cells, the human genetic interaction map is far from complete. Here, we present a novel approach to predict this map by exploiting patterns in cancer genome evolution. First, we show that empirically determined SL interactions are reflected in various gene presence, absence, and duplication patterns in hundreds of cancer genomes. The most evident pattern that we discovered is that when one member of an SL interaction gene pair is lost, the other gene tends not to be lost, i.e. the absence of co-loss. This observation is in line with expectation, because the loss of an SL interacting pair will be lethal to the cancer cell. SL interactions are also reflected in gene expression profiles, such as an under representation of cases where the genes in an SL pair are both under expressed, and an over representation of cases where one gene of an SL pair is under expressed, while the other one is over expressed. We integrated the various previously unknown cancer genome patterns and the gene expression patterns into a computational model to identify SL pairs. This simple, genome-wide model achieves a high prediction power (AUC = 0.75 for known genetic interactions. It allows us to present for the first time a comprehensive genome-wide list of SL interactions with a high estimated prediction precision, covering up to 591,000 gene pairs. This unique list can potentially be used in various application areas ranging from biotechnology to medical genetics.

  7. Osteoarthritis year 2012 in review: genetics and genomics.

    Science.gov (United States)

    van Meurs, J B J; Uitterlinden, A G

    2012-12-01

    The field of genetics and genomics is a highly technological driven field that is advancing fast. The purpose of this year in review of genetics and genomics was to highlight the publications that apply these new technologies tools to improve understanding of the pathophysiology of osteoarthritis (OA). In addition, most recent developments in genetics and genomics research and their relevance to OA are discussed in this review.

  8. Citrus breeding, genetics and genomics in Japan

    Science.gov (United States)

    Omura, Mitsuo; Shimada, Takehiko

    2016-01-01

    Citrus is one of the most cultivated fruits in the world, and satsuma mandarin (Citrus unshiu Marc.) is a major cultivated citrus in Japan. Many excellent cultivars derived from satsuma mandarin have been released through the improvement of mandarins using a conventional breeding method. The citrus breeding program is a lengthy process owing to the long juvenility, and it is predicted that marker-assisted selection (MAS) will overcome the obstacle and improve the efficiency of conventional breeding methods. To promote citrus molecular breeding in Japan, a genetic mapping was initiated in 1987, and the experimental tools and resources necessary for citrus functional genomics have been developed in relation to the physiological analysis of satsuma mandarin. In this paper, we review the progress of citrus breeding and genome researches in Japan and report the studies on genetic mapping, expression sequence tag cataloguing, and molecular characterization of breeding characteristics, mainly in terms of the metabolism of bio-functional substances as well as factors relating to, for example, fruit quality, disease resistance, polyembryony, and flowering. PMID:27069387

  9. Citrus breeding, genetics and genomics in Japan.

    Science.gov (United States)

    Omura, Mitsuo; Shimada, Takehiko

    2016-01-01

    Citrus is one of the most cultivated fruits in the world, and satsuma mandarin (Citrus unshiu Marc.) is a major cultivated citrus in Japan. Many excellent cultivars derived from satsuma mandarin have been released through the improvement of mandarins using a conventional breeding method. The citrus breeding program is a lengthy process owing to the long juvenility, and it is predicted that marker-assisted selection (MAS) will overcome the obstacle and improve the efficiency of conventional breeding methods. To promote citrus molecular breeding in Japan, a genetic mapping was initiated in 1987, and the experimental tools and resources necessary for citrus functional genomics have been developed in relation to the physiological analysis of satsuma mandarin. In this paper, we review the progress of citrus breeding and genome researches in Japan and report the studies on genetic mapping, expression sequence tag cataloguing, and molecular characterization of breeding characteristics, mainly in terms of the metabolism of bio-functional substances as well as factors relating to, for example, fruit quality, disease resistance, polyembryony, and flowering.

  10. Genetic data for groundfish - Genetics and genomics of northeastern Pacific groundfish

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Conduct genetic analyses of groundfish in the northeastern Pacific, with a focus on population genetics and genomics of rockfishes and sablefish. Genetic data for...

  11. High-definition genome profiling for genetic marker discovery.

    Science.gov (United States)

    Zhu, Tong; Salmeron, John

    2007-05-01

    Genetic mapping is a key step towards isolating genes and genetic markers associated with phenotypic traits by elucidating their genetic positions. The success of this approach depends on precision in pinpointing genetic positions and the effectiveness of the discovery process. Recent advances in microarray technology and the increasing availability of genomic information have provided an opportunity to use microarrays to scan effectively for genetic variations at the whole-genome scale, enabling the production of high-definition gene-based genetic maps, in combination with functional analyses and identification of trait-associated genetic marker candidates with high precision. In this review, we discuss the concept, process, tools and applications of microarray-based high-definition genetic analysis. This post-genomics approach should help to identify causative genetic variation by uniting genetic and functional information.

  12. Introduction to the Special Issue: Public Health Genetics and Genomics.

    Science.gov (United States)

    McWalter, Kirsty; Gaviglio, Amy

    2015-06-01

    This special issue of the Journal of Genetic Counseling is dedicated to public health genetics and genomics. The seventeen papers featured in this issue span such topics as genetic counselors in public health roles, newborn screening, population screening, ethics, and health beliefs and behaviors. In this introduction to the special issue, we review some history of public health genetics and genomics, present the Centers for Disease Control and Prevention's "10 Essential Public Health Services" with associated genetics specific recommendations and priorities, and briefly overview how each article ties into the world of public health genetics and genomics. We hope this issue encourages genetic counselors to visualize their ever expanding and important roles in public health genetics and genomics, as well as their contributions to improving population health.

  13. Genomic determinants of cancer immunotherapy.

    Science.gov (United States)

    Miao, Diana; Van Allen, Eliezer M

    2016-08-01

    Cancer immunotherapies - including therapeutic vaccines, adoptive cell transfer, oncolytic viruses, and immune checkpoint blockade - yield durable responses in many cancer types, but understanding of predictors of response is incomplete. Genomic characterization of human cancers has already contributed to the success of targeted therapies; in cancer immunotherapy, identification of tumor-specific antigens through whole-exome sequencing may be key to designing individualized, highly immunogenic therapeutic vaccines. Additionally, pre-treatment tumor mutational and gene expression signatures can predict which patients are most likely to benefit from cancer immunotherapy. Continued work in harnessing genomic, transcriptomic, and immunological data from clinical cohorts of immunotherapy-treated patients will bring the promises of precision medicine to immuno-oncology.

  14. Genetics and genomics of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Michael Dean; Hong Lou

    2013-01-01

    Prostate cancer (PCa) is one of the most common malignancies in the world with over 890 000 cases and over 258 000 deaths worldwide each year.Nearly all mortalities from PCa are due to metastatic disease,typically through tumors that evolve to be hormone-refractory or castrate-resistant.Despite intensive epidemiological study,there are few known environmental risk factors,and age and family history are the major determinants.However,there is extreme heterogeneity in PCa incidence worldwide,suggesting that major determining factors have not been described.Genome-wide association studies have been performed and a considerable number of significant,but low-risk loci have been identified.In addition,several groups have analyzed PCa by determination of genomic copy number,fusion gene generation and targeted resequencing of candidate genes,as well as exome and whole genome sequencing.These initial studies have examined both primary and metastatic tumors as well as murine xenografts and identified somatic alterations in TP53 and other potential driver genes,and the disturbance of androgen response and cell cycle pathways.It is hoped that continued characterization of risk factors as well as gene mutation and misregulation in tumors will aid in understanding,diagnosing and better treating PCa.

  15. The increasing role of genetics and genomics in women's health.

    Science.gov (United States)

    Klein, Elisabeth Lisa Z

    2014-01-01

    Genetic and genomic testing are a clinical reality in health care today. Persons at risk for disease or who are simply curious about their genomes can have them analyzed. An individual's genome is a function of ancestry, family history and personal health and environmental exposures. Clinical and pharmacologic information can be obtained through genomic analysis. Genomic testing can be done by health care providers but some results can now be obtained through direct-to-consumer tests. Many ethical questions are being raised regarding genomic testing. Nurses can provide more optimal care by understanding the process of genomic testing as well as the implications of the results.

  16. [Investigation on the integrative course of genetics and genomics].

    Science.gov (United States)

    Liu, Zhi-Xiang; Xu, Gang-Biao; Zeng, Chao-Zhen; Wang, Ai-Yun; Wu, Ruo-Yan

    2011-07-01

    Genomics is an important subdiscipline of genetics, and it forms a complete research system based on novel theories and techniques. Incorporating genomics in undergraduate curriculum is a response to the need of the development of genetics. The teaching of genomics has significant advantages on developing scientific thinking, enhances bioethics accomplishment, and professional interests in undergraduate students. The integration of genomics into genetics is in accordance with the principles of subject development and education. Related textbooks for undergraduate education are currently available in China, and it is feasible to set up a genetics and genomics integrative course by modifying teaching contents of the genetics course, selecting appropriate teaching approaches, and optimal application of the computer-assisted instruction.

  17. Cancer genetics and genomics: essentials for oncology nurses.

    Science.gov (United States)

    Boucher, Jean; Habin, Karleen; Underhill, Meghan

    2014-06-01

    Cancer genetics and genomics are rapidly evolving, with new discoveries emerging in genetic mutations, variants, genomic sequencing, risk-reduction methods, and targeted therapies. To educate patients and families, state-of-the-art care requires nurses to understand terminology, scientific and technological advances, and pharmacogenomics. Clinical application of cancer genetics and genomics involves working in interdisciplinary teams to properly identify patient risk through assessing family history, facilitating genetic testing and counseling services, applying risk-reduction methods, and administering and monitoring targeted therapies.

  18. Sequence imputation of HPV16 genomes for genetic association studies.

    Directory of Open Access Journals (Sweden)

    Benjamin Smith

    Full Text Available BACKGROUND: Human Papillomavirus type 16 (HPV16 causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs determine oncogenicity. METHODS: A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica. RESULTS: HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution. CONCLUSIONS: Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable

  19. Comparative Whole-Genome Mapping To Determine Staphylococcus aureus Genome Size, Virulence Motifs, and Clonality

    Science.gov (United States)

    Pantrang, Madhulatha; Stahl, Buffy; Briska, Adam M.; Stemper, Mary E.; Wagner, Trevor K.; Zentz, Emily B.; Callister, Steven M.; Lovrich, Steven D.; Henkhaus, John K.; Dykes, Colin W.

    2012-01-01

    Despite being a clonal pathogen, Staphylococcus aureus continues to acquire virulence and antibiotic-resistant genes located on mobile genetic elements such as genomic islands, prophages, pathogenicity islands, and the staphylococcal chromosomal cassette mec (SCCmec) by horizontal gene transfer from other staphylococci. The potential virulence of a S. aureus strain is often determined by comparing its pulsed-field gel electrophoresis (PFGE) or multilocus sequence typing profiles to that of known epidemic or virulent clones and by PCR of the toxin genes. Whole-genome mapping (formerly optical mapping), which is a high-resolution ordered restriction mapping of a bacterial genome, is a relatively new genomic tool that allows comparative analysis across entire bacterial genomes to identify regions of genomic similarities and dissimilarities, including small and large insertions and deletions. We explored whether whole-genome maps (WGMs) of methicillin-resistant S. aureus (MRSA) could be used to predict the presence of methicillin resistance, SCCmec type, and Panton-Valentine leukocidin (PVL)-producing genes on an S. aureus genome. We determined the WGMs of 47 diverse clinical isolates of S. aureus, including well-characterized reference MRSA strains, and annotated the signature restriction pattern in SCCmec types, arginine catabolic mobile element (ACME), and PVL-carrying prophage, PhiSa2 or PhiSa2-like regions on the genome. WGMs of these isolates accurately characterized them as MRSA or methicillin-sensitive S. aureus based on the presence or absence of the SCCmec motif, ACME and the unique signature pattern for the prophage insertion that harbored the PVL genes. Susceptibility to methicillin resistance and the presence of mecA, SCCmec types, and PVL genes were confirmed by PCR. A WGM clustering approach was further able to discriminate isolates within the same PFGE clonal group. These results showed that WGMs could be used not only to genotype S. aureus but also to

  20. Sex Determination, Sex Ratios, and Genetic Conflict

    NARCIS (Netherlands)

    Werren, John H.; Beukeboom, Leo W.

    1998-01-01

    Genetic mechanisms of sex determination are unexpectedly diverse and change rapidly during evolution. We review the role of genetic conflict as the driving force behind this diversity and turnover. Genetic conflict occurs when different components of a genetic system are subject to selection in

  1. Sex Determination, Sex Ratios, and Genetic Conflict

    NARCIS (Netherlands)

    Werren, John H.; Beukeboom, Leo W.

    1998-01-01

    Genetic mechanisms of sex determination are unexpectedly diverse and change rapidly during evolution. We review the role of genetic conflict as the driving force behind this diversity and turnover. Genetic conflict occurs when different components of a genetic system are subject to selection in oppo

  2. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.

    Directory of Open Access Journals (Sweden)

    Eleanor Wheeler

    2017-09-01

    Full Text Available Glycated hemoglobin (HbA1c is used to diagnose type 2 diabetes (T2D and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits or glycemic (associated with other glucose-related traits. In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E or glycemic variants (GS-G were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241. Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29; whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60. In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in

  3. Genetic variation and the de novo assembly of human genomes.

    Science.gov (United States)

    Chaisson, Mark J P; Wilson, Richard K; Eichler, Evan E

    2015-11-01

    The discovery of genetic variation and the assembly of genome sequences are both inextricably linked to advances in DNA-sequencing technology. Short-read massively parallel sequencing has revolutionized our ability to discover genetic variation but is insufficient to generate high-quality genome assemblies or resolve most structural variation. Full resolution of variation is only guaranteed by complete de novo assembly of a genome. Here, we review approaches to genome assembly, the nature of gaps or missing sequences, and biases in the assembly process. We describe the challenges of generating a complete de novo genome assembly using current technologies and the impact that being able to perfectly sequence the genome would have on understanding human disease and evolution. Finally, we summarize recent technological advances that improve both contiguity and accuracy and emphasize the importance of complete de novo assembly as opposed to read mapping as the primary means to understanding the full range of human genetic variation.

  4. Genetic determinants of facial clefting

    DEFF Research Database (Denmark)

    Jugessur, Astanand; Shi, Min; Gjessing, Håkon Kristian

    2009-01-01

    BACKGROUND: Facial clefts are common birth defects with a strong genetic component. To identify fetal genetic risk factors for clefting, 1536 SNPs in 357 candidate genes were genotyped in two population-based samples from Scandinavia (Norway: 562 case-parent and 592 control-parent triads; Denmark...

  5. Whole-genome sequencing and genetic variant analysis of a Quarter Horse mare.

    Science.gov (United States)

    Doan, Ryan; Cohen, Noah D; Sawyer, Jason; Ghaffari, Noushin; Johnson, Charlie D; Dindot, Scott V

    2012-02-17

    The catalog of genetic variants in the horse genome originates from a few select animals, the majority originating from the Thoroughbred mare used for the equine genome sequencing project. The purpose of this study was to identify genetic variants, including single nucleotide polymorphisms (SNPs), insertion/deletion polymorphisms (INDELs), and copy number variants (CNVs) in the genome of an individual Quarter Horse mare sequenced by next-generation sequencing. Using massively parallel paired-end sequencing, we generated 59.6 Gb of DNA sequence from a Quarter Horse mare resulting in an average of 24.7X sequence coverage. Reads were mapped to approximately 97% of the reference Thoroughbred genome. Unmapped reads were de novo assembled resulting in 19.1 Mb of new genomic sequence in the horse. Using a stringent filtering method, we identified 3.1 million SNPs, 193 thousand INDELs, and 282 CNVs. Genetic variants were annotated to determine their impact on gene structure and function. Additionally, we genotyped this Quarter Horse for mutations of known diseases and for variants associated with particular traits. Functional clustering analysis of genetic variants revealed that most of the genetic variation in the horse's genome was enriched in sensory perception, signal transduction, and immunity and defense pathways. This is the first sequencing of a horse genome by next-generation sequencing and the first genomic sequence of an individual Quarter Horse mare. We have increased the catalog of genetic variants for use in equine genomics by the addition of novel SNPs, INDELs, and CNVs. The genetic variants described here will be a useful resource for future studies of genetic variation regulating performance traits and diseases in equids.

  6. Whole-Genome sequencing and genetic variant analysis of a quarter Horse mare

    Directory of Open Access Journals (Sweden)

    Doan Ryan

    2012-02-01

    Full Text Available Abstract Background The catalog of genetic variants in the horse genome originates from a few select animals, the majority originating from the Thoroughbred mare used for the equine genome sequencing project. The purpose of this study was to identify genetic variants, including single nucleotide polymorphisms (SNPs, insertion/deletion polymorphisms (INDELs, and copy number variants (CNVs in the genome of an individual Quarter Horse mare sequenced by next-generation sequencing. Results Using massively parallel paired-end sequencing, we generated 59.6 Gb of DNA sequence from a Quarter Horse mare resulting in an average of 24.7X sequence coverage. Reads were mapped to approximately 97% of the reference Thoroughbred genome. Unmapped reads were de novo assembled resulting in 19.1 Mb of new genomic sequence in the horse. Using a stringent filtering method, we identified 3.1 million SNPs, 193 thousand INDELs, and 282 CNVs. Genetic variants were annotated to determine their impact on gene structure and function. Additionally, we genotyped this Quarter Horse for mutations of known diseases and for variants associated with particular traits. Functional clustering analysis of genetic variants revealed that most of the genetic variation in the horse's genome was enriched in sensory perception, signal transduction, and immunity and defense pathways. Conclusions This is the first sequencing of a horse genome by next-generation sequencing and the first genomic sequence of an individual Quarter Horse mare. We have increased the catalog of genetic variants for use in equine genomics by the addition of novel SNPs, INDELs, and CNVs. The genetic variants described here will be a useful resource for future studies of genetic variation regulating performance traits and diseases in equids.

  7. Whole-genome sequencing and genetic variant analysis of a Quarter Horse mare.

    KAUST Repository

    Doan, Ryan

    2012-02-17

    BACKGROUND: The catalog of genetic variants in the horse genome originates from a few select animals, the majority originating from the Thoroughbred mare used for the equine genome sequencing project. The purpose of this study was to identify genetic variants, including single nucleotide polymorphisms (SNPs), insertion/deletion polymorphisms (INDELs), and copy number variants (CNVs) in the genome of an individual Quarter Horse mare sequenced by next-generation sequencing. RESULTS: Using massively parallel paired-end sequencing, we generated 59.6 Gb of DNA sequence from a Quarter Horse mare resulting in an average of 24.7X sequence coverage. Reads were mapped to approximately 97% of the reference Thoroughbred genome. Unmapped reads were de novo assembled resulting in 19.1 Mb of new genomic sequence in the horse. Using a stringent filtering method, we identified 3.1 million SNPs, 193 thousand INDELs, and 282 CNVs. Genetic variants were annotated to determine their impact on gene structure and function. Additionally, we genotyped this Quarter Horse for mutations of known diseases and for variants associated with particular traits. Functional clustering analysis of genetic variants revealed that most of the genetic variation in the horse\\'s genome was enriched in sensory perception, signal transduction, and immunity and defense pathways. CONCLUSIONS: This is the first sequencing of a horse genome by next-generation sequencing and the first genomic sequence of an individual Quarter Horse mare. We have increased the catalog of genetic variants for use in equine genomics by the addition of novel SNPs, INDELs, and CNVs. The genetic variants described here will be a useful resource for future studies of genetic variation regulating performance traits and diseases in equids.

  8. Value of genetic and genomic technologies: workshop summary

    National Research Council Canada - National Science Library

    Wizemann, Theresa M; Berger, Adam C

    2010-01-01

    .... The IOM's Roundtable on Translating Genomic-Based Research for Health held a workshop on March 22, 2010, to bring together diverse perspectives on the value of genetic testing, and to discuss its use...

  9. Genome-Wide Prediction of C. elegans Genetic Interactions

    OpenAIRE

    Zhong, Weiwei; Sternberg, Paul W.

    2006-01-01

    To obtain a global view of functional interactions among genes in a metazoan genome, we computationally integrated interactome data, gene expression data, phenotype data, and functional annotation data from three model organisms—Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster—and predicted genome-wide genetic interactions in C. elegans. The resulting genetic interaction network (consisting of 18,183 interactions) provides a framework for system-level understandin...

  10. Cancer genetic association studies in the genome-wide age

    OpenAIRE

    Savage, Sharon A

    2008-01-01

    Genome-wide association studies of hundreds of thousands of SNPs have led to a deluge of studies of genetic variation in cancer and other common diseases. Large case–control and cohort studies have identified novel SNPs as markers of cancer risk. Genome-wide association study SNP data have also advanced understanding of population-specific genetic variation. While studies of risk profiles, combinations of SNPs that may increase cancer risk, are not yet clinically applicable, future, large-sca...

  11. Primer on Molecular Genetics; DOE Human Genome Program

    Science.gov (United States)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  12. Resources to increase genetics and genomics capacity of oncology nurses.

    Science.gov (United States)

    Aiello, Lisa B

    2015-03-01

    Since the completion of the Human Genome Project (HGP) in 2003, the understanding of genetics and its influence on disease, particularly cancer, has increased dramatically. The initial focus after the completion of HGP was on identifying single-gene disorders, such as many hereditary cancer syndromes (e.g., BRCA1, BRCA2, HNPCC). As research continues, the major impact that genetics and genomics have across the healthcare continuum is only beginning to become clear.

  13. Primer on molecular genetics. DOE Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  14. Sinbase: an integrated database to study genomics, genetics and comparative genomics in Sesamum indicum.

    Science.gov (United States)

    Wang, Linhai; Yu, Jingyin; Li, Donghua; Zhang, Xiurong

    2015-01-01

    Sesame (Sesamum indicum L.) is an ancient and important oilseed crop grown widely in tropical and subtropical areas. It belongs to the gigantic order Lamiales, which includes many well-known or economically important species, such as olive (Olea europaea), leonurus (Leonurus japonicus) and lavender (Lavandula spica), many of which have important pharmacological properties. Despite their importance, genetic and genomic analyses on these species have been insufficient due to a lack of reference genome information. The now available S. indicum genome will provide an unprecedented opportunity for studying both S. indicum genetic traits and comparative genomics. To deliver S. indicum genomic information to the worldwide research community, we designed Sinbase, a web-based database with comprehensive sesame genomic, genetic and comparative genomic information. Sinbase includes sequences of assembled sesame pseudomolecular chromosomes, protein-coding genes (27,148), transposable elements (372,167) and non-coding RNAs (1,748). In particular, Sinbase provides unique and valuable information on colinear regions with various plant genomes, including Arabidopsis thaliana, Glycine max, Vitis vinifera and Solanum lycopersicum. Sinbase also provides a useful search function and data mining tools, including a keyword search and local BLAST service. Sinbase will be updated regularly with new features, improvements to genome annotation and new genomic sequences, and is freely accessible at http://ocri-genomics.org/Sinbase/.

  15. Contribution of genetics and genomics to seagrass biology and conservation

    NARCIS (Netherlands)

    Procaccini, Gabriele; Olsen, Jeanine L.; Reusch, Thorsten B. H.

    2007-01-01

    Genetic diversity is one of three forms of biodiversity recognized by the IUCN as deserving conservation along with species and ecosystems. Seagrasses provide all three levels in one. This review addresses the latest advances in our understanding of seagrass population genetics and genomics within t

  16. Genetics, Epigenetics, and Genomics of Systemic Sclerosis.

    Science.gov (United States)

    Salazar, Gloria; Mayes, Maureen D

    2015-08-01

    Systemic sclerosis (SSc) is a complex autoimmune disease that occurs in a genetically susceptible host. Genetic studies performed so far reveal that multiple genetic loci contribute to disease susceptibility in SSc. The purpose of this review is to discuss the current knowledge of genetics in SSc by exploring the observational evidence, the different genetic studies, and their modalities as well as the most relevant genes discovered by these. The importance of gene expression variation and the different mechanisms that govern it, including the recently discovered field of epigenetics, are also explored, with an emphasis on microRNA. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Quantification of genetic relationships among A genomes of wheats.

    Science.gov (United States)

    Brandolini, A; Vaccino, P; Boggini, G; Ozkan, H; Kilian, B; Salamini, F

    2006-04-01

    The genetic relationships of A genomes of Triticum urartu (Au) and Triticum monococcum (Am) in polyploid wheats are explored and quantified by AFLP fingerprinting. Forty-one accessions of A-genome diploid wheats, 3 of AG-genome wheats, 19 of AB-genome wheats, 15 of ABD-genome wheats, and 1 of the D-genome donor Ae. tauschii have been analysed. Based on 7 AFLP primer combinations, 423 bands were identified as potentially A genome specific. The bands were reduced to 239 by eliminating those present in autoradiograms of Ae. tauschii, bands interpreted as common to all wheat genomes. Neighbour-joining analysis separates T. urartu from T. monococcum. Triticum urartu has the closest relationship to polyploid wheats. Triticum turgidum subsp. dicoccum and T. turgidum subsp. durum lines are included in tightly linked clusters. The hexaploid spelts occupy positions in the phylogenetic tree intermediate between bread wheats and T. turgidum. The AG-genome accessions cluster in a position quite distant from both diploid and other polyploid wheats. The estimates of similarity between A genomes of diploid and polyploid wheats indicate that, compared with Am, Au has around 20% higher similarity to the genomes of polyploid wheats. Triticum timo pheevii AG genome is molecularly equidistant from those of Au and Am wheats.

  18. A genome-wide Asian genetic map and ethnic comparison: The GENDISCAN study

    Directory of Open Access Journals (Sweden)

    Sung Joohon

    2008-11-01

    Full Text Available Abstract Background Genetic maps provide specific positions of genetic markers, which are required for performing genetic studies. Linkage analyses of Asian families have been performed with Caucasian genetic maps, since appropriate genetic maps of Asians were not available. Different ethnic groups may have different recombination rates as a result of genomic variations, which would generate misspecification of the genetic map and reduce the power of linkage analyses. Results We constructed the genetic map of a Mongolian population in Asia with CRIMAP software. This new map, called the GENDISCAN map, is based on genotype data collected from 1026 individuals of 73 large Mongolian families, and includes 1790 total and 1500 observable meioses. The GENDISCAN map provides sex-averaged and sex-specific genetic positions of 1039 microsatellite markers in Kosambi centimorgans (cM with physical positions. We also determined 95% confidence intervals of genetic distances of the adjacent marker intervals. Genetic lengths of the whole genome, chromosomes and adjacent marker intervals are compared with those of Rutgers Map v.2, which was constructed based on Caucasian populations (Centre d'Etudes du Polymorphisme Humain (CEPH and Icelandic families by mapping methods identical to those of the GENDISCAN map, CRIMAP software and the Kosambi map function. Mongolians showed approximately 1.9 fewer recombinations per meiosis than Caucasians. As a result, genetic lengths of the whole genome and chromosomes of the GENDISCAN map are shorter than those of Rutgers Map v.2. Thirty-eight marker intervals differed significantly between the Mongolian and Caucasian genetic maps. Conclusion The new GENDISCAN map is applicable to the genetic study of Asian populations. Differences in the genetic distances between the GENDISCAN and Caucasian maps could facilitate elucidation of genomic variations between different ethnic groups.

  19. Genetic determinants of eating disorders

    NARCIS (Netherlands)

    Slof-Op 't Landt, Margarita Cornelia Theodora

    2011-01-01

    In this thesis, a series of studies on different aspects of the genetics of eating disorders is presented. The heritability of disordered eating behavior and attitudes in relation with body mass index (BMI) was evaluated in a large adolescent twin-family sample ascertained through the Netherlands Tw

  20. Genetic determinants of eating disorders

    NARCIS (Netherlands)

    Slof-Op 't Landt, Margarita Cornelia Theodora

    2011-01-01

    In this thesis, a series of studies on different aspects of the genetics of eating disorders is presented. The heritability of disordered eating behavior and attitudes in relation with body mass index (BMI) was evaluated in a large adolescent twin-family sample ascertained through the Netherlands

  1. Impact of genomics approaches on plant genetics and physiology.

    Science.gov (United States)

    Tabata, Satoshi

    2002-08-01

    Comprehensive analysis of genetic information in higher plants is under way for several plants of biological and agronomical importance. Among them, Arabidopsis thaliana, a member of Brassica family, and Oryza sativa(rice) have been chosen as model plants most suitable for genome analysis. Sequencing of the genome of A. thaliana was completed in December 2000, and rice genome sequencing is in progress. The accumulated genome sequences, together with the hundreds of thousands of ESTs from several tens of plant species, have drastically changed the strategy of plant genetics. By utilizing the information on the genome and gene structures, comprehensive approaches for genome-wide functional analysis of the genes, including transcriptome analysis using microarray systems and a comprehensive analysis of a large number of insertion mutant lines, have been widely adopted. As a consequence, a large quantity of information on both the structure and function of genes in these model plants has been accumulated. However, other plant species may have their own characteristics and advantages to study individual phenomena. Application of knowledge from the model plants to other plant species and vice versa through the common language, namely the genome information, should facilitate understanding of the genetic systems underlying a variety of biological phenomena. Introduction of this common language may not be very simple, especially in the case of complex pathways such as a process of cell-covering formation. Nevertheless, it should be emphasized that genomics approaches are the most promising way to understand these processes.

  2. Improving Genetic Gain with Genomic Selection in Autotetraploid Potato

    Directory of Open Access Journals (Sweden)

    Anthony T. Slater

    2016-11-01

    Full Text Available Potato ( L. breeders consider a large number of traits during cultivar development and progress in conventional breeding can be slow. There is accumulating evidence that some of these traits, such as yield, are affected by a large number of genes with small individual effects. Recently, significant efforts have been applied to the development of genomic resources to improve potato breeding, culminating in a draft genome sequence and the identification of a large number of single nucleotide polymorphisms (SNPs. The availability of these genome-wide SNPs is a prerequisite for implementing genomic selection for improvement of polygenic traits such as yield. In this review, we investigate opportunities for the application of genomic selection to potato, including novel breeding program designs. We have considered a number of factors that will influence this process, including the autotetraploid and heterozygous genetic nature of potato, the rate of decay of linkage disequilibrium, the number of required markers, the design of a reference population, and trait heritability. Based on estimates of the effective population size derived from a potato breeding program, we have calculated the expected accuracy of genomic selection for four key traits of varying heritability and propose that it will be reasonably accurate. We compared the expected genetic gain from genomic selection with the expected gain from phenotypic and pedigree selection, and found that genetic gain can be substantially improved by using genomic selection.

  3. How Darwinian reductionism refutes genetic determinism.

    Science.gov (United States)

    Rosoff, Philip M; Rosenberg, Alex

    2006-03-01

    Genetic determinism labels the morally problematical claim that some socially significant traits, traits we care about, such as sexual orientation, gender roles, violence, alcoholism, mental illness, intelligence, are largely the results of the operation of genes and not much alterable by environment, learning or other human intervention. Genetic determinism does not require that genes literally fix these socially significant traits, but rather that they constrain them within narrow channels beyond human intervention. In this essay we analyze genetic determinism in light of what is now known about the inborn error of metabolism phenylketonuria (PKU), which has for so long been the poster child 'simple' argument in favor of some form of genetic determinism. We demonstrate that this case proves the exact opposite of what it has been proposed to support and provides a strong refutation of genetic determinism in all its guises.

  4. The ethics of creating genetically modified children using genome editing.

    Science.gov (United States)

    Ishii, Tetsuya

    2017-09-06

    To review the recent ethical, legal, and social issues surrounding human reproduction involving germline genome editing. Genome editing techniques, such as CRISPR/Cas9, have facilitated genetic modification in human embryos. The most likely purpose of germline genome editing is the prevention of serious genetic disease in offspring. However, complex issues still remain, including irremediable risks to fetuses and future generations, the role of women, the availability of alternatives, long-term follow-up, health insurance coverage, misuse for human enhancement, and the potential effects on adoption. Further discussions, a broad consensus, and appropriate regulations are required before human germline genome editing is introduced into the global society. Before germline genome editing is used for disease prevention, a broad consensus must be formed by carefully discussing its ethical, legal, and social issues.

  5. From integrative genomics to systems genetics in the rat to link genotypes to phenotypes

    Science.gov (United States)

    Moreno-Moral, Aida

    2016-01-01

    ABSTRACT Complementary to traditional gene mapping approaches used to identify the hereditary components of complex diseases, integrative genomics and systems genetics have emerged as powerful strategies to decipher the key genetic drivers of molecular pathways that underlie disease. Broadly speaking, integrative genomics aims to link cellular-level traits (such as mRNA expression) to the genome to identify their genetic determinants. With the characterization of several cellular-level traits within the same system, the integrative genomics approach evolved into a more comprehensive study design, called systems genetics, which aims to unravel the complex biological networks and pathways involved in disease, and in turn map their genetic control points. The first fully integrated systems genetics study was carried out in rats, and the results, which revealed conserved trans-acting genetic regulation of a pro-inflammatory network relevant to type 1 diabetes, were translated to humans. Many studies using different organisms subsequently stemmed from this example. The aim of this Review is to describe the most recent advances in the fields of integrative genomics and systems genetics applied in the rat, with a focus on studies of complex diseases ranging from inflammatory to cardiometabolic disorders. We aim to provide the genetics community with a comprehensive insight into how the systems genetics approach came to life, starting from the first integrative genomics strategies [such as expression quantitative trait loci (eQTLs) mapping] and concluding with the most sophisticated gene network-based analyses in multiple systems and disease states. Although not limited to studies that have been directly translated to humans, we will focus particularly on the successful investigations in the rat that have led to primary discoveries of genes and pathways relevant to human disease. PMID:27736746

  6. BRAD, the genetics and genomics database for Brassica plants

    Directory of Open Access Journals (Sweden)

    Li Pingxia

    2011-10-01

    Full Text Available Abstract Background Brassica species include both vegetable and oilseed crops, which are very important to the daily life of common human beings. Meanwhile, the Brassica species represent an excellent system for studying numerous aspects of plant biology, specifically for the analysis of genome evolution following polyploidy, so it is also very important for scientific research. Now, the genome of Brassica rapa has already been assembled, it is the time to do deep mining of the genome data. Description BRAD, the Brassica database, is a web-based resource focusing on genome scale genetic and genomic data for important Brassica crops. BRAD was built based on the first whole genome sequence and on further data analysis of the Brassica A genome species, Brassica rapa (Chiifu-401-42. It provides datasets, such as the complete genome sequence of B. rapa, which was de novo assembled from Illumina GA II short reads and from BAC clone sequences, predicted genes and associated annotations, non coding RNAs, transposable elements (TE, B. rapa genes' orthologous to those in A. thaliana, as well as genetic markers and linkage maps. BRAD offers useful searching and data mining tools, including search across annotation datasets, search for syntenic or non-syntenic orthologs, and to search the flanking regions of a certain target, as well as the tools of BLAST and Gbrowse. BRAD allows users to enter almost any kind of information, such as a B. rapa or A. thaliana gene ID, physical position or genetic marker. Conclusion BRAD, a new database which focuses on the genetics and genomics of the Brassica plants has been developed, it aims at helping scientists and breeders to fully and efficiently use the information of genome data of Brassica plants. BRAD will be continuously updated and can be accessed through http://brassicadb.org.

  7. Genetics and genomics of ovarian sex cord-stromal tumors.

    Science.gov (United States)

    Fuller, P J; Leung, D; Chu, S

    2017-02-01

    Ovarian sex cord-stromal tumors (SCST) represent approximately 8% of malignant ovarian tumors. The most common are granulosa cell tumors (GCT) which account for approximately 90% of malignant SCST. Recent studies have unraveled the key genomic and genetic events contributing to their pathogenesis. SCST are found in the hereditary syndromes: Peutz-Jeghers syndrome, Ollier disease and Maffucci syndrome, and DICER1 syndrome. Genomic studies have largely been limited to GCT where a number of recurring chromosomal abnormalities (monsomy and trisomy) have been identified although their contribution to pathogenesis remains unclear. In addition to the recurrent DICER1 mutations reported in non-hereditary cases of Sertoli cell and Sertoli-Leydig cell tumors, recurrent somatic mutations in both the juvenile (j) and adult (a) forms of GCT have been reported. Approximately 30% of jGCT contain a somatic mutation, the gsp oncogene, while a further 60% have an activating mutation in the AKT gene. In the case of aGCT, a well characterized mutation in the FOXL2 transcription factor (FOXL2 C134W) is found in almost all cases, which arguably defines the disease, although the molecular events that determine the stage, behavior and prognosis of aGCT remain to be determined. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Genetic resources offer efficient tools for rice functional genomics research.

    Science.gov (United States)

    Lo, Shuen-Fang; Fan, Ming-Jen; Hsing, Yue-Ie; Chen, Liang-Jwu; Chen, Shu; Wen, Ien-Chie; Liu, Yi-Lun; Chen, Ku-Ting; Jiang, Mirng-Jier; Lin, Ming-Kuang; Rao, Meng-Yen; Yu, Lin-Chih; Ho, Tuan-Hua David; Yu, Su-May

    2016-05-01

    Rice is an important crop and major model plant for monocot functional genomics studies. With the establishment of various genetic resources for rice genomics, the next challenge is to systematically assign functions to predicted genes in the rice genome. Compared with the robustness of genome sequencing and bioinformatics techniques, progress in understanding the function of rice genes has lagged, hampering the utilization of rice genes for cereal crop improvement. The use of transfer DNA (T-DNA) insertional mutagenesis offers the advantage of uniform distribution throughout the rice genome, but preferentially in gene-rich regions, resulting in direct gene knockout or activation of genes within 20-30 kb up- and downstream of the T-DNA insertion site and high gene tagging efficiency. Here, we summarize the recent progress in functional genomics using the T-DNA-tagged rice mutant population. We also discuss important features of T-DNA activation- and knockout-tagging and promoter-trapping of the rice genome in relation to mutant and candidate gene characterizations and how to more efficiently utilize rice mutant populations and datasets for high-throughput functional genomics and phenomics studies by forward and reverse genetics approaches. These studies may facilitate the translation of rice functional genomics research to improvements of rice and other cereal crops.

  9. Diatom genomics: genetic acquisitions and mergers.

    Science.gov (United States)

    Nisbet, R Ellen R; Kilian, Oliver; McFadden, Geoffrey I

    2004-12-29

    Diatom algae arose by two-step endosymbiosis. The complete genome of the diatom Thalassiosira pseudonana has now been sequenced, allowing us to reconstruct the remarkable intracellular gene transfers that occurred during this convoluted cellular evolution.

  10. Plastid genomics in horticultural species: importance and applications for plant population genetics, evolution, and biotechnology

    Science.gov (United States)

    Rogalski, Marcelo; do Nascimento Vieira, Leila; Fraga, Hugo P.; Guerra, Miguel P.

    2015-01-01

    During the evolution of the eukaryotic cell, plastids, and mitochondria arose from an endosymbiotic process, which determined the presence of three genetic compartments into the incipient plant cell. After that, these three genetic materials from host and symbiont suffered several rearrangements, bringing on a complex interaction between nuclear and organellar gene products. Nowadays, plastids harbor a small genome with ∼130 genes in a 100–220 kb sequence in higher plants. Plastid genes are mostly highly conserved between plant species, being useful for phylogenetic analysis in higher taxa. However, intergenic spacers have a relatively higher mutation rate and are important markers to phylogeographical and plant population genetics analyses. The predominant uniparental inheritance of plastids is like a highly desirable feature for phylogeny studies. Moreover, the gene content and genome rearrangements are efficient tools to capture and understand evolutionary events between different plant species. Currently, genetic engineering of the plastid genome (plastome) offers a number of attractive advantages as high-level of foreign protein expression, marker gene excision, gene expression in operon and transgene containment because of maternal inheritance of plastid genome in most crops. Therefore, plastid genome can be used for adding new characteristics related to synthesis of metabolic compounds, biopharmaceutical, and tolerance to biotic and abiotic stresses. Here, we describe the importance and applications of plastid genome as tools for genetic and evolutionary studies, and plastid transformation focusing on increasing the performance of horticultural species in the field. PMID:26284102

  11. Genetic modification of mammalian genome at chromosome level

    Directory of Open Access Journals (Sweden)

    OLEG L. SEROV

    2000-09-01

    Full Text Available The review is concerned with a progress in genetic modification of a mammalian genome in vitro and in vivo at chromosomal level. Recently three new approaches for the chromosome biotechnology have been developed: Using Cre/loxP-system a researcher is able to produce targeted rearrangements of whole chromosomes or their segments or particular genes within the genome, and therefore to modify the set, position and copy number of the endogenous elements of the genome. Mammalian artificial chromosomes (MACs provide a possibility to introduce into genome relatively large segments of alien chromosome material, either artificially constructed or derived from the genome of different species. Using ES-somatic cell hybrids allows to transfer whole chromosomes or their fragments between different genomes within and between species. Advantages and limitations of these approaches are discussed.

  12. Conservation genetics in transition to conservation genomics

    NARCIS (Netherlands)

    Ouborg, N. Joop; Pertoldi, Cino; Loeschcke, Volker; Bijlsma, R. (Kuke); Hedrick, Phil W.

    2010-01-01

    Over the past twenty years conservation genetics has progressed from being mainly a theory-based field of population biology to a full-grown empirical discipline. Technological developments in molecular genetics have led to extensive use of neutral molecular markers such as microsatellites in conser

  13. Castor bean organelle genome sequencing and worldwide genetic diversity analysis.

    Directory of Open Access Journals (Sweden)

    Maximo Rivarola

    Full Text Available Castor bean is an important oil-producing plant in the Euphorbiaceae family. Its high-quality oil contains up to 90% of the unusual fatty acid ricinoleate, which has many industrial and medical applications. Castor bean seeds also contain ricin, a highly toxic Type 2 ribosome-inactivating protein, which has gained relevance in recent years due to biosafety concerns. In order to gain knowledge on global genetic diversity in castor bean and to ultimately help the development of breeding and forensic tools, we carried out an extensive chloroplast sequence diversity analysis. Taking advantage of the recently published genome sequence of castor bean, we assembled the chloroplast and mitochondrion genomes extracting selected reads from the available whole genome shotgun reads. Using the chloroplast reference genome we used the methylation filtration technique to readily obtain draft genome sequences of 7 geographically and genetically diverse castor bean accessions. These sequence data were used to identify single nucleotide polymorphism markers and phylogenetic analysis resulted in the identification of two major clades that were not apparent in previous population genetic studies using genetic markers derived from nuclear DNA. Two distinct sub-clades could be defined within each major clade and large-scale genotyping of castor bean populations worldwide confirmed previously observed low levels of genetic diversity and showed a broad geographic distribution of each sub-clade.

  14. Castor bean organelle genome sequencing and worldwide genetic diversity analysis.

    Science.gov (United States)

    Rivarola, Maximo; Foster, Jeffrey T; Chan, Agnes P; Williams, Amber L; Rice, Danny W; Liu, Xinyue; Melake-Berhan, Admasu; Huot Creasy, Heather; Puiu, Daniela; Rosovitz, M J; Khouri, Hoda M; Beckstrom-Sternberg, Stephen M; Allan, Gerard J; Keim, Paul; Ravel, Jacques; Rabinowicz, Pablo D

    2011-01-01

    Castor bean is an important oil-producing plant in the Euphorbiaceae family. Its high-quality oil contains up to 90% of the unusual fatty acid ricinoleate, which has many industrial and medical applications. Castor bean seeds also contain ricin, a highly toxic Type 2 ribosome-inactivating protein, which has gained relevance in recent years due to biosafety concerns. In order to gain knowledge on global genetic diversity in castor bean and to ultimately help the development of breeding and forensic tools, we carried out an extensive chloroplast sequence diversity analysis. Taking advantage of the recently published genome sequence of castor bean, we assembled the chloroplast and mitochondrion genomes extracting selected reads from the available whole genome shotgun reads. Using the chloroplast reference genome we used the methylation filtration technique to readily obtain draft genome sequences of 7 geographically and genetically diverse castor bean accessions. These sequence data were used to identify single nucleotide polymorphism markers and phylogenetic analysis resulted in the identification of two major clades that were not apparent in previous population genetic studies using genetic markers derived from nuclear DNA. Two distinct sub-clades could be defined within each major clade and large-scale genotyping of castor bean populations worldwide confirmed previously observed low levels of genetic diversity and showed a broad geographic distribution of each sub-clade.

  15. Castor Bean Organelle Genome Sequencing and Worldwide Genetic Diversity Analysis

    Science.gov (United States)

    Chan, Agnes P.; Williams, Amber L.; Rice, Danny W.; Liu, Xinyue; Melake-Berhan, Admasu; Huot Creasy, Heather; Puiu, Daniela; Rosovitz, M. J.; Khouri, Hoda M.; Beckstrom-Sternberg, Stephen M.; Allan, Gerard J.; Keim, Paul; Ravel, Jacques; Rabinowicz, Pablo D.

    2011-01-01

    Castor bean is an important oil-producing plant in the Euphorbiaceae family. Its high-quality oil contains up to 90% of the unusual fatty acid ricinoleate, which has many industrial and medical applications. Castor bean seeds also contain ricin, a highly toxic Type 2 ribosome-inactivating protein, which has gained relevance in recent years due to biosafety concerns. In order to gain knowledge on global genetic diversity in castor bean and to ultimately help the development of breeding and forensic tools, we carried out an extensive chloroplast sequence diversity analysis. Taking advantage of the recently published genome sequence of castor bean, we assembled the chloroplast and mitochondrion genomes extracting selected reads from the available whole genome shotgun reads. Using the chloroplast reference genome we used the methylation filtration technique to readily obtain draft genome sequences of 7 geographically and genetically diverse castor bean accessions. These sequence data were used to identify single nucleotide polymorphism markers and phylogenetic analysis resulted in the identification of two major clades that were not apparent in previous population genetic studies using genetic markers derived from nuclear DNA. Two distinct sub-clades could be defined within each major clade and large-scale genotyping of castor bean populations worldwide confirmed previously observed low levels of genetic diversity and showed a broad geographic distribution of each sub-clade. PMID:21750729

  16. Human Genome Epidemiology : A scientific foundation for using genetic information to improve health and prevent disease

    Directory of Open Access Journals (Sweden)

    Stefania Boccia

    2005-03-01

    Full Text Available

    Human health is determined by the interplay of genetic factors and the environment. In this context the recent advances in human genomics are expected to play a central role in medicine and public health by providing genetic information for disease prediction and prevention.

    After the completion of the human genome sequencing, a fundamental step will be represented by the translation of these discoveries into meaningful actions to improve health and prevent diseases, and the field of epidemiology plays a central role in this effort. These are some of the issues addressed by Human Genome Epidemiology –A scientific foundation for using genetic information to improve health and prevent disease, a volume edited by Prof. M. Khoury, Prof. J. Little, Prof.W. Burke and published by Oxford university Press 2004.

    This book describes the important role that epidemiological methods play in the continuum from gene discovery to the development and application of genetic tests. The Authors calls this continuum human genome epidemiology (HuGE to denote an evolving field of inquiry that uses systematic applications of epidemiological methods to assess the impact of human genetic variation on health and disease.

    The book is divided into four sections and it is structured to allow readers to proceed systematically from the fundamentals of genome technology and discovery, to the epidemiological approaches, to gene characterisation, to the evaluation of genetic tests and their use in health services and public health.

  17. Human genetic determinants of dengue virus susceptibility.

    Science.gov (United States)

    Coffey, Lark L; Mertens, Eva; Brehin, Anne-Claire; Fernandez-Garcia, Maria Dolores; Amara, Ali; Després, Philippe; Sakuntabhai, Anavaj

    2009-02-01

    Dengue virus (DENV) is an emerging mosquito-borne pathogen that produces significant morbidity worldwide resulting in an estimated 50-100 million infections annually. DENV causes a spectrum of illness ranging from inapparent infection to life-threatening hemorrhagic fever and shock. The varied DENV disease outcome is determined by complex interactions between immunopathologic, viral, and human genetic factors. This review summarizes these interactions with a focus on human genetic determinants of DENV susceptibility, including human leukocyte antigens, blood type, and single nucleotide polymorphisms in immune response genes that have been associated with DENV disease. We also discuss other factors related to DENV outcome including viral genetic determinants, age, ethnicity, and nutritional status as they relate to DENV susceptibility. We emphasize the need for functional genetics studies to complement association-based data and we call for controlled study designs and standard clinical DENV disease definitions that will strengthen conclusions based on human genetic DENV studies.

  18. Plant MITEs: Useful Tools for Plant Genetics and Genomics

    Institute of Scientific and Technical Information of China (English)

    Ying Feng

    2003-01-01

    MITEs (Miniature inverted-repeat transposable elements) are reminiscence of non-autonomous DNA (class Ⅱ) elements, which are distinguished from other transpos-able elements by their small size, short terminal inverted repeats (TIRs), high copynumbers, genic preference, and DNA sequence identity among family members. Al-though MITEs were first discovered in plants and still actively reshaping genomes,they have been isolated from a wide range of eukaryotic organisms. MITEs canbe divided into Tourist-like, Stowaway-like, and pogo-like groups, according tosimilarities of their TIRs and TSDs (target site duplications). In despite of sev-eral models to explain the origin and amplification of MITEs, their mechanisms oftransposition and accumulation in eukaryotic genomes remain poorly understoodowing to insufficient experimental data. The unique properties of MITEs have beenexploited as useful genetic tools for plant genome analysis. Utilization of MITEsas effective and informative genomic markers and potential application of MITEsin plants systematic, phylogenetic, and genetic studies are discussed.

  19. Indel Group in Genomes (IGG) Molecular Genetic Markers1[OPEN

    Science.gov (United States)

    Burkart-Waco, Diana; Kuppu, Sundaram; Britt, Anne; Chetelat, Roger

    2016-01-01

    Genetic markers are essential when developing or working with genetically variable populations. Indel Group in Genomes (IGG) markers are primer pairs that amplify single-locus sequences that differ in size for two or more alleles. They are attractive for their ease of use for rapid genotyping and their codominant nature. Here, we describe a heuristic algorithm that uses a k-mer-based approach to search two or more genome sequences to locate polymorphic regions suitable for designing candidate IGG marker primers. As input to the IGG pipeline software, the user provides genome sequences and the desired amplicon sizes and size differences. Primer sequences flanking polymorphic insertions/deletions are produced as output. IGG marker files for three sets of genomes, Solanum lycopersicum/Solanum pennellii, Arabidopsis (Arabidopsis thaliana) Columbia-0/Landsberg erecta-0 accessions, and S. lycopersicum/S. pennellii/Solanum tuberosum (three-way polymorphic) are included. PMID:27436831

  20. THE MEANING OF GENOMIC IMPRINTING IN HUMAN GENETIC AND DEFECTOLOGY

    Directory of Open Access Journals (Sweden)

    Anastas LAKOSKI

    2000-12-01

    Full Text Available Several genetic phenomena do not appear to conform the Mendel's low in the sense that they are not inherited in simple way through the generations. Such exceptions to Mendel's laws include new mutations, changes in chromosomes, expanded triplet sequences, and genomic imprinting. Many genetic diseases involve spontaneous mutations that are not inherited from generation to generation. Changes in chromosomes include nondisjunction, which is the most important cause of mental retardation, the trisomy of Dowen syndrome. Expanded triplet repeats are responsible for the next important cause of mental retardation, fragile X, and for Huntington's disease. Genomic imprinting occurs when the expression of a gene depends on whether it is inherited from the mother or from the father. In this paper the phenomenon of genomic imprinting is explained on the occurrence of Angelman and Prader-Willi syndromes. It's essential for the counselor to be able during the genetic counseling to recognize this phenomenon and to make a proper decision.

  1. Conservation genetics and genomics of amphibians and reptiles.

    Science.gov (United States)

    Shaffer, H Bradley; Gidiş, Müge; McCartney-Melstad, Evan; Neal, Kevin M; Oyamaguchi, Hilton M; Tellez, Marisa; Toffelmier, Erin M

    2015-01-01

    Amphibians and reptiles as a group are often secretive, reach their greatest diversity often in remote tropical regions, and contain some of the most endangered groups of organisms on earth. Particularly in the past decade, genetics and genomics have been instrumental in the conservation biology of these cryptic vertebrates, enabling work ranging from the identification of populations subject to trade and exploitation, to the identification of cryptic lineages harboring critical genetic variation, to the analysis of genes controlling key life history traits. In this review, we highlight some of the most important ways that genetic analyses have brought new insights to the conservation of amphibians and reptiles. Although genomics has only recently emerged as part of this conservation tool kit, several large-scale data sources, including full genomes, expressed sequence tags, and transcriptomes, are providing new opportunities to identify key genes, quantify landscape effects, and manage captive breeding stocks of at-risk species.

  2. Genomic and Genetic Diversity within the Pseudomonas fluorescens Complex.

    Directory of Open Access Journals (Sweden)

    Daniel Garrido-Sanz

    Full Text Available The Pseudomonas fluorescens complex includes Pseudomonas strains that have been taxonomically assigned to more than fifty different species, many of which have been described as plant growth-promoting rhizobacteria (PGPR with potential applications in biocontrol and biofertilization. So far the phylogeny of this complex has been analyzed according to phenotypic traits, 16S rDNA, MLSA and inferred by whole-genome analysis. However, since most of the type strains have not been fully sequenced and new species are frequently described, correlation between taxonomy and phylogenomic analysis is missing. In recent years, the genomes of a large number of strains have been sequenced, showing important genomic heterogeneity and providing information suitable for genomic studies that are important to understand the genomic and genetic diversity shown by strains of this complex. Based on MLSA and several whole-genome sequence-based analyses of 93 sequenced strains, we have divided the P. fluorescens complex into eight phylogenomic groups that agree with previous works based on type strains. Digital DDH (dDDH identified 69 species and 75 subspecies within the 93 genomes. The eight groups corresponded to clustering with a threshold of 31.8% dDDH, in full agreement with our MLSA. The Average Nucleotide Identity (ANI approach showed inconsistencies regarding the assignment to species and to the eight groups. The small core genome of 1,334 CDSs and the large pan-genome of 30,848 CDSs, show the large diversity and genetic heterogeneity of the P. fluorescens complex. However, a low number of strains were enough to explain most of the CDSs diversity at core and strain-specific genomic fractions. Finally, the identification and analysis of group-specific genome and the screening for distinctive characters revealed a phylogenomic distribution of traits among the groups that provided insights into biocontrol and bioremediation applications as well as their role as

  3. Genomic and Genetic Diversity within the Pseudomonas fluorescens Complex.

    Science.gov (United States)

    Garrido-Sanz, Daniel; Meier-Kolthoff, Jan P; Göker, Markus; Martín, Marta; Rivilla, Rafael; Redondo-Nieto, Miguel

    2016-01-01

    The Pseudomonas fluorescens complex includes Pseudomonas strains that have been taxonomically assigned to more than fifty different species, many of which have been described as plant growth-promoting rhizobacteria (PGPR) with potential applications in biocontrol and biofertilization. So far the phylogeny of this complex has been analyzed according to phenotypic traits, 16S rDNA, MLSA and inferred by whole-genome analysis. However, since most of the type strains have not been fully sequenced and new species are frequently described, correlation between taxonomy and phylogenomic analysis is missing. In recent years, the genomes of a large number of strains have been sequenced, showing important genomic heterogeneity and providing information suitable for genomic studies that are important to understand the genomic and genetic diversity shown by strains of this complex. Based on MLSA and several whole-genome sequence-based analyses of 93 sequenced strains, we have divided the P. fluorescens complex into eight phylogenomic groups that agree with previous works based on type strains. Digital DDH (dDDH) identified 69 species and 75 subspecies within the 93 genomes. The eight groups corresponded to clustering with a threshold of 31.8% dDDH, in full agreement with our MLSA. The Average Nucleotide Identity (ANI) approach showed inconsistencies regarding the assignment to species and to the eight groups. The small core genome of 1,334 CDSs and the large pan-genome of 30,848 CDSs, show the large diversity and genetic heterogeneity of the P. fluorescens complex. However, a low number of strains were enough to explain most of the CDSs diversity at core and strain-specific genomic fractions. Finally, the identification and analysis of group-specific genome and the screening for distinctive characters revealed a phylogenomic distribution of traits among the groups that provided insights into biocontrol and bioremediation applications as well as their role as PGPR.

  4. Inference of distant genetic relations in humans using "1000 genomes".

    Science.gov (United States)

    Al-Khudhair, Ahmed; Qiu, Shuhao; Wyse, Meghan; Chowdhury, Shilpi; Cheng, Xi; Bekbolsynov, Dulat; Saha-Mandal, Arnab; Dutta, Rajib; Fedorova, Larisa; Fedorov, Alexei

    2015-01-07

    Nucleotide sequence differences on the whole-genome scale have been computed for 1,092 people from 14 populations publicly available by the 1000 Genomes Project. Total number of differences in genetic variants between 96,464 human pairs has been calculated. The distributions of these differences for individuals within European, Asian, or African origin were characterized by narrow unimodal peaks with mean values of 3.8, 3.5, and 5.1 million, respectively, and standard deviations of 0.1-0.03 million. The total numbers of genomic differences between pairs of all known relatives were found to be significantly lower than their respective population means and in reverse proportion to the distance of their consanguinity. By counting the total number of genomic differences it is possible to infer familial relations for people that share down to 6% of common loci identical-by-descent. Detection of familial relations can be radically improved when only very rare genetic variants are taken into account. Counting of total number of shared very rare single nucleotide polymorphisms (SNPs) from whole-genome sequences allows establishing distant familial relations for persons with eighth and ninth degrees of relationship. Using this analysis we predicted 271 distant familial pairwise relations among 1,092 individuals that have not been declared by 1000 Genomes Project. Particularly, among 89 British and 97 Chinese individuals we found three British-Chinese pairs with distant genetic relationships. Individuals from these pairs share identical-by-descent DNA fragments that represent 0.001%, 0.004%, and 0.01% of their genomes. With affordable whole-genome sequencing techniques, very rare SNPs should become important genetic markers for familial relationships and population stratification. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  5. PLANT GENETICS:From Genome to Functional Genomics.

    Science.gov (United States)

    Kaiser, J

    2000-06-09

    Even before the first genetic sequence of a flowering plant, a wild mustard called Arabidopsis thaliana, is completed, a group of plant scientists has hatched an ambitious plan for the next phase: figuring out the functions of all 25,000 genes. Announced last week, the plan, which has the blessing of the National Science Foundation, came with another bit of good news for the Arabidopsis community: the unexpected release of a set of molecular markers for finding those genes.

  6. Genome-wide prediction of C. elegans genetic interactions.

    Science.gov (United States)

    Zhong, Weiwei; Sternberg, Paul W

    2006-03-10

    To obtain a global view of functional interactions among genes in a metazoan genome, we computationally integrated interactome data, gene expression data, phenotype data, and functional annotation data from three model organisms-Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster-and predicted genome-wide genetic interactions in C. elegans. The resulting genetic interaction network (consisting of 18,183 interactions) provides a framework for system-level understanding of gene functions. We experimentally tested the predicted interactions for two human disease-related genes and identified 14 new modifiers.

  7. From Genetics to Genomics: A Short Introduction for Pediatric Neurologists.

    Science.gov (United States)

    Neubauer, Bernd A; Lemke, Johannes R

    2016-01-01

    It is estimated that in humans approximately 50% of all 22500 genes are needed for the development and maintenance of the nervous system. The introduction of high-throughput technology in genetic analysis has therefore major implications, not only for the investigation of specific disease entities but also for the diagnostic workup of single individuals with neurologic disorders of genetic origin. A short primer for clinicians is presented, addressing aspects of current developments in medical genomics. Significant findings of the last years are exemplified in an educational manner to provide a basic understanding of disease mechanisms that were unraveled by recent genomic analysis.

  8. Genetic determinants of pathogenesis by feline infectious peritonitis virus.

    Science.gov (United States)

    Brown, Meredith A

    2011-10-15

    Feline infectious peritonitis (FIP) is a fatal, immune-augmented, and progressive viral disease of cats associated with feline coronavirus (FCoV). Viral genetic determinants specifically associated with FIPV pathogenesis have not yet been discovered. Viral gene signatures in the spike, non-structural protein 3c, and membrane of the coronavirus genome have been shown to often correlate with disease manifestation. An "in vivo mutation transition hypothesis" is widely accepted and postulates that de novo virus mutation occurs in vivo giving rise to virulence. The existence of "distinct circulating avirulent and virulent strains" is an alternative hypothesis of viral pathogenesis. It may be possible that viral dynamics from both hypotheses are at play in the occurrence of FIP. Epidemiologic data suggests that the genetic background of the cat contributes to the manifestation of FIP. Further studies exploring both viral and host genetic determinants of disease in FIP offer specific opportunities for the management of this disease.

  9. Mouse gestation length is genetically determined.

    Directory of Open Access Journals (Sweden)

    Stephen A Murray

    Full Text Available BACKGROUND: Preterm birth is an enormous public health problem, affecting over 12% of live births and costing over $26 billion in the United States alone. The causes are complex, but twin studies support the role of genetics in determining gestation length. Despite widespread use of the mouse in studies of the genetics of preterm birth, there have been few studies that actually address the precise natural gestation length of the mouse, and to what degree the timing of labor and birth is genetically determined. METHODOLOGY/PRINCIPAL FINDINGS: To further develop the mouse as a genetic model of preterm birth, we developed a high-throughput monitoring system and measured the gestation length in 15 inbred strains. Our results show an unexpectedly wide variation in overall gestation length between strains that approaches two full days, while intra-strain variation is quite low. Although litter size shows a strong inverse correlation with gestation length, genetic difference alone accounts for a significant portion of the variation. In addition, ovarian transplant experiments support a primary role of maternal genetics in the determination of gestation length. Preliminary analysis of gestation length in the C57BL/6J-Chr#(A/J/NaJ chromosome substitution strain (B.A CSS panel suggests complex genetic control of gestation length. CONCLUSIONS/SIGNIFICANCE: Together, these data support the role of genetics in regulating gestation length and present the mouse as an important tool for the discovery of genes governing preterm birth.

  10. Multi-ethnic minority nurses' knowledge and practice of genetics and genomics.

    Science.gov (United States)

    Coleman, Bernice; Calzone, Kathleen A; Jenkins, Jean; Paniagua, Carmen; Rivera, Reynaldo; Hong, Oi Saeng; Spruill, Ida; Bonham, Vence

    2014-07-01

    Exploratory studies establishing how well nurses have integrated genomics into practice have demonstrated there remains opportunity for education. However, little is known about educational gaps in multi-ethnic minority nurse populations. The purpose of this study was to determine minority nurses' beliefs, practices, and competency in integrating genetics-genomics information into practice using an online survey tool. A cross-sectional survey with registered nurses (RNs) from the participating National Coalition of Ethnic Minority Organizations (NCEMNA). Two phases were used: Phase one had a sample of 27 nurses who determined the feasibility of an online approach to survey completion and need for tool revision. Phase two was a main survey with 389 participants who completed the revised survey. The survey ascertained the genomic knowledge, beliefs, and practice of a sample of multi-ethnic minority nurses who were members of associations comprising the NCEMNA. The survey was administered online. Descriptive survey responses were analyzed using frequencies and percentages. Categorical responses in which comparisons were analyzed used chi square tests. About 40% of the respondents held a master's degree (39%) and 42% worked in direct patient care. The majority of respondents (79%) reported that education in genomics was important. Ninety-five percent agreed or strongly agreed that family health history could identify at-risk families, 85% reported knowing how to complete a second- and third-generation family history, and 63% felt family history was important to nursing. Conversely, 50% of the respondents felt that their understanding of the genetics of common disease was fair or poor, supported by 54% incorrectly reporting they thought heart disease and diabetes are caused by a single gene variant. Only 30% reported taking a genetics course since licensure, and 94% reported interest in learning more about genomics. Eighty-four percent believed that their ethnic

  11. Anaerobic catabolism of aromatic compounds: a genetic and genomic view.

    Science.gov (United States)

    Carmona, Manuel; Zamarro, María Teresa; Blázquez, Blas; Durante-Rodríguez, Gonzalo; Juárez, Javier F; Valderrama, J Andrés; Barragán, María J L; García, José Luis; Díaz, Eduardo

    2009-03-01

    Aromatic compounds belong to one of the most widely distributed classes of organic compounds in nature, and a significant number of xenobiotics belong to this family of compounds. Since many habitats containing large amounts of aromatic compounds are often anoxic, the anaerobic catabolism of aromatic compounds by microorganisms becomes crucial in biogeochemical cycles and in the sustainable development of the biosphere. The mineralization of aromatic compounds by facultative or obligate anaerobic bacteria can be coupled to anaerobic respiration with a variety of electron acceptors as well as to fermentation and anoxygenic photosynthesis. Since the redox potential of the electron-accepting system dictates the degradative strategy, there is wide biochemical diversity among anaerobic aromatic degraders. However, the genetic determinants of all these processes and the mechanisms involved in their regulation are much less studied. This review focuses on the recent findings that standard molecular biology approaches together with new high-throughput technologies (e.g., genome sequencing, transcriptomics, proteomics, and metagenomics) have provided regarding the genetics, regulation, ecophysiology, and evolution of anaerobic aromatic degradation pathways. These studies revealed that the anaerobic catabolism of aromatic compounds is more diverse and widespread than previously thought, and the complex metabolic and stress programs associated with the use of aromatic compounds under anaerobic conditions are starting to be unraveled. Anaerobic biotransformation processes based on unprecedented enzymes and pathways with novel metabolic capabilities, as well as the design of novel regulatory circuits and catabolic networks of great biotechnological potential in synthetic biology, are now feasible to approach.

  12. From genetics to genomics in plants and animals

    Directory of Open Access Journals (Sweden)

    Todorovska Elena

    2010-01-01

    Full Text Available The classical concepts in plant and livestock selection for economically important quantitative traits traditionally are based on phenotypic records, aiming at improvement of the traits by obtaining better genetic gain. The increase in genetic variation together with shortening of the generation interval is the major target of long term improvement of methods and tools for selection activities. The discoveries and implementations of biotechnology and molecular biology for selection purposes provide a stable background for generating of new knowledge and practical use in agricultural research and practice as well as to meet the growing demand for more and with better quality food and feed. The innovations in molecular knowledge related to practical selection aside with the quick quantification in breeding schemes allowed to reconsider the opportunities for sustainable development of selection methods for improvement of the traits of interest in agriculture, the quick invention and practical application of new high-throughput technologies for studying of the genomic variation, evolution, translation of proteins and metabolite determination altogether put in an open and communicative environment of information technologies provide a new holistic platform for better research and more knowledge for practical application of selection decisions.

  13. Genome-wide genetic changes during modern breeding of maize.

    Science.gov (United States)

    Jiao, Yinping; Zhao, Hainan; Ren, Longhui; Song, Weibin; Zeng, Biao; Guo, Jinjie; Wang, Baobao; Liu, Zhipeng; Chen, Jing; Li, Wei; Zhang, Mei; Xie, Shaojun; Lai, Jinsheng

    2012-06-03

    The success of modern maize breeding has been demonstrated by remarkable increases in productivity over the last four decades. However, the underlying genetic changes correlated with these gains remain largely unknown. We report here the sequencing of 278 temperate maize inbred lines from different stages of breeding history, including deep resequencing of 4 lines with known pedigree information. The results show that modern breeding has introduced highly dynamic genetic changes into the maize genome. Artificial selection has affected thousands of targets, including genes and non-genic regions, leading to a reduction in nucleotide diversity and an increase in the proportion of rare alleles. Genetic changes during breeding happen rapidly, with extensive variation (SNPs, indels and copy-number variants (CNVs)) occurring, even within identity-by-descent regions. Our genome-wide assessment of genetic changes during modern maize breeding provides new strategies as well as practical targets for future crop breeding and biotechnology.

  14. Homing endonucleases: from genetic anomalies to programmable genomic clippers.

    Science.gov (United States)

    Belfort, Marlene; Bonocora, Richard P

    2014-01-01

    Homing endonucleases are strong drivers of genetic exchange and horizontal transfer of both their own genes and their local genetic environment. The mechanisms that govern the function and evolution of these genetic oddities have been well documented over the past few decades at the genetic, biochemical, and structural levels. This wealth of information has led to the manipulation and reprogramming of the endonucleases and to their exploitation in genome editing for use as therapeutic agents, for insect vector control and in agriculture. In this chapter we summarize the molecular properties of homing endonucleases and discuss their strengths and weaknesses in genome editing as compared to other site-specific nucleases such as zinc finger endonucleases, TALEN, and CRISPR-derived endonucleases.

  15. Comparative genomics of Brachyspira pilosicoli strains: genome rearrangements, reductions and correlation of genetic compliment with phenotypic diversity

    Directory of Open Access Journals (Sweden)

    Mappley Luke J

    2012-09-01

    Full Text Available Abstract Background The anaerobic spirochaete Brachyspira pilosicoli causes enteric disease in avian, porcine and human hosts, amongst others. To date, the only available genome sequence of B. pilosicoli is that of strain 95/1000, a porcine isolate. In the first intra-species genome comparison within the Brachyspira genus, we report the whole genome sequence of B. pilosicoli B2904, an avian isolate, the incomplete genome sequence of B. pilosicoli WesB, a human isolate, and the comparisons with B. pilosicoli 95/1000. We also draw on incomplete genome sequences from three other Brachyspira species. Finally we report the first application of the high-throughput Biolog phenotype screening tool on the B. pilosicoli strains for detailed comparisons between genotype and phenotype. Results Feature and sequence genome comparisons revealed a high degree of similarity between the three B. pilosicoli strains, although the genomes of B2904 and WesB were larger than that of 95/1000 (~2,765, 2.890 and 2.596 Mb, respectively. Genome rearrangements were observed which correlated largely with the positions of mobile genetic elements. Through comparison of the B2904 and WesB genomes with the 95/1000 genome, features that we propose are non-essential due to their absence from 95/1000 include a peptidase, glycine reductase complex components and transposases. Novel bacteriophages were detected in the newly-sequenced genomes, which appeared to have involvement in intra- and inter-species horizontal gene transfer. Phenotypic differences predicted from genome analysis, such as the lack of genes for glucuronate catabolism in 95/1000, were confirmed by phenotyping. Conclusions The availability of multiple B. pilosicoli genome sequences has allowed us to demonstrate the substantial genomic variation that exists between these strains, and provides an insight into genetic events that are shaping the species. In addition, phenotype screening allowed determination of how

  16. THE MEANING OF GENOMIC IMPRINTING IN HUMAN GENETIC AND DEFECTOLOGY

    OpenAIRE

    Anastas LAKOSKI

    2000-01-01

    Several genetic phenomena do not appear to conform the Mendel's low in the sense that they are not inherited in simple way through the generations. Such exceptions to Mendel's laws include new mutations, changes in chromosomes, expanded triplet sequences, and genomic imprinting. Many genetic diseases involve spontaneous mutations that are not inherited from generation to generation. Changes in chromosomes include nondisjunction, which is the most important cause of mental retardation, the tri...

  17. Did genetic drift drive increases in genome complexity?

    Directory of Open Access Journals (Sweden)

    Kenneth D Whitney

    2010-08-01

    Full Text Available Mechanisms underlying the dramatic patterns of genome size variation across the tree of life remain mysterious. Effective population size (N(e has been proposed as a major driver of genome size: selection is expected to efficiently weed out deleterious mutations increasing genome size in lineages with large (but not small N(e. Strong support for this model was claimed from a comparative analysis of N(eu and genome size for ≈30 phylogenetically diverse species ranging from bacteria to vertebrates, but analyses at that scale have so far failed to account for phylogenetic nonindependence of species. In our reanalysis, accounting for phylogenetic history substantially altered the perceived strength of the relationship between N(eu and genomic attributes: there were no statistically significant associations between N(eu and gene number, intron size, intron number, the half-life of gene duplicates, transposon number, transposons as a fraction of the genome, or overall genome size. We conclude that current datasets do not support the hypothesis of a mechanistic connection between N(e and these genomic attributes, and we suggest that further progress requires larger datasets, phylogenetic comparative methods, more robust estimators of genetic drift, and a multivariate approach that accounts for correlations between putative explanatory variables.

  18. Genetical Genomics of Plants: From Genotype to Phenotype

    NARCIS (Netherlands)

    Joosen, R.V.L.; Ligterink, W.; Hilhorst, H.W.M.; Keurentjes, J.J.B.

    2013-01-01

    Natural variation provides a valuable resource to study the genetic regulation of quantitative traits. In quantitative trait locus (QTL) analyses this variation, captured in segregating mapping populations, is used to identify the genomic regions affecting these traits. The identification of the cau

  19. Estimates of genetic variance and variance of predicted genetic merits using pedigree or genomic relationship matrices in six Brown Swiss cattle populations for different traits.

    Science.gov (United States)

    Loberg, A; Dürr, J W; Fikse, W F; Jorjani, H; Crooks, L

    2015-10-01

    The amount of variance captured in genetic estimations may depend on whether a pedigree-based or genomic relationship matrix is used. The purpose of this study was to investigate the genetic variance as well as the variance of predicted genetic merits (PGM) using pedigree-based or genomic relationship matrices in Brown Swiss cattle. We examined a range of traits in six populations amounting to 173 population-trait combinations. A main aim was to determine how using different relationship matrices affect variance estimation. We calculated ratios between different types of estimates and analysed the impact of trait heritability and population size. The genetic variances estimated by REML using a genomic relationship matrix were always smaller than the variances that were similarly estimated using a pedigree-based relationship matrix. The variances from the genomic relationship matrix became closer to estimates from a pedigree relationship matrix as heritability and population size increased. In contrast, variances of predicted genetic merits obtained using a genomic relationship matrix were mostly larger than variances of genetic merit predicted using pedigree-based relationship matrix. The ratio of the genomic to pedigree-based PGM variances decreased as heritability and population size rose. The increased variance among predicted genetic merits is important for animal breeding because this is one of the factors influencing genetic progress. © 2015 Blackwell Verlag GmbH.

  20. Genomics in pediatric endocrinology-genetic disorders and new techniques.

    Science.gov (United States)

    Tenore, Alfred; Driul, Daniela

    2011-10-01

    In the last few years, there have been remarkable advances in the development of new and more sophisticated genetic techniques. These have allowed a better understanding of the molecular mechanisms of genetically determined pediatric endocrine disorders and are paving the way for a radical change in diagnosis and treatment. This article introduces some of these concepts and some of the genetic techniques being used.

  1. Whole mitochondrial genome genetic diversity in an Estonian population sample.

    Science.gov (United States)

    Stoljarova, Monika; King, Jonathan L; Takahashi, Maiko; Aaspõllu, Anu; Budowle, Bruce

    2016-01-01

    Mitochondrial DNA is a useful marker for population studies, human identification, and forensic analysis. Commonly used hypervariable regions I and II (HVI/HVII) were reported to contain as little as 25% of mitochondrial DNA variants and therefore the majority of power of discrimination of mitochondrial DNA resides in the coding region. Massively parallel sequencing technology enables entire mitochondrial genome sequencing. In this study, buccal swabs were collected from 114 unrelated Estonians and whole mitochondrial genome sequences were generated using the Illumina MiSeq system. The results are concordant with previous mtDNA control region reports of high haplogroup HV and U frequencies (47.4 and 23.7% in this study, respectively) in the Estonian population. One sample with the Northern Asian haplogroup D was detected. The genetic diversity of the Estonian population sample was estimated to be 99.67 and 95.85%, for mtGenome and HVI/HVII data, respectively. The random match probability for mtGenome data was 1.20 versus 4.99% for HVI/HVII. The nucleotide mean pairwise difference was 27 ± 11 for mtGenome and 7 ± 3 for HVI/HVII data. These data describe the genetic diversity of the Estonian population sample and emphasize the power of discrimination of the entire mitochondrial genome over the hypervariable regions.

  2. Genetical genomics identifies the genetic architecture for growth and weevil resistance in spruce.

    Science.gov (United States)

    Porth, Ilga; White, Richard; Jaquish, Barry; Alfaro, René; Ritland, Carol; Ritland, Kermit

    2012-01-01

    In plants, relationships between resistance to herbivorous insect pests and growth are typically controlled by complex interactions between genetically correlated traits. These relationships often result in tradeoffs in phenotypic expression. In this study we used genetical genomics to elucidate genetic relationships between tree growth and resistance to white pine terminal weevil (Pissodes strobi Peck.) in a pedigree population of interior spruce (Picea glauca, P. engelmannii and their hybrids) that was growing at Vernon, B.C. and segregating for weevil resistance. Genetical genomics uses genetic perturbations caused by allelic segregation in pedigrees to co-locate quantitative trait loci (QTLs) for gene expression and quantitative traits. Bark tissue of apical leaders from 188 trees was assayed for gene expression using a 21.8K spruce EST-spotted microarray; the same individuals were genotyped for 384 SNP markers for the genetic map. Many of the expression QTLs (eQTL) co-localized with resistance trait QTLs. For a composite resistance phenotype of six attack and oviposition traits, 149 positional candidate genes were identified. Resistance and growth QTLs also overlapped with eQTL hotspots along the genome suggesting that: 1) genetic pleiotropy of resistance and growth traits in interior spruce was substantial, and 2) master regulatory genes were important for weevil resistance in spruce. These results will enable future work on functional genetic studies of insect resistance in spruce, and provide valuable information about candidate genes for genetic improvement of spruce.

  3. Genetical genomics identifies the genetic architecture for growth and weevil resistance in spruce.

    Directory of Open Access Journals (Sweden)

    Ilga Porth

    Full Text Available In plants, relationships between resistance to herbivorous insect pests and growth are typically controlled by complex interactions between genetically correlated traits. These relationships often result in tradeoffs in phenotypic expression. In this study we used genetical genomics to elucidate genetic relationships between tree growth and resistance to white pine terminal weevil (Pissodes strobi Peck. in a pedigree population of interior spruce (Picea glauca, P. engelmannii and their hybrids that was growing at Vernon, B.C. and segregating for weevil resistance. Genetical genomics uses genetic perturbations caused by allelic segregation in pedigrees to co-locate quantitative trait loci (QTLs for gene expression and quantitative traits. Bark tissue of apical leaders from 188 trees was assayed for gene expression using a 21.8K spruce EST-spotted microarray; the same individuals were genotyped for 384 SNP markers for the genetic map. Many of the expression QTLs (eQTL co-localized with resistance trait QTLs. For a composite resistance phenotype of six attack and oviposition traits, 149 positional candidate genes were identified. Resistance and growth QTLs also overlapped with eQTL hotspots along the genome suggesting that: 1 genetic pleiotropy of resistance and growth traits in interior spruce was substantial, and 2 master regulatory genes were important for weevil resistance in spruce. These results will enable future work on functional genetic studies of insect resistance in spruce, and provide valuable information about candidate genes for genetic improvement of spruce.

  4. Introduction to International Ethical Standards Related to Genetics and Genomics

    Directory of Open Access Journals (Sweden)

    Seon-Hee Yim

    2013-12-01

    Full Text Available The rapid advances in genetic knowledge and technology raise various, sometimes unprecedented, ethical dilemmas in the scientific community as well as the public realm. To deal with these dilemmas, the international community has prepared and issued ethical standards in various formats. In this review, seven international standards regarding genetics and genomics will be briefly introduced in chronological order. Critical reflections on them will not be provided in this review, and naturally, they have their own problems and shortcomings. However, a common set of the principles expressed in them will be highlighted here, because they are still relevant, and many of them will be more relevant in the future. Some of the interesting contents will be selected and described. After that, the morality of one recent event related to whole-genome sequencing and person-identifiable genetic data will be explored based on those international standards.

  5. Population genomic analysis of ancient and modern genomes yields new insights into the genetic ancestry of the Tyrolean Iceman and the genetic structure of Europe.

    Directory of Open Access Journals (Sweden)

    Martin Sikora

    2014-05-01

    Full Text Available Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture.

  6. Genomic multiple sequence alignments: refinement using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Lefkowitz Elliot J

    2005-08-01

    Full Text Available Abstract Background Genomic sequence data cannot be fully appreciated in isolation. Comparative genomics – the practice of comparing genomic sequences from different species – plays an increasingly important role in understanding the genotypic differences between species that result in phenotypic differences as well as in revealing patterns of evolutionary relationships. One of the major challenges in comparative genomics is producing a high-quality alignment between two or more related genomic sequences. In recent years, a number of tools have been developed for aligning large genomic sequences. Most utilize heuristic strategies to identify a series of strong sequence similarities, which are then used as anchors to align the regions between the anchor points. The resulting alignment is globally correct, but in many cases is suboptimal locally. We describe a new program, GenAlignRefine, which improves the overall quality of global multiple alignments by using a genetic algorithm to improve local regions of alignment. Regions of low quality are identified, realigned using the program T-Coffee, and then refined using a genetic algorithm. Because a better COFFEE (Consistency based Objective Function For alignmEnt Evaluation score generally reflects greater alignment quality, the algorithm searches for an alignment that yields a better COFFEE score. To improve the intrinsic slowness of the genetic algorithm, GenAlignRefine was implemented as a parallel, cluster-based program. Results We tested the GenAlignRefine algorithm by running it on a Linux cluster to refine sequences from a simulation, as well as refine a multiple alignment of 15 Orthopoxvirus genomic sequences approximately 260,000 nucleotides in length that initially had been aligned by Multi-LAGAN. It took approximately 150 minutes for a 40-processor Linux cluster to optimize some 200 fuzzy (poorly aligned regions of the orthopoxvirus alignment. Overall sequence identity increased only

  7. Public opinion on policy issues in genetics and genomics.

    Science.gov (United States)

    Almeling, Rene; Gadarian, Shana Kushner

    2014-06-01

    The aim of this study was to examine public opinion on major policy issues in genetics and genomics, including federal spending on genetic research, the perceived significance of the Genetic Information Nondiscrimination Act of 2008, and whether clinicians should be involved in direct-to-consumer genetic testing. This was a survey with a nationally representative sample of 2,100 American adults administered by the nonpartisan research firm YouGov in January 2011. The majority of the respondents (57%) believe that the federal government should spend more on genetic research, 82% rank the 2008 antidiscrimination law as "important," and 65% say that clinicians should be involved in explaining genetic test results (contra the practice of some direct-to-consumer companies). On all three policy issues, gender and political party affiliation were statistically significantly associated with respondents' views, whereas race/ethnicity and education were less consistently associated with policy opinions. Americans demonstrate widespread support for scientific research on genetics, laws protecting citizens against genetic discrimination, and the need to involve medical professionals in the process of genetic testing. These results are useful for scientists designing research projects, clinicians interacting with patients, professional organizations lobbying for resources, federal agencies setting budget priorities, and legislators designing regulation.

  8. Macromolecular structure determination in the post-genome era

    CERN Document Server

    Kuhn, P

    2001-01-01

    Recent advances in genetics, molecular biology and crystallographic instrumentation and methodology have led to a revolution in the field of Structural Molecular Biology (SMB). These combined advances have paved the way to a more complete and detailed understanding of the biological macromolecules that make up an organism, both in terms of their individual functions and also the interactions between them. In this paper we describe a large-scale, genomic approach to the three-dimensional structure determination of macromolecules and their complexes, using high-throughput methodology to streamline all aspects of the process. This task requires the development of automated high-intensity synchrotron beam lines for X-ray diffraction data collection from single crystal samples. Furthermore, these beam lines must be operated within a sophisticated software and hardware environment, which is capable of delivering a completely automated structure determination pipeline. The SMB resource at SSRL is developing a system...

  9. Genetic Variability of Myxoma Virus Genomes

    Science.gov (United States)

    Braun, Christoph; Thürmer, Andrea; Daniel, Rolf; Schultz, Anne-Kathrin; Bulla, Ingo; Schirrmeier, Horst; Mayer, Dietmar; Neubert, Andreas

    2016-01-01

    ABSTRACT Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 myxoma virus (MYXV) strains were sequenced: German field isolates Munich-1, FLI-H, 2604, and 3207; vaccine strain MAV; and challenge strain ZA. The analyzed genomes ranged from 147.6 kb (strain MAV) to 161.8 kb (strain 3207). All sequences were affected by several mutations, covering 24 to 93 open reading frames (ORFs) and resulted in amino acid substitutions, insertions, or deletions. Only strains Munich-1 and MAV revealed the deletion of 10 ORFs (M007L to M015L) and 11 ORFs (M007L to M008.1L and M149R to M008.1R), respectively. Major differences were observed in the 27 immunomodulatory proteins encoded by MYXV. Compared to the reference strain Lausanne, strains FLI-H, 2604, 3207, and ZA showed the highest amino acid identity (>98.4%). In strains Munich-1 and MAV, deletion of 5 and 10 ORFs, respectively, was observed, encoding immunomodulatory proteins with ankyrin repeats or members of the family of serine protease inhibitors. Furthermore, putative immunodominant surface proteins with homology to vaccinia virus (VACV) were investigated in the sequenced strains. Only strain MAV revealed above-average frequencies of amino acid substitutions and frameshift mutations. Finally, we performed recombination analysis and found signs of recombination in vaccine strain MAV. Phylogenetic analysis showed a close relationship of strain MAV and the MSW strain of Californian MYXV. However, in a challenge model, strain MAV provided full protection against lethal challenges with strain ZA. IMPORTANCE Myxoma virus (MYXV) is pathogenic for European rabbits and two North American species. Due to sophisticated strategies in immune evasion and oncolysis, MYXV is an important model virus for immunological and

  10. Genetic Variability of Myxoma Virus Genomes.

    Science.gov (United States)

    Braun, Christoph; Thürmer, Andrea; Daniel, Rolf; Schultz, Anne-Kathrin; Bulla, Ingo; Schirrmeier, Horst; Mayer, Dietmar; Neubert, Andreas; Czerny, Claus-Peter

    2017-02-15

    Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 myxoma virus (MYXV) strains were sequenced: German field isolates Munich-1, FLI-H, 2604, and 3207; vaccine strain MAV; and challenge strain ZA. The analyzed genomes ranged from 147.6 kb (strain MAV) to 161.8 kb (strain 3207). All sequences were affected by several mutations, covering 24 to 93 open reading frames (ORFs) and resulted in amino acid substitutions, insertions, or deletions. Only strains Munich-1 and MAV revealed the deletion of 10 ORFs (M007L to M015L) and 11 ORFs (M007L to M008.1L and M149R to M008.1R), respectively. Major differences were observed in the 27 immunomodulatory proteins encoded by MYXV. Compared to the reference strain Lausanne, strains FLI-H, 2604, 3207, and ZA showed the highest amino acid identity (>98.4%). In strains Munich-1 and MAV, deletion of 5 and 10 ORFs, respectively, was observed, encoding immunomodulatory proteins with ankyrin repeats or members of the family of serine protease inhibitors. Furthermore, putative immunodominant surface proteins with homology to vaccinia virus (VACV) were investigated in the sequenced strains. Only strain MAV revealed above-average frequencies of amino acid substitutions and frameshift mutations. Finally, we performed recombination analysis and found signs of recombination in vaccine strain MAV. Phylogenetic analysis showed a close relationship of strain MAV and the MSW strain of Californian MYXV. However, in a challenge model, strain MAV provided full protection against lethal challenges with strain ZA. Myxoma virus (MYXV) is pathogenic for European rabbits and two North American species. Due to sophisticated strategies in immune evasion and oncolysis, MYXV is an important model virus for immunological and pathological research. In

  11. Plant genetics: RNA cache or genome trash?

    Science.gov (United States)

    Ray, Animesh

    2005-09-01

    According to classical mendelian genetics, individuals homozygous for an allele always breed true. Lolle et al. report a pattern of non-mendelian inheritance in the hothead (hth) mutant of Arabidopsis thaliana, in which a plant homozygous at a particular locus upon self-crossing produces progeny that are 10% heterozygous; they claim that this is the result of the emerging allele having been reintroduced into the chromosome from a cache of RNA inherited from a previous generation. Here I suggest that these results are equally compatible with a gene conversion that occurred through the use as a template of DNA fragments that were inherited from a previous generation and propagated in archival form in the meristem cells that generate the plant germ lines. This alternative model is compatible with several important observations by Lolle et al..

  12. Genetic mapping and genomic selection using recombination breakpoint data.

    Science.gov (United States)

    Xu, Shizhong

    2013-11-01

    The correct models for quantitative trait locus mapping are the ones that simultaneously include all significant genetic effects. Such models are difficult to handle for high marker density. Improving statistical methods for high-dimensional data appears to have reached a plateau. Alternative approaches must be explored to break the bottleneck of genomic data analysis. The fact that all markers are located in a few chromosomes of the genome leads to linkage disequilibrium among markers. This suggests that dimension reduction can also be achieved through data manipulation. High-density markers are used to infer recombination breakpoints, which then facilitate construction of bins. The bins are treated as new synthetic markers. The number of bins is always a manageable number, on the order of a few thousand. Using the bin data of a recombinant inbred line population of rice, we demonstrated genetic mapping, using all bins in a simultaneous manner. To facilitate genomic selection, we developed a method to create user-defined (artificial) bins, in which breakpoints are allowed within bins. Using eight traits of rice, we showed that artificial bin data analysis often improves the predictability compared with natural bin data analysis. Of the eight traits, three showed high predictability, two had intermediate predictability, and two had low predictability. A binary trait with a known gene had predictability near perfect. Genetic mapping using bin data points to a new direction of genomic data analysis.

  13. The African Genome Variation Project shapes medical genetics in Africa.

    Science.gov (United States)

    Gurdasani, Deepti; Carstensen, Tommy; Tekola-Ayele, Fasil; Pagani, Luca; Tachmazidou, Ioanna; Hatzikotoulas, Konstantinos; Karthikeyan, Savita; Iles, Louise; Pollard, Martin O; Choudhury, Ananyo; Ritchie, Graham R S; Xue, Yali; Asimit, Jennifer; Nsubuga, Rebecca N; Young, Elizabeth H; Pomilla, Cristina; Kivinen, Katja; Rockett, Kirk; Kamali, Anatoli; Doumatey, Ayo P; Asiki, Gershim; Seeley, Janet; Sisay-Joof, Fatoumatta; Jallow, Muminatou; Tollman, Stephen; Mekonnen, Ephrem; Ekong, Rosemary; Oljira, Tamiru; Bradman, Neil; Bojang, Kalifa; Ramsay, Michele; Adeyemo, Adebowale; Bekele, Endashaw; Motala, Ayesha; Norris, Shane A; Pirie, Fraser; Kaleebu, Pontiano; Kwiatkowski, Dominic; Tyler-Smith, Chris; Rotimi, Charles; Zeggini, Eleftheria; Sandhu, Manjinder S

    2015-01-15

    Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

  14. An integrated genetic and cytogenetic map of the cucumber genome.

    Directory of Open Access Journals (Sweden)

    Yi Ren

    Full Text Available The Cucurbitaceae includes important crops such as cucumber, melon, watermelon, squash and pumpkin. However, few genetic and genomic resources are available for plant improvement. Some cucurbit species such as cucumber have a narrow genetic base, which impedes construction of saturated molecular linkage maps. We report herein the development of highly polymorphic simple sequence repeat (SSR markers originated from whole genome shotgun sequencing and the subsequent construction of a high-density genetic linkage map. This map includes 995 SSRs in seven linkage groups which spans in total 573 cM, and defines approximately 680 recombination breakpoints with an average of 0.58 cM between two markers. These linkage groups were then assigned to seven corresponding chromosomes using fluorescent in situ hybridization (FISH. FISH assays also revealed a chromosomal inversion between Cucumis subspecies [C. sativus var. sativus L. and var. hardwickii (R. Alef], which resulted in marker clustering on the genetic map. A quarter of the mapped markers showed relatively high polymorphism levels among 11 inbred lines of cucumber. Among the 995 markers, 49%, 26% and 22% were conserved in melon, watermelon and pumpkin, respectively. This map will facilitate whole genome sequencing, positional cloning, and molecular breeding in cucumber, and enable the integration of knowledge of gene and trait in cucurbits.

  15. "It's all very well reading the letters in the genome, but it's a long way to being able to write": Men's interpretations of undergoing genetic profiling to determine future risk of prostate cancer.

    Science.gov (United States)

    Bancroft, Elizabeth K; Castro, Elena; Ardern-Jones, Audrey; Moynihan, Clare; Page, Elizabeth; Taylor, Natalie; Eeles, Rosalind A; Rowley, Emma; Cox, Karen

    2014-12-01

    A family history of prostate cancer (PC) is one of the main risk factors for the disease. A number of common single nucleotide polymorphisms (SNPs) that confer small but cumulatively substantial risks of PC have been identified, opening the possibility for the use of SNPs in PC risk stratification for targeted screening and prevention in the future. The objective of this study was to explore the psychosocial impact of receiving information about genetic risk of PC. The participants were men who had a family history of PC and were enrolled in a screening study providing research genetic profiling alongside screening for PC. A combination of questionnaires and in-depth interviews were used. Questionnaires were completed by men at two time points: both before and after joining the study and going through the genetic profiling process. The interviews were completed after all study process were complete and were analysed using a framework analysis. In total 95 men completed both questionnaires and 26 men were interviewed. A number of issues facing men at risk of PC were identified. The results fell into two main categories: personal relevance and societal relevance. The strength of men's innate beliefs about their risk, shaped by genetic and environmental assumptions, outweigh the information provided by genetic testing. Men felt genetic profile results would have future use for accessing prostate screening, being aware of symptoms and in communicating with others. The findings reinforce the importance of providing contextual information alongside genetic profiling test results, and emphasises the importance of the counselling process in providing genetic risk information. This research raises some key issues to facilitate clinical practice and future research related to the use of genetic profiling to determine risk of PC and other diseases.

  16. Genetically determined coagulation disorders in ischemic stroke

    NARCIS (Netherlands)

    M.P.J. van Goor (Marie-Louise)

    2004-01-01

    textabstractThe aim of the research described in this thesis was to investigate the role of genetically determined coagulation disorders in ischemic stroke. We therefore performed several retrospective studies and one prospective case-control study of patients with recent ischemic stroke (the COCOS

  17. Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation.

    Science.gov (United States)

    Kidd, Jeffrey M; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F; Peckham, Heather E; Omberg, Larsson; Bormann Chung, Christina A; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G; Russell, Archie; Reynolds, Andy; Clark, Andrew G; Reese, Martin G; Lincoln, Stephen E; Butte, Atul J; De La Vega, Francisco M; Bustamante, Carlos D

    2012-10-05

    Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago.

  18. The impact of genomics on population genetics of parasitic diseases.

    Science.gov (United States)

    Hupalo, Daniel N; Bradic, Martina; Carlton, Jane M

    2015-02-01

    Parasites, defined as eukaryotic microbes and parasitic worms that cause global diseases of human and veterinary importance, span many lineages in the eukaryotic Tree of Life. Historically challenging to study due to their complicated life-cycles and association with impoverished settings, their inherent complexities are now being elucidated by genome sequencing. Over the course of the last decade, projects in large sequencing centers, and increasingly frequently in individual research labs, have sequenced dozens of parasite reference genomes and field isolates from patient populations. This 'tsunami' of genomic data is answering questions about parasite genetic diversity, signatures of evolution orchestrated through anti-parasitic drug and host immune pressure, and the characteristics of populations. This brief review focuses on the state of the art of parasitic protist genomics, how the peculiar genomes of parasites are driving creative methods for their sequencing, and the impact that next-generation sequencing is having on our understanding of parasite population genomics and control of the diseases they cause.

  19. Genome-wide Association Studies from the Cancer Genetic Markers of Susceptibility (CGEMS) Initiative | Office of Cancer Genomics

    Science.gov (United States)

    CGEMS identifies common inherited genetic variations associated with a number of cancers, including breast and prostate. Data from these genome-wide association studies (GWAS) are available through the Division of Cancer Epidemiology & Genetics website.

  20. Beyond the thale: comparative genomics and genetics of Arabidopsis relatives.

    Science.gov (United States)

    Koenig, Daniel; Weigel, Detlef

    2015-05-01

    For decades a small number of model species have rightly occupied a privileged position in laboratory experiments, but it is becoming increasingly clear that our knowledge of biology is greatly improved when informed by a broader diversity of species and evolutionary context. Arabidopsis thaliana has been the primary model organism for plants, benefiting from a high-quality reference genome sequence and resources for reverse genetics. However, recent studies have made a group of species also in the Brassicaceae family and closely related to A. thaliana a focal point for comparative molecular, genomic, phenotypic and evolutionary studies. In this Review, we emphasize how such studies complement continued study of the model plant itself, provide an evolutionary perspective and summarize our current understanding of genetic and phenotypic diversity in plants.

  1. Genetic tools for manipulating Acinetobacter baumannii genome: an overview.

    Science.gov (United States)

    Biswas, Indranil

    2015-07-01

    Acinetobacter baumannii is an emerging nosocomial pathogen involved in a variety of infections ranging from minor soft-tissue infections to more severe infections such as ventilator-associated pneumonia and bacteraemia. A. baumannii has become resistant to most of the commonly used antibiotics and multidrug-resistant isolates are becoming a severe problem in the healthcare setting. In the past few years, whole-genome sequences of >200 A. baumannii isolates have been generated. Several methods and molecular tools have been used for genetic manipulation of various Acinetobacter spp. Here, we review recent developments of various genetic tools used for modification of the A. baumannii genome, including various ways to inactivate gene function, chromosomal integration and transposon mutagenesis.

  2. Plant MITEs: useful tools for plant genetics and genomics.

    Science.gov (United States)

    Feng, Ying

    2003-05-01

    MITEs (Miniature inverted-repeat transposable elements) are reminiscence of non-autonomous DNA (class II) elements, which are distinguished from other transposable elements by their small size, short terminal inverted repeats (TIRs), high copy numbers, genic preference, and DNA sequence identity among family members. Although MITEs were first discovered in plants and still actively reshaping genomes, they have been isolated from a wide range of eukaryotic organisms. MITEs can be divided into Tourist-like, Stowaway-like, and pogo-like groups, according to similarities of their TIRs and TSDs (target site duplications). In despite of several models to explain the origin and amplification of MITEs, their mechanisms of transposition and accumulation in eukaryotic genomes remain poorly understood owing to insufficient experimental data. The unique properties of MITEs have been exploited as useful genetic tools for plant genome analysis. Utilization of MITEs as effective and informative genomic markers and potential application of MITEs in plants systematic, phylogenetic, and genetic studies are discussed.

  3. Osteoarthritis year in review 2014: genetics and genomics.

    Science.gov (United States)

    Tsezou, A

    2014-12-01

    Recent developments in genetics/genomics of osteoarthritis (OA) are discussed to improve our understanding of OA pathophysiology. The discovery of a novel variant near the NCOA3 (nuclear receptor coactivator 3) gene associated with hip OA and the regulation of GDF5 gene by four transcription factors via the OA susceptibility locus rs143383 are among important findings in OA genetics. Several microarray-based gene expression studies were published for different tissues of the joint. In OA synovium elevation of collagens and cross-linking enzymes (COL1A1, COL5A1, PLOD2, LOX and TIMP1) responsive to TGF-β was found as well as differential expression pattern between different areas of the osteoarthritic synovial membrane. In OA peripheral blood the role of apoptotic genes was highlighted, while whole genome expression profiling in OA subchondral bone and cartilage revealed common genes in cartilage and bone to be involved in OA development. In epigenetics, several microRNAs (miRNAs) were found to regulate genes' expression in chondrocytes, among which miR-125, miR-127b miR-21, miR-148a and their use as potential drug targets was highlighted. Future studies must focus on the integration of genetics, genomics and epigenetics for the identification of signaling pathways and regulatory networks responsible for OA development.

  4. Using Genetic Distance to Infer the Accuracy of Genomic Prediction.

    Directory of Open Access Journals (Sweden)

    Marco Scutari

    2016-09-01

    Full Text Available The prediction of phenotypic traits using high-density genomic data has many applications such as the selection of plants and animals of commercial interest; and it is expected to play an increasing role in medical diagnostics. Statistical models used for this task are usually tested using cross-validation, which implicitly assumes that new individuals (whose phenotypes we would like to predict originate from the same population the genomic prediction model is trained on. In this paper we propose an approach based on clustering and resampling to investigate the effect of increasing genetic distance between training and target populations when predicting quantitative traits. This is important for plant and animal genetics, where genomic selection programs rely on the precision of predictions in future rounds of breeding. Therefore, estimating how quickly predictive accuracy decays is important in deciding which training population to use and how often the model has to be recalibrated. We find that the correlation between true and predicted values decays approximately linearly with respect to either FST or mean kinship between the training and the target populations. We illustrate this relationship using simulations and a collection of data sets from mice, wheat and human genetics.

  5. GDR (Genome Database for Rosaceae: integrated web resources for Rosaceae genomics and genetics research

    Directory of Open Access Journals (Sweden)

    Ficklin Stephen

    2004-09-01

    Full Text Available Abstract Background Peach is being developed as a model organism for Rosaceae, an economically important family that includes fruits and ornamental plants such as apple, pear, strawberry, cherry, almond and rose. The genomics and genetics data of peach can play a significant role in the gene discovery and the genetic understanding of related species. The effective utilization of these peach resources, however, requires the development of an integrated and centralized database with associated analysis tools. Description The Genome Database for Rosaceae (GDR is a curated and integrated web-based relational database. GDR contains comprehensive data of the genetically anchored peach physical map, an annotated peach EST database, Rosaceae maps and markers and all publicly available Rosaceae sequences. Annotations of ESTs include contig assembly, putative function, simple sequence repeats, and anchored position to the peach physical map where applicable. Our integrated map viewer provides graphical interface to the genetic, transcriptome and physical mapping information. ESTs, BACs and markers can be queried by various categories and the search result sites are linked to the integrated map viewer or to the WebFPC physical map sites. In addition to browsing and querying the database, users can compare their sequences with the annotated GDR sequences via a dedicated sequence similarity server running either the BLAST or FASTA algorithm. To demonstrate the utility of the integrated and fully annotated database and analysis tools, we describe a case study where we anchored Rosaceae sequences to the peach physical and genetic map by sequence similarity. Conclusions The GDR has been initiated to meet the major deficiency in Rosaceae genomics and genetics research, namely a centralized web database and bioinformatics tools for data storage, analysis and exchange. GDR can be accessed at http://www.genome.clemson.edu/gdr/.

  6. Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing.

    Science.gov (United States)

    Abdolrasouli, Alireza; Rhodes, Johanna; Beale, Mathew A; Hagen, Ferry; Rogers, Thomas R; Chowdhary, Anuradha; Meis, Jacques F; Armstrong-James, Darius; Fisher, Matthew C

    2015-06-02

    A rapid and global emergence of azole resistance has been observed in the pathogenic fungus Aspergillus fumigatus over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51A gene, which encodes a protein targeted by triazole antifungal drugs. Whole-genome sequencing (WGS) was performed for high-resolution single-nucleotide polymorphism (SNP) analysis of 24 A. fumigatus isolates, including azole-resistant and susceptible clinical and environmental strains obtained from India, the Netherlands, and the United Kingdom, in order to assess the utility of WGS for characterizing the alleles causing resistance. WGS analysis confirmed that TR34/L98H (a mutation comprising a tandem repeat [TR] of 34 bases in the promoter of the cyp51A gene and a leucine-to-histidine change at codon 98) is the sole mechanism of azole resistance among the isolates tested in this panel of isolates. We used population genomic analysis and showed that A. fumigatus was panmictic, with as much genetic diversity found within a country as is found between continents. A striking exception to this was shown in India, where isolates are highly related despite being isolated from both clinical and environmental sources across >1,000 km; this broad occurrence suggests a recent selective sweep of a highly fit genotype that is associated with the TR34/L98H allele. We found that these sequenced isolates are all recombining, showing that azole-resistant alleles are segregating into diverse genetic backgrounds. Our analysis delineates the fundamental population genetic parameters that are needed to enable the use of genome-wide association studies to identify the contribution of SNP diversity to the generation and spread of azole resistance in this medically important fungus. Resistance to azoles in the ubiquitous ascomycete fungus A. fumigatus was first reported from clinical isolates collected in the United States during the late 1980s

  7. Genetic determination of irritable bowel syndrome

    Institute of Scientific and Technical Information of China (English)

    Cristina Hotoleanu; Radu Popp; Adrian Pavel Trifa; Laurentiu Nedelcu; Dan L Dumitrascu

    2008-01-01

    Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder.According to the Rome Ⅲ criteria,IBS is defined as recurrent abdominal pain or discomfort for at least 3 d per month during the previous 3 mo associated with two or more of the following symptoms:improvement with defecation,onset associated with a change in the frequency of stool and/or onset associated with a change in form or appearance of stool.There is growing evidence regarding the genetic contribution in IBS,however the precise etiology of IBS is still unknown.The evaluation of the genetic influence is based on twin studies,familial aggregation and genetic epidemiological investigations.Most studies showed a concordance for IBS significantly greater in monozygotic than in dizygotic twins.The majority of the studies have shown that familial aggregation may represent exposures to a similar environment,as well as the influence of genetic factors.Whereas no specific gene has been identified in association with IBS,recent studies have noticed the importance of polymorphisms in the promoter region of the serotonin reuptake transporter gene,G-protein beta 3 subunit gene (C825T),cholecystokinin receptor (CCKAR gene 779T>C),and high-producer tumornecrosis factor genotype.Further studies are necessary to determine how genetic factors influence the clinical manifestations and therapeutical response in IBS patients.

  8. Genetic determinants of obesity and related vascular diseases.

    Science.gov (United States)

    Winter, Yaroslav; Sankowski, Roman; Back, Tobias

    2013-01-01

    Obesity is one of the major risk factors of vascular diseases, and its prevalence is increasing worldwide. In the past decade, progress has been made in the understanding of genetic determinants of obesity and obesity-associated diseases. Genome-wide association studies identified a number of genetic variants associated with obesity. In addition to common variants, FTO and MC4R, new loci, such as TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, and NEGR1 have been detected. In the past years, abdominal obesity has been shown to be a more important vascular risk factor than the body mass index. In the context of vascular risk assessment, identification of genetic polymorphisms associated with accumulation of visceral fat is of special importance. Some polymorphisms associated with abdominal obesity, such as variants of gene encoding microsomal triglyceride transfer protein, have been already discovered. In this chapter, we provide a review of genetic determinants of obesity and discuss their role in obesity-related vascular diseases.

  9. Breeding, genetic and genomic of citrus for disease resistance

    Directory of Open Access Journals (Sweden)

    Marcos A. Machado

    2011-10-01

    Full Text Available Although the citriculture is one of the most important economic activities in Brazil, it is based on a small number of varieties. This fact has contributed for the vulnerability of the culture regarding the phytosanitary problems. A higher number of varieties/genotypes with potential for commercial growing, either for the industry or fresh market, has been one of the main objectives of citrus breeding programs. The genetic breeding of citrus has improved, in the last decades, due to the possibility of an association between biotechnological tools and classical methods of breeding. The use of molecular markers for early selection of zygotic seedlings from controlled crosses resulted in the possibility of selection of a high number of new combination and, as a consequence, the establishment of a great number of hybrids in field experiments. The faster new tools are incorporated in the program, the faster is possibility to reach new genotypes that can be tested as a new variety. Good traits should be kept or incorporate, whereas bad traits have to be excluded or minimized in the new genotype. Scion and rootstock can not be considered separately, and graft compatibility, fruit quality and productivity are essential traits to be evaluated in the last stages of the program. The mapping of QTLs has favored breeding programs of several perennial species and in citrus it was possible to map several characteristics with qualitative and quantitative inheritance. The existence of linkage maps and QTLs already mapped, the development of EST and BAC library and the sequencing of the Citrus complete genome altogether make very demanding and urgent the exploration of such data to launch a wider genetic study of citrus. The rising of information on genome of several organisms has opened new approaches looking for integration between breeding, genetic and genome. Genome assisted selection (GAS involves more than gene or complete genome sequencing and is becoming

  10. A genomic scale map of genetic diversity in Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Ackermann Alejandro A

    2012-12-01

    Full Text Available Abstract Background Trypanosoma cruzi, the causal agent of Chagas Disease, affects more than 16 million people in Latin America. The clinical outcome of the disease results from a complex interplay between environmental factors and the genetic background of both the human host and the parasite. However, knowledge of the genetic diversity of the parasite, is currently limited to a number of highly studied loci. The availability of a number of genomes from different evolutionary lineages of T. cruzi provides an unprecedented opportunity to look at the genetic diversity of the parasite at a genomic scale. Results Using a bioinformatic strategy, we have clustered T. cruzi sequence data available in the public domain and obtained multiple sequence alignments in which one or two alleles from the reference CL-Brener were included. These data covers 4 major evolutionary lineages (DTUs: TcI, TcII, TcIII, and the hybrid TcVI. Using these set of alignments we have identified 288,957 high quality single nucleotide polymorphisms and 1,480 indels. In a reduced re-sequencing study we were able to validate ~ 97% of high-quality SNPs identified in 47 loci. Analysis of how these changes affect encoded protein products showed a 0.77 ratio of synonymous to non-synonymous changes in the T. cruzi genome. We observed 113 changes that introduce or remove a stop codon, some causing significant functional changes, and a number of tri-allelic and tetra-allelic SNPs that could be exploited in strain typing assays. Based on an analysis of the observed nucleotide diversity we show that the T. cruzi genome contains a core set of genes that are under apparent purifying selection. Interestingly, orthologs of known druggable targets show statistically significant lower nucleotide diversity values. Conclusions This study provides the first look at the genetic diversity of T. cruzi at a genomic scale. The analysis covers an estimated ~ 60% of the genetic diversity present in the

  11. Genetic stability of pestivirus genomes cloned into BACs

    DEFF Research Database (Denmark)

    Rasmussen, Thomas Bruun; Reimann, Ilona; Uttenthal, Åse;

    chromosome (BAC) vector “pBeloBAC11”. This BAC vector provides a markedly higher stability of cloned sequences in E. coli compared to plasmids that form the basis for the existing pestivirus cDNA clones. In this study, two of the newly constructed BAC clones were analysed for genetic stability of the cloned...... pestivirus genomes to demonstrate the suitability of the BAC vector for harbouring pestivirus genomes. Two BAC clones, comprising the complete genomes of BDV Gifhorn (pBeloGif3) and CSFV Paderborn (pBeloPader10) were passaged 15 times in E.coli representing at least 360 bacteria generations. From 15th...... passage of the BAC clones, the entire 5’ and 3’ ends of the cloned genomes and parts of the open reading frame were sequenced and compared to the sequences of the parent BAC clones. The sequenced areas represent approximately 20 % of the cloned genome. No mutations were observed after the extensive...

  12. Genetic control of flowering time in rice: integration of Mendelian genetics and genomics.

    Science.gov (United States)

    Hori, Kiyosumi; Matsubara, Kazuki; Yano, Masahiro

    2016-12-01

    Integration of previous Mendelian genetic analyses and recent molecular genomics approaches, such as linkage mapping and QTL cloning, dramatically strengthened our current understanding of genetic control of rice flowering time. Flowering time is one of the most important agronomic traits for seed production in rice (Oryza sativa L.). It is controlled mainly by genes associated with photoperiod sensitivity, particularly in short-day plants such as rice. Since the early twentieth century, rice breeders and researchers have been interested in elucidating the genetic basis of flowering time because its modification is important for regional adaptation and yield optimization. Although flowering time is a complex trait controlled by many quantitative trait loci (QTLs), classical genetic studies have shown that many associated genes are inherited in accordance with Mendelian laws. Decoding the rice genome sequence opened a new era in understanding the genetic control of flowering time on the basis of genome-wide mapping and gene cloning. Heading date 1 (Hd1) was the first flowering time QTL to be isolated using natural variation in rice. Recent accumulation of information on rice genome has facilitated the cloning of other QTLs, including those with minor effects on flowering time. This information has allowed us to rediscover some of the flowering genes that were identified by classical Mendelian genetics. The genes characterized so far, including Hd1, have been assigned to specific photoperiod pathways. In this review, we provide an overview of the studies that led to an in-depth understanding of the genetic control of flowering time in rice, and of the current state of improving and fine-tuning this trait for rice breeding.

  13. Family Competition Pheromone Genetic Algorithm for Comparative Genome Assembly

    Institute of Scientific and Technical Information of China (English)

    Chien-Hao Su; Chien-Shun Chiou; Jung-Che Kuo; Pei-Jen Wang; Cheng-Yan Kao; Hsueh-Ting Chu

    2014-01-01

    Genome assembly is a prerequisite step for analyzing next generation sequencing data and also far from being solved. Many assembly tools have been proposed and used extensively. Majority of them aim to assemble sequencing reads into contigs; however, we focus on the assembly of contigs into scaffolds in this paper. This is called scaffolding, which estimates the relative order of the contigs as well as the size of the gaps between these contigs. Pheromone trail-based genetic algorithm (PGA) was previously proposed and had decent performance according to their paper. From our previous study, we found that family competition mechanism in genetic algorithm is able to further improve the results. Therefore, we propose family competition pheromone genetic algorithm (FCPGA) and demonstrate the improvement over PGA.

  14. Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.

    Science.gov (United States)

    Dichgans, Martin; Malik, Rainer; König, Inke R; Rosand, Jonathan; Clarke, Robert; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Mitchell, Braxton D; Assimes, Themistocles L; Levi, Christopher; O'Donnell, Christopher J; Fornage, Myriam; Thorsteinsdottir, Unnur; Psaty, Bruce M; Hengstenberg, Christian; Seshadri, Sudha; Erdmann, Jeanette; Bis, Joshua C; Peters, Annette; Boncoraglio, Giorgio B; März, Winfried; Meschia, James F; Kathiresan, Sekar; Ikram, M Arfan; McPherson, Ruth; Stefansson, Kari; Sudlow, Cathie; Reilly, Muredach P; Thompson, John R; Sharma, Pankaj; Hopewell, Jemma C; Chambers, John C; Watkins, Hugh; Rothwell, Peter M; Roberts, Robert; Markus, Hugh S; Samani, Nilesh J; Farrall, Martin; Schunkert, Heribert

    2014-01-01

    Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (Pstroke (LAS) subtype. Common variants associated with CAD at Pgenetic risk of IS and particularly the LAS subtype with CAD.

  15. Expectation and futurity: The remarkable success of genetic determinism.

    Science.gov (United States)

    Esposito, Maurizio

    2017-04-01

    Genetic determinism is nowadays largely questioned and widely criticized. However, if we look at the history of biology in the last one hundred years, we realize that genetic determinism has always been controversial. Why, then, did it acquire such relevance in the past despite facing longstanding criticism? Through the analysis of some of the ambitious expectations of future scientific applications, this article explores the possibility that part of the historical success of genetic determinism lies in the powerful rhetorical strategies that have connected the germinal matter with alluring bio-technological visions. Indeed, in drawing on the recent perspectives of "expectation studies" in science and technology, it will be shown that there has been an interesting historical relationship between reductionist notions of the gene as a hereditary unit, coded information or functional DNA segment, and startling prophecies of what controlling such an entity might achieve. It will also be suggested that the well-known promissory nature of genomics is far older than the emergence of biotechnology in the 1970s. At least from the time of the bio-utopias predicted by J.B.S. Haldane and J. S. Huxley, the gene has often been surrounded by what I call the "rhetoric of futurity": a promissory rhetoric that, despite momentous changes in the life sciences throughout the 20th century, has remained relatively consistent over time.

  16. Call for papers--Legume Genomics and Genetics (ISSN 1925-1580)

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Legume Genomics and Genetics (LGG) (IS SN 1925-1580 online, http://lgg, sophiapublisher.com) propscd by legume geneticist Dr. Da Luo from Sun Yat-Sen University in China, is an open access and peer-reviewed journal publishing original research papers relevant to genomics and genetics in legume plants. It is committed to serving for legume genomics and genetics, especially featuring innovative research findings in the basic and applied fields of structural genomics, functional genomics, proteomics, epigenomics within the field of Legume sciences, as well as legume genetics from the molecular level to whole plant level.

  17. Reflections and perspectives of African-American community leaders regarding genetics and genomics research: sentiment and wisdom of Sankofa.

    Science.gov (United States)

    Underwood, Sandra Millon; Buseh, Aaron G; Stevens, Patricia E; Townsend, Leolia; Kelber, Sheryl T

    2013-07-01

    Advances in genetic and genomic research are shifting the typical disease timeline. For those afflicted by disease and for population groups known to experience excess disease-related morbidity and mortality, the ability to use genetics and genomics to predict an individuals' predisposition for developing a disease and/or to anticipate an individual's response to treatments holds tremendous promise. Over the past two decades several public and private institutions within the United States have been established for the purpose of collecting and storing biological specimens for the purpose of conducting genetic/genomic research. Multiple reports indicate that the involvement of racial/ethnic minority participants in these bio-repositories is limited. Little is known about the willingness of African-Americans, one of the largest and most vulnerable racial/ethnic population groups, to participate in genetic research, genomic research, and to contribute biological specimens to bio-repositories. An exploratory study was undertaken using principles of community engagement and community-based participatory research to examine the perspectives of leaders within the African-American community about participation in genetics research, genomics research, and bio-banking. Semi-structured focus groups with twenty-one African-American community leaders were the primary means of gathering the study data. Reflections and commentary of the community leaders were interspersed with sentiments of "Sankofa." The emergent themes, health-related disparities, historical injustices in medical research, the promise of genetic and genomic research, and genetics/genomic research engagement, implicated the importance of conducting genetics/genomics research in the context of the community interdependent with efforts to address determinants of health and health disparities.

  18. GDR (Genome Database for Rosaceae): integrated web-database for Rosaceae genomics and genetics data.

    Science.gov (United States)

    Jung, Sook; Staton, Margaret; Lee, Taein; Blenda, Anna; Svancara, Randall; Abbott, Albert; Main, Dorrie

    2008-01-01

    The Genome Database for Rosaceae (GDR) is a central repository of curated and integrated genetics and genomics data of Rosaceae, an economically important family which includes apple, cherry, peach, pear, raspberry, rose and strawberry. GDR contains annotated databases of all publicly available Rosaceae ESTs, the genetically anchored peach physical map, Rosaceae genetic maps and comprehensively annotated markers and traits. The ESTs are assembled to produce unigene sets of each genus and the entire Rosaceae. Other annotations include putative function, microsatellites, open reading frames, single nucleotide polymorphisms, gene ontology terms and anchored map position where applicable. Most of the published Rosaceae genetic maps can be viewed and compared through CMap, the comparative map viewer. The peach physical map can be viewed using WebFPC/WebChrom, and also through our integrated GDR map viewer, which serves as a portal to the combined genetic, transcriptome and physical mapping information. ESTs, BACs, markers and traits can be queried by various categories and the search result sites are linked to the mapping visualization tools. GDR also provides online analysis tools such as a batch BLAST/FASTA server for the GDR datasets, a sequence assembly server and microsatellite and primer detection tools. GDR is available at http://www.rosaceae.org.

  19. Osteoarthritis year 2013 in review: genetics and genomics.

    Science.gov (United States)

    Gonzalez, A

    2013-10-01

    Progress in genetic research has delivered important highlights in the last year. One of the widest impact is the publication of the Encyclopedia of DNA Elements (ENCODE) project showing the impressive complexity of the human genome and providing information useful for all areas of genetics. More specific of osteoarthritis (OA) has been the incorporation of DOT1-like, histone H3 methyltransferase (DOT1L) to the list of 11 OA loci with genome-wide significant association, the demonstration of significant overlap between OA genetics and height or body mass index (BMI) genetics, and the tentative prioritization of HMG-box transcription factor 1 (HBP1) in the 7q22 locus based on functional analysis. In addition, the first large scale analysis of DNA methylation has found modest differences between OA and normal cartilage, but has identified a subgroup of OA patients with a very differentiated phenotype. The role of DNA methylation in regulation of NOS2, SOX9, MMP13 and IL1B has been further clarified. MicroRNA expression studies in turn have shown some replication of differences between OA and control cartilage from previous profiling studies and have identified potential regulators of TGFβ signaling and of IL1β effects. In addition, non-coding RNAs showed promising results as serum biomarkers of cartilage damage. Gene expression microarray studies have found important differences between studies of hip or knee OA that reinforce the idea of joint specificity in OA. Expression differences between articular cartilage and other types of cartilage highlighted the WNT pathway whose regulation is proposed as critical for maintaining the articular cartilage phenotype. Many of these results need confirmation but they signal the exciting progress that is taking place in all areas of OA genetics, indicate questions requiring more study and augur further interesting discoveries.

  20. Prospects for advancing defense to cereal rusts through genetical genomics.

    Science.gov (United States)

    Ballini, Elsa; Lauter, Nick; Wise, Roger

    2013-01-01

    Rusts are one of the most severe threats to cereal crops because new pathogen races emerge regularly, resulting in infestations that lead to large yield losses. In 1999, a new race of stem rust, Puccinia graminis f. sp. tritici (Pgt TTKSK or Ug99), was discovered in Uganda. Most of the wheat and barley cultivars grown currently worldwide are susceptible to this new race. Pgt TTKSK has already spread northward into Iran and will likely spread eastward throughout the Indian subcontinent in the near future. This scenario is not unique to stem rust; new races of leaf rust (Puccinia triticina) and stripe rust (Puccinia striiformis) have also emerged recently. One strategy for countering the persistent adaptability of these pathogens is to stack complete- and partial-resistance genes, which requires significant breeding efforts in order to reduce deleterious effects of linkage drag. These varied resistance combinations are typically more difficult for the pathogen to defeat, since they would be predicted to apply lower selection pressure. Genetical genomics or expression Quantitative Trait Locus (eQTL) analysis enables the identification of regulatory loci that control the expression of many to hundreds of genes. Integrated deployment of these technologies coupled with efficient phenotyping offers significant potential to elucidate the regulatory nodes in genetic networks that orchestrate host defense responses. The focus of this review will be to present advances in genetical genomic experimental designs and analysis, particularly as they apply to the prospects for discovering partial disease resistance alleles in cereals.

  1. Pseudomonas putida CSV86: a candidate genome for genetic bioaugmentation.

    Directory of Open Access Journals (Sweden)

    Vasundhara Paliwal

    Full Text Available Pseudomonas putida CSV86, a plasmid-free strain possessing capability to transfer the naphthalene degradation property, has been explored for its metabolic diversity through genome sequencing. The analysis of draft genome sequence of CSV86 (6.4 Mb revealed the presence of genes involved in the degradation of naphthalene, salicylate, benzoate, benzylalcohol, p-hydroxybenzoate, phenylacetate and p-hydroxyphenylacetate on the chromosome thus ensuring the stability of the catabolic potential. Moreover, genes involved in the metabolism of phenylpropanoid and homogentisate, as well as heavy metal resistance, were additionally identified. Ability to grow on vanillin, veratraldehyde and ferulic acid, detection of inducible homogentisate dioxygenase and growth on aromatic compounds in the presence of heavy metals like copper, cadmium, cobalt and arsenic confirm in silico observations reflecting the metabolic versatility. In silico analysis revealed the arrangement of genes in the order: tRNA(Gly, integrase followed by nah operon, supporting earlier hypothesis of existence of a genomic island (GI for naphthalene degradation. Deciphering the genomic architecture of CSV86 for aromatic degradation pathways and identification of elements responsible for horizontal gene transfer (HGT suggests that genetic bioaugmentation strategies could be planned using CSV86 for effective bioremediation.

  2. Genetic and environmental determinants of menstrual characteristics

    Directory of Open Access Journals (Sweden)

    Shayesteh Jahanfar

    2012-01-01

    Full Text Available Background: The impact of women′s menstrual cycle on her quality of life, health, work, and community is substantial. Menstrual disturbance is linked with general ill conditions such as migraine, asthma, and endocrinopathies. The clinical significance of medical interventions to prevent these conditions becomes clear if the role of genetic or environment is clarified. Aims: To identify the genetic and environmental contribution on menstrual characteristics. Setting and Design: This was a cross-sectional study in 2 Asian countries. Materials and Methods: 2 cohorts of monozygotic and dizygotic twins born between (1945-1988, n = 122 and (1951-1993, n = 71 were taken. A standard questionnaire was designed inclusive of socio- demographic characteristics of subjects as well as menstrual history (duration, interval, amount, irregularity. Subjects were interviewed by phone. Statistical Analysis: Quantitative variables were analyzed using Falconars′ formula as well as maximum likelihood analysis. Structural modeling was then applied to twin correlations to provide estimates of the relative genetic and/or environmental factors contribution in determining the measured trait. Results: Menstrual characteristics were found to be under environmental influence where the best fitting model for menstrual interval and duration was common environment. CDF plotting confirmed the results for both variables. Proband-wise concordance analysis for amount of menstruation, amenorrhea, and irregular menstruation revealed no genetic influence. The best fitting model for menstrual irregularity was CE (C73%, E27%. The same model was defined for amenorrhea (C48%, E52%. Conclusions: Environmental factors are most likely responsible to determine the menstrual flow, its integrity, and regularity. These factors need to be studied further.

  3. Genomic view of bipolar disorder revealed by whole genome sequencing in a genetic isolate.

    Directory of Open Access Journals (Sweden)

    Benjamin Georgi

    2014-03-01

    Full Text Available Bipolar disorder is a common, heritable mental illness characterized by recurrent episodes of mania and depression. Despite considerable effort to elucidate the genetic underpinnings of bipolar disorder, causative genetic risk factors remain elusive. We conducted a comprehensive genomic analysis of bipolar disorder in a large Old Order Amish pedigree. Microsatellite genotypes and high-density SNP-array genotypes of 388 family members were combined with whole genome sequence data for 50 of these subjects, comprising 18 parent-child trios. This study design permitted evaluation of candidate variants within the context of haplotype structure by resolving the phase in sequenced parent-child trios and by imputation of variants into multiple unsequenced siblings. Non-parametric and parametric linkage analysis of the entire pedigree as well as on smaller clusters of families identified several nominally significant linkage peaks, each of which included dozens of predicted deleterious variants. Close inspection of exonic and regulatory variants in genes under the linkage peaks using family-based association tests revealed additional credible candidate genes for functional studies and further replication in population-based cohorts. However, despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implications for the design of studies of bipolar and other related disorders.

  4. Genomic diversity of cercarial clones of Himasthla elongata (Trematoda, Echinostomatidae) determined with AFLP technique.

    Science.gov (United States)

    Galaktionov, N K; Podgornaya, O I; Strelkov, P P; Galaktionov, K V

    2016-12-01

    The aim of this study was to reveal genomic diversity formed during parthenogenetic reproduction of rediae of the trematode Himasthla elongata in its molluskan host Littorina littorea. We applied amplification fragment length polymorphism (AFLP) to determine the genomic diversity of individual cercariae within the clone, that is, the infrapopulation of parthenogenetic progeny in a single molluskan host. The level of genomic diversity of particular cercariae isolates from a single clone, detected with EcoR1/Mse1 AFLP reaction, was significantly lower than the variability of cercariae from different clones. The presence of intraclonal genomic diversity indicates a nonsexual shuffle of alleles during parthenogenesis in the rediae of H. elongata. The obtained polymorphic AFLP fragments were long enough to detect the sequences that may be responsible for clonal genomic variability. Based on this, AFLP can be recommended as a tool for the study of genetic mechanisms of this variability.

  5. Genetics and Genomics of Longitudinal Lung Function Patterns in Asthmatics

    NARCIS (Netherlands)

    McGeachie, Michael J; Yates, Katherine P; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L; Van Natta, Mark L; Wise, Robert A; Szefler, Stanley J; Sharma, Sunita; Kho, Alvin T; Cho, Michael H; Croteau-Chonka, Damien C; Castaldi, Peter J; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A; Zeiger, Robert S; Adkinson, N Franklin; Williams, Paul V; Kelly, H William; Grasemann, Hartmut; Vonk, Judith M; Koppelman, Gerard H; Postma, Dirkje S; Raby, Benjamin A; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L; Tantisira, Kelan G; Silverman, Edwin K; Tonascia, James; Strunk, Robert C; Weiss, Scott T

    2016-01-01

    RATIONALE: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine the genetic und

  6. MaizeGDB: The Maize Genetics and Genomics Database.

    Science.gov (United States)

    Harper, Lisa; Gardiner, Jack; Andorf, Carson; Lawrence, Carolyn J

    2016-01-01

    MaizeGDB is the community database for biological information about the crop plant Zea mays. Genomic, genetic, sequence, gene product, functional characterization, literature reference, and person/organization contact information are among the datatypes stored at MaizeGDB. At the project's website ( http://www.maizegdb.org ) are custom interfaces enabling researchers to browse data and to seek out specific information matching explicit search criteria. In addition, pre-compiled reports are made available for particular types of data and bulletin boards are provided to facilitate communication and coordination among members of the community of maize geneticists.

  7. Identification of genetic markers for Mycobacterium pinnipedii through genome analysis.

    Science.gov (United States)

    Bigi, Fabiana; Garcia-Pelayo, M Carmen; Nuñez-García, Javier; Peralta, Andrea; Caimi, Karina C; Golby, Paul; Hinds, Jason; Cataldi, Angel; Gordon, Stephen V; Romano, Maria I

    2005-07-15

    Tuberculosis in seals is caused by Mycobacterium pinnipedii, a member of the Mycobacterium tuberculosis complex. In this study, we evaluated the extent of genetic variability among Mycobacterium bovis and M. pinnipedii by microarray-based comparative genomics. We identified two deletions that are exclusive to M. pinnipedii: PiD1 that removes the orthologues of the M. tuberculosis genes Rv3530c and Rv3531c, and PiD2 that encompasses genes Rv1977 and Rv1978. Interestingly, a deletion overlapping the previously described RD2 region was identified in some isolates of Mycobacterium microti and further characterised.

  8. Chapter 10: Mining genome-wide genetic markers.

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    Full Text Available Genome-wide association study (GWAS aims to discover genetic factors underlying phenotypic traits. The large number of genetic factors poses both computational and statistical challenges. Various computational approaches have been developed for large scale GWAS. In this chapter, we will discuss several widely used computational approaches in GWAS. The following topics will be covered: (1 An introduction to the background of GWAS. (2 The existing computational approaches that are widely used in GWAS. This will cover single-locus, epistasis detection, and machine learning methods that have been recently developed in biology, statistic, and computer science communities. This part will be the main focus of this chapter. (3 The limitations of current approaches and future directions.

  9. Genetic basis of triatomine behavior: lessons from available insect genomes

    Directory of Open Access Journals (Sweden)

    Jose Manuel Latorre-Estivalis

    2013-01-01

    Full Text Available Triatomines have been important model organisms for behavioural research. Diverse reports about triatomine host search, pheromone communication in the sexual, shelter and alarm contexts, daily cycles of activity, refuge choice and behavioural plasticity have been published in the last two decades. In recent times, a variety of molecular genetics techniques has allowed researchers to investigate elaborate and complex questions about the genetic bases of the physiology of insects. This, together with the current characterisation of the genome sequence of Rhodnius prolixus allows the resurgence of this excellent insect physiology model in the omics era. In the present revision, we suggest that studying the molecular basis of behaviour and sensory ecology in triatomines will promote a deeper understanding of fundamental aspects of insect and, particularly, vector biology. This will allow uncovering unknown features of essential insect physiology questions for a hemimetabolous model organism, promoting more robust comparative studies of insect sensory function and cognition.

  10. The Population Genomics of Sunflowers and Genomic Determinants of Protein Evolution Revealed by RNAseq

    Directory of Open Access Journals (Sweden)

    Loren H. Rieseberg

    2012-10-01

    Full Text Available Few studies have investigated the causes of evolutionary rate variation among plant nuclear genes, especially in recently diverged species still capable of hybridizing in the wild. The recent advent of Next Generation Sequencing (NGS permits investigation of genome wide rates of protein evolution and the role of selection in generating and maintaining divergence. Here, we use individual whole-transcriptome sequencing (RNAseq to refine our understanding of the population genomics of wild species of sunflowers (Helianthus spp. and the factors that affect rates of protein evolution. We aligned 35 GB of transcriptome sequencing data and identified 433,257 polymorphic sites (SNPs in a reference transcriptome comprising 16,312 genes. Using SNP markers, we identified strong population clustering largely corresponding to the three species analyzed here (Helianthus annuus, H. petiolaris, H. debilis, with one distinct early generation hybrid. Then, we calculated the proportions of adaptive substitution fixed by selection (alpha and identified gene ontology categories with elevated values of alpha. The “response to biotic stimulus” category had the highest mean alpha across the three interspecific comparisons, implying that natural selection imposed by other organisms plays an important role in driving protein evolution in wild sunflowers. Finally, we examined the relationship between protein evolution (dN/dS ratio and several genomic factors predicted to co-vary with protein evolution (gene expression level, divergence and specificity, genetic divergence [FST], and nucleotide diversity pi. We find that variation in rates of protein divergence was correlated with gene expression level and specificity, consistent with results from a broad range of taxa and timescales. This would in turn imply that these factors govern protein evolution both at a microevolutionary and macroevolutionary timescale. Our results contribute to a general understanding of the

  11. The Population Genomics of Sunflowers and Genomic Determinants of Protein Evolution Revealed by RNAseq.

    Science.gov (United States)

    Renaut, Sébastien; Grassa, Christopher J; Moyers, Brook T; Kane, Nolan C; Rieseberg, Loren H

    2012-10-25

    Few studies have investigated the causes of evolutionary rate variation among plant nuclear genes, especially in recently diverged species still capable of hybridizing in the wild. The recent advent of Next Generation Sequencing (NGS) permits investigation of genome wide rates of protein evolution and the role of selection in generating and maintaining divergence. Here, we use individual whole-transcriptome sequencing (RNAseq) to refine our understanding of the population genomics of wild species of sunflowers (Helianthus spp.) and the factors that affect rates of protein evolution. We aligned 35 GB of transcriptome sequencing data and identified 433,257 polymorphic sites (SNPs) in a reference transcriptome comprising 16,312 genes. Using SNP markers, we identified strong population clustering largely corresponding to the three species analyzed here (Helianthus annuus, H. petiolaris, H. debilis), with one distinct early generation hybrid. Then, we calculated the proportions of adaptive substitution fixed by selection (alpha) and identified gene ontology categories with elevated values of alpha. The "response to biotic stimulus" category had the highest mean alpha across the three interspecific comparisons, implying that natural selection imposed by other organisms plays an important role in driving protein evolution in wild sunflowers. Finally, we examined the relationship between protein evolution (dN/dS ratio) and several genomic factors predicted to co-vary with protein evolution (gene expression level, divergence and specificity, genetic divergence [FST], and nucleotide diversity pi). We find that variation in rates of protein divergence was correlated with gene expression level and specificity, consistent with results from a broad range of taxa and timescales. This would in turn imply that these factors govern protein evolution both at a microevolutionary and macroevolutionary timescale. Our results contribute to a general understanding of the determinants of

  12. Weight Stigma Reduction and Genetic Determinism.

    Science.gov (United States)

    Hilbert, Anja

    2016-01-01

    One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of-and responsibility for-obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention's gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity.

  13. Weight Stigma Reduction and Genetic Determinism

    Science.gov (United States)

    Hilbert, Anja

    2016-01-01

    One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of—and responsibility for—obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention’s gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity. PMID:27631384

  14. Learning directed acyclic graphical structures with genetical genomics data.

    Science.gov (United States)

    Gao, Bin; Cui, Yuehua

    2015-12-15

    Large amount of research efforts have been focused on estimating gene networks based on gene expression data to understand the functional basis of a living organism. Such networks are often obtained by considering pairwise correlations between genes, thus may not reflect the true connectivity between genes. By treating gene expressions as quantitative traits while considering genetic markers, genetical genomics analysis has shown its power in enhancing the understanding of gene regulations. Previous works have shown the improved performance on estimating the undirected network graphical structure by incorporating genetic markers as covariates. Knowing that gene expressions are often due to directed regulations, it is more meaningful to estimate the directed graphical network. In this article, we introduce a covariate-adjusted Gaussian graphical model to estimate the Markov equivalence class of the directed acyclic graphs (DAGs) in a genetical genomics analysis framework. We develop a two-stage estimation procedure to first estimate the regression coefficient matrix by [Formula: see text] penalization. The estimated coefficient matrix is then used to estimate the mean values in our multi-response Gaussian model to estimate the regulatory networks of gene expressions using PC-algorithm. The estimation consistency for high dimensional sparse DAGs is established. Simulations are conducted to demonstrate our theoretical results. The method is applied to a human Alzheimer's disease dataset in which differential DAGs are identified between cases and controls. R code for implementing the method can be downloaded at http://www.stt.msu.edu/∼cui. R code for implementing the method is freely available at http://www.stt.msu.edu/∼cui/software.html. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Genetic Transformation and Genomic Resources for Next-Generation Precise Genome Engineering in Vegetable Crops

    Science.gov (United States)

    Cardi, Teodoro; D’Agostino, Nunzio; Tripodi, Pasquale

    2017-01-01

    In the frame of modern agriculture facing the predicted increase of population and general environmental changes, the securement of high quality food remains a major challenge to deal with. Vegetable crops include a large number of species, characterized by multiple geographical origins, large genetic variability and diverse reproductive features. Due to their nutritional value, they have an important place in human diet. In recent years, many crop genomes have been sequenced permitting the identification of genes and superior alleles associated with desirable traits. Furthermore, innovative biotechnological approaches allow to take a step forward towards the development of new improved cultivars harboring precise genome modifications. Sequence-based knowledge coupled with advanced biotechnologies is supporting the widespread application of new plant breeding techniques to enhance the success in modification and transfer of useful alleles into target varieties. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 system, zinc-finger nucleases, and transcription activator-like effector nucleases represent the main methods available for plant genome engineering through targeted modifications. Such technologies, however, require efficient transformation protocols as well as extensive genomic resources and accurate knowledge before they can be efficiently exploited in practical breeding programs. In this review, we revise the state of the art in relation to availability of such scientific and technological resources in various groups of vegetables, describe genome editing results obtained so far and discuss the implications for future applications. PMID:28275380

  16. Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines.

    Science.gov (United States)

    Huang, Wen; Massouras, Andreas; Inoue, Yutaka; Peiffer, Jason; Ràmia, Miquel; Tarone, Aaron M; Turlapati, Lavanya; Zichner, Thomas; Zhu, Dianhui; Lyman, Richard F; Magwire, Michael M; Blankenburg, Kerstin; Carbone, Mary Anna; Chang, Kyle; Ellis, Lisa L; Fernandez, Sonia; Han, Yi; Highnam, Gareth; Hjelmen, Carl E; Jack, John R; Javaid, Mehwish; Jayaseelan, Joy; Kalra, Divya; Lee, Sandy; Lewis, Lora; Munidasa, Mala; Ongeri, Fiona; Patel, Shohba; Perales, Lora; Perez, Agapito; Pu, LingLing; Rollmann, Stephanie M; Ruth, Robert; Saada, Nehad; Warner, Crystal; Williams, Aneisa; Wu, Yuan-Qing; Yamamoto, Akihiko; Zhang, Yiqing; Zhu, Yiming; Anholt, Robert R H; Korbel, Jan O; Mittelman, David; Muzny, Donna M; Gibbs, Richard A; Barbadilla, Antonio; Johnston, J Spencer; Stone, Eric A; Richards, Stephen; Deplancke, Bart; Mackay, Trudy F C

    2014-07-01

    The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions. Weaker selection on insertions than deletions is consistent with our observed distribution of genome size determined by flow cytometry, which is skewed toward larger genomes. Insertion/deletion and single nucleotide polymorphisms are positively correlated with each other and with local recombination, suggesting that their nonrandom distributions are due to hitchhiking and background selection. Our cytogenetic analysis identified 16 polymorphic inversions in the DGRP. Common inverted and standard karyotypes are genetically divergent and account for most of the variation in relatedness among the DGRP lines. Intriguingly, variation in genome size and many quantitative traits are significantly associated with inversions. Approximately 50% of the DGRP lines are infected with Wolbachia, and four lines have germline insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP, and genome-wide analyses of quantitative traits identify novel candidate genes. The DGRP lines, sequence data, genotypes, quality scores, phenotypes, and analysis and visualization tools are publicly available.

  17. Review:Whole genome amplification in preimplantation genetic diagnosis

    Institute of Scientific and Technical Information of China (English)

    Ying-ming ZHENG; Ning WANG; Lei LI; Fan JIN

    2011-01-01

    Preimplantation genetic diagnosis(PGD)refers to a procedure for genetically analyzing embryos prior to implantation,improving the chance of conception for patients at high risk of transmitting specific inherited disorders.This method has been widely used for a large number of genetic disorders since the first successful application in the early 1990s.Polymerase chain reaction(PCR)and fluorescent in situ hybridization(FISH)are the two main methods in PGD,but there are some inevitable shortcomings limiting the scope of genetic diagnosis.Fortunately,different whole genome amplification(WGA)techniques have been developed to overcome these problems.Sufficient DNA can be amplified and multiple tasks which need abundant DNA can be performed.Moreover,WGA products can be analyzed as a template for multi-loci and multi-gene during the subsequent DNA analysis.In this review,we will focus on the currently available WGA techniques and their applications,as well as the new technical trends from WGA products.

  18. An integrated map of genetic variation from 1.092 human genomes

    DEFF Research Database (Denmark)

    Abecasis, Goncalo R.; Auton, Adam; Brooks, Lisa D.

    2012-01-01

    By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination...... deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding...... consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites...

  19. Decoding the non-coding genome: elucidating genetic risk outside the coding genome.

    Science.gov (United States)

    Barr, C L; Misener, V L

    2016-01-01

    Current evidence emerging from genome-wide association studies indicates that the genetic underpinnings of complex traits are likely attributable to genetic variation that changes gene expression, rather than (or in combination with) variation that changes protein-coding sequences. This is particularly compelling with respect to psychiatric disorders, as genetic changes in regulatory regions may result in differential transcriptional responses to developmental cues and environmental/psychosocial stressors. Until recently, however, the link between transcriptional regulation and psychiatric genetic risk has been understudied. Multiple obstacles have contributed to the paucity of research in this area, including challenges in identifying the positions of remote (distal from the promoter) regulatory elements (e.g. enhancers) and their target genes and the underrepresentation of neural cell types and brain tissues in epigenome projects - the availability of high-quality brain tissues for epigenetic and transcriptome profiling, particularly for the adolescent and developing brain, has been limited. Further challenges have arisen in the prediction and testing of the functional impact of DNA variation with respect to multiple aspects of transcriptional control, including regulatory-element interaction (e.g. between enhancers and promoters), transcription factor binding and DNA methylation. Further, the brain has uncommon DNA-methylation marks with unique genomic distributions not found in other tissues - current evidence suggests the involvement of non-CG methylation and 5-hydroxymethylation in neurodevelopmental processes but much remains unknown. We review here knowledge gaps as well as both technological and resource obstacles that will need to be overcome in order to elucidate the involvement of brain-relevant gene-regulatory variants in genetic risk for psychiatric disorders. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  20. Identification of RAN1 orthologue associated with sex determination through whole genome sequencing analysis in fig (Ficus carica L.).

    Science.gov (United States)

    Mori, Kazuki; Shirasawa, Kenta; Nogata, Hitoshi; Hirata, Chiharu; Tashiro, Kosuke; Habu, Tsuyoshi; Kim, Sangwan; Himeno, Shuichi; Kuhara, Satoru; Ikegami, Hidetoshi

    2017-01-25

    With the aim of identifying sex determinants of fig, we generated the first draft genome sequence of fig and conducted the subsequent analyses. Linkage analysis with a high-density genetic map established by a restriction-site associated sequencing technique, and genome-wide association study followed by whole-genome resequencing analysis identified two missense mutations in RESPONSIVE-TO-ANTAGONIST1 (RAN1) orthologue encoding copper-transporting ATPase completely associated with sex phenotypes of investigated figs. This result suggests that RAN1 is a possible sex determinant candidate in the fig genome. The genomic resources and genetic findings obtained in this study can contribute to general understanding of Ficus species and provide an insight into fig's and plant's sex determination system.

  1. Identifying trait clusters by linkage profiles: application in genetical genomics.

    Science.gov (United States)

    Sampson, Joshua N; Self, Steven G

    2008-04-01

    Genes often regulate multiple traits. Identifying clusters of traits influenced by a common group of genes helps elucidate regulatory networks and can improve linkage mapping. We show that the Pearson correlation coefficient, rho L, between two LOD score profiles can, with high specificity and sensitivity, identify pairs of genes that have their transcription regulated by shared quantitative trait loci (QTL). Furthermore, using theoretical and/or empirical methods, we can approximate the distribution of rho L under the null hypothesis of no common QTL. Therefore, it is possible to calculate P-values and false discovery rates for testing whether two traits share common QTL. We then examine the properties of rho L through simulation and use rho L to cluster genes in a genetical genomics experiment examining Saccharomyces cerevisiae. Simulations show that rho L can have more power than the clustering methods currently used in genetical genomics. Combining experimental results with Gene Ontology (GO) annotations show that genes within a purported cluster often share similar function. R-code included in online Supplementary Material.

  2. Advancing the biobehavioral research of fatigue with genetics and genomics.

    Science.gov (United States)

    Lyon, Debra E; McCain, Nancy L; Pickler, Rita H; Munro, Cindy; Elswick, R K

    2011-09-01

    To examine phenotypic considerations in the study of fatigue and to explore significant issues affecting the extension of biobehavioral research of fatigue by the inclusion of genetic and genomic markers. THEORETICAL ORGANIZATION: Fatigue is a condition that has an adverse effect on quality of life that has been a focus of nursing inquiry. Yet, the study of fatigue has been stymied by the lack of phenotypic clarity. To expand the biobehavioral inquiry of fatigue, phenotypic clarity is needed. In addition, examining genomic factors associated with fatigue may help to elucidate the pathophysiology of fatigue and, in the future, lead to targeted interventions that address the molecular basis of fatigue. Given that nursing has been at the forefront of the study of fatigue, nurse scientists should consider enhancing phenotypic clarity by the development of a case-definition and use of a core measure of fatigue, one that can be augmented by condition- or population-specific measures as needed. Following the establishment of phenotypic clarity, the integration of genomics into biobehavioral research offers an opportunity for further clarity of phenotypes and for theoretical specification of the pathophysiology of conditions such as fatigue. The development of targeted interventions for fatigue depend on a more precise definition of fatigue and a better understanding of the biologic processes that contribute to its development and persistence. © 2011 Sigma Theta Tau International.

  3. cDNA-AFLP-based genetical genomics in cotton fibers.

    Science.gov (United States)

    Claverie, Michel; Souquet, Marlène; Jean, Janine; Forestier-Chiron, Nelly; Lepitre, Vincent; Pré, Martial; Jacobs, John; Llewellyn, Danny; Lacape, Jean-Marc

    2012-03-01

    Genetical genomics, or genetic analysis applied to gene expression data, has not been widely used in plants. We used quantitative cDNA-AFLP to monitor the variation in the expression level of cotton fiber transcripts among a population of inter-specific Gossypium hirsutum × G. barbadense recombinant inbred lines (RILs). Two key fiber developmental stages, elongation (10 days post anthesis, dpa), and secondary cell wall thickening (22 dpa), were studied. Normalized intensity ratios of 3,263 and 1,201 transcript-derived fragments (TDFs) segregating over 88 RILs were analyzed for quantitative trait loci (QTL) mapping for the 10 and 22 dpa fibers, respectively. Two-thirds of all TDFs mapped between 1 and 6 eQTLs (LOD > 3.5). Chromosome 21 had a higher density of eQTLs than other chromosomes in both data sets and, within chromosomes, hotspots of presumably trans-acting eQTLs were identified. The eQTL hotspots were compared to the location of phenotypic QTLs for fiber characteristics among the RILs, and several cases of co-localization were detected. Quantitative RT-PCR for 15 sequenced TDFs showed that 3 TDFs had at least one eQTL at a similar location to those identified by cDNA-AFLP, while 3 other TDFs mapped an eQTL at a similar location but with opposite additive effect. In conclusion, cDNA-AFLP proved to be a cost-effective and highly transferable platform for genome-wide and population-wide gene expression profiling. Because TDFs are anonymous, further validation and interpretation (in silico analysis, qPCR gene profiling) of the eQTL and eQTL hotspots will be facilitated by the increasing availability of cDNA and genomic sequence resources in cotton.

  4. Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery Disease A Genome-Wide Analysis of Common Variants

    OpenAIRE

    Dichgans, Martin; Malik, Rainer; König, Inke R.; Rosand, Jonathan; Clarke, Robert; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Mitchell, Braxton D.; Assimes, Themistocles L.; Levi, Christopher; O′Donnell, Christopher J.; Fornage, Myriam; Thorsteinsdottir, Unnur; Psaty, Bruce M.; Hengstenberg, Christian

    2014-01-01

    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Genome-wide association data were obtained from ...

  5. Genetic linkage map of a wild genome: genomic structure, recombination and sexual dimorphism in bighorn sheep

    Directory of Open Access Journals (Sweden)

    Miller Joshua M

    2010-09-01

    Full Text Available Abstract Background The construction of genetic linkage maps in free-living populations is a promising tool for the study of evolution. However, such maps are rare because it is difficult to develop both wild pedigrees and corresponding sets of molecular markers that are sufficiently large. We took advantage of two long-term field studies of pedigreed individuals and genomic resources originally developed for domestic sheep (Ovis aries to construct a linkage map for bighorn sheep, Ovis canadensis. We then assessed variability in genomic structure and recombination rates between bighorn sheep populations and sheep species. Results Bighorn sheep population-specific maps differed slightly in contiguity but were otherwise very similar in terms of genomic structure and recombination rates. The joint analysis of the two pedigrees resulted in a highly contiguous map composed of 247 microsatellite markers distributed along all 26 autosomes and the X chromosome. The map is estimated to cover about 84% of the bighorn sheep genome and contains 240 unique positions spanning a sex-averaged distance of 3051 cM with an average inter-marker distance of 14.3 cM. Marker synteny, order, sex-averaged interval lengths and sex-averaged total map lengths were all very similar between sheep species. However, in contrast to domestic sheep, but consistent with the usual pattern for a placental mammal, recombination rates in bighorn sheep were significantly greater in females than in males (~12% difference, resulting in an autosomal female map of 3166 cM and an autosomal male map of 2831 cM. Despite differing genome-wide patterns of heterochiasmy between the sheep species, sexual dimorphism in recombination rates was correlated between orthologous intervals. Conclusions We have developed a first-generation bighorn sheep linkage map that will facilitate future studies of the genetic architecture of trait variation in this species. While domestication has been hypothesized

  6. Functional genomics bridges the gap between quantitative genetics and molecular biology.

    Science.gov (United States)

    Lappalainen, Tuuli

    2015-10-01

    Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field.

  7. On the Mapping of Epistatic Genetic Interactions in Natural Isolates: Combining Classical Genetics and Genomics.

    Science.gov (United States)

    Hou, Jing; Schacherer, Joseph

    2016-01-01

    Genetic variation within species is the substrate of evolution. Epistasis, which designates the non-additive interaction between loci affecting a specific phenotype, could be one of the possible outcomes of genetic diversity. Dissecting the basis of such interactions is of current interest in different fields of biology, from exploring the gene regulatory network, to complex disease genetics, to the onset of reproductive isolation and speciation. We present here a general workflow to identify epistatic interactions between independently evolving loci in natural populations of the yeast Saccharomyces cerevisiae. The idea is to exploit the genetic diversity present in the species by evaluating a large number of crosses and analyzing the phenotypic distribution in the offspring. For a cross of interest, both parental strains would have a similar phenotypic value, whereas the resulting offspring would have a bimodal distribution of the phenotype, possibly indicating the presence of epistasis. Classical segregation analysis of the tetrads uncovers the penetrance and complexity of the interaction. In addition, this segregation could serve as the guidelines for choosing appropriate mapping strategies to narrow down the genomic regions involved. Depending on the segregation patterns observed, we propose different mapping strategies based on bulk segregant analysis or consecutive backcrosses followed by high-throughput genome sequencing. Our method is generally applicable to all systems with a haplodiplobiontic life cycle and allows high resolution mapping of interacting loci that govern various DNA polymorphisms from single nucleotide mutations to large-scale structural variations.

  8. The genetics of loneliness: linking evolutionary theory to genome-wide genetics, epigenetics, and social science.

    Science.gov (United States)

    Goossens, Luc; van Roekel, Eeske; Verhagen, Maaike; Cacioppo, John T; Cacioppo, Stephanie; Maes, Marlies; Boomsma, Dorret I

    2015-03-01

    As a complex trait, loneliness is likely to be influenced by the interplay of numerous genetic and environmental factors. Studies in behavioral genetics indicate that loneliness has a sizable degree of heritability. Candidate-gene and gene-expression studies have pointed to several genes related to neurotransmitters and the immune system. The notion that these genes are related to loneliness is compatible with the basic tenets of the evolutionary theory of loneliness. Research on gene-environment interactions indicates that social-environmental factors (e.g., low social support) may have a more pronounced effect and lead to higher levels of loneliness if individuals carry the sensitive variant of these candidate genes. Currently, there is no extant research on loneliness based on genome-wide association studies, gene-environment-interaction studies, or studies in epigenetics. Such studies would allow researchers to identify networks of genes that contribute to loneliness. The contribution of genetics to loneliness research will become stronger when genome-wide genetics and epigenetics are integrated and used along with well-established methods in psychology to analyze the complex process of gene-environment interplay.

  9. Achilles' heel of pluripotent stem cells: genetic, genomic and epigenetic variations during prolonged culture.

    Science.gov (United States)

    Rebuzzini, Paola; Zuccotti, Maurizio; Redi, Carlo Alberto; Garagna, Silvia

    2016-07-01

    Pluripotent stem cells differentiate into almost any specialized adult cell type of an organism. PSCs can be derived either from the inner cell mass of a blastocyst-giving rise to embryonic stem cells-or after reprogramming of somatic terminally differentiated cells to obtain ES-like cells, named induced pluripotent stem cells. The potential use of these cells in the clinic, for investigating in vitro early embryonic development or for screening the effects of new drugs or xenobiotics, depends on capability to maintain their genome integrity during prolonged culture and differentiation. Both human and mouse PSCs are prone to genomic and (epi)genetic instability during in vitro culture, a feature that seriously limits their real potential use. Culture-induced variations of specific chromosomes or genes, are almost all unpredictable and, as a whole, differ among independent cell lines. They may arise at different culture passages, suggesting the absence of a safe passage number maintaining genome integrity and rendering the control of genomic stability mandatory since the very early culture passages. The present review highlights the urgency for further studies on the mechanisms involved in determining (epi)genetic and chromosome instability, exploiting the knowledge acquired earlier on other cell types.

  10. Genomic Analysis of Pathogenicity Determinants in Mycobacterium kansasii Type I

    KAUST Repository

    Guan, Qingtian

    2016-05-01

    Mycobacteria, a genus within Actinobacteria Phylum, are well known for two pathogens that cause human diseases: leprosy and tuberculosis. Other than the obligate human mycobacteria, there is a group of bacteria that are present in the environment and occasionally cause diseases in immunocompromised persons: the non-tuberculosis mycobacteria (NTM). Mycobacterium kansasii, which was first discovered in the Kansas state, is the main etiologic agent responsible for lung infections caused by NTM and raises attention because of its co-infection with human immunodeficiency virus (HIV). Five subspecies of M. kansasii (Type I-V) were described and only M. kansasii Type I is pathogenic to humans. M. kansasii is a Gram-positive bacteria that has a unique cell wall and secretion system, which is essential for its pathogenicity. We undertook a comparative genomics and transcriptomic approach to identify components of M. kansasii Type I pathogenicity. Our previous study showed that espA (ESX-1 essential protein) operon, a major component of the secretion system, is exclusively present in M. kansasii Type I. The purpose of this study was to test the functional role of the espA operon in pathogenicity and identify other components that may also be involved in pathogenicity. This study provides a new molecular diagnostic method for M. kansasii Type I infection using PCR (Polymerase Chain Reaction) technique to target the espAoperon. With detailed manual curation of the comparative genomics datasets, we found several genes exclusively present in M. kansasii Type I including ppsA/ppsC and whiB6, that we believe are involved, or have an effect on ESX-mediated secretion system. We have also highlighted, in our study, the differences in genetic components coding for the cell membrane composition between the five subspecies of M. kansasii. These results shed light on genetic components that are responsible for pathogenicity determinants in Type I M. kansasii and may help to design better

  11. Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma

    NARCIS (Netherlands)

    van Koolwijk, Leonieke M. E.; Ramdas, Wishal D.; Ikram, M. Kamran; Jansonius, Nomdo M.; Pasutto, Francesca; Hysi, Pirro G.; Macgregor, Stuart; Janssen, Sarah F.; Hewitt, Alex W.; Viswanathan, Ananth C.; ten Brink, Jacoline B.; Hosseini, S. Mohsen; Amin, Najaf; Despriet, Dominiek D. G.; Willemse-Assink, Jacqueline J. M.; Kramer, Rogier; Rivadeneira, Fernando; Struchalin, Maksim; Aulchenko, Yurii S.; Weisschuh, Nicole; Zenkel, Matthias; Mardin, Christian Y.; Gramer, Eugen; Welge-Luessen, Ulrich; Montgomery, Grant W.; Carbonaro, Francis; Young, Terri L.; Bellenguez, Celine; McGuffin, Peter; Foster, Paul J.; Topouzis, Fotis; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Y.; Czudowska, Monika A.; Hofman, Albert; Uitterlinden, Andre G.; Wolfs, Roger C. W.; de Jong, Paulus T. V. M.; Oostra, Ben A.; Paterson, Andrew D.; Mackey, David A.; Bergen, Arthur A. B.; Reis, Andre; Hammond, Christopher J.; Vingerling, Johannes R.; Lemij, Hans G.; Klaver, Caroline C. W.; van Duijn, Cornelia M.

    2012-01-01

    Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independen

  12. Pathogenicity determinants in smut fungi revealed by genome comparison.

    Science.gov (United States)

    Schirawski, Jan; Mannhaupt, Gertrud; Münch, Karin; Brefort, Thomas; Schipper, Kerstin; Doehlemann, Gunther; Di Stasio, Maurizio; Rössel, Nicole; Mendoza-Mendoza, Artemio; Pester, Doris; Müller, Olaf; Winterberg, Britta; Meyer, Elmar; Ghareeb, Hassan; Wollenberg, Theresa; Münsterkötter, Martin; Wong, Philip; Walter, Mathias; Stukenbrock, Eva; Güldener, Ulrich; Kahmann, Regine

    2010-12-10

    Biotrophic pathogens, such as the related maize pathogenic fungi Ustilago maydis and Sporisorium reilianum, establish an intimate relationship with their hosts by secreting protein effectors. Because secreted effectors interacting with plant proteins should rapidly evolve, we identified variable genomic regions by sequencing the genome of S. reilianum and comparing it with the U. maydis genome. We detected 43 regions of low sequence conservation in otherwise well-conserved syntenic genomes. These regions primarily encode secreted effectors and include previously identified virulence clusters. By deletion analysis in U. maydis, we demonstrate a role in virulence for four previously unknown diversity regions. This highlights the power of comparative genomics of closely related species for identification of virulence determinants.

  13. Genetics, genomics, and evolutionary biology of NKG2D ligands.

    Science.gov (United States)

    Carapito, Raphael; Bahram, Seiamak

    2015-09-01

    Human and mouse NKG2D ligands (NKG2DLs) are absent or only poorly expressed by most normal cells but are upregulated by cell stress, hence, alerting the immune system in case of malignancy or infection. Although these ligands are numerous and highly variable (at genetic, genomic, structural, and biochemical levels), they all belong to the major histocompatibility complex class I gene superfamily and bind to a single, invariant, receptor: NKG2D. NKG2D (CD314) is an activating receptor expressed on NK cells and subsets of T cells that have a key role in the recognition and lysis of infected and tumor cells. Here, we review the molecular diversity of NKG2DLs, discuss the increasing appreciation of their roles in a variety of medical conditions, and propose several explanations for the evolutionary force(s) that seem to drive the multiplicity and diversity of NKG2DLs while maintaining their interaction with a single invariant receptor.

  14. Molecular genetics and genomics progress in urothelial bladder cancer.

    Science.gov (United States)

    Netto, George J

    2013-11-01

    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  15. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

    NARCIS (Netherlands)

    Lee, S. Hong; Ripke, Stephan; Neale, Benjamin M.; Faraone, Stephen V.; Purcell, Shaun M.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breen, Gerome; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gallagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Geschwind, Daniel H.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A.; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Langstrom, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lee, Phil H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nurnberger, John I.; Nwulia, Evaristus A.; Nyholt, Dale R.; O'Dushlaine, Colm; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Posthuma, Danielle; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Antoni Ramos-Quiroga, Josep; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnstroem, Karola; Reif, Andreas; Ribases, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rossin, Lizzy; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutcliffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J. C. G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zoellner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Sullivan, Patrick F.; Smoller, Jordan W.; Kendler, Kenneth S.; Wray, Naomi R.

    2013-01-01

    Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases

  16. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

    NARCIS (Netherlands)

    Lee, S. Hong; Ripke, Stephan; Neale, Benjamin M.; Faraone, Stephen V.; Purcell, Shaun M.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breen, Gerome; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gallagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Geschwind, Daniel H.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A.; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Langstrom, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lee, Phil H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nurnberger, John I.; Nwulia, Evaristus A.; Nyholt, Dale R.; O'Dushlaine, Colm; Oades, Robert D.

    Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases

  17. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

    DEFF Research Database (Denmark)

    Lee, S Hong; Ripke, Stephan; Neale, Benjamin M

    2013-01-01

    Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cas...

  18. Myeloma genetics and genomics: practice implications and future directions.

    Science.gov (United States)

    Faiman, Beth

    2014-12-01

    Multiple myeloma (MM) is a heterogeneous, clonal disorder of the plasma cells originating from the B-cell line. The diagnosis and monitoring of MM requires routine measurement of biomarkers such as serum protein electrophoresis, urine protein electrophoresis, serum free light chains, among others. Prognostic models such as the Durie-Salmon staging system and International Staging System are available and account for the disease burden. Advanced biomarker and genetic testing includes cytogenetics, fluorescent in situ hybridization, and gene expression profiling to estimate the aggressiveness of the disease and personalize the patient's treatment. Future goals of therapy will be to achieve minimal residual disease (MRD), which incorporates biomarkers and genomic data. MRD testing might provide a better estimate of the depth of response to therapy and overall survival. A robust genomic program of research is still needed to provide additional information for the best MM care practices and to gain new strategies to treat the disease, in particular, in the relapsed and/or refractory setting.

  19. Analysis of genetic variation and potential applications in genome-scale metabolic modeling

    Directory of Open Access Journals (Sweden)

    João Gonçalo Rocha Cardoso

    2015-02-01

    Full Text Available Genetic variation is the motor of evolution and allows organisms to overcome the environmental challenges they encounter. It can be both beneficial and harmful in the process of engineering cell factories for the production of proteins and chemicals. Throughout the history of biotechnology, there have been efforts to exploit genetic variation in our favor to create strains with favorable phenotypes. Genetic variation can either be present in natural populations or it can be artificially created by mutagenesis and selection or adaptive laboratory evolution. On the other hand, unintended genetic variation during a long term production process may lead to significant economic losses and it is important to understand how to control this type of variation. With the emergence of next-generation sequencing technologies, genetic variation in microbial strains can now be determined on an unprecedented scale and resolution by re-sequencing thousands of strains systematically. In this article, we review challenges in the integration and analysis of large-scale re-sequencing data, present an extensive overview of bioinformatics methods for predicting the effects of genetic variants on protein function, and discuss approaches for interfacing existing bioinformatics approaches with genome-scale models of cellular processes in order to predict effects of sequence variation on cellular phenotypes.

  20. Genetic and environmental determinants of risk for cholangiocarcinoma in Thailand

    Institute of Scientific and Technical Information of China (English)

    Masanao; Miwa; Satoshi; Honjo; Gyokukou; You; Masakazu; Tanaka; Kazuhiko; Uchida; Petcharin; Srivatanakul; Thiravud; Khuhaprema; Watcharin; Loilome; Anchalee; Techasen; Chaisiri; Wongkham; Temduang; Limpaiboon; Puangrat; Yongvanit; Sopit; Wongkham

    2014-01-01

    Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients’ lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.

  1. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui

    2011-01-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations....... these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination...

  2. Genetic backgrounds determine brown remodeling of white fat in rodents

    Directory of Open Access Journals (Sweden)

    Giulia Ferrannini

    2016-10-01

    Conclusion: Rodent genetic background determines the brown remodeling of different white fat depots. This study provides new insights into the role of genetic variation in fat remodeling in susceptibility to metabolic diseases.

  3. Genetic Study of the Manganese Use Efficiency Trait in Winter Barley (Hordeum vulgare L.) by Genome- Wide Association and Genomic Selection

    DEFF Research Database (Denmark)

    Leplat, Florian Jean Victor

    Manganese (Mn) deficiency remains an unsolved nutritional problem affecting crop production worldwide. The tolerance to Mn limiting conditions, known as Mn efficiency, is a quantitative abiotic stress trait, generally controlled by several genes. However the underlying genetic background of Mn...... efficiency remained elusive. This PhD study aimed to understand better the genetic determination of the trait and propose new insights for plant breeding purposes. Two genome-wide approaches were used in a winter barley collection to characterize the genetic control of the trait. First, a Genome......-wide association study (GWAS) and chlorophyll a fluorescence phenotyping allowed to identify several QTLs involved in the plant response to Mn deficiency. Multiple candidate coding genes were fund, among which, photosystem II PsbP subunit, germin-like proteins or Mn-Superoxide Dismutase. It supports the Mn...

  4. An everlasting role of genetics and genomics in public health: a meeting report of ACGA-HKSMG International Conference on Genetic and Genomic Medicine 2008

    Institute of Scientific and Technical Information of China (English)

    Wai-Yee Chan; Stephen T.S.Lam; Bai-Lin Wu

    2009-01-01

    @@ The Association of Chinese Geneticists in America (ACGA) and the Hong Kong Society of Medical Genetics (HKSMG) held their first joint Conference on Genetic and Genomic Medicine in Hong Kong from June 9-11 in 2008at the Cheung Kung Hai Conference Center, William MW Mong Block, Li Ka Shing Faculty of Medicine, the University of Hong Kong.

  5. Combined use of genetic and genomics resources to understand virus resistance and fruit quality traits in melon.

    Science.gov (United States)

    Argyris, Jason M; Pujol, Marta; Martín-Hernández, Ana Montserrat; Garcia-Mas, Jordi

    2015-09-01

    The availability of the genome sequence of many crop species during the past few years has opened a new era in plant biology, allowing for the performance of massive genomic studies in plant species other than the classical models Arabidopsis and rice. One of these crop species is melon (Cucumis melo), a cucurbit of high economic value that has become an interesting model for the study of biological processes such as fruit ripening, sex determination and phloem transport. The recent availability of the melon genome sequence, together with a number of genetic and genomic resources, provides powerful tools that can be used to assist in the main melon breeding targets, namely disease resistance and fruit quality. In this review, we will describe recent data obtained combining the use of a melon near isogenic line (NIL) population and genomic resources to gain insight into agronomically important traits as fruit ripening, resistance to Cucumber Mosaic virus (CMV) and the accumulation of sugars in fruits.

  6. Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites

    Science.gov (United States)

    Chebon, Lorna J.; Ngalah, Bidii S.; Ingasia, Luicer A.; Juma, Dennis W.; Muiruri, Peninah; Cheruiyot, Jelagat; Opot, Benjamin; Mbuba, Emmanuel; Imbuga, Mabel; Akala, Hoseah M.; Bulimo, Wallace; Andagalu, Ben; Kamau, Edwin

    2016-01-01

    Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p resistance in Kenya. PMID:27611315

  7. Genetical Genomics of Behavior: A Novel Chicken Genomic Model for Anxiety Behavior.

    Science.gov (United States)

    Johnsson, Martin; Williams, Michael J; Jensen, Per; Wright, Dominic

    2016-01-01

    The identification of genetic variants responsible for behavioral variation is an enduring goal in biology, with wide-scale ramifications, ranging from medical research to evolutionary theory on personality syndromes. Here, we use for the first time a large-scale genetical genomics analysis in the brains of chickens to identify genes affecting anxiety as measured by an open field test. We combine quantitative trait locus (QTL) analysis in 572 individuals and expression QTL (eQTL) analysis in 129 individuals from an advanced intercross between domestic chickens and Red Junglefowl. We identify 10 putative quantitative trait genes affecting anxiety behavior. These genes were tested for an association in the mouse Heterogeneous Stock anxiety (open field) data set and human GWAS data sets for bipolar disorder, major depressive disorder, and schizophrenia. Although comparisons between species are complex, associations were observed for four of the candidate genes in mice and three of the candidate genes in humans. Using a multimodel approach we have therefore identified a number of putative quantitative trait genes affecting anxiety behavior, principally in chickens but also with some potentially translational effects as well. This study demonstrates that chickens are an excellent model organism for the genetic dissection of behavior.

  8. Genome survey and high-density genetic map construction provide genomic and genetic resources for the Pacific White Shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Yu, Yang; Zhang, Xiaojun; Yuan, Jianbo; Li, Fuhua; Chen, Xiaohan; Zhao, Yongzhen; Huang, Long; Zheng, Hongkun; Xiang, Jianhai

    2015-10-27

    The Pacific white shrimp Litopenaeus vannamei is the dominant crustacean species in global seafood mariculture. Understanding the genome and genetic architecture is useful for deciphering complex traits and accelerating the breeding program in shrimp. In this study, a genome survey was conducted and a high-density linkage map was constructed using a next-generation sequencing approach. The genome survey was used to identify preliminary genome characteristics and to generate a rough reference for linkage map construction. De novo SNP discovery resulted in 25,140 polymorphic markers. A total of 6,359 high-quality markers were selected for linkage map construction based on marker coverage among individuals and read depths. For the linkage map, a total of 6,146 markers spanning 4,271.43 cM were mapped to 44 sex-averaged linkage groups, with an average marker distance of 0.7 cM. An integration analysis linked 5,885 genome scaffolds and 1,504 BAC clones to the linkage map. Based on the high-density linkage map, several QTLs for body weight and body length were detected. This high-density genetic linkage map reveals basic genomic architecture and will be useful for comparative genomics research, genome assembly and genetic improvement of L. vannamei and other penaeid shrimp species.

  9. Good use and misuse of "genetic determinism".

    Science.gov (United States)

    Roubertoux, Pierre L; Carlier, Michèle

    2011-12-01

    After sequencing the human genome, scientists believed it would be possible to draw up a list of diseases, morphological characteristics and behavioral traits linked to each gene, but the post-genome era has shown that while links between genes and phenotypes, including behavioral phenotypes, do exist, they are more complex than was previously thought. There is no linear connection between genotype and brain and between brain and behavior; consequently, genomic and behavioral levels of organization are not isomorphous. There is no isomorphism because one gene plays many different roles, which means that the integrative processes needed for the development and functioning of an organism inevitably occurs in situations of non-linear multiple causality. Pleiotropy and epistasis, interactions between genes and the environment, alternative splicing and neuronal integration are all crucial mechanisms contributing to the many and varied aspects of brain-related genes.

  10. Genetic Mapping of Millions of SNPs in Safflower (Carthamus tinctorius L. via Whole-Genome Resequencing

    Directory of Open Access Journals (Sweden)

    John E. Bowers

    2016-07-01

    Full Text Available Accurate assembly of complete genomes is facilitated by very high density genetic maps. We performed low-coverage, whole-genome shotgun sequencing on 96 F6 recombinant inbred lines (RILs of a cross between safflower (Carthamus tinctorius L. and its wild progenitor (C. palaestinus Eig. We also produced a draft genome assembly of C. tinctorius covering 866 million bp (∼two-thirds of the expected 1.35 Gbp genome after sequencing a single, short insert library to ∼21 × depth. Sequence reads from the RILs were mapped to this genome assembly to facilitate SNP identification, and the resulting polymorphisms were used to construct a genetic map. The resulting map included 2,008,196 genetically located SNPs in 1178 unique positions. A total of 57,270 scaffolds, each containing five or more mapped SNPs, were anchored to the map. This resulted in the assignment of sequence covering 14% of the expected genome length to a genetic position. Comparison of this safflower map to genetic maps of sunflower and lettuce revealed numerous chromosomal rearrangements, and the resulting patterns were consistent with a whole-genome duplication event in the lineage leading to sunflower. This sequence-based genetic map provides a powerful tool for the assembly of a low-cost draft genome of safflower, and the same general approach is expected to work for other species.

  11. Genetic Mapping of Millions of SNPs in Safflower (Carthamus tinctorius L.) via Whole-Genome Resequencing.

    Science.gov (United States)

    Bowers, John E; Pearl, Stephanie A; Burke, John M

    2016-07-07

    Accurate assembly of complete genomes is facilitated by very high density genetic maps. We performed low-coverage, whole-genome shotgun sequencing on 96 F6 recombinant inbred lines (RILs) of a cross between safflower (Carthamus tinctorius L.) and its wild progenitor (C. palaestinus Eig). We also produced a draft genome assembly of C. tinctorius covering 866 million bp (∼two-thirds) of the expected 1.35 Gbp genome after sequencing a single, short insert library to ∼21 × depth. Sequence reads from the RILs were mapped to this genome assembly to facilitate SNP identification, and the resulting polymorphisms were used to construct a genetic map. The resulting map included 2,008,196 genetically located SNPs in 1178 unique positions. A total of 57,270 scaffolds, each containing five or more mapped SNPs, were anchored to the map. This resulted in the assignment of sequence covering 14% of the expected genome length to a genetic position. Comparison of this safflower map to genetic maps of sunflower and lettuce revealed numerous chromosomal rearrangements, and the resulting patterns were consistent with a whole-genome duplication event in the lineage leading to sunflower. This sequence-based genetic map provides a powerful tool for the assembly of a low-cost draft genome of safflower, and the same general approach is expected to work for other species.

  12. The prospect of genome-guided preventive medicine: a need and opportunity for genetic counselors.

    Science.gov (United States)

    O'Daniel, Julianne M

    2010-08-01

    One of the major anticipated benefits of genomic medicine is the area of preventive medicine. Commercially available genomic profiling is now able to generate risk information for a number of common conditions several of which have recognized preventive guidelines. Similarly, family history assessment affords powerful health risk prediction based on the shared genetic, physical and lifestyle environments within families. Thus, with the ability to help predict disease risk and enable preemptive health plans, genome-guided preventive medicine has the potential to improve population health on an individualized level. To realize this potential, steps to broaden access to accurate genomic health information must be considered. With expertise in genetic science, risk assessment and communication, and a patient-centered practice approach, genetic counselors are poised to play a critical role in facilitating the incorporation of genomic health risks into the burgeoning field of genome-guided preventive medicine.

  13. Cancer genomics

    DEFF Research Database (Denmark)

    Norrild, Bodil; Guldberg, Per; Ralfkiær, Elisabeth Methner

    2007-01-01

    Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines whe...

  14. [The genetic determinism of polygenic diseases].

    Science.gov (United States)

    Bach, Jean-François

    2005-05-01

    Progress in molecular biology has opened the way to identifying genes involved in predisposition to multigene diseases. The two methods currently used for this purpose--analysis of candidate genes and systematic genomic screening--have given interesting but only very partial results. The problem is complicated by the large number of genes involved, their low penetrance, and linkage disequilibrium.

  15. Computational approaches to identify functional genetic variants in cancer genomes

    DEFF Research Database (Denmark)

    Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris

    2013-01-01

    The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discu......The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result...

  16. [Genetics and Genomics of Wheat: Storage Proteins, Ecological Plasticity, and Immunity].

    Science.gov (United States)

    Novoselskaya-Dragovich, A Yu

    2015-05-01

    Recent advances in genetics and genetic research methods made it possible to explain the large polymorphism observed among storage proteins of wheat weevil (gliadins and glutenins), to determine their genetic control mechanism, and to develop a system for the identification of wheat genotypes on the basis of multiple allelism. This system has extremely high sensitivity and efficiency, which makes it possible to conduct studies to determine the purity and authenticity of wheat varieties, the dynamics of alleles diversity in time and space, the phylogenetics, etc., through the use of an extensive database on the allelic composition of gliadin loci. An investigation of the molecular structure of genes controlling the synthesis of storage proteins and their organization on chromosomes, as well as an analysis of wheat genome structure, revealed the molecular mechanisms of variability in the wheat genome and its reorganization in response to changes in environmental conditions and cultivation technologies. The multilevel genetic system of protection against pathogens and adverse environmental factors that developed in the course of wheat evolution continues to astound researchers' imagination with new resistance genes and novel types of antimicrobial peptides having been discovered and sequenced in recent years and the diversity of their structures and mechanisms of action in response to pathogens. An analysis of gene sequences involved in wheat domestication, namely, those that define ecological plasticity, i. e. the type of plant development (Vrn genes), and those responsible for spikelet traits (Q genes), which ensured the successful cultivation of wheat by humans, revealed that the basis for these features are specific mutations.

  17. Determination and analysis of the complete mitochondrial genome sequence of Taoyuan chicken.

    Science.gov (United States)

    Liu, Li-Li; Xie, Hong-Bing; Yu, Qi-Fang; He, Shao-Ping; He, Jian-Hua

    2016-01-01

    Taoyuan chicken is excellent native breeds in China. This study firstly determined the complete mitochondrial genome sequence of Taoyuan chicken using PCR-based amplification and Sanger sequencing. The characteristic of the entire mitochondrial genome was analyzed in detail, with the base composition of 30.26% A, 23.79% T, 32.44% C, 13.50% G in the Taoyuan chicken (16,784 bp in length). It contained 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and a major non-coding control region (D-loop region). The complete mitochondrial genome sequence of Taoyuan chicken will be useful for the phylogenetics of poultry, and be available as basic data for the genetics and breeding.

  18. Genetic compatibility determines endophyte-grass combinations.

    Directory of Open Access Journals (Sweden)

    Kari Saikkonen

    Full Text Available Even highly mutually beneficial microbial-plant interactions, such as mycorrhizal- and rhizobial-plant exchanges, involve selfishness, cheating and power-struggles between the partners, which depending on prevailing selective pressures, lead to a continuum of interactions from antagonistic to mutualistic. Using manipulated grass-endophyte combinations in a five year common garden experiment, we show that grass genotypes and genetic mismatches constrain genetic combinations between the vertically (via host seeds transmitted endophytes and the out-crossing host, thereby reducing infections in established grass populations. Infections were lost in both grass tillers and seedlings in F(1 and F(2 generations, respectively. Experimental plants were collected as seeds from two different environments, i.e., meadows and nearby riverbanks. Endophyte-related benefits to the host included an increased number of inflorescences, but only in meadow plants and not until the last growing season of the experiment. Our results illustrate the importance of genetic host specificity and trans-generational maternal effects on the genetic structure of a host population, which act as destabilizing forces in endophyte-grass symbioses. We propose that (1 genetic mismatches may act as a buffering mechanism against highly competitive endophyte-grass genotype combinations threatening the biodiversity of grassland communities and (2 these mismatches should be acknowledged, particularly in breeding programmes aimed at harnessing systemic and heritable endophytes to improve the agriculturally valuable characteristics of cultivars.

  19. Estimating Additive and Non-Additive Genetic Variances and Predicting Genetic Merits Using Genome-Wide Dense Single Nucleotide Polymorphism Markers

    DEFF Research Database (Denmark)

    Su, Guosheng; Christensen, Ole Fredslund; Ostersen, Tage;

    2012-01-01

    Non-additive genetic variation is usually ignored when genome-wide markers are used to study the genetic architecture and genomic prediction of complex traits in human, wild life, model organisms or farm animals. However, non-additive genetic effects may have an important contribution to total...... genetic variation of complex traits. This study presented a genomic BLUP model including additive and non-additive genetic effects, in which additive and non-additive genetic relation matrices were constructed from information of genome-wide dense single nucleotide polymorphism (SNP) markers. In addition...... of genomic predictions for daily gain in pigs. In the analysis of daily gain, four linear models were used: 1) a simple additive genetic model (MA), 2) a model including both additive and additive by additive epistatic genetic effects (MAE), 3) a model including both additive and dominance genetic effects...

  20. 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.

  1. Genetic Control of Canine Leishmaniasis: Genome-Wide Association Study and Genomic Selection Analysis

    OpenAIRE

    Javier Quilez; Verónica Martínez; Woolliams, John A; Armand Sanchez; Ricardo Pong-Wong; Kennedy, Lorna J.; Quinnell, Rupert J.; Ollier, William E R; Xavier Roura; Lluís Ferrer; Laura Altet; Olga Francino

    2012-01-01

    BACKGROUND: The current disease model for leishmaniasis suggests that only a proportion of infected individuals develop clinical disease, while others are asymptomatically infected due to immune control of infection. The factors that determine whether individuals progress to clinical disease following Leishmania infection are unclear, although previous studies suggest a role for host genetics. Our hypothesis was that canine leishmaniasis is a complex disease with multiple loci responsible for...

  2. Genetics and Genomics of Sjogren's Syndrome: Research provides Clues to Pathogenesis and Novel Therapies

    Science.gov (United States)

    Segal, Barbara M.; Nazmul-Hossain, Abu N. M.; Patel, Ketan; Hughes, Pamela; Moser, Kathy L.; Rhodus, Nelson L.

    2011-01-01

    Purpose While the key inciting events that drive the progression from autoantibodies to clinical disease remain to be clarified, new light has been shed on the factors contributing to disease susceptibility and the role of genetic factors in determining Sjogren's syndrome (SS) disease phenotypes. The purpose of this review is to provide an update on the role of genetic markers in the susceptibility to and pathogenesis of Sjogren's syndrome. This paper also discusses how genomic and proteomic technology can help in the design of specific therapeutics. Key Findings Recent evidence suggests that inflammatory genes associated with interferon pathways, and specific regulatory genes that control the maturation and proliferation of B cells, contribute to the pathogenesis of Sjogren's syndrome. Both gene expression profiling technology and gene association studies have been used to identify these key biologic pathways. Molecularly defined subsets of pSS patients are also being revealed by these studies. Previously identified gene loci which predispose to multiple autoimmune disorders have been confirmed supporting the paradigm of “general” autoimmune disease genes. Association of SS with many additional susceptibility loci are likely to be established through ongoing genome-wide association scans (GWAS). Clues from genetic studies suggest that targeting B cells will prove to be an effective way of reducing the systemic manifestations of pSS and are supported by early clinical trials. Summary Genome-wide technologies are likely to identify new genes and molecular pathways in the pathogenesis of SS that will be useful not only to identify patients at risk for SS, but also to identify subsets of patients at risk for variable levels of disease severity. In the future, these studies could identify novel biomarkers that will lead to significant advances in management by providing the means to tailor therapeutic strategies to individual patients. PMID:21497524

  3. CORAL REEFS. Genomic determinants of coral heat tolerance across latitudes.

    Science.gov (United States)

    Dixon, Groves B; Davies, Sarah W; Aglyamova, Galina A; Meyer, Eli; Bay, Line K; Matz, Mikhail V

    2015-06-26

    As global warming continues, reef-building corals could avoid local population declines through "genetic rescue" involving exchange of heat-tolerant genotypes across latitudes, but only if latitudinal variation in thermal tolerance is heritable. Here, we show an up-to-10-fold increase in odds of survival of coral larvae under heat stress when their parents come from a warmer lower-latitude location. Elevated thermal tolerance was associated with heritable differences in expression of oxidative, extracellular, transport, and mitochondrial functions that indicated a lack of prior stress. Moreover, two genomic regions strongly responded to selection for thermal tolerance in interlatitudinal crosses. These results demonstrate that variation in coral thermal tolerance across latitudes has a strong genetic basis and could serve as raw material for natural selection. Copyright © 2015, American Association for the Advancement of Science.

  4. Perspectives on Genetic and Genomic Technologies in an Academic Medical Center: The Duke Experience

    Directory of Open Access Journals (Sweden)

    Sara Huston Katsanis

    2015-04-01

    Full Text Available In this age of personalized medicine, genetic and genomic testing is expected to become instrumental in health care delivery, but little is known about its actual implementation in clinical practice. Methods. We surveyed Duke faculty and healthcare providers to examine the extent of genetic and genomic testing adoption. We assessed providers’ use of genetic and genomic testing options and indications in clinical practice, providers’ awareness of pharmacogenetic applications, and providers’ opinions on returning research-generated genetic test results to participants. Most clinician respondents currently use family history routinely in their clinical practice, but only 18 percent of clinicians use pharmacogenetics. Only two respondents correctly identified the number of drug package inserts with pharmacogenetic indications. We also found strong support for the return of genetic research results to participants. Our results demonstrate that while Duke healthcare providers are enthusiastic about genomic technologies, use of genomic tools outside of research has been limited. Respondents favor return of research-based genetic results to participants, but clinicians lack knowledge about pharmacogenetic applications. We identified challenges faced by this institution when implementing genetic and genomic testing into patient care that should inform a policy and education agenda to improve provider support and clinician-researcher partnerships.

  5. Genome size determination in peronosporales (Oomycota) by Feulgen image analysis.

    Science.gov (United States)

    Voglmayr, H; Greilhuber, J

    1998-12-01

    Genome size was determined, by nuclear Feulgen staining and image analysis, in 46 accessions of 31 species of Peronosporales (Oomycota), including important plant pathogens such as Bremia lactucae, Plasmopara viticola, Pseudoperonospora cubensis, and Pseudoperonospora humuli. The 1C DNA contents ranged from 0.046 (45. 6 Mb) to 0.163 pg (159.9 Mb). This is 0.041- to 0.144-fold that of Glycine max (soybean, 1C = 1.134 pg), which was used as an internal standard for genome size determination. The linearity of Feulgen absorbance photometry method over this range was demonstrated by calibration of Aspergillus species (1C = 31-38 Mb) against Glycine, which revealed differences of less than 6% compared to the published CHEF data. The low coefficients of variation (usually between 5 and 10%), repeatability of the results, and compatibility with CHEF data prove the resolution power of Feulgen image analysis. The applicability and limitations of Feulgen photometry are discussed in relation to other methods of genome size determination (CHEF gel electrophoresis, reassociation kinetics, genomic reconstruction) that have been previously applied to Oomycota. Copyright 1998 Academic Press.

  6. Demographic and genetic consequences of disturbed sex determination.

    OpenAIRE

    Wedekind, C

    2017-01-01

    During sex determination, genetic and/or environmental factors determine the cascade of processes of gonad development. Many organisms, therefore, have a developmental window in which their sex determination can be sensitive to, for example, unusual temperatures or chemical pollutants. Disturbed environments can distort population sex ratios and may even cause sex reversal in species with genetic sex determination. The resulting genotype-phenotype mismatches can have long-lasting effects on p...

  7. INNER EAR EMBRYOGENESIS: GENETIC AND ENVIRONMENTAL DETERMINANTS

    Science.gov (United States)

    The anatomy and developmental molecular genetics of the inner ear from establishment of the otic placode to formation of the definitive cochlea and vestibular apparatus will be reviewed and the complex 3-D structural changes that shape the developing inner ear will be illustrated...

  8. Genetic Diversity of Marine Anaerobic Ammonium-Oxidizing Bacteria as Revealed by Genomic and Proteomic Analyses of 'Candidatus Scalindua japonica'.

    Science.gov (United States)

    Oshiki, Mamoru; Mizuto, Keisuke; Kimura, Zenichiro; Kindaichi, Tomonori; Satoh, Hisashi; Okabe, Satoshi

    2017-09-11

    Anaerobic ammonium-oxidizing (anammox) bacteria affiliated with the genus 'Candidatus Scalindua' are responsible for significant nitrogen loss in oceans, and thus their ecophysiology is of great interest. Here, we enriched a marine anammox bacterium, 'Ca. S. japonica' from a Hiroshima bay sediment in Japan, and comparative genomic and proteomic analyses of 'Ca. S. japonica' were conducted. Sequence of the 4.81-Mb genome containing 4,019 coding regions of genes (CDSs) composed of 47 contigs was determined. In the proteome, 1,762 out of 4,019 CDSs in the 'Ca. S. japonica' genome were detected. Based on the genomic and proteomic data, the core anammox process and carbon fixation of 'Ca. S. japonica' were further investigated. Additionally, the present study provides the first detailed insights into the genetic background responsible for iron acquisition and menaquinone biosynthesis in anammox bacterial cells. Comparative analysis of the 'Ca. Scalindua' genomes revealed that the 1,502 genes found in the 'Ca. S. japonica' genome were not present in the 'Ca. S. profunda' and 'Ca. S. rubra' genomes, showing a high genomic diversity. This result may reflect a high phylogenetic diversity of the genus 'Ca. Scalindua'. This article is protected by copyright. All rights reserved. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  9. Integrating genetics and genomics into nursing curricula: you can do it too!

    Science.gov (United States)

    Daack-Hirsch, Sandra; Jackson, Barbara; Belchez, Chito A; Elder, Betty; Hurley, Roxanne; Kerr, Peg; Nissen, Mary Kay

    2013-12-01

    Rapid advances in knowledge and technology related to genomics cross health care disciplines and touch almost every aspect of patient care. The ability to sequence a genome holds the promise that health care can be personalized. Health care professionals are faced with a gap in the ability to use the rapidly expanding technology and knowledge related to genomics in practice. Yet, nurses are key to bridging the gap between genomic discoveries and the human experience of illness. This article presents a case study documenting the experience of five nursing schools/colleges of nursing as they work to integrate genetics and genomics into their curricula.

  10. Identification of genetic bases of vibrio fluvialis species-specific biochemical pathways and potential virulence factors by comparative genomic analysis.

    Science.gov (United States)

    Lu, Xin; Liang, Weili; Wang, Yunduan; Xu, Jialiang; Zhu, Jun; Kan, Biao

    2014-03-01

    Vibrio fluvialis is an important food-borne pathogen that causes diarrheal illness and sometimes extraintestinal infections in humans. In this study, we sequenced the genome of a clinical V. fluvialis strain and determined its phylogenetic relationships with other Vibrio species by comparative genomic analysis. We found that the closest relationship was between V. fluvialis and V. furnissii, followed by those with V. cholerae and V. mimicus. Moreover, based on genome comparisons and gene complementation experiments, we revealed genetic mechanisms of the biochemical tests that differentiate V. fluvialis from closely related species. Importantly, we identified a variety of genes encoding potential virulence factors, including multiple hemolysins, transcriptional regulators, and environmental survival and adaptation apparatuses, and the type VI secretion system, which is indicative of complex regulatory pathways modulating pathogenesis in this organism. The availability of V. fluvialis genome sequences may promote our understanding of pathogenic mechanisms for this emerging pathogen.

  11. Quantitative genetics model as the unifying model for defining genomic relationship and inbreeding coefficient.

    Science.gov (United States)

    Wang, Chunkao; Da, Yang

    2014-01-01

    The traditional quantitative genetics model was used as the unifying approach to derive six existing and new definitions of genomic additive and dominance relationships. The theoretical differences of these definitions were in the assumptions of equal SNP effects (equivalent to across-SNP standardization), equal SNP variances (equivalent to within-SNP standardization), and expected or sample SNP additive and dominance variances. The six definitions of genomic additive and dominance relationships on average were consistent with the pedigree relationships, but had individual genomic specificity and large variations not observed from pedigree relationships. These large variations may allow finding least related genomes even within the same family for minimizing genomic relatedness among breeding individuals. The six definitions of genomic relationships generally had similar numerical results in genomic best linear unbiased predictions of additive effects (GBLUP) and similar genomic REML (GREML) estimates of additive heritability. Predicted SNP dominance effects and GREML estimates of dominance heritability were similar within definitions assuming equal SNP effects or within definitions assuming equal SNP variance, but had differences between these two groups of definitions. We proposed a new measure of genomic inbreeding coefficient based on parental genomic co-ancestry coefficient and genomic additive correlation as a genomic approach for predicting offspring inbreeding level. This genomic inbreeding coefficient had the highest correlation with pedigree inbreeding coefficient among the four methods evaluated for calculating genomic inbreeding coefficient in a Holstein sample and a swine sample.

  12. Genetic Diseases and Genetic Determinism Models in French Secondary School Biology Textbooks

    Science.gov (United States)

    Castera, Jeremy; Bruguiere, Catherine; Clement, Pierre

    2008-01-01

    The presentation of genetic diseases in French secondary school biology textbooks is analysed to determine the major conceptions taught in the field of human genetics. References to genetic diseases, and the processes by which they are explained (monogeny, polygeny, chromosomal anomaly and environmental influence) are studied in recent French…

  13. Genetic Diseases and Genetic Determinism Models in French Secondary School Biology Textbooks

    Science.gov (United States)

    Castera, Jeremy; Bruguiere, Catherine; Clement, Pierre

    2008-01-01

    The presentation of genetic diseases in French secondary school biology textbooks is analysed to determine the major conceptions taught in the field of human genetics. References to genetic diseases, and the processes by which they are explained (monogeny, polygeny, chromosomal anomaly and environmental influence) are studied in recent French…

  14. Comparative assessment of genetic diversity in cytoplasmic and nuclear genome of upland cotton.

    Science.gov (United States)

    Egamberdiev, Sharof S; Saha, Sukumar; Salakhutdinov, Ilkhom; Jenkins, Johnie N; Deng, Dewayne; Y Abdurakhmonov, Ibrokhim

    2016-06-01

    The importance of the cytoplasmic genome for many economically important traits is well documented in several crop species, including cotton. There is no report on application of cotton chloroplast specific SSR markers as a diagnostic tool to study genetic diversity among improved Upland cotton lines. The complete plastome sequence information in GenBank provided us an opportunity to report on 17 chloroplast specific SSR markers using a cost-effective data mining strategy. Here we report the comparative analysis of genetic diversity among a set of 42 improved Upland cotton lines using SSR markers specific to chloroplast and nuclear genome, respectively. Our results revealed that low to moderate level of genetic diversity existed in both nuclear and cytoplasm genome among this set of cotton lines. However, the specific estimation suggested that genetic diversity is lower in cytoplasmic genome compared to the nuclear genome among this set of Upland cotton lines. In summary, this research is important from several perspectives. We detected a set of cytoplasm genome specific SSR primer pairs by using a cost-effective data mining strategy. We reported for the first time the genetic diversity in the cytoplasmic genome within a set of improved Upland cotton accessions. Results revealed that the genetic diversity in cytoplasmic genome is narrow, compared to the nuclear genome within this set of Upland cotton accessions. Our results suggested that most of these polymorphic chloroplast SSRs would be a valuable complementary tool in addition to the nuclear SSR in the study of evolution, gene flow and genetic diversity in Upland cotton.

  15. Genetic and genomic dissection of Prolactin revealed potential association with milk production traits in riverine buffalo.

    Science.gov (United States)

    Nadeem, A; Maryam, J

    2016-08-01

    Milk yield and quality has been a major selection criterion for genetic improvement in livestock species. Role of Prolactin gene in determining milk quality in terms of protein profile, lactose, lipids and other imperative macromolecules is very important. In this context, genetic profiling of Prolactin gene in riverine buffalo of Pakistan was performed and potential genetic markers were identified illustrating worth of this gene in marker-assisted selection of superior dairy buffaloes. Series of wet and dry lab experimentation was performed starting with genomic DNA isolation from true to breed representatives of indigenous river buffalo (Nili-Ravi). After amplification of coding regions of Prolactin gene, products were eluted and sequenced by Sanger's chain termination method and aligned to get variations in genomic region. A total of 15 novel variations were identified and analyzed statistically for their significance at population level, haplotypes were constructed, and association was estimated. Phylogenetic analysis was performed to evaluate the rate of evolution for Prolactin gene in various mammalian species. Lastly, biological networking for this molecule was predicted to get the bigger pictorial of its functional machinery. Pathway analysis was performed to find its physiological mode of action in milk synthesis. This is a first report toward complete genetic screening of Prolactin gene in Pakistani buffaloes. Results of this study not only provide an insight for potential role of Prolactin gene in milk-producing abilities of buffalo but also suggest new directions for exploration of more genes that may have promising role to enhance future milk production capabilities of river buffalo breeds of Asian region through marker-assisted selection.

  16. Variation in human recombination rates and its genetic determinants.

    Directory of Open Access Journals (Sweden)

    Adi Fledel-Alon

    Full Text Available BACKGROUND: Despite the fundamental role of crossing-over in the pairing and segregation of chromosomes during human meiosis, the rates and placements of events vary markedly among individuals. Characterizing this variation and identifying its determinants are essential steps in our understanding of the human recombination process and its evolution. STUDY DESIGN/RESULTS: Using three large sets of European-American pedigrees, we examined variation in five recombination phenotypes that capture distinct aspects of crossing-over patterns. We found that the mean recombination rate in males and females and the historical hotspot usage are significantly heritable and are uncorrelated with one another. We then conducted a genome-wide association study in order to identify loci that influence them. We replicated associations of RNF212 with the mean rate in males and in females as well as the association of Inversion 17q21.31 with the female mean rate. We also replicated the association of PRDM9 with historical hotspot usage, finding that it explains most of the genetic variance in this phenotype. In addition, we identified a set of new candidate regions for further validation. SIGNIFICANCE: These findings suggest that variation at broad and fine scales is largely separable and that, beyond three known loci, there is no evidence for common variation with large effects on recombination phenotypes.

  17. Methods for determining the genetic affinity of microorganisms and viruses

    Science.gov (United States)

    Fox, George E. (Inventor); Willson, III, Richard C. (Inventor); Zhang, Zhengdong (Inventor)

    2012-01-01

    Selecting which sub-sequences in a database of nucleic acid such as 16S rRNA are highly characteristic of particular groupings of bacteria, microorganisms, fungi, etc. on a substantially phylogenetic tree. Also applicable to viruses comprising viral genomic RNA or DNA. A catalogue of highly characteristic sequences identified by this method is assembled to establish the genetic identity of an unknown organism. The characteristic sequences are used to design nucleic acid hybridization probes that include the characteristic sequence or its complement, or are derived from one or more characteristic sequences. A plurality of these characteristic sequences is used in hybridization to determine the phylogenetic tree position of the organism(s) in a sample. Those target organisms represented in the original sequence database and sufficient characteristic sequences can identify to the species or subspecies level. Oligonucleotide arrays of many probes are especially preferred. A hybridization signal can comprise fluorescence, chemiluminescence, or isotopic labeling, etc.; or sequences in a sample can be detected by direct means, e.g. mass spectrometry. The method's characteristic sequences can also be used to design specific PCR primers. The method uniquely identifies the phylogenetic affinity of an unknown organism without requiring prior knowledge of what is present in the sample. Even if the organism has not been previously encountered, the method still provides useful information about which phylogenetic tree bifurcation nodes encompass the organism.

  18. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

    OpenAIRE

    Lee, Hong; Ripke, Stephan; Neale, Benjamin; Faraone, Stephen,; Purcell, Shaun; Perlis, Roy,; Mowry, Bryan; Thapar, Anita; Goddard, Michael; Witte, John,; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole,

    2013-01-01

    International audience; Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply uni...

  19. Groundnut improvement: use of genetic and genomic tools

    Directory of Open Access Journals (Sweden)

    Janila ePasupuleti

    2013-02-01

    Full Text Available Groundnut (Arachis hypogaea L., a self-pollinated legume is an important crop cultivated in 24 million ha world over for extraction of edible oil and food uses. The kernels are rich in oil (48-50% and protein (25-28%, and are source of several vitamins, minerals, antioxidants, biologically active polyphenols, flavonoids, and isoflavones. Improved varieties of groundnut with high yield potential were developed and released for cultivation world over. The improved varieties belong to different maturity durations and possess resistance to diseases, tolerance to drought, enhanced oil content, and improved quality traits for food uses. Conventional breeding procedures along with the tools for phenotyping were largely used in groundnut improvement programs. Mutations were used to induce variability and wide hybridization was attempted to tap variability from wild species. Low genetic variability has been a bottleneck for groundnut improvement. The vast potential of wild species, reservoir of new alleles remains under-utilized. Development of linkage maps of groundnut during the last decade was followed by identification of markers and QTLs for the target traits. Consequently, the last decade has witnessed the deployment of molecular breeding approaches to complement the ongoing groundnut improvement programs in USA, China, India, and Japan. The other potential advantages of molecular breeding are the feasibility to target multiple traits for improvement and provide tools to tap new alleles from wild species. The first groundnut variety developed through marker-assisted backcrossing (MABC is a root knot nematode resistant variety, NemaTAM in USA. The uptake of molecular breeding approaches in groundnut improvement programs by NARS partners in India and many African countries is slow or needs to be initiated in part due to inadequate infrastructure, high genotyping costs, and human capacities. Availability of draft genome sequence for diploid (AA & BB

  20. Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project.

    Science.gov (United States)

    Nannya, Yasuhito; Taura, Kenjiro; Kurokawa, Mineo; Chiba, Shigeru; Ogawa, Seishi

    2007-10-15

    With recent advances in high-throughput single nucleotide polymorphism (SNP) typing technologies, genome-wide association studies have become a realistic approach to identify the causative genes that are responsible for common diseases of complex genetic traits. In this strategy, a trade-off between the increased genome coverage and a chance of finding SNPs incidentally showing a large statistics becomes serious due to extreme multiple-hypothesis testing. We investigated the extent to which this trade-off limits the genome-wide power with this approach by simulating a large number of case-control panels based on the empirical data from the HapMap Project. In our simulations, statistical costs of multiple hypothesis testing were evaluated by empirically calculating distributions of the maximum value of the chi(2) statistics for a series of marker sets having increasing numbers of SNPs, which were used to determine a genome-wide threshold in the following power simulations. With a practical study size, the cost of multiple testing largely offsets the potential benefits from increased genome coverage given modest genetic effects and/or low frequencies of causal alleles. In most realistic scenarios, increasing genome coverage becomes less influential on the power, while sample size is the predominant determinant of the feasibility of genome-wide association tests. Increasing genome coverage without corresponding increase in sample size will only consume resources without little gain in power. For common causal alleles with relatively large effect sizes [genotype relative risk > or =1.7], we can expect satisfactory power with currently available large-scale genotyping platforms using realistic sample size ( approximately 1000 per arm).

  1. Progress in unraveling the genetic etiology of Parkinson disease in a genomic era.

    Science.gov (United States)

    Verstraeten, Aline; Theuns, Jessie; Van Broeckhoven, Christine

    2015-03-01

    Parkinson disease (PD) and Parkinson-plus syndromes are genetically heterogeneous neurological diseases. Initial studies into the genetic causes of PD relied on classical molecular genetic approaches in well-documented case families. More recently, these approaches have been combined with exome sequencing and together have identified 15 causal genes. Additionally, genome-wide association studies (GWASs) have discovered over 25 genetic risk factors. Elucidation of the genetic architecture of sporadic and familial parkinsonism, however, has lagged behind that of simple Mendelian conditions, suggesting the existence of features confounding genetic data interpretation. Here we discuss the successes and potential pitfalls of gene discovery in PD and related disorders in the post-genomic era. With an estimated 30% of trait variance currently unexplained, tackling current limitations will further expedite gene discovery and lead to increased application of these genetic insights in molecular diagnostics using gene panel and exome sequencing strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Novel genomic approaches unravel genetic architecture of complex traits in apple.

    NARCIS (Netherlands)

    Kumar, S.; Garrick, D.J.; Bink, M.C.A.M.; Whitworth, C.; Chagné, D.

    2013-01-01

    BACKGROUND: Understanding the genetic architecture of quantitative traits is important for developing genome-based crop improvement methods. Genome-wide association study (GWAS) is a powerful technique for mining novel functional variants. Using a family-based design involving 1,200 apple (Malus × d

  3. Semiconservative replication, genetic repair, and many-gened genomes: Extending the quasispecies paradigm to living systems

    Science.gov (United States)

    Tannenbaum, Emmanuel; Shakhnovich, Eugene I.

    2005-12-01

    Quasispecies theory has emerged as an important tool for modeling the evolutionary dynamics of biological systems. We review recent advances in the field, with an emphasis on the quasispecies dynamics of semiconservatively replicating genomes. Applications to cancer and adult stem cell growth are discussed. Additional topics, such as genetic repair and many-gene genomes, are covered as well.

  4. [Elucidation of key genes in sex determination in genetics teaching].

    Science.gov (United States)

    Li, Meng; He, Zhumei

    2014-06-01

    Sex is an important and complex feature of organisms, which is controlled by the genetic and environmental factors. The genetic factors, i.e., genes, are vital in sex determination. However, not all the related genes play the same roles, and some key genes play a vital role in the sex determination and differentiation. With the development of the modern genetics, a great progress on the key genes has been made in sex determination. In this review, we summarize the mechanism of sex determination and the strategy of how to study the key genes in sex determination. It will help us to understand the mechanism of sex determination better in the teaching of genetics.

  5. Genomic imprinting and maternal effect genes in haplodiploid sex determination.

    Science.gov (United States)

    van de Zande, L; Verhulst, E C

    2014-01-01

    The research into the Drosophila melanogaster sex-determining system has been at the basis of all further research on insect sex determination. This further research has made it clear that, for most insect species, the presence of sufficient functional Transformer (TRA) protein in the early embryonic stage is essential for female sexual development. In Hymenoptera, functional analysis of sex determination by knockdown studies of sex-determining genes has only been performed for 2 species. The first is the social insect species Apis mellifera, the honeybee, which has single-locus complementary sex determination (CSD). The other species is the parasitoid Nasonia vitripennis, the jewel wasp. Nasonia has a non-CSD sex-determining system, described as the maternal effect genomic imprinting sex determination system (MEGISD). Here, we describe the arguments that eventually led to the formulation of MEGISD and the experimental data that supported and refined this model. We evaluate the possibility that DNA methylation lies at the basis of MEGISD and briefly address the role of genomic imprinting in non-CSD sex determination in other Hymenoptera.

  6. Shared genetic susceptibility to ischemic stroke and coronary artery disease – a genome-wide analysis of common variants

    Science.gov (United States)

    Dichgans, Martin; Malik, Rainer; König, Inke R.; Rosand, Jonathan; Clarke, Robert; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Mitchell, Braxton D.; Assimes, Themistocles L.; Levi, Christopher; O′Donnell, Christopher J.; Fornage, Myriam; Thorsteinsdottir, Unnur; Psaty, Bruce M.; Hengstenberg, Christian; Seshadri, Sudha; Erdmann, Jeanette; Bis, Joshua C.; Peters, Annette; Boncoraglio, Giorgio B.; März, Winfried; Meschia, James F.; Kathiresan, Sekar; Ikram, M. Arfan; McPherson, Ruth; Stefansson, Kari; Sudlow, Cathie; Reilly, Muredach P.; Thompson, John R.; Sharma, Pankaj; Hopewell, Jemma C.; Chambers, John C.; Watkins, Hugh; Rothwell, Peter M.; Roberts, Robert; Markus, Hugh S.; Samani, Nilesh J.; Farrall, Martin; Schunkert, Heribert

    2014-01-01

    Summary Background and Purpose Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each have a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Methods Genome-wide association data were obtained from the METASTROKE, CARDIoGRAM, and C4D consortia. We first analyzed common variants reaching a nominal threshold of significance (pstroke (LAS) subtype. Results Common variants associated with CAD at pgenetic risk of ischemic stroke and particularly the large artery stroke subtype with coronary artery disease. PMID:24262325

  7. Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

    Energy Technology Data Exchange (ETDEWEB)

    Lemaire, D. [Universidade Federal da Bahia and Universidade Estadual da Bahia, Salvador, BA (Brazil); Barbosa, T. [Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA (Brazil); Rihet, P. [TAGC-INSERM U928, Aix-Marseille Université, Marseille (France)

    2011-10-28

    Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.

  8. Genome-scale genetic engineering in Escherichia coli.

    Science.gov (United States)

    Jeong, Jaehwan; Cho, Namjin; Jung, Daehee; Bang, Duhee

    2013-11-01

    Genome engineering has been developed to create useful strains for biological studies and industrial uses. However, a continuous challenge remained in the field: technical limitations in high-throughput screening and precise manipulation of strains. Today, technical improvements have made genome engineering more rapid and efficient. This review introduces recent advances in genome engineering technologies applied to Escherichia coli as well as multiplex automated genome engineering (MAGE), a recent technique proposed as a powerful toolkit due to its straightforward process, rapid experimental procedures, and highly efficient properties.

  9. RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

    Science.gov (United States)

    Sanchis, Marta; Lopez-Fernandez, Loida; Torres-Martínez, Santiago; Garre, Victoriano; Ruiz-Vázquez, Rosa María

    2017-01-01

    Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies. PMID:28107502

  10. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Pant, Sameer Dinkar; Fredholm, Merete;

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome...... of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation...

  11. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Pant, Sameer Dinkar; Fredholm, Merete

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome...... of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation...

  12. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    Science.gov (United States)

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  13. Computational discovery of pathway-level genetic vulnerabilities in non-small-cell lung cancer | Office of Cancer Genomics

    Science.gov (United States)

    Novel approaches are needed for discovery of targeted therapies for non-small-cell lung cancer (NSCLC) that are specific to certain patients. Whole genome RNAi screening of lung cancer cell lines provides an ideal source for determining candidate drug targets. Unsupervised learning algorithms uncovered patterns of differential vulnerability across lung cancer cell lines to loss of functionally related genes. Such genetic vulnerabilities represent candidate targets for therapy and are found to be involved in splicing, translation and protein folding.

  14. Attitudes of medical students towards human genome research and genetic counselling and testing

    Directory of Open Access Journals (Sweden)

    Schäfer, Mike Steffen

    2005-04-01

    Full Text Available Purpose: The study aimed to describe students' attitudes towards human genome research and towards genetic counselling and testing at cancer patients. The background of this investigation provided the increasing relevance ob human genetics research for clinical practice.Methods: A total of 167 medical students (54% female, aged 24 +/- 2 years from the second phase of their studies were surveyed in obligatory courses at the University of Leipzig, using a standardized questionnaire. Topics of the survey were attitudes towards human genome research and genetic counselling and testing at cancer patients as well as general values and socio-demographic data of the students.Results: The students consider human genome research as relevant and evaluate it positively, mainly based on expectations of medical uses. Genetic counselling and testing at cancer patients as an application of human genetics is also evaluated as important. The students attribute high relevance to clinical procedures for identification of genetic backgrounds for cancer (family history, information about genetic diagnostic. Nevertheless, deficits in their medical education are highlighted und reflected upon: the increased integration of human genetic content into medical curricula is demanded.Discussion: In accordance with the newly formulated „Approbationsordnung für Ärzte", the results suggest that current human genetic development should be more emphasized in medical education. This could be realized by an enlarged ratio of human genetic courses within curricula and by the transformation of these courses from facultative into obligatory.

  15. Genome sequence and genetic diversity of the common carp, Cyprinus carpio.

    Science.gov (United States)

    Xu, Peng; Zhang, Xiaofeng; Wang, Xumin; Li, Jiongtang; Liu, Guiming; Kuang, Youyi; Xu, Jian; Zheng, Xianhu; Ren, Lufeng; Wang, Guoliang; Zhang, Yan; Huo, Linhe; Zhao, Zixia; Cao, Dingchen; Lu, Cuiyun; Li, Chao; Zhou, Yi; Liu, Zhanjiang; Fan, Zhonghua; Shan, Guangle; Li, Xingang; Wu, Shuangxiu; Song, Lipu; Hou, Guangyuan; Jiang, Yanliang; Jeney, Zsigmond; Yu, Dan; Wang, Li; Shao, Changjun; Song, Lai; Sun, Jing; Ji, Peifeng; Wang, Jian; Li, Qiang; Xu, Liming; Sun, Fanyue; Feng, Jianxin; Wang, Chenghui; Wang, Shaolin; Wang, Baosen; Li, Yan; Zhu, Yaping; Xue, Wei; Zhao, Lan; Wang, Jintu; Gu, Ying; Lv, Weihua; Wu, Kejing; Xiao, Jingfa; Wu, Jiayan; Zhang, Zhang; Yu, Jun; Sun, Xiaowen

    2014-11-01

    The common carp, Cyprinus carpio, is one of the most important cyprinid species and globally accounts for 10% of freshwater aquaculture production. Here we present a draft genome of domesticated C. carpio (strain Songpu), whose current assembly contains 52,610 protein-coding genes and approximately 92.3% coverage of its paleotetraploidized genome (2n = 100). The latest round of whole-genome duplication has been estimated to have occurred approximately 8.2 million years ago. Genome resequencing of 33 representative individuals from worldwide populations demonstrates a single origin for C. carpio in 2 subspecies (C. carpio Haematopterus and C. carpio carpio). Integrative genomic and transcriptomic analyses were used to identify loci potentially associated with traits including scaling patterns and skin color. In combination with the high-resolution genetic map, the draft genome paves the way for better molecular studies and improved genome-assisted breeding of C. carpio and other closely related species.

  16. Genomics into Healthcare: the 5th Pan Arab Human Genetics Conference and 2013 Golden Helix Symposium.

    Science.gov (United States)

    Fortina, Paolo; Al Khaja, Najib; Al Ali, Mahmoud Taleb; Hamzeh, Abdul Rezzak; Nair, Pratibha; Innocenti, Federico; Patrinos, George P; Kricka, Larry J

    2014-05-01

    The joint 5th Pan Arab Human Genetics conference and 2013 Golden Helix Symposium, "Genomics into Healthcare" was coorganized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in collaboration with the Golden Helix Foundation (http://www.goldenhelix.org) in Dubai, United Arab Emirates from 17 to 19 November, 2013. The meeting was attended by over 900 participants, doctors and biomedical students from over 50 countries and was organized into a series of nine themed sessions that covered cancer genomics and epigenetics, genomic and epigenetic studies, genomics of blood and metabolic disorders, cytogenetic diagnosis and molecular profiling, next-generation sequencing, consanguinity and hereditary diseases, clinical genomics, clinical applications of pharmacogenomics, and genomics in public health.

  17. Interspecific Chromosome Substitution Lines as Genetic Resources for Improvement,Trait Analysis and Genomic Inference

    Institute of Scientific and Technical Information of China (English)

    RASKA Dwaine A; SAHA Sukumar; JENKINS Johnie N; MCCARTY Jack C; WU Ji-xiang; STELLY David M

    2008-01-01

    @@ The genetic base that cotton breeders commonly use to improve Upland cultivars is very narrow.The AD-genome species Gossypium barbadense,G.tomentosum,and G.mustelinum are part of the primary germplasm pool,too,and constitute genetic reservoirs of genes for resistance to abiotic stress,pests,and pathogens,as well as agronomic and fiber traits.

  18. Viral genome segmentation can result from a trade-off between genetic content and particle stability.

    Science.gov (United States)

    Ojosnegros, Samuel; García-Arriaza, Juan; Escarmís, Cristina; Manrubia, Susanna C; Perales, Celia; Arias, Armando; Mateu, Mauricio García; Domingo, Esteban

    2011-03-01

    The evolutionary benefit of viral genome segmentation is a classical, yet unsolved question in evolutionary biology and RNA genetics. Theoretical studies anticipated that replication of shorter RNA segments could provide a replicative advantage over standard size genomes. However, this question has remained elusive to experimentalists because of the lack of a proper viral model system. Here we present a study with a stable segmented bipartite RNA virus and its ancestor non-segmented counterpart, in an identical genomic nucleotide sequence context. Results of RNA replication, protein expression, competition experiments, and inactivation of infectious particles point to a non-replicative trait, the particle stability, as the main driver of fitness gain of segmented genomes. Accordingly, measurements of the volume occupation of the genome inside viral capsids indicate that packaging shorter genomes involves a relaxation of the packaging density that is energetically favourable. The empirical observations are used to design a computational model that predicts the existence of a critical multiplicity of infection for domination of segmented over standard types. Our experiments suggest that viral segmented genomes may have arisen as a molecular solution for the trade-off between genome length and particle stability. Genome segmentation allows maximizing the genetic content without the detrimental effect in stability derived from incresing genome length.

  19. Viral genome segmentation can result from a trade-off between genetic content and particle stability.

    Directory of Open Access Journals (Sweden)

    Samuel Ojosnegros

    2011-03-01

    Full Text Available The evolutionary benefit of viral genome segmentation is a classical, yet unsolved question in evolutionary biology and RNA genetics. Theoretical studies anticipated that replication of shorter RNA segments could provide a replicative advantage over standard size genomes. However, this question has remained elusive to experimentalists because of the lack of a proper viral model system. Here we present a study with a stable segmented bipartite RNA virus and its ancestor non-segmented counterpart, in an identical genomic nucleotide sequence context. Results of RNA replication, protein expression, competition experiments, and inactivation of infectious particles point to a non-replicative trait, the particle stability, as the main driver of fitness gain of segmented genomes. Accordingly, measurements of the volume occupation of the genome inside viral capsids indicate that packaging shorter genomes involves a relaxation of the packaging density that is energetically favourable. The empirical observations are used to design a computational model that predicts the existence of a critical multiplicity of infection for domination of segmented over standard types. Our experiments suggest that viral segmented genomes may have arisen as a molecular solution for the trade-off between genome length and particle stability. Genome segmentation allows maximizing the genetic content without the detrimental effect in stability derived from incresing genome length.

  20. Viral Genome Segmentation Can Result from a Trade-Off between Genetic Content and Particle Stability

    Science.gov (United States)

    Ojosnegros, Samuel; García-Arriaza, Juan; Escarmís, Cristina; Manrubia, Susanna C.; Perales, Celia; Arias, Armando; Mateu, Mauricio García; Domingo, Esteban

    2011-01-01

    The evolutionary benefit of viral genome segmentation is a classical, yet unsolved question in evolutionary biology and RNA genetics. Theoretical studies anticipated that replication of shorter RNA segments could provide a replicative advantage over standard size genomes. However, this question has remained elusive to experimentalists because of the lack of a proper viral model system. Here we present a study with a stable segmented bipartite RNA virus and its ancestor non-segmented counterpart, in an identical genomic nucleotide sequence context. Results of RNA replication, protein expression, competition experiments, and inactivation of infectious particles point to a non-replicative trait, the particle stability, as the main driver of fitness gain of segmented genomes. Accordingly, measurements of the volume occupation of the genome inside viral capsids indicate that packaging shorter genomes involves a relaxation of the packaging density that is energetically favourable. The empirical observations are used to design a computational model that predicts the existence of a critical multiplicity of infection for domination of segmented over standard types. Our experiments suggest that viral segmented genomes may have arisen as a molecular solution for the trade-off between genome length and particle stability. Genome segmentation allows maximizing the genetic content without the detrimental effect in stability derived from incresing genome length. PMID:21437265

  1. The Resurgence of Genetic Determinism: Is It a Distraction?

    Science.gov (United States)

    Jackson, Jacquelyne F.

    1998-01-01

    Argues that there is a wealth of little known but rapidly growing evidence that contradicts the assumptions and claims of genetic determinism. Recent research showing the impacts of child maltreatment and environmental pollutants suggest interventions that might alleviate the problems sometimes attributed to genetic deficiencies. (SLD)

  2. Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs.

    Science.gov (United States)

    Gonen, Serap; Jenko, Janez; Gorjanc, Gregor; Mileham, Alan J; Whitelaw, C Bruce A; Hickey, John M

    2017-01-04

    This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance [Formula: see text], rate of change in inbreeding ([Formula: see text]), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency

  3. Genomic and pedigree-based genetic parameters for scarcely recorded traits when some animals are genotyped.

    Science.gov (United States)

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

    2011-08-01

    Genetic parameters were estimated using relationships between animals that were based either on pedigree, 43,011 single nucleotide polymorphisms, or a combination of these, considering genotyped and non-genotyped animals. The standard error of the estimates and a parametric bootstrapping procedure was used to investigate sampling properties of the estimated variance components. The data set contained milk yield, dry matter intake and body weight for 517 first-lactation heifers with genotypes and phenotypes, and another 112 heifers with phenotypes only. Multivariate models were fitted using the different relationships in ASReml software. Estimates of genetic variance were lower based on genomic relationships than using pedigree relationships. Genetic variances from genomic and pedigree relationships were, however, not directly comparable because they apply to different base populations. Standard errors indicated that using the genomic relationships gave more accurate estimates of heritability but equally accurate estimates of genetic correlation. However, the estimates of standard errors were affected by the differences in scale between the 2 relationship matrices, causing differences in values of the genetic parameters. The bootstrapping results (with genetic parameters at the same level), confirmed that both heritability and genetic correlations were estimated more accurately with genomic relationships in comparison with using the pedigree relationships. Animals without genotype were included in the analysis by merging genomic and pedigree relationships. This allowed all phenotypes to be used, including those from non-genotyped animals. This combination of genomic and pedigree relationships gave the most accurate estimates of genetic variance. When a small data set is available it might be more advantageous for the estimation of genetic parameters to genotype existing animals, rather than collecting more phenotypes. Copyright © 2011 American Dairy Science

  4. [Implications in primary health care of medical genetics and genomic in type 2 diabetes mellitus].

    Science.gov (United States)

    Ramirez-Garcia, Sergio Alberto; Cabrera-Pivaral, Carlos E; Huacuja-Ruiz, Luis; Flores-Alvarado, Luis Javier; Pérez-García, Guillermo; González-Rico, José Luis; López-Velázquez, Alma; Topete-González, Luz Rosalba; Rosales-Góme, Roberto Carlos; Candelario-Mejía, Gerardo; Villa-Ruano, Nemesio

    2013-01-01

    Type 2 diabetes mellitus is a complex disease and a global health problem. Therefore, the first level of health care should handle the approaches of medical genetics and genomics to reduce its incidence. The aim is to present perspectives analyzed by our group in two areas of genetics and its clinical application. Emphasis is placed on the coexistence of several genetic forms clinically detectable in patients with diabetes, missing heritability associated with low penetrance, and epigenomics mechanism. It is discussed the effect of genetic variation associated with resistance to insulin, beta-cell dysfunction, shaft incretin, and other points of interest, such as thrifty genotype hypothesis, conformational disease, genetically unknown foods, phenocopies as clinically silent hypercortisolism, molecular phytopharmacology in the clinical management. Finally, the result was displayed in the Mexican population from genetic studies and new findings of clinical importance, such as involvement of melatonin and effect of variations in the number of copies in a genomic region.

  5. The genome of a Mongolian individual reveals the genetic imprints of Mongolians on modern human populations.

    Science.gov (United States)

    Bai, Haihua; Guo, Xiaosen; Zhang, Dong; Narisu, Narisu; Bu, Junjie; Jirimutu, Jirimutu; Liang, Fan; Zhao, Xiang; Xing, Yanping; Wang, Dingzhu; Li, Tongda; Zhang, Yanru; Guan, Baozhu; Yang, Xukui; Yang, Zili; Shuangshan, Shuangshan; Su, Zhe; Wu, Huiguang; Li, Wenjing; Chen, Ming; Zhu, Shilin; Bayinnamula, Bayinnamula; Chang, Yuqi; Gao, Ying; Lan, Tianming; Suyalatu, Suyalatu; Huang, Hui; Su, Yan; Chen, Yujie; Li, Wenqi; Yang, Xu; Feng, Qiang; Wang, Jian; Yang, Huanming; Wang, Jun; Wu, Qizhu; Yin, Ye; Zhou, Huanmin

    2014-11-05

    Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians.

  6. InterStoreDB: A Generic Integration Resource for Genetic and Genomic Data

    Institute of Scientific and Technical Information of China (English)

    Christopher G.Love; Ambrose E.Andongabo; Jun Wang; Pierre W.C.Carion; Christopher J.Rawlings; Graham J.King

    2012-01-01

    Associating phenotypic traits and quantitative trait loci (QTL) to causative regions of the underlying genome is a key goal in agricultural research.InterStoreDB is a suite of integrated databases designed to assist in this process.The individual databases are species independent and generic in design,providing access to curated datasets relating to plant populations,phenotypic traits,genetic maps,marker loci and QTL,with links to functional gene annotation and genomic sequence data.Each component database provides access to associated metadata,including data provenance and parameters used in analyses,thus providing users with information to evaluate the relative worth of any associations identified.The databases include CropStoreDB,for management of population,genetic map,QTL and trait measurement data,SeqStoreDB for sequence-related data and AlignStoreDB,which stores sequence alignment information,and allows navigation between genetic and genomic datasets.Genetic maps are visualized and compared using the CMAP tool,and functional annotation from sequenced genomes is provided via an EnsEMBL-based genome browser.This framework facilitates navigation of the multiple biological domains involved in genetics and genomics research in a transparent manner within a single portal.We demonstrate the value of InterStoreDB as a tool for Brassica research.InterStoreDB is available from:http:llwww.interstoredb.org

  7. Genetic redundancy is prevalent within the 6.7 Mb Sinorhizobium meliloti genome.

    Science.gov (United States)

    diCenzo, George C; Finan, Turlough M

    2015-08-01

    Biological pathways are frequently identified via a genetic loss-of-function approach. While this approach has proven to be powerful, it is imperfect as illustrated by well-studied pathways continuing to have missing steps. One potential limiting factor is the masking of phenotypes through genetic redundancy. The prevalence of genetic redundancy in bacterial species has received little attention, although isolated examples of functionally redundant gene pairs exist. Here, we made use of a strain of Sinorhizobium meliloti whose genome was reduced by 45 % through the complete removal of a megaplasmid and a chromid (3 Mb of the 6.7 Mb genome was removed) to begin quantifying the level of genetic redundancy within a large bacterial genome. A mutagenesis of the strain with the reduced genome identified a set of transposon insertions precluding growth of this strain on minimal medium. Transfer of these mutations to the wild-type background revealed that 10-15 % of these chromosomal mutations were located within duplicated genes, as they did not prevent growth of cells with the full genome. The functionally redundant genes were involved in a variety of metabolic pathways, including central carbon metabolism, transport, and amino acid biosynthesis. These results indicate that genetic redundancy may be prevalent within large bacterial genomes. Failing to account for redundantly encoded functions in loss-of-function studies will impair our understanding of a broad range of biological processes and limit our ability to use synthetic biology in the construction of designer cell factories.

  8. Genomic testing interacts with reproductive surplus in reducing genetic lag and increasing economic net return

    DEFF Research Database (Denmark)

    Hjortø, Line; Ettema, Jehan Frans; Kargo, Morten

    2015-01-01

    , especially if genomic tests are used in combination with sexed semen or a high management level for reproductive performance, because both factors provide the opportunity for generating a reproductive surplus in the herd. In this study, sexed semen is used in combination with beef semen to produce high-value...... simulates the parity distribution of the dams of heifer calves. The ADAM program estimates genetic merit per year in a herd under different strategies for use of sexed semen and genomic tests. The annual net return per slot was calculated as the sum of operational return and value of genetic lag minus costs......Until now, genomic information has mainly been used to improve the accuracy of genomic breeding values for breeding animals at a population level. However, we hypothesize that the use of information from genotyped females also opens up the possibility of reducing genetic lag in a dairy herd...

  9. Genomic landscapes of endogenous retroviruses unveil intricate genetics of conventional and genetically-engineered laboratory mouse strains.

    Science.gov (United States)

    Lee, Kang-Hoon; Lim, Debora; Chiu, Sophia; Greenhalgh, David; Cho, Kiho

    2016-04-01

    Laboratory strains of mice, both conventional and genetically engineered, have been introduced as critical components of a broad range of studies investigating normal and disease biology. Currently, the genetic identity of laboratory mice is primarily confirmed by surveying polymorphisms in selected sets of "conventional" genes and/or microsatellites in the absence of a single completely sequenced mouse genome. First, we examined variations in the genomic landscapes of transposable repetitive elements, named the TREome, in conventional and genetically engineered mouse strains using murine leukemia virus-type endogenous retroviruses (MLV-ERVs) as a probe. A survey of the genomes from 56 conventional strains revealed strain-specific TREome landscapes, and certain families (e.g., C57BL) of strains were discernible with defined patterns. Interestingly, the TREome landscapes of C3H/HeJ (toll-like receptor-4 [TLR4] mutant) inbred mice were different from its control C3H/HeOuJ (TLR4 wild-type) strain. In addition, a CD14 knock-out strain had a distinct TREome landscape compared to its control/backcross C57BL/6J strain. Second, an examination of superantigen (SAg, a "TREome gene") coding sequences of mouse mammary tumor virus-type ERVs in the genomes of the 46 conventional strains revealed a high diversity, suggesting a potential role of SAgs in strain-specific immune phenotypes. The findings from this study indicate that unexplored and intricate genomic variations exist in laboratory mouse strains, both conventional and genetically engineered. The TREome-based high-resolution genetics surveillance system for laboratory mice would contribute to efficient study design with quality control and accurate data interpretation. This genetics system can be easily adapted to other species ranging from plants to humans.

  10. Report - 21st century medical genetic and genomic medicine in China

    Institute of Scientific and Technical Information of China (English)

    HUANG Taosheng; QI Ming

    2005-01-01

    @@ The First Hangzhou International Symposium on the Medical and Laboratory Applications of Medical Genetics and Genomics was held in Hangzhou from October 6~8, 2005. The symposium was organized and sponsored by the First Affiliated Hospital, School of Medicine, Zhejiang University and co-sponsored by the Zhejiang Medical Association;School of Medicine of Zhejiang University; the James Watson Institute of Genomics Sciences and Beijing Genomics Institute/Huada Genomics Center of the Chinese Academy of Science. Many internationally prominent geneticists were invited to the meeting,including Arno Motulsky, Peter Byers, Douglas Wallace, Judith Hall, and David Weatherall. The invited speakers presented discussions of recent advances in human and medical genetics, genomics, and in cutting-edge research.

  11. GENETICALLY DETERMINED WAY OF COGNITION IN THE RUSSIAN TRADITION

    Directory of Open Access Journals (Sweden)

    Tatyana M. Klimenkova

    2016-01-01

    Full Text Available It is reviles stages of cognition and comprehension according to natural genetic determinate pass of cognition, modern discovery in methodology and archetype code of cognition/comprehension, saving up in Slavonic culture.

  12. Genetic Mapping of Millions of SNPs in Safflower (Carthamus tinctorius L.) via Whole-Genome Resequencing

    OpenAIRE

    Bowers, John E.; Pearl, Stephanie A; Burke, John M.

    2016-01-01

    Accurate assembly of complete genomes is facilitated by very high density genetic maps. We performed low-coverage, whole-genome shotgun sequencing on 96 F6 recombinant inbred lines (RILs) of a cross between safflower (Carthamus tinctorius L.) and its wild progenitor (C. palaestinus Eig). We also produced a draft genome assembly of C. tinctorius covering 866 million bp (∼two-thirds) of the expected 1.35 Gbp genome after sequencing a single, short insert library to ∼21 × depth. Sequence reads f...

  13. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui;

    2011-01-01

    throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has......A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...

  14. Understanding our genetic inheritance: The US Human Genome Project, The first five years FY 1991--1995

    Energy Technology Data Exchange (ETDEWEB)

    None

    1990-04-01

    The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will by of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that affect mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focused on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. The basic data produced will be collected in electronic databases that will make the information readily accessible on convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project.

  15. Understanding our Genetic Inheritance: The U.S. Human Genome Project, The First Five Years FY 1991--1995

    Science.gov (United States)

    1990-04-01

    The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will by of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that affect mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focused on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. The basic data produced will be collected in electronic databases that will make the information readily accessible on convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project.

  16. Evaluation of plasmid and genomic DNA calibrants used for the quantification of genetically modified organisms.

    Science.gov (United States)

    Caprioara-Buda, M; Meyer, W; Jeynov, B; Corbisier, P; Trapmann, S; Emons, H

    2012-07-01

    The reliable quantification of genetically modified organisms (GMOs) by real-time PCR requires, besides thoroughly validated quantitative detection methods, sustainable calibration systems. The latter establishes the anchor points for the measured value and the measurement unit, respectively. In this paper, the suitability of two types of DNA calibrants, i.e. plasmid DNA and genomic DNA extracted from plant leaves, for the certification of the GMO content in reference materials as copy number ratio between two targeted DNA sequences was investigated. The PCR efficiencies and coefficients of determination of the calibration curves as well as the measured copy number ratios for three powder certified reference materials (CRMs), namely ERM-BF415e (NK603 maize), ERM-BF425c (356043 soya), and ERM-BF427c (98140 maize), originally certified for their mass fraction of GMO, were compared for both types of calibrants. In all three systems investigated, the PCR efficiencies of plasmid DNA were slightly closer to the PCR efficiencies observed for the genomic DNA extracted from seed powders rather than those of the genomic DNA extracted from leaves. Although the mean DNA copy number ratios for each CRM overlapped within their uncertainties, the DNA copy number ratios were significantly different using the two types of calibrants. Based on these observations, both plasmid and leaf genomic DNA calibrants would be technically suitable as anchor points for the calibration of the real-time PCR methods applied in this study. However, the most suitable approach to establish a sustainable traceability chain is to fix a reference system based on plasmid DNA.

  17. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses

    Directory of Open Access Journals (Sweden)

    Lisette J. A. Kogelman

    2014-07-01

    Full Text Available Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH and differentially wired (DW networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g. NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g. metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways

  18. Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network, and pathway analyses.

    Science.gov (United States)

    Kogelman, Lisette J A; Pant, Sameer D; Fredholm, Merete; Kadarmideen, Haja N

    2014-01-01

    Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH) and differentially wired (DW) networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g., NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g., metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic) obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways that underlie

  19. Genetic and Epigenetic Determinants in Autoinflammatory Diseases

    Science.gov (United States)

    Álvarez-Errico, Damiana; Vento-Tormo, Roser; Ballestar, Esteban

    2017-01-01

    The concept of autoinflammation has evolved over the past 20 years, beginning with the discovery that mutations in the Mediterranean Fever (MEFV) gene were causative of Familial Mediterranean Fever. Currently, autoinflammatory diseases comprise a wide range of disorders with the common features of recurrent fever attacks, prevalence of hyperreactive innate immune cells, and signs of inflammation that can be systemic or organ specific in the absence of pathogenic infection of autoimmunity. Innate immune cells from the myeloid compartment are the main effectors of uncontrolled inflammation that is caused in great extent by the overproduction of inflammatory cytokines such as IL-1β and IL-18. Defects in several signaling pathways that control innate immune defense, particularly the hyperreactivity of one or more inflammasomes, are at the core of pathologic autoinflammatory phenotypes. Although many of the autoinflammatory syndromes are known to be monogenic, some of them are genetically complex and are impacted by environmental factors. Recently, epigenetic dysregulation has surfaced as an additional contributor to pathogenesis. In the present review, we discuss data that are currently available to describe the contribution of epigenetic mechanisms in autoinflammatory diseases.

  20. A new holistic genome viewer for molecular genetics.

    NARCIS (Netherlands)

    H.J.F.M.M. Eussen (Bert); M.J. Moorhouse (Michael); M. Lesnussa (Michael); M. Muetgeert (Maarten); T.A. Knoch (Tobias)

    2006-01-01

    textabstractGenomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of the

  1. A new holistic genome viewer for molecular genetics

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); L.V. de Zeeuw (Luc)

    2006-01-01

    textabstractGenomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of th

  2. Genetics/Genomics Research in the Central Region

    Science.gov (United States)

    ,

    2006-01-01

    Genetics-based research within the Biological Resources Discipline (BRD) Science Centers in the Central Region incorporates many aspects of the field of genetics. Research activities range from documenting patterns of genetic variation in order to investigate relationships among species, populations and individuals to investigating the structure, function and expression of genes and their response to environmental stressors. Research in the broad areas of genetics requires multidisciplinary expertise and specialized equipment and instrumentation. Brief summaries of the capabilities of the five BRD Centers are given below.

  3. Genetic Drift, Not Life History or RNAi, Determine Long-Term Evolution of Transposable Elements.

    Science.gov (United States)

    Szitenberg, Amir; Cha, Soyeon; Opperman, Charles H; Bird, David M; Blaxter, Mark L; Lunt, David H

    2016-10-05

    Transposable elements (TEs) are a major source of genome variation across the branches of life. Although TEs may play an adaptive role in their host's genome, they are more often deleterious, and purifying selection is an important factor controlling their genomic loads. In contrast, life history, mating system, GC content, and RNAi pathways have been suggested to account for the disparity of TE loads in different species. Previous studies of fungal, plant, and animal genomes have reported conflicting results regarding the direction in which these genomic features drive TE evolution. Many of these studies have had limited power, however, because they studied taxonomically narrow systems, comparing only a limited number of phylogenetically independent contrasts, and did not address long-term effects on TE evolution. Here, we test the long-term determinants of TE evolution by comparing 42 nematode genomes spanning over 500 million years of diversification. This analysis includes numerous transitions between life history states, and RNAi pathways, and evaluates if these forces are sufficiently persistent to affect the long-term evolution of TE loads in eukaryotic genomes. Although we demonstrate statistical power to detect selection, we find no evidence that variation in these factors influence genomic TE loads across extended periods of time. In contrast, the effects of genetic drift appear to persist and control TE variation among species. We suggest that variation in the tested factors are largely inconsequential to the large differences in TE content observed between genomes, and only by these large-scale comparisons can we distinguish long-term and persistent effects from transient or random changes.

  4. Technology-Driven and Evidence-Based Genomic Analysis for Integrated Pediatric and Prenatal Genetics Evaluation

    Institute of Scientific and Technical Information of China (English)

    Yuan Wei; Fang Xu; Peining Li

    2013-01-01

    The first decade since the completion of the Human Genome Project has been marked with rapid development of genomic technologies and their immediate clinical applications.Genomic analysis using oligonucleotide array comparative genomic hybridization (aCGH) or single nucleotide polymorphism (SNP) chips has been applied to pediatric patients with developmental and intellectual disabilities (DD/ID),multiple congenital anomalies (MCA) and autistic spectrum disorders (ASD).Evaluation of analytical and clinical validities of aCGH showed > 99% sensitivity and specificity and increased analytical resolution by higher density probe coverage.Reviews of case series,multi-center comparison and large patient-control studies demonstrated a diagnostic yield of 12%-20%; approximately 60% of these abnormalities were recurrent genomic disorders.This pediatric experience has been extended toward prenatal diagnosis.A series of reports indicated approximately 10% of pregnancies with ultrasound-detected structural anomalies and normal cytogenetic findings had genomic abnormalities,and 30% of these abnormalities were syndromic genomic disorders.Evidence-based practice guidelines and standards for implementing genomic analysis and web-delivered knowledge resources for interpreting genomic findings have been established.The progress from this technology-driven and evidence-based genomic analysis provides not only opportunities to dissect disease-causing mechanisms and develop rational therapeutic interventions but also important lessons for integrating genomic sequencing into pediatric and prenatal genetic evaluation.

  5. Did RNA editing in plant organellar genomes originate under natural selection or through genetic drift?

    Directory of Open Access Journals (Sweden)

    Jobson Richard W

    2008-10-01

    Full Text Available Abstract Background The C↔U substitution types of RNA editing have been observed frequently in organellar genomes of land plants. Although various attempts have been made to explain why such a seemingly inefficient genetic mechanism would have evolved, no satisfactory explanation exists in our view. In this study, we examined editing patterns in chloroplast genomes of the hornwort Anthoceros formosae and the fern Adiantum capillus-veneris and in mitochondrial genomes of the angiosperms Arabidopsis thaliana, Beta vulgaris and Oryza sativa, to gain an understanding of the question of how RNA editing originated. Results We found that 1 most editing sites were distributed at the 2nd and 1st codon positions, 2 editing affected codons that resulted in larger hydrophobicity and molecular size changes much more frequently than those with little change involved, 3 editing uniformly increased protein hydrophobicity, 4 editing occurred more frequently in ancestrally T-rich sequences, which were more abundant in genes encoding membrane-bound proteins with many hydrophobic amino acids than in genes encoding soluble proteins, and 5 editing occurred most often in genes found to be under strong selective constraint. Conclusion These analyses show that editing mostly affects functionally important and evolutionarily conserved codon positions, codons and genes encoding membrane-bound proteins. In particular, abundance of RNA editing in plant organellar genomes may be associated with disproportionately large percentages of genes in these two genomes that encode membrane-bound proteins, which are rich in hydrophobic amino acids and selectively constrained. These data support a hypothesis that natural selection imposed by protein functional constraints has contributed to selective fixation of certain editing sites and maintenance of the editing activity in plant organelles over a period of more than four hundred millions years. The retention of genes encoding RNA

  6. Regulation of sex determination in mice by a non-coding genomic region.

    Science.gov (United States)

    Arboleda, Valerie A; Fleming, Alice; Barseghyan, Hayk; Délot, Emmanuèle; Sinsheimer, Janet S; Vilain, Eric

    2014-07-01

    To identify novel genomic regions that regulate sex determination, we utilized the powerful C57BL/6J-Y(POS) (B6-Y(POS)) model of XY sex reversal where mice with autosomes from the B6 strain and a Y chromosome from a wild-derived strain, Mus domesticus poschiavinus (Y(POS)), show complete sex reversal. In B6-Y(POS), the presence of a 55-Mb congenic region on chromosome 11 protects from sex reversal in a dose-dependent manner. Using mouse genetic backcross designs and high-density SNP arrays, we narrowed the congenic region to a 1.62-Mb genomic region on chromosome 11 that confers 80% protection from B6-Y(POS) sex reversal when one copy is present and complete protection when two copies are present. It was previously believed that the protective congenic region originated from the 129S1/SviMJ (129) strain. However, genomic analysis revealed that this region is not derived from 129 and most likely is derived from the semi-inbred strain POSA. We show that the small 1.62-Mb congenic region that protects against B6-Y(POS) sex reversal is located within the Sox9 promoter and promotes the expression of Sox9, thereby driving testis development within the B6-Y(POS) background. Through 30 years of backcrossing, this congenic region was maintained, as it promoted male sex determination and fertility despite the female-promoting B6-Y(POS) genetic background. Our findings demonstrate that long-range enhancer regions are critical to developmental processes and can be used to identify the complex interplay between genome variants, epigenetics, and developmental gene regulation.

  7. Sequential Turnovers of Sex Chromosomes in African Clawed Frogs (Xenopus Suggest Some Genomic Regions Are Good at Sex Determination

    Directory of Open Access Journals (Sweden)

    Benjamin L. S. Furman

    2016-11-01

    Full Text Available Sexual differentiation is fundamentally important for reproduction, yet the genetic triggers of this developmental process can vary, even between closely related species. Recent studies have uncovered, for example, variation in the genetic triggers for sexual differentiation within and between species of African clawed frogs (genus Xenopus. Here, we extend these discoveries by demonstrating that yet another sex determination system exists in Xenopus, specifically in the species Xenopus borealis. This system evolved recently in an ancestor of X. borealis that had the same sex determination system as X. laevis, a system which itself is newly evolved. Strikingly, the genomic region carrying the sex determination factor in X. borealis is homologous to that of therian mammals, including humans. Our results offer insights into how the genetic underpinnings of conserved phenotypes evolve, and suggest an important role for cooption of genetic building blocks with conserved developmental roles.

  8. Optimization of genomic selection training populations with a genetic algorithm

    Science.gov (United States)

    In this article, we derive a computationally efficient statistic to measure the reliability of estimates of genetic breeding values for a fixed set of genotypes based on a given training set of genotypes and phenotypes. We adopt a genetic algorithm scheme to find a training set of certain size from ...

  9. Establishing the outcome indicators for the essential nursing competencies and curricula guidelines for genetics and genomics.

    Science.gov (United States)

    Calzone, Kathleen A; Jenkins, Jean; Prows, Cynthia A; Masny, Agnes

    2011-01-01

    The translation of genetics/genomics to clinical care has implications for nurses. The Essential Nursing Competencies and Curricula Guidelines for Genetics and Genomics, established by consensus, apply to all registered nurses. Learning outcomes and clinical practice indicators have been developed to provide additional guidance. The Essentials Advisory Group (EAG) established a team to establish the Outcome Indicators. A draft was developed based on published peer-reviewed documents and syllabi. The draft underwent three layers of review: (a) critique by the EAG; (b) review by representatives at a Genetics/Genomics Toolkit for Faculty meeting; and (c) review by workshop attendees of the American Association of Colleges of Nursing's baccalaureate and master's education conferences, followed by EAG's final approval. Outcome Indicators clarify specific knowledge areas and suggest clinical performance indicators for each competency. They provide the foundation to establish a competency-based education repository with outcome indicator mapping matrixes for genetic/genomic education resources. A gap analysis of education resources identified resource deficits, and online unfolding case studies were developed. Outcome Indicators assist the academic and continuing education nurse community to prepare the nursing workforce in genetics/genomics and provide a platform from which to build tools needed to achieve this goal.

  10. Current status and prospects for the study of Nicotiana genomics, genetics, and nicotine biosynthesis genes.

    Science.gov (United States)

    Wang, Xuewen; Bennetzen, Jeffrey L

    2015-02-01

    Nicotiana, a member of the Solanaceae family, is one of the most important research model plants, and of high agricultural and economic value worldwide. To better understand the substantial and rapid research progress with Nicotiana in recent years, its genomics, genetics, and nicotine gene studies are summarized, with useful web links. Several important genetic maps, including a high-density map of N. tabacum consisting of ~2,000 markers published in 2012, provide tools for genetics research. Four whole genome sequences are from allotetraploid species, including N. benthamiana in 2012, and three N. tabacum cultivars (TN90, K326, and BX) in 2014. Three whole genome sequences are from diploids, including progenitors N. sylvestris and N. tomentosiformis in 2013 and N. otophora in 2014. These and additional studies provide numerous insights into genome evolution after polyploidization, including changes in gene composition and transcriptome expression in N. tabacum. The major genes involved in the nicotine biosynthetic pathway have been identified and the genetic basis of the differences in nicotine levels among Nicotiana species has been revealed. In addition, other progress on chloroplast, mitochondrial, and NCBI-registered projects on Nicotiana are discussed. The challenges and prospects for genomic, genetic and application research are addressed. Hence, this review provides important resources and guidance for current and future research and application in Nicotiana.

  11. RadishBase: a database for genomics and genetics of radish.

    Science.gov (United States)

    Shen, Di; Sun, Honghe; Huang, Mingyun; Zheng, Yi; Li, Xixiang; Fei, Zhangjun

    2013-02-01

    Radish is an economically important vegetable crop. During the past several years, large-scale genomics and genetics resources have been accumulated for this species. To store, query, analyze and integrate these radish resources efficiently, we have developed RadishBase (http://bioinfo.bti.cornell.edu/radish), a genomics and genetics database of radish. Currently the database contains radish mitochondrial genome sequences, expressed sequence tag (EST) and unigene sequences and annotations, biochemical pathways, EST-derived single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) markers, and genetic maps. RadishBase is designed to enable users easily to retrieve and visualize biologically important information through a set of efficient query interfaces and analysis tools, including the BLAST search and unigene annotation query interfaces, and tools to classify unigenes functionally, to identify enriched gene ontology (GO) terms and to visualize genetic maps. A database containing radish pathways predicted from unigene sequences is also included in RadishBase. The tools and interfaces in RadishBase allow efficient mining of recently released and continually expanding large-scale radish genomics and genetics data sets, including the radish genome sequences and RNA-seq data sets.

  12. High resolution genetic mapping by genome sequencing reveals genome duplication and tetraploid genetic structure of the diploid Miscanthus sinensis.

    Directory of Open Access Journals (Sweden)

    Xue-Feng Ma

    Full Text Available We have created a high-resolution linkage map of Miscanthus sinensis, using genotyping-by-sequencing (GBS, identifying all 19 linkage groups for the first time. The result is technically significant since Miscanthus has a very large and highly heterozygous genome, but has no or limited genomics information to date. The composite linkage map containing markers from both parental linkage maps is composed of 3,745 SNP markers spanning 2,396 cM on 19 linkage groups with a 0.64 cM average resolution. Comparative genomics analyses of the M. sinensis composite linkage map to the genomes of sorghum, maize, rice, and Brachypodium distachyon indicate that sorghum has the closest syntenic relationship to Miscanthus compared to other species. The comparative results revealed that each pair of the 19 M. sinensis linkages aligned to one sorghum chromosome, except for LG8, which mapped to two sorghum chromosomes (4 and 7, presumably due to a chromosome fusion event after genome duplication. The data also revealed several other chromosome rearrangements relative to sorghum, including two telomere-centromere inversions of the sorghum syntenic chromosome 7 in LG8 of M. sinensis and two paracentric inversions of sorghum syntenic chromosome 4 in LG7 and LG8 of M. sinensis. The results clearly demonstrate, for the first time, that the diploid M. sinensis is tetraploid origin consisting of two sub-genomes. This complete and high resolution composite linkage map will not only serve as a useful resource for novel QTL discoveries, but also enable informed deployment of the wealth of existing genomics resources of other species to the improvement of Miscanthus as a high biomass energy crop. In addition, it has utility as a reference for genome sequence assembly for the forthcoming whole genome sequencing of the Miscanthus genus.

  13. Advances in ecological genomics in forest trees and applications to genetic resources conservation and breeding.

    Science.gov (United States)

    Holliday, Jason A; Aitken, Sally N; Cooke, Janice E K; Fady, Bruno; González-Martínez, Santiago C; Heuertz, Myriam; Jaramillo-Correa, Juan-Pablo; Lexer, Christian; Staton, Margaret; Whetten, Ross W; Plomion, Christophe

    2017-02-01

    Forest trees are an unparalleled group of organisms in their combined ecological, economic and societal importance. With widespread distributions, predominantly random mating systems and large population sizes, most tree species harbour extensive genetic variation both within and among populations. At the same time, demographic processes associated with Pleistocene climate oscillations and land-use change have affected contemporary range-wide diversity and may impinge on the potential for future adaptation. Understanding how these adaptive and neutral processes have shaped the genomes of trees species is therefore central to their management and conservation. As for many other taxa, the advent of high-throughput sequencing methods is expected to yield an understanding of the interplay between the genome and environment at a level of detail and depth not possible only a few years ago. An international conference entitled 'Genomics and Forest Tree Genetics' was held in May 2016, in Arcachon (France), and brought together forest geneticists with a wide range of research interests to disseminate recent efforts that leverage contemporary genomic tools to probe the population, quantitative and evolutionary genomics of trees. An important goal of the conference was to discuss how such data can be applied to both genome-enabled breeding and the conservation of forest genetic resources under land use and climate change. Here, we report discoveries presented at the meeting and discuss how the ecological genomic toolkit can be used to address both basic and applied questions in tree biology.

  14. A genome wide survey of SNP variation reveals the genetic structure of sheep breeds.

    Directory of Open Access Journals (Sweden)

    James W Kijas

    Full Text Available The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability.

  15. The physical and genetic framework of the maize B73 genome.

    Directory of Open Access Journals (Sweden)

    Fusheng Wei

    2009-11-01

    Full Text Available Maize is a major cereal crop and an important model system for basic biological research. Knowledge gained from maize research can also be used to genetically improve its grass relatives such as sorghum, wheat, and rice. The primary objective of the Maize Genome Sequencing Consortium (MGSC was to generate a reference genome sequence that was integrated with both the physical and genetic maps. Using a previously published integrated genetic and physical map, combined with in-coming maize genomic sequence, new sequence-based genetic markers, and an optical map, we dynamically picked a minimum tiling path (MTP of 16,910 bacterial artificial chromosome (BAC and fosmid clones that were used by the MGSC to sequence the maize genome. The final MTP resulted in a significantly improved physical map that reduced the number of contigs from 721 to 435, incorporated a total of 8,315 mapped markers, and ordered and oriented the majority of FPC contigs. The new integrated physical and genetic map covered 2,120 Mb (93% of the 2,300-Mb genome, of which 405 contigs were anchored to the genetic map, totaling 2,103.4 Mb (99.2% of the 2,120 Mb physical map. More importantly, 336 contigs, comprising 94.0% of the physical map ( approximately 1,993 Mb, were ordered and oriented. Finally we used all available physical, sequence, genetic, and optical data to generate a golden path (AGP of chromosome-based pseudomolecules, herein referred to as the B73 Reference Genome Sequence version 1 (B73 RefGen_v1.

  16. Target selection and determination of function in structural genomics.

    Science.gov (United States)

    Watson, James D; Todd, Annabel E; Bray, James; Laskowski, Roman A; Edwards, Aled; Joachimiak, Andrzej; Orengo, Christine A; Thornton, Janet M

    2003-01-01

    The first crucial step in any structural genomics project is the selection and prioritization of target proteins for structure determination. There may be a number of selection criteria to be satisfied, including that the proteins have novel folds, that they be representatives of large families for which no structure is known, and so on. The better the selection at this stage, the greater is the value of the structures obtained at the end of the experimental process. This value can be further enhanced once the protein structures have been solved if the functions of the given proteins can also be determined. Here we describe the methods used at either end of the experimental process: firstly, sensitive sequence comparison techniques for selecting a high-quality list of target proteins, and secondly the various computational methods that can be applied to the eventual 3D structures to determine the most likely biochemical function of the proteins in question.

  17. Genetic markers cannot determine Jewish descent

    Directory of Open Access Journals (Sweden)

    Raphael eFalk

    2015-01-01

    Full Text Available Social interaction is a basic property of human Darwinian evolution. Presumably inherent differential physical as well as behavioural properties have always been criteria for identifying friend or foe. Yet, biological determinism is a relatively modern term, and scientific racism is, oddly enough, largely a consequence or a product of the Age of Enlightenment and the establishment of the notion of human equality. In recent decades ever-increasing efforts and ingenuity were invested in identifying Biblical Israelite genotypic common denominators by analysing assorted phenotypes, like facial patterns, blood types, diseases, DNA-sequences, and more. It becomes overwhelmingly clear that although Jews by their socio-religious-cultural relationship maintained also considerable consanguinity, there is no Jewish genotype to identify.

  18. Gene ontology analysis of pairwise genetic associations in two genome-wide studies of sporadic ALS

    Directory of Open Access Journals (Sweden)

    Kim Nora

    2012-07-01

    Full Text Available Abstract Background It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO. Results We first estimated all pairwise additive and nonadditive genetic effects using the multifactor dimensionality reduction (MDR method that makes few assumptions about the underlying genetic model. Statistical significance was evaluated using permutation testing in two genome-wide association studies of ALS. The detection data consisted of 276 subjects with ALS and 271 healthy controls while the replication data consisted of 221 subjects with ALS and 211 healthy controls. Both studies included genotypes from approximately 550,000 single-nucleotide polymorphisms (SNPs. Each SNP was mapped to a gene if it was within 500 kb of the start or end. Each SNP was assigned a p-value based on its strongest joint effect with the other SNPs. We then used the Exploratory Visual Analysis (EVA method and software to assign a p-value to each gene based on the overabundance of significant SNPs at the α = 0.05 level in the gene. We also used EVA to assign p-values to each GO group based on the overabundance of significant genes at the α = 0.05 level. A GO category was determined to replicate if that category was significant at the α = 0.05 level in both studies. We found two GO categories that replicated in both studies. The first, ‘Regulation of Cellular Component Organization and Biogenesis’, a GO Biological Process, had p-values of 0.010 and 0.014 in the detection and replication studies, respectively. The second, ‘Actin Cytoskeleton’, a GO Cellular Component, had p-values of 0.040 and 0.046 in the detection and replication studies, respectively. Conclusions Pathway

  19. Genetic susceptibility to male infertility: news from genome-wide association studies.

    Science.gov (United States)

    Aston, K I

    2014-05-01

    A thorough understanding of the genetic basis of male infertility has eluded researchers in spite of significant efforts to identify novel genetic causes of the disease, particularly over the past decade. Approximately half of male factor infertility cases have no known cause; however, it is likely that the majority of idiopathic male factor infertility cases have some unidentified genetic basis. Well-established genetic causes of male infertility are limited to Y chromosome microdeletions and Klinefelter's syndrome, together accounting for 10-20% of cases of severe spermatogenic failure. In addition to these, several genetic polymorphisms have been demonstrated to be significantly associated with male infertility. The discovery of new genetic associations with male infertility has been hampered by two primary factors. First, most studies are underpowered because of insufficient sample size and ethnic and phenotypic heterogeneity. Second, most studies evaluate a single gene, an approach that is very inefficient in the context of male infertility, considering that many hundreds of genes are involved in the process of testicular development and spermatogenesis. Significant recent advances in microarray and next-generation sequencing technologies have enabled the application of whole-genome approaches to the study of male infertility. We recently performed a pilot genome-wide association study (GWAS) for severe spermatogenic failure, and several additional male infertility GWAS have since been published. More recently, genomic microarray tools have been applied to the association of copy number variants with male infertility. These studies are beginning to shed additional light on the genetic architecture of male infertility, and whole-genome studies have proven effective in identifying novel genetic causes of the disease. This review will discuss some of the recent findings of these whole-genome studies as well as future directions for this research that will likely

  20. Genome sequence and genetic diversity of European ash trees

    DEFF Research Database (Denmark)

    Sollars, Elizabeth S A; Harper, Andrea L; Kelly, Laura J;

    2016-01-01

    Ash trees (genus Fraxinus, family Oleaceae) are widespread throughout the Northern Hemisphere, but are being devastated in Europe by the fungus Hymenoscyphus fraxineus, causing ash dieback, and in North America by the herbivorous beetle Agrilus planipennis. Here we sequence the genome of a low......-heterozygosity Fraxinus excelsior tree from Gloucestershire, UK, annotating 38,852 protein-coding genes of which 25% appear ash specific when compared with the genomes of ten other plant species. Analyses of paralogous genes suggest a whole-genome duplication shared with olive (Olea europaea, Oleaceae). We also re......-sequence 37 F. excelsior trees from Europe, finding evidence for apparent long-term decline in effective population size. Using our reference sequence, we re-analyse association transcriptomic data, yielding improved markers for reduced susceptibility to ash dieback. Surveys of these markers in British...

  1. Genomic and genetic alterations influence the progression of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Stefania Nobili; Lorenzo Bruno; Ida Landini; Cristina Napoli; Paolo Bechi; Francesco Tonelli; Carlos A Rubio; Enrico Mini; Gabriella Nesi

    2011-01-01

    Gastric cancer is one of the leading causes of cancerrelated deaths worldwide, although the incidence has gradually decreased in many Western countries. Twomain gastric cancer histotypes, intestinal and diffuse, are recognised. Although most of the described genetic alterations have been observed in both types, different genetic pathways have been hypothesized. Genetic and epigenetic events, including 1q loss of heterozygosity (LOH), microsatellite instability and hypermethylation, have mostly been reported in intestinal-type gastric carcinoma and its precursor lesions, whereas 17p LOH, mutation or loss of E-cadherin are more often implicated in the development of diffuse-type gastric cancer.

  2. Genetic and genomic analysis of RNases in model cyanobacteria.

    Science.gov (United States)

    Cameron, Jeffrey C; Gordon, Gina C; Pfleger, Brian F

    2015-10-01

    Cyanobacteria are diverse photosynthetic microbes with the ability to convert CO2 into useful products. However, metabolic engineering of cyanobacteria remains challenging because of the limited resources for modifying the expression of endogenous and exogenous biochemical pathways. Fine-tuned control of protein production will be critical to optimize the biological conversion of CO2 into desirable molecules. Messenger RNAs (mRNAs) are labile intermediates that play critical roles in determining the translation rate and steady-state protein concentrations in the cell. The majority of studies on mRNA turnover have focused on the model heterotrophic bacteria Escherichia coli and Bacillus subtilis. These studies have elucidated many RNA modifying and processing enzymes and have highlighted the differences between these Gram-negative and Gram-positive bacteria, respectively. In contrast, much less is known about mRNA turnover in cyanobacteria. We generated a compendium of the major ribonucleases (RNases) and provide an in-depth analysis of RNase III-like enzymes in commonly studied and diverse cyanobacteria. Furthermore, using targeted gene deletion, we genetically dissected the RNases in Synechococcus sp. PCC 7002, one of the fastest growing and industrially attractive cyanobacterial strains. We found that all three cyanobacterial homologs of RNase III and a member of the RNase II/R family are not essential under standard laboratory conditions, while homologs of RNase E/G, RNase J1/J2, PNPase, and a different member of the RNase II/R family appear to be essential for growth. This work will enhance our understanding of native control of gene expression and will facilitate the development of an RNA-based toolkit for metabolic engineering in cyanobacteria.

  3. Determination of the melon chloroplast and mitochondrial genome sequences reveals that the largest reported mitochondrial genome in plants contains a significant amount of DNA having a nuclear origin

    Science.gov (United States)

    2011-01-01

    Background The melon belongs to the Cucurbitaceae family, whose economic importance among vegetable crops is second only to Solanaceae. The melon has a small genome size (454 Mb), which makes it suitable for molecular and genetic studies. Despite similar nuclear and chloroplast genome sizes, cucurbits show great variation when their mitochondrial genomes are compared. The melon possesses the largest plant mitochondrial genome, as much as eight times larger than that of other cucurbits. Results The nucleotide sequences of the melon chloroplast and mitochondrial genomes were determined. The chloroplast genome (156,017 bp) included 132 genes, with 98 single-copy genes dispersed between the small (SSC) and large (LSC) single-copy regions and 17 duplicated genes in the inverted repeat regions (IRa and IRb). A comparison of the cucumber and melon chloroplast genomes showed differences in only approximately 5% of nucleotides, mainly due to short indels and SNPs. Additionally, 2.74 Mb of mitochondrial sequence, accounting for 95% of the estimated mitochondrial genome size, were assembled into five scaffolds and four additional unscaffolded contigs. An 84% of the mitochondrial genome is contained in a single scaffold. The gene-coding region accounted for 1.7% (45,926 bp) of the total sequence, including 51 protein-coding genes, 4 conserved ORFs, 3 rRNA genes and 24 tRNA genes. Despite the differences observed in the mitochondrial genome sizes of cucurbit species, Citrullus lanatus (379 kb), Cucurbita pepo (983 kb) and Cucumis melo (2,740 kb) share 120 kb of sequence, including the predicted protein-coding regions. Nevertheless, melon contained a high number of repetitive sequences and a high content of DNA of nuclear origin, which represented 42% and 47% of the total sequence, respectively. Conclusions Whereas the size and gene organisation of chloroplast genomes are similar among the cucurbit species, mitochondrial genomes show a wide variety of sizes, with a non

  4. Breeding rootstocks for Prunus species: Advances in genetic and genomics of peach and cherry as a model

    Directory of Open Access Journals (Sweden)

    Verónica Guajardo

    2015-08-01

    Full Text Available Prunus rootstock is an important choice in optimizing productivity of grafted cultivars. Nevertheless, many Prunus rootstocks are notoriously intolerant to hypoxia which is caused by waterlogging and/or heavy soils. There is no available information to help select Prunus rootstocks that are tolerant to stress conditions such as root hypoxia caused by excess moisture. Information from genetic maps has demonstrated a high level of synteny among Prunus species, and this suggests that they all share a similar genomic structure. It should be possible to identify the genetic determinants involved in tolerance to hypoxia and other traits in Prunus rootstocks by applying methods to identify regions of the genome involved in the expression of important traits; these have been developed mainly in peach which is the model species for the genus. Molecular markers that are tightly linked to major genes would be useful in marker-assisted selection (MAS to optimize new rootstock selection. This article provides insight on the advances in the development of molecular markers, genetic maps, and gene identification in Prunus, mainly in peach; the aim is to provide a general approach for identifying the genetic determinants of hypoxia stress in rootstocks.

  5. Aquaculture genomics, genetics and breeding in the United States: Current status, challenges, and priorities for future research

    Science.gov (United States)

    Advancing the production efficiency and profitability of aquaculture is dependent upon the ability to utilize a diverse array of genetic resources. The ultimate goals of aquaculture genomics, genetics and breeding research are to enhance aquaculture production efficiency, sustainability, product qua...

  6. Genetic Characterization and Comparative Genome Analysis of Brucella melitensis Isolates from India

    Directory of Open Access Journals (Sweden)

    Sarwar Azam

    2016-01-01

    Full Text Available Brucellosis is the most frequent zoonotic disease worldwide, with over 500,000 new human infections every year. Brucella melitensis, the most virulent species in humans, primarily affects goats and the zoonotic transmission occurs by ingestion of unpasteurized milk products or through direct contact with fetal tissues. Brucellosis is endemic in India but no information is available on population structure and genetic diversity of Brucella spp. in India. We performed multilocus sequence typing of four B. melitensis strains isolated from naturally infected goats from India. For more detailed genetic characterization, we carried out whole genome sequencing and comparative genome analysis of one of the B. melitensis isolates, Bm IND1. Genome analysis identified 141 unique SNPs, 78 VNTRs, 51 Indels, and 2 putative prophage integrations in the Bm IND1 genome. Our data may help to develop improved epidemiological typing tools and efficient preventive strategies to control brucellosis.

  7. Genetic Characterization and Comparative Genome Analysis of Brucella melitensis Isolates from India

    Science.gov (United States)

    Azam, Sarwar; Rao, Sashi Bhushan; Jakka, Padmaja; NarasimhaRao, Veera; Bhargavi, Bindu; Gupta, Vivek Kumar

    2016-01-01

    Brucellosis is the most frequent zoonotic disease worldwide, with over 500,000 new human infections every year. Brucella melitensis, the most virulent species in humans, primarily affects goats and the zoonotic transmission occurs by ingestion of unpasteurized milk products or through direct contact with fetal tissues. Brucellosis is endemic in India but no information is available on population structure and genetic diversity of Brucella spp. in India. We performed multilocus sequence typing of four B. melitensis strains isolated from naturally infected goats from India. For more detailed genetic characterization, we carried out whole genome sequencing and comparative genome analysis of one of the B. melitensis isolates, Bm IND1. Genome analysis identified 141 unique SNPs, 78 VNTRs, 51 Indels, and 2 putative prophage integrations in the Bm IND1 genome. Our data may help to develop improved epidemiological typing tools and efficient preventive strategies to control brucellosis. PMID:27525259

  8. Genetic Characterization and Comparative Genome Analysis of Brucella melitensis Isolates from India.

    Science.gov (United States)

    Azam, Sarwar; Rao, Sashi Bhushan; Jakka, Padmaja; NarasimhaRao, Veera; Bhargavi, Bindu; Gupta, Vivek Kumar; Radhakrishnan, Girish

    2016-01-01

    Brucellosis is the most frequent zoonotic disease worldwide, with over 500,000 new human infections every year. Brucella melitensis, the most virulent species in humans, primarily affects goats and the zoonotic transmission occurs by ingestion of unpasteurized milk products or through direct contact with fetal tissues. Brucellosis is endemic in India but no information is available on population structure and genetic diversity of Brucella spp. in India. We performed multilocus sequence typing of four B. melitensis strains isolated from naturally infected goats from India. For more detailed genetic characterization, we carried out whole genome sequencing and comparative genome analysis of one of the B. melitensis isolates, Bm IND1. Genome analysis identified 141 unique SNPs, 78 VNTRs, 51 Indels, and 2 putative prophage integrations in the Bm IND1 genome. Our data may help to develop improved epidemiological typing tools and efficient preventive strategies to control brucellosis.

  9. Genetic architecture of open angle glaucoma and related determinants

    NARCIS (Netherlands)

    Ramdas, W.D.; Amin, N.; van Koolwijk, L.M.E.; Janssens, A.C.J.W.; Demirkan, A.; de Jong, P.T.V.M.; Aulchenko, Y.S.; Wolfs, R.C.W.; Hofman, A.; Rivadeneira, F.; Uitterlinden, A.G.; Oostra, B.A.; Lemij, H.G.; Klaver, C.C.W.; Vingerling, J.R.; Jansonius, N.M.; van Duijn, C.M.

    2011-01-01

    Background Although the vertical cup-disc ratio (VCDR) and intraocular pressure (IOP) are important determinants of open angle glaucoma (OAG), it is unclear to what extent the genetic origin of these traits overlap with those of OAG. We evaluated whether the same genes that determine VCDR and IOP al

  10. A Genomic Encyclopedia of the Root Nodule Bacteria: assessing genetic diversity through a systematic biogeographic survey.

    Science.gov (United States)

    Reeve, Wayne; Ardley, Julie; Tian, Rui; Eshragi, Leila; Yoon, Je Won; Ngamwisetkun, Pinyaruk; Seshadri, Rekha; Ivanova, Natalia N; Kyrpides, Nikos C

    2015-01-01

    Root nodule bacteria are free-living soil bacteria, belonging to diverse genera within the Alphaproteobacteria and Betaproteobacteria, that have the capacity to form nitrogen-fixing symbioses with legumes. The symbiosis is specific and is governed by signaling molecules produced from both host and bacteria. Sequencing of several model RNB genomes has provided valuable insights into the genetic basis of symbiosis. However, the small number of sequenced RNB genomes available does not currently reflect the phylogenetic diversity of RNB, or the variety of mechanisms that lead to symbiosis in different legume hosts. This prevents a broad understanding of symbiotic interactions and the factors that govern the biogeography of host-microbe symbioses. Here, we outline a proposal to expand the number of sequenced RNB strains, which aims to capture this phylogenetic and biogeographic diversity. Through the Vavilov centers of diversity (Proposal ID: 231) and GEBA-RNB (Proposal ID: 882) projects we will sequence 107 RNB strains, isolated from diverse legume hosts in various geographic locations around the world. The nominated strains belong to nine of the 16 currently validly described RNB genera. They include 13 type strains, as well as elite inoculant strains of high commercial importance. These projects will strongly support systematic sequence-based studies of RNB and contribute to our understanding of the effects of biogeography on the evolution of different species of RNB, as well as the mechanisms that determine the specificity and effectiveness of nodulation and symbiotic nitrogen fixation by RNB with diverse legume hosts.

  11. Genetic determinants of trabecular and cortical volumetric bone mineral densities and bone microstructure.

    Directory of Open Access Journals (Sweden)

    Lavinia Paternoster

    Full Text Available Most previous genetic epidemiology studies within the field of osteoporosis have focused on the genetics of the complex trait areal bone mineral density (aBMD, not being able to differentiate genetic determinants of cortical volumetric BMD (vBMD, trabecular vBMD, and bone microstructural traits. The objective of this study was to separately identify genetic determinants of these bone traits as analysed by peripheral quantitative computed tomography (pQCT. Separate GWA meta-analyses for cortical and trabecular vBMDs were performed. The cortical vBMD GWA meta-analysis (n = 5,878 followed by replication (n = 1,052 identified genetic variants in four separate loci reaching genome-wide significance (RANKL, rs1021188, p = 3.6×10⁻¹⁴; LOC285735, rs271170, p = 2.7×10⁻¹²; OPG, rs7839059, p = 1.2×10⁻¹⁰; and ESR1/C6orf97, rs6909279, p = 1.1×10⁻⁹. The trabecular vBMD GWA meta-analysis (n = 2,500 followed by replication (n = 1,022 identified one locus reaching genome-wide significance (FMN2/GREM2, rs9287237, p = 1.9×10⁻⁹. High-resolution pQCT analyses, giving information about bone microstructure, were available in a subset of the GOOD cohort (n = 729. rs1021188 was significantly associated with cortical porosity while rs9287237 was significantly associated with trabecular bone fraction. The genetic variant in the FMN2/GREM2 locus was associated with fracture risk in the MrOS Sweden cohort (HR per extra T allele 0.75, 95% confidence interval 0.60-0.93 and GREM2 expression in human osteoblasts. In conclusion, five genetic loci associated with trabecular or cortical vBMD were identified. Two of these (FMN2/GREM2 and LOC285735 are novel bone-related loci, while the other three have previously been reported to be associated with aBMD. The genetic variants associated with cortical and trabecular bone parameters differed, underscoring the complexity of the genetics of bone parameters. We propose

  12. Diversification and genetic differentiation of cultivated melon inferred from sequence polymorphism in the chloroplast genome

    OpenAIRE

    Tanaka, Katsunori; Akashi, Yukari; FUKUNAGA, Kenji; Yamamoto, Tatsuya; Aierken, Yasheng; Nishida, Hidetaka; Long, Chun Lin; Yoshino, Hiromichi; Sato, Yo-Ichiro; KATO, Kenji

    2013-01-01

    Molecular analysis encouraged discovery of genetic diversity and relationships of cultivated melon (Cucumis melo L.). We sequenced nine inter- and intra-genic regions of the chloroplast genome, about 5500 bp, using 60 melon accessions and six reference accessions of wild species of Cucumis to show intra-specific variation of the chloroplast genome. Sequence polymorphisms were detected among melon accessions and other Cucumis species, indicating intra-specific diversification of the chloroplas...

  13. The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

    OpenAIRE

    Guerra, Daniel J.

    2011-01-01

    Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting th...

  14. Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin.

    Science.gov (United States)

    Kazadi, Kayole; Loeuillet, Corinne; Deutsch, Samuel; Ciuffi, Angela; Muñoz, Miguel; Beckmann, Jacques S; Moradpour, Darius; Antonarakis, Stylianos E; Telenti, Amalio

    2008-12-01

    Variation in cellular gene expression levels has been shown to be inherited. Expression is controlled at transcriptional and post-transcriptional levels. Internal ribosome entry sites (IRES) are used by viruses to bypass inhibition of cap-dependent translation, and by eukaryotic cells to control translation under conditions when protein synthesis is inhibited. We aimed at identifying genomic determinants of variability in IRES-mediated translation of viral [Encephalomyocarditis virus (EMCV)] and cellular IRES [X-linked inhibitor-of-apoptosis (XIAP) and c-myc]. Bicistronic lentiviral constructs expressing two fluorescent reporters were used to transduce laboratory and B lymphoblastoid cell lines [15 CEPH pedigrees (n = 205) and 50 unrelated individuals]. IRES efficiency varied according to cell type and among individuals. Control of IRES activity has a significant genetic component (h(2) of 0.47 and 0.36 for EMCV and XIAP, respectively). Quantitative linkage analysis identified a suggestive locus (LOD 2.35) on chromosome 18q21.2, and genome-wide association analysis revealed of a cluster of SNPs on chromosome 3, intronic to the FHIT gene, marginally associated (P = 5.9E-7) with XIAP IRES function. This study illustrates the in vitro generation of intermediate phenotypes by using cell lines for the evaluation of genetic determinants of control of elements such as IRES.

  15. Genome sequence and genetic diversity of European ash trees

    DEFF Research Database (Denmark)

    Sollars, Elizabeth S A; Harper, Andrea L; Kelly, Laura J;

    2016-01-01

    Ash trees (genus Fraxinus, family Oleaceae) are widespread throughout the Northern Hemisphere, but are being devastated in Europe by the fungus Hymenoscyphus fraxineus, causing ash dieback, and in North America by the herbivorous beetle Agrilus planipennis. Here we sequence the genome of a low...... to an emerging health threat in a non-model organism opens the way for mitigation of the epidemic....

  16. Estimating quantitative genetic parameters in wild populations: a comparison of pedigree and genomic approaches.

    Science.gov (United States)

    Bérénos, Camillo; Ellis, Philip A; Pilkington, Jill G; Pemberton, Josephine M

    2014-07-01

    The estimation of quantitative genetic parameters in wild populations is generally limited by the accuracy and completeness of the available pedigree information. Using relatedness at genomewide markers can potentially remove this limitation and lead to less biased and more precise estimates. We estimated heritability, maternal genetic effects and genetic correlations for body size traits in an unmanaged long-term study population of Soay sheep on St Kilda using three increasingly complete and accurate estimates of relatedness: (i) Pedigree 1, using observation-derived maternal links and microsatellite-derived paternal links; (ii) Pedigree 2, using SNP-derived assignment of both maternity and paternity; and (iii) whole-genome relatedness at 37 037 autosomal SNPs. In initial analyses, heritability estimates were strikingly similar for all three methods, while standard errors were systematically lower in analyses based on Pedigree 2 and genomic relatedness. Genetic correlations were generally strong, differed little between the three estimates of relatedness and the standard errors declined only very slightly with improved relatedness information. When partitioning maternal effects into separate genetic and environmental components, maternal genetic effects found in juvenile traits increased substantially across the three relatedness estimates. Heritability declined compared to parallel models where only a maternal environment effect was fitted, suggesting that maternal genetic effects are confounded with direct genetic effects and that more accurate estimates of relatedness were better able to separate maternal genetic effects from direct genetic effects. We found that the heritability captured by SNP markers asymptoted at about half the SNPs available, suggesting that denser marker panels are not necessarily required for precise and unbiased heritability estimates. Finally, we present guidelines for the use of genomic relatedness in future quantitative genetics

  17. 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.

  18. Genetic determinism in the Finnish upper secondary school biology textbooks

    Directory of Open Access Journals (Sweden)

    Tuomas Aivelo

    2015-05-01

    Full Text Available Genetics is a fast-developing field and it has been argued that genetics education is lagging behind. Genetics education has, for example, been suspected of indoctrinating strong genetic determinism. As the updating of the national upper secondary school curricula is about to start, we decided to study how the current curriculum manifests in Finnish biology textbooks. We studied the main four textbooks for historical gene models and definitions of genes using content analysis. Hybrid models were pervasive in textbooks. The textbooks expressed sometimes even strong genetic determinism, which might be linked to the dominance of older historical models in the textbooks. We also found instances of determinism which we call ‘weak determinism’: genes were depicted as more important factor than environment in relation to the expressed properties. Subsequently, there were no modern gene models found. We suggest gene models should be presented explicitly to reduce misconceptions about genes. We argue that genetics education needs to take more into account than environmental effects and there needs to be more emphasis on the temporal and developmental aspect of genotype-phenotype link. Specifically in Finland this could be done by a more explicit formulation of the national curriculum.

  19. Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study

    Directory of Open Access Journals (Sweden)

    Wernimont Susan M

    2011-11-01

    Full Text Available Abstract Background Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease. Methods 330 SNPs in 52 genes were studied in relation to plasma homocysteine and global genomic DNA methylation. SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform. Age-, smoking-, and nutrient-adjusted genotype--phenotype associations were estimated in regression models. Results Using a nominal P ≤ 0.005 threshold for statistical significance, 20 SNPs were associated with plasma homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in FTCD, SLC19A1, and SLC19A3 genes remained associated with plasma homocysteine. Gene by vitamin B-6 interactions were identified for both Alu and LINE-1 methylation, and epistatic interactions with the MTHFR rs1801133 SNP were identified for the plasma homocysteine phenotype. Pleiotropy involving the MTHFD1L and SARDH genes for both plasma homocysteine and Alu methylation phenotypes was identified. Conclusions No single gene was associated with all three phenotypes, and the set of the most statistically significant SNPs predictive of homocysteine or Alu or LINE-1 methylation was unique to each phenotype. Genetic variation in folate-mediated one-carbon metabolism, other than the well-known effects of the MTHFR c.665C>T (known as c.677 C>T, rs1801133, p.Ala222Val, is predictive of cardiovascular disease biomarkers.

  20. Genetic diversity and genomic strategies for improving drought and waterlogging tolerance in soybeans.

    Science.gov (United States)

    Valliyodan, Babu; Ye, Heng; Song, Li; Murphy, MacKensie; Shannon, J Grover; Nguyen, Henry T

    2016-12-07

    Drought and its interaction with high temperature are the major abiotic stress factors affecting soybean yield and production stability. Ongoing climate changes are anticipated to intensify drought events, which will further impact crop production and food security. However, excessive water also limits soybean production. The success of soybean breeding programmes for crop improvement is dependent on the extent of genetic variation present in the germplasm base. Screening for natural genetic variation in drought- and flooding tolerance-related traits, including root system architecture, water and nitrogen-fixation efficiency, and yield performance indices, has helped to identify the best resources for genetic studies in soybean. Genomic resources, including whole-genome sequences of diverse germplasms, millions of single-nucleotide polymorphisms, and high-throughput marker genotyping platforms, have expedited gene and marker discovery for translational genomics in soybean. This review highlights the current knowledge of the genetic diversity and quantitative trait loci associated with root system architecture, canopy wilting, nitrogen-fixation ability, and flooding tolerance that contributes to the understanding of drought- and flooding-tolerance mechanisms in soybean. Next-generation mapping approaches and high-throughput phenotyping will facilitate a better understanding of phenotype-genotype associations and help to formulate genomic-assisted breeding strategies, including genomic selection, in soybean for tolerance to drought and flooding stress.

  1. Targeted analysis of whole genome sequence data to diagnose genetic cardiomyopathy.

    Science.gov (United States)

    Golbus, Jessica R; Puckelwartz, Megan J; Dellefave-Castillo, Lisa; Fahrenbach, John P; Nelakuditi, Viswateja; Pesce, Lorenzo L; Pytel, Peter; McNally, Elizabeth M

    2014-12-01

    Cardiomyopathy is highly heritable but genetically diverse. At present, genetic testing for cardiomyopathy uses targeted sequencing to simultaneously assess the coding regions of >50 genes. New genes are routinely added to panels to improve the diagnostic yield. With the anticipated $1000 genome, it is expected that genetic testing will shift toward comprehensive genome sequencing accompanied by targeted gene analysis. Therefore, we assessed the reliability of whole genome sequencing and targeted analysis to identify cardiomyopathy variants in 11 subjects with cardiomyopathy. Whole genome sequencing with an average of 37× coverage was combined with targeted analysis focused on 204 genes linked to cardiomyopathy. Genetic variants were scored using multiple prediction algorithms combined with frequency data from public databases. This pipeline yielded 1 to 14 potentially pathogenic variants per individual. Variants were further analyzed using clinical criteria and segregation analysis, where available. Three of 3 previously identified primary mutations were detected by this analysis. In 6 subjects for whom the primary mutation was previously unknown, we identified mutations that segregated with disease, had clinical correlates, and had additional pathological correlation to provide evidence for causality. For 2 subjects with previously known primary mutations, we identified additional variants that may act as modifiers of disease severity. In total, we identified the likely pathological mutation in 9 of 11 (82%) subjects. These pilot data demonstrate that ≈30 to 40× coverage whole genome sequencing combined with targeted analysis is feasible and sensitive to identify rare variants in cardiomyopathy-associated genes. © 2014 American Heart Association, Inc.

  2. Advances in maize genomics and their value for enhancing genetic gains from breeding.

    Science.gov (United States)

    Xu, Yunbi; Skinner, Debra J; Wu, Huixia; Palacios-Rojas, Natalia; Araus, Jose Luis; Yan, Jianbing; Gao, Shibin; Warburton, Marilyn L; Crouch, Jonathan H

    2009-01-01

    Maize is an important crop for food, feed, forage, and fuel across tropical and temperate areas of the world. Diversity studies at genetic, molecular, and functional levels have revealed that, tropical maize germplasm, landraces, and wild relatives harbor a significantly wider range of genetic variation. Among all types of markers, SNP markers are increasingly the marker-of-choice for all genomics applications in maize breeding. Genetic mapping has been developed through conventional linkage mapping and more recently through linkage disequilibrium-based association analyses. Maize genome sequencing, initially focused on gene-rich regions, now aims for the availability of complete genome sequence. Conventional insertion mutation-based cloning has been complemented recently by EST- and map-based cloning. Transgenics and nutritional genomics are rapidly advancing fields targeting important agronomic traits including pest resistance and grain quality. Substantial advances have been made in methodologies for genomics-assisted breeding, enhancing progress in yield as well as abiotic and biotic stress resistances. Various genomic databases and informatics tools have been developed, among which MaizeGDB is the most developed and widely used by the maize research community. In the future, more emphasis should be given to the development of tools and strategic germplasm resources for more effective molecular breeding of tropical maize products.

  3. Advances in Maize Genomics and Their Value for Enhancing Genetic Gains from Breeding

    Science.gov (United States)

    Xu, Yunbi; Skinner, Debra J.; Wu, Huixia; Palacios-Rojas, Natalia; Araus, Jose Luis; Yan, Jianbing; Gao, Shibin; Warburton, Marilyn L.; Crouch, Jonathan H.

    2009-01-01

    Maize is an important crop for food, feed, forage, and fuel across tropical and temperate areas of the world. Diversity studies at genetic, molecular, and functional levels have revealed that, tropical maize germplasm, landraces, and wild relatives harbor a significantly wider range of genetic variation. Among all types of markers, SNP markers are increasingly the marker-of-choice for all genomics applications in maize breeding. Genetic mapping has been developed through conventional linkage mapping and more recently through linkage disequilibrium-based association analyses. Maize genome sequencing, initially focused on gene-rich regions, now aims for the availability of complete genome sequence. Conventional insertion mutation-based cloning has been complemented recently by EST- and map-based cloning. Transgenics and nutritional genomics are rapidly advancing fields targeting important agronomic traits including pest resistance and grain quality. Substantial advances have been made in methodologies for genomics-assisted breeding, enhancing progress in yield as well as abiotic and biotic stress resistances. Various genomic databases and informatics tools have been developed, among which MaizeGDB is the most developed and widely used by the maize research community. In the future, more emphasis should be given to the development of tools and strategic germplasm resources for more effective molecular breeding of tropical maize products. PMID:19688107

  4. Whole-Genome Sequencing Reveals Genetic Variation in the Asian House Rat

    Directory of Open Access Journals (Sweden)

    Huajing Teng

    2016-07-01

    Full Text Available Whole-genome sequencing of wild-derived rat species can provide novel genomic resources, which may help decipher the genetics underlying complex phenotypes. As a notorious pest, reservoir of human pathogens, and colonizer, the Asian house rat, Rattus tanezumi, is successfully adapted to its habitat. However, little is known regarding genetic variation in this species. In this study, we identified over 41,000,000 single-nucleotide polymorphisms, plus insertions and deletions, through whole-genome sequencing and bioinformatics analyses. Moreover, we identified over 12,000 structural variants, including 143 chromosomal inversions. Further functional analyses revealed several fixed nonsense mutations associated with infection and immunity-related adaptations, and a number of fixed missense mutations that may be related to anticoagulant resistance. A genome-wide scan for loci under selection identified various genes related to neural activity. Our whole-genome sequencing data provide a genomic resource for future genetic studies of the Asian house rat species and have the potential to facilitate understanding of the molecular adaptations of rats to their ecological niches.

  5. Whole-Genome Sequencing Reveals Genetic Variation in the Asian House Rat.

    Science.gov (United States)

    Teng, Huajing; Zhang, Yaohua; Shi, Chengmin; Mao, Fengbiao; Hou, Lingling; Guo, Hongling; Sun, Zhongsheng; Zhang, Jianxu

    2016-07-07

    Whole-genome sequencing of wild-derived rat species can provide novel genomic resources, which may help decipher the genetics underlying complex phenotypes. As a notorious pest, reservoir of human pathogens, and colonizer, the Asian house rat, Rattus tanezumi, is successfully adapted to its habitat. However, little is known regarding genetic variation in this species. In this study, we identified over 41,000,000 single-nucleotide polymorphisms, plus insertions and deletions, through whole-genome sequencing and bioinformatics analyses. Moreover, we identified over 12,000 structural variants, including 143 chromosomal inversions. Further functional analyses revealed several fixed nonsense mutations associated with infection and immunity-related adaptations, and a number of fixed missense mutations that may be related to anticoagulant resistance. A genome-wide scan for loci under selection identified various genes related to neural activity. Our whole-genome sequencing data provide a genomic resource for future genetic studies of the Asian house rat species and have the potential to facilitate understanding of the molecular adaptations of rats to their ecological niches.

  6. Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

    Directory of Open Access Journals (Sweden)

    D. Lemaire

    2012-05-01

    Full Text Available Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii population genetic differences that are a rationale behind group-targeted vaccines; iv an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.

  7. Limitations to estimating bacterial cross-speciestransmission using genetic and genomic markers: inferencesfrom simulation modeling

    Science.gov (United States)

    Julio Andre, Benavides; Cross, Paul C.; Luikart, Gordon; Scott, Creel

    2014-01-01

    Cross-species transmission (CST) of bacterial pathogens has major implications for human health, livestock, and wildlife management because it determines whether control actions in one species may have subsequent effects on other potential host species. The study of bacterial transmission has benefitted from methods measuring two types of genetic variation: variable number of tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). However, it is unclear whether these data can distinguish between different epidemiological scenarios. We used a simulation model with two host species and known transmission rates (within and between species) to evaluate the utility of these markers for inferring CST. We found that CST estimates are biased for a wide range of parameters when based on VNTRs and a most parsimonious reconstructed phylogeny. However, estimations of CST rates lower than 5% can be achieved with relatively low bias using as low as 250 SNPs. CST estimates are sensitive to several parameters, including the number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort. Our results suggest that, even with whole-genome sequences, unbiased estimates of CST will be difficult when sampling is limited, mutation rates are low, or for pathogens that were recently introduced.

  8. Moving towards system genetics through multiple trait analysis in genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Daniel eShriner

    2012-01-01

    Full Text Available Association studies are a staple of genotype-phenotype mapping studies, whether they are based on single markers, haplotypes, candidate genes, genome-wide genotypes, or whole genome sequences. Although genetic epidemiological studies typically contain data collected on multiple traits which themselves are often correlated, most analyses have been performed on single traits. Here, I review several methods that have been developed to perform multiple trait analysis. These methods range from traditional multivariate models for systems of equations to recently developed graphical approaches based on network theory. The application of network theory to genetics is termed systems genetics and has the potential to address long-standing questions in genetics about complex processes such as coordinate regulation, homeostasis, and pleiotropy.

  9. Genetic and genomic perspective to understand the molecular pathogenesis of keratoconus

    Directory of Open Access Journals (Sweden)

    Nallathambi Jeyabalan

    2013-01-01

    Full Text Available Keratoconus (KC; Mendelian Inheritance in Man (OMIM 14830 is a bilateral, progressive corneal defect affecting all ethnic groups around the world. It is the leading cause of corneal transplantation. The age of onset is at puberty, and the disorder is progressive until the 3 rd -4 th decade of life when it usually arrests. It is one of the major ocular problems with significant social and economic impacts as the disease affects young generation. Although genetic and environmental factors are associated with KC, but the precise etiology is still elusive. Results from complex segregation analysis suggests that genetic abnormalities may play an essential role in the susceptibility to KC. Due to genetic heterogeneity, a recent study revealed 17 different genomic loci identified in KC families by linkage mapping in various populations. The focus of this review is to provide a concise update on the current knowledge of the genetic basis of KC and genomic approaches to understand the disease pathogenesis.

  10. Genetic Diversity and Fingerprint Profiles of Commercial Lentinula edodes Cultivars Based on SSR Markers Developed from the Whole Genome Sequence

    Institute of Scientific and Technical Information of China (English)

    ZHANG Dan; SONG Chunyan; ZHANG Lujun; WU Ping; BAO Dapeng; SHANG Xiaodong; TAN Qi

    2014-01-01

    Lentinula edodes is an important cultivated mushroom in China, and accurate and reliable identification of individual cultivars is a prerequisite for successful cultivation and variety protection.In this study,the whole genome sequence of L.edodes was used to generate 200 simple sequence repeat (SSR) markers for delineating 25 commercial cultivars and for determining their genetic diversity.Our data revealed a relatively high level of genetic similarity among the cultivars,with average,minimum and maximum genetic similarity coefficient values of 0.776,0.567 and 1.000,respectively.Seven SSR primer pairs delineated eleven of the cultivars (Cr-02,Minfeng-1,Xianggu 241-4,Senyuan-1,Senyuan-8404,Xiang-9,Guangxiang-51,Huaxiang-5,L952,L9319 and L808)based on their unique multilocus SSR fingerprint profiles.

  11. NIG_MoG: a mouse genome navigator for exploring intersubspecific genetic polymorphisms.

    Science.gov (United States)

    Takada, Toyoyuki; Yoshiki, Atsushi; Obata, Yuichi; Yamazaki, Yukiko; Shiroishi, Toshihiko

    2015-08-01

    The National Institute of Genetics Mouse Genome database (NIG_MoG; http://molossinus.lab.nig.ac.jp/msmdb/) primarily comprises the whole-genome sequence data of two inbred mouse strains, MSM/Ms and JF1/Ms. These strains were established at NIG and originated from the Japanese subspecies Mus musculus molossinus. NIG_MoG provides visualized genome polymorphism information, browsing single-nucleotide polymorphisms and short insertions and deletions in the genomes of MSM/Ms and JF1/Ms with respect to C57BL/6J (whose genome is predominantly derived from the West European subspecies M. m. domesticus). This allows users, especially wet-lab biologists, to intuitively recognize intersubspecific genome divergence in these mouse strains using visual data. The database also supports the in silico screening of bacterial artificial chromosome (BAC) clones that contain genomic DNA from MSM/Ms and the standard classical laboratory strain C57BL/6N. NIG_MoG is thus a valuable navigator for exploring mouse genome polymorphisms and BAC clones that are useful for studies of gene function and regulation based on intersubspecific genome divergence.

  12. How agricultural management shapes soil microbial communities: patterns emerging from genetic and genomic studies

    Science.gov (United States)

    Daly, Amanda; Grandy, A. Stuart

    2016-04-01

    Agriculture is a predominant land use and thus a large influence on global carbon (C) and nitrogen (N) balances, climate, and human health. If we are to produce food, fiber, and fuel sustainably we must maximize agricultural yield while minimizing negative environmental consequences, goals towards which we have made great strides through agronomic advances. However, most agronomic strategies have been designed with a view of soil as a black box, largely ignoring the way management is mediated by soil biota. Because soil microbes play a central role in many of the processes that deliver nutrients to crops and support their health and productivity, agricultural management strategies targeted to exploit or support microbial activity should deliver additional benefits. To do this we must determine how microbial community structure and function are shaped by agricultural practices, but until recently our characterizations of soil microbial communities in agricultural soils have been largely limited to broad taxonomic classes due to methodological constraints. With advances in high-throughput genetic and genomic sequencing techniques, better taxonomic resolution now enables us to determine how agricultural management affects specific microbes and, in turn, nutrient cycling outcomes. Here we unite findings from published research that includes genetic or genomic data about microbial community structure (e.g. 454, Illumina, clone libraries, qPCR) in soils under agricultural management regimes that differ in type and extent of tillage, cropping selections and rotations, inclusion of cover crops, organic amendments, and/or synthetic fertilizer application. We delineate patterns linking agricultural management to microbial diversity, biomass, C- and N-content, and abundance of microbial taxa; furthermore, where available, we compare patterns in microbial communities to patterns in soil extracellular enzyme activities, catabolic profiles, inorganic nitrogen pools, and nitrogen

  13. Ecological and genetic factors linked to contrasting genome dynamics in seed plants.

    Science.gov (United States)

    Leitch, A R; Leitch, I J

    2012-05-01

    The large-scale replacement of gymnosperms by angiosperms in many ecological niches over time and the huge disparity in species numbers have led scientists to explore factors (e.g. polyploidy, developmental systems, floral evolution) that may have contributed to the astonishing rise of angiosperm diversity. Here, we explore genomic and ecological factors influencing seed plant genomes. This is timely given the recent surge in genomic data. We compare and contrast the genomic structure and evolution of angiosperms and gymnosperms and find that angiosperm genomes are more dynamic and diverse, particularly amongst the herbaceous species. Gymnosperms typically have reduced frequencies of a number of processes (e.g. polyploidy) that have shaped the genomes of other vascular plants and have alternative mechanisms to suppress genome dynamism (e.g. epigenetics and activity of transposable elements). Furthermore, the presence of several characters in angiosperms (e.g. herbaceous habit, short minimum generation time) has enabled them to exploit new niches and to be viable with small population sizes, where the power of genetic drift can outweigh that of selection. Together these processes have led to increased rates of genetic divergence and faster fixation times of variation in many angiosperms compared with gymnosperms.

  14. Whole genome sequence and analysis of the Marwari horse breed and its genetic origin.

    Science.gov (United States)

    Jun, JeHoon; Cho, Yun Sung; Hu, Haejin; Kim, Hak-Min; Jho, Sungwoong; Gadhvi, Priyvrat; Park, Kyung Mi; Lim, Jeongheui; Paek, Woon Kee; Han, Kyudong; Manica, Andrea; Edwards, Jeremy S; Bhak, Jong

    2014-01-01

    The horse (Equus ferus caballus) is one of the earliest domesticated species and has played an important role in the development of human societies over the past 5,000 years. In this study, we characterized the genome of the Marwari horse, a rare breed with unique phenotypic characteristics, including inwardly turned ear tips. It is thought to have originated from the crossbreeding of local Indian ponies with Arabian horses beginning in the 12th century. We generated 101 Gb (~30 × coverage) of whole genome sequences from a Marwari horse using the Illumina HiSeq2000 sequencer. The sequences were mapped to the horse reference genome at a mapping rate of ~98% and with ~95% of the genome having at least 10 × coverage. A total of 5.9 million single nucleotide variations, 0.6 million small insertions or deletions, and 2,569 copy number variation blocks were identified. We confirmed a strong Arabian and Mongolian component in the Marwari genome. Novel variants from the Marwari sequences were annotated, and were found to be enriched in olfactory functions. Additionally, we suggest a potential functional genetic variant in the TSHZ1 gene (p.Ala344>Val) associated with the inward-turning ear tip shape of the Marwari horses. Here, we present an analysis of the Marwari horse genome. This is the first genomic data for an Asian breed, and is an invaluable resource for future studies of genetic variation associated with phenotypes and diseases in horses.

  15. Origin and evolution of the dependent lineages in the genetic caste determination system of Pogonomyrmex ants.

    Science.gov (United States)

    Sirviö, Anu; Pamilo, Pekka; Johnson, Robert A; Page, Robert E; Gadau, Jürgen

    2011-03-01

    Hybridizing harvester ants of the Pogonomyrmex barbatus/rugosus complex have an exceptional genetic caste determination (GCD) mechanism. We combined computer simulations, population genomics, and linkage mapping using >1000 nuclear AFLP markers and a partial mtDNA sequence to explore the genetic architecture and origin of the dependent lineages. Our samples included two pairs of hybridizing lineages, and the mitochondrial and nuclear data showed contradicting affinities between them. Clustering of individual genotypes based on nuclear markers indicated some exceptions to the general GCD system, that is, interlineage hybrid genes as well as some pure-line workers. A genetic linkage map of P. rugosus showed one of the highest recombination rates ever measured in insects (14.0 cM/Mb), supporting the view that social insects are characterized by high recombination rates. The population data had 165 markers in which sibling pairs showed a significant genetic difference depending on the caste. The differences were scattered in the genome; 13 linkage groups had loci with F(ST)>0.9 between the hybridizing lineages J1 and J2.The mapping results and the population data indicate that the dependent lineages have been initially formed through hybridization at different points in time but the role of introgression has been insignificant in their later evolution.

  16. The Utility of Breastmilk for Genetic or Genomic Studies: A Systematic Review

    OpenAIRE

    2013-01-01

    This study synthesized scientific literature that applies genetic or genomic approaches to breastmilk. A literature search of PubMed was conducted in March 2012 using the key words "breast milk," "lactation," "genetic," "gene expression," and "epigenetic." Additional articles were identified/selected for evaluation with MeSH term searches, and a review of article reference lists was obtained from the search. The initial 657 abstracts retrieved from the literature search were reviewed, and 16 ...

  17. Genomic and Network Patterns of Schizophrenia Genetic Variation in Human Evolutionary Accelerated Regions

    OpenAIRE

    Xu, Ke; Schadt, Eric E.; Pollard, Katherine S.; Roussos, Panos; Joel T Dudley

    2015-01-01

    The population persistence of schizophrenia despite associated reductions in fitness and fecundity suggests that the genetic basis of schizophrenia has a complex evolutionary history. A recent meta-analysis of schizophrenia genome-wide association studies offers novel opportunities for assessment of the evolutionary trajectories of schizophrenia-associated loci. In this study, we hypothesize that components of the genetic architecture of schizophrenia are attributable to human lineage-specifi...

  18. Genomic and Network Patterns of Schizophrenia Genetic Variation in Human Evolutionary Accelerated Regions

    OpenAIRE

    Xu, Ke; Schadt, Eric E.; Pollard, Katherine S.; Roussos, Panos; Dudley, Joel T

    2015-01-01

    The population persistence of schizophrenia despite associated reductions in fitness and fecundity suggests that the genetic basis of schizophrenia has a complex evolutionary history. A recent meta-analysis of schizophrenia genome-wide association studies offers novel opportunities for assessment of the evolutionary trajectories of schizophrenia-associated loci. In this study, we hypothesize that components of the genetic architecture of schizophrenia are attributable to human lineage-specifi...

  19. Genomic and population genetic analysis of deep-sea vent chemoautotrophs

    Science.gov (United States)

    Nakagawa, S.; Shimamura, S.; Takaki, Y.; Mino, S.; Makita, H.; Sawabe, T.; Takai, K.

    2012-12-01

    Deep-sea vents are the light-independent, highly productive ecosystems driven primarily by chemoautotrophs. Most of the invertebrates thrive there through their relationship with symbiotic chemoautotrophs. Chemoautotrophs are microorganisms that are able to fix inorganic carbon using a chemical energy obtained through the oxidation of reduced compounds. Following the discovery of deep-sea vent ecosystems in 1977, there has been an increasing knowledge that deep-sea vent chemoautotrophs display remarkable physiological and phylogenetic diversity. Recent microbiological studies have led to an emerging view that the majority of deep-sea vent chemoautotrophs have the ability to derive energy from multiple redox couples other than the conventional sulfur-oxygen couple. Genomic, metagenomic and postgenomic studies have considerably accelerated the comprehensive understanding of molecular mechanisms of deep-sea vent chemoautotrophy, even in unculturable endosymbionts of vent fauna. For example, genomic analysis suggested that there were previously unrecognized evolutionary links between deep-sea vent chemoautotrophs and important human/animal pathogens. However, relatively little is known about the genome of horizontally transmitted endosymbionts. In this study, we sequenced whole genomes of the probably horizontally transmitted endosymbionts of two different gastropod species from a deep-sea hydrothermal field, as an effort to address questions about 1) the genome evolution of horizontally transmitted, facultative endosymbionts, 2) their genomic variability, and 3) genetic differences among symbionts of various deep-sea vent invertebrates. Both endosymbiont genomes display features consistent with ongoing genome reduction such as large proportions of pseudogenes and transposable elements. The genomes encode multiple functions for chemoautotrophic respirations, probably reflecting their adaptation to their niches with continuous changes in environmental conditions. When

  20. Genome sequence and genetic diversity of European ash trees.

    Science.gov (United States)

    Sollars, Elizabeth S A; Harper, Andrea L; Kelly, Laura J; Sambles, Christine M; Ramirez-Gonzalez, Ricardo H; Swarbreck, David; Kaithakottil, Gemy; Cooper, Endymion D; Uauy, Cristobal; Havlickova, Lenka; Worswick, Gemma; Studholme, David J; Zohren, Jasmin; Salmon, Deborah L; Clavijo, Bernardo J; Li, Yi; He, Zhesi; Fellgett, Alison; McKinney, Lea Vig; Nielsen, Lene Rostgaard; Douglas, Gerry C; Kjær, Erik Dahl; Downie, J Allan; Boshier, David; Lee, Steve; Clark, Jo; Grant, Murray; Bancroft, Ian; Caccamo, Mario; Buggs, Richard J A

    2017-01-12

    Ash trees (genus Fraxinus, family Oleaceae) are widespread throughout the Northern Hemisphere, but are being devastated in Europe by the fungus Hymenoscyphus fraxineus, causing ash dieback, and in North America by the herbivorous beetle Agrilus planipennis. Here we sequence the genome of a low-heterozygosity Fraxinus excelsior tree from Gloucestershire, UK, annotating 38,852 protein-coding genes of which 25% appear ash specific when compared with the genomes of ten other plant species. Analyses of paralogous genes suggest a whole-genome duplication shared with olive (Olea europaea, Oleaceae). We also re-sequence 37 F. excelsior trees from Europe, finding evidence for apparent long-term decline in effective population size. Using our reference sequence, we re-analyse association transcriptomic data, yielding improved markers for reduced susceptibility to ash dieback. Surveys of these markers in British populations suggest that reduced susceptibility to ash dieback may be more widespread in Great Britain than in Denmark. We also present evidence that susceptibility of trees to H. fraxineus is associated with their iridoid glycoside levels. This rapid, integrated, multidisciplinary research response to an emerging health threat in a non-model organism opens the way for mitigation of the epidemic.

  1. Error analysis on heading determination via genetic algorithms

    Institute of Scientific and Technical Information of China (English)

    Zhong Bing; Xu Jiangning; Ma Heng

    2006-01-01

    A new error analysis method is presented via genetic algorithms for high precise heading determination model based on two total positioning stations (TPSs). The method has the ability to search all possible solution space by the genetic operators of elitist model and restriction. The result of analyzing the error of this model shows that the accuracy of this model is precise enough to meet the need of calibration for navigation systems on ship, and the search space is only 0.03% of the total search space, and the precision of heading determination is 4" in a general dock.

  2. Genetically Determined Variation in Developmental Physiology of Bivalve Larvae (Crassostrea gigas).

    Science.gov (United States)

    Francis Pan, T-C; Applebaum, Scott L; Manahan, Donal T

    2015-01-01

    Understanding the complex interactions that regulate growth and form is a central question in developmental physiology. We used experimental crosses of pedigreed lines of the Pacific oyster, Crassostrea gigas, to investigate genetically determined variations in larval growth and nutrient transport. We show that (i) transport rates at 10 and 100 μM glycine scale differentially with size; (ii) size-specific maximum transport capacity (Jmax) is genetically determined; and (iii) Jmax serves as an early predictive index of subsequent growth rate. This relationship between genetically determined Jmax and growth suggests the potential use of transporter genes as biomarkers of growth potential. Analysis of the genome of C. gigas revealed 23 putative amino acid transporter genes. The complexity of gene families that underpin physiological traits has additional precedents in this species and others and warrants caution in the use of gene expression as a biomarker for physiological state. Direct in vivo measurements of physiological processes using species with defined genotypes are required to understand genetically determined variance of nutrient flux and other processes that regulate development and growth.

  3. CTLA-4 as a genetic determinant in autoimmune Addison's disease.

    Science.gov (United States)

    Wolff, A S B; Mitchell, A L; Cordell, H J; Short, A; Skinningsrud, B; Ollier, W; Badenhoop, K; Meyer, G; Falorni, A; Kampe, O; Undlien, D; Pearce, S H S; Husebye, E S

    2015-09-01

    In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.

  4. Genetic diversity analysis of two commercial breeds of pigs using genomic and pedigree data.

    Science.gov (United States)

    Zanella, Ricardo; Peixoto, Jane O; Cardoso, Fernando F; Cardoso, Leandro L; Biegelmeyer, Patrícia; Cantão, Maurício E; Otaviano, Antonio; Freitas, Marcelo S; Caetano, Alexandre R; Ledur, Mônica C

    2016-03-30

    Genetic improvement in livestock populations can be achieved without significantly affecting genetic diversity if mating systems and selection decisions take genetic relationships among individuals into consideration. The objective of this study was to examine the genetic diversity of two commercial breeds of pigs. Genotypes from 1168 Landrace (LA) and 1094 Large White (LW) animals from a commercial breeding program in Brazil were obtained using the Illumina PorcineSNP60 Beadchip. Inbreeding estimates based on pedigree (F x) and genomic information using runs of homozygosity (F ROH) and the single nucleotide polymorphisms (SNP) by SNP inbreeding coefficient (F SNP) were obtained. Linkage disequilibrium (LD), correlation of linkage phase (r) and effective population size (N e ) were also estimated. Estimates of inbreeding obtained with pedigree information were lower than those obtained with genomic data in both breeds. We observed that the extent of LD was slightly larger at shorter distances between SNPs in the LW population than in the LA population, which indicates that the LW population was derived from a smaller N e . Estimates of N e based on genomic data were equal to 53 and 40 for the current populations of LA and LW, respectively. The correlation of linkage phase between the two breeds was equal to 0.77 at distances up to 50 kb, which suggests that genome-wide association and selection should be performed within breed. Although selection intensities have been stronger in the LA breed than in the LW breed, levels of genomic and pedigree inbreeding were lower for the LA than for the LW breed. The use of genomic data to evaluate population diversity in livestock animals can provide new and more precise insights about the effects of intense selection for production traits. Resulting information and knowledge can be used to effectively increase response to selection by appropriately managing the rate of inbreeding, minimizing negative effects of inbreeding

  5. Genetic association of marbling score with intragenic nucleotide variants at selection signals of the bovine genome.

    Science.gov (United States)

    Ryu, J; Lee, C

    2016-04-01

    Selection signals of Korean cattle might be attributed largely to artificial selection for meat quality. Rapidly increased intragenic markers of newly annotated genes in the bovine genome would help overcome limited findings of genetic markers associated with meat quality at the selection signals in a previous study. The present study examined genetic associations of marbling score (MS) with intragenic nucleotide variants at selection signals of Korean cattle. A total of 39 092 nucleotide variants of 407 Korean cattle were utilized in the association analysis. A total of 129 variants were selected within newly annotated genes in the bovine genome. Their genetic associations were analyzed using the mixed model with random polygenic effects based on identical-by-state genetic relationships among animals in order to control for spurious associations produced by population structure. Genetic associations of MS were found (PCSPG4). In particular, the genetic associations with CDC42BPA and LARGE were confirmed using an independent data set of Korean cattle. The results implied that allele frequencies of functional variants and their proximity variants have been augmented by directional selection for greater MS and remain selection signals in the bovine genome. Further studies of fine mapping would be useful to incorporate favorable alleles in marker-assisted selection for MS of Korean cattle.

  6. A genome-wide survey of genetic variation in gorillas using reduced representation sequencing.

    Directory of Open Access Journals (Sweden)

    Aylwyn Scally

    Full Text Available All non-human great apes are endangered in the wild, and it is therefore important to gain an understanding of their demography and genetic diversity. Whole genome assembly projects have provided an invaluable foundation for understanding genetics in all four genera, but to date genetic studies of multiple individuals within great ape species have largely been confined to mitochondrial DNA and a small number of other loci. Here, we present a genome-wide survey of genetic variation in gorillas using a reduced representation sequencing approach, focusing on the two lowland subspecies. We identify 3,006,670 polymorphic sites in 14 individuals: 12 western lowland gorillas (Gorilla gorilla gorilla and 2 eastern lowland gorillas (Gorilla beringei graueri. We find that the two species are genetically distinct, based on levels of heterozygosity and patterns of allele sharing. Focusing on the western lowland population, we observe evidence for population substructure, and a deficit of rare genetic variants suggesting a recent episode of population contraction. In western lowland gorillas, there is an elevation of variation towards telomeres and centromeres on the chromosomal scale. On a finer scale, we find substantial variation in genetic diversity, including a marked reduction close to the major histocompatibility locus, perhaps indicative of recent strong selection there. These findings suggest that despite their maintaining an overall level of genetic diversity equal to or greater than that of humans, population decline, perhaps associated with disease, has been a significant factor in recent and long-term pressures on wild gorilla populations.

  7. Exploring human brain lateralization with molecular genetics and genomics.

    Science.gov (United States)

    Francks, Clyde

    2015-11-01

    Lateralizations of brain structure and motor behavior have been observed in humans as early as the first trimester of gestation, and are likely to arise from asymmetrical genetic-developmental programs, as in other animals. Studies of gene expression levels in postmortem tissue samples, comparing the left and right sides of the human cerebral cortex, have generally not revealed striking transcriptional differences between the hemispheres. This is likely due to lateralization of gene expression being subtle and quantitative. However, a recent re-analysis and meta-analysis of gene expression data from the adult superior temporal and auditory cortex found lateralization of transcription of genes involved in synaptic transmission and neuronal electrophysiology. Meanwhile, human subcortical mid- and hindbrain structures have not been well studied in relation to lateralization of gene activity, despite being potentially important developmental origins of asymmetry. Genetic polymorphisms with small effects on adult brain and behavioral asymmetries are beginning to be identified through studies of large datasets, but the core genetic mechanisms of lateralized human brain development remain unknown. Identifying subtly lateralized genetic networks in the brain will lead to a new understanding of how neuronal circuits on the left and right are differently fine-tuned to preferentially support particular cognitive and behavioral functions. © 2015 New York Academy of Sciences.

  8. The characterization of goat genetic diversity : Towards a genomic approach

    NARCIS (Netherlands)

    Ajmone-Marsan, P.; Colli, L.; Han, J. L.; Achilli, A.; Lancioni, H.; Joost, S.; Crepaldi, P.; Pilla, F.; Stella, A.; Taberlet, P.; Boettcher, P.; Negrini, R.; Lenstra, J. A.

    2014-01-01

    The investigation of genetic diversity at molecular level has been proposed as a valuable complement and sometimes proxy to phenotypic diversity of local breeds and is presently considered as one of the FAO priorities for breed characterization. By recommending a set of selected molecular markers fo

  9. The characterization of goat genetic diversity : Towards a genomic approach

    NARCIS (Netherlands)

    Ajmone-Marsan, P.; Colli, L.; Han, J. L.; Achilli, A.; Lancioni, H.; Joost, S.; Crepaldi, P.; Pilla, F.; Stella, A.; Taberlet, P.; Boettcher, P.; Negrini, R.; Lenstra, J. A.|info:eu-repo/dai/nl/067852335

    2014-01-01

    The investigation of genetic diversity at molecular level has been proposed as a valuable complement and sometimes proxy to phenotypic diversity of local breeds and is presently considered as one of the FAO priorities for breed characterization. By recommending a set of selected molecular markers

  10. Annotation Of Novel And Conserved MicroRNA Genes In The Build 10 Sus scrofa Reference Genome And Determination Of Their Expression Levels In Ten Different Tissues

    DEFF Research Database (Denmark)

    Thomsen, Bo; Nielsen, Mathilde; Hedegaard, Jakob

    The DNA template used in the pig genome sequencing project was provided by a Duroc pig named TJ Tabasco. In an effort to annotate microRNA (miRNA) genes in the reference genome we have conducted deep sequencing to determine the miRNA transcriptomes in ten different tissues isolated from Pinky......, a genetically identical clone of TJ Tabasco. The purpose was to generate miRNA sequences that are highly homologous to the reference genome sequence, which along with computational prediction will improve confidence in the genomic annotation of miRNA genes. Based on homology searches of the sequence data...

  11. A genetic approach for the identification of exosporium assembly determinants of Bacillus anthracis

    Science.gov (United States)

    Spreng, Krista A.; Thompson, Brian M.; Stewart, George C.

    2013-01-01

    The exosporium is the outermost layer of spores of the zoonotic pathogen Bacillus anthracis. The composition of the exosporium and its functions are only partly understood. Because this outer spore layer is refractive to traditional biochemical analysis, a genetic approach is needed in order to define the proteins which comprise this important spore layer and its assembly pathway. We have created a novel genetic screening system for the identification and isolation of mutants with defects in exosporium assembly during B. anthracis spore maturation. The system is based on the targeting sequence of the BclA exosporium nap layer glycoprotein and a fluorescent reporter. By utilizing this screening system and gene inactivation with Tn916, several novel putative exosporium-associated determinants were identified. A sampling of the mutants obtained was further characterized, confirming their exosporium defect and validating the utility of this screen to identify novel spore determinants in the genome of this pathogen. PMID:23411372

  12. Comparative analysis of the Mycoplasma capricolum subsp. capricolum GM508D genome reveals subrogation of phase-variable contingency genes and a novel integrated genetic element.

    Science.gov (United States)

    Calcutt, Michael J; Foecking, Mark F

    2015-08-01

    Mycoplasma capricolum subspecies capricolum is both a pathogen of small ruminants and a model recipient organism for gene transplantation and synthetic biology. With the availability of the complete genome of the type strain California kid (released in 2005), a draft genome of strain GM508D was determined to investigate genomic variation in this subspecies. Differences in mobile genetic element location and complement, catabolic pathway genes, contingency loci, surface antigen genes and type II restriction-modification systems highlight the plasticity and diversity within this taxon.

  13. Comparative genetic mapping between clementine, pummelo and sweet orange and the interspecicic structure of the Clementine genome

    Science.gov (United States)

    Comparative genetic mapping between clementine, pummelo and sweet orange and the interspecicic structure of the Clementine genome The availability of a saturated genetic map of Clementine was identified by the International Citrus Genome Consortium as an essential prerequisite to assist the assembly...

  14. Genetics and Genomics of Single-Gene Cardiovascular Diseases : Common Hereditary Cardiomyopathies as Prototypes of Single-Gene Disorders

    NARCIS (Netherlands)

    Marian, Ali J; van Rooij, Eva; Roberts, Robert

    2016-01-01

    This is the first of 2 review papers on genetics and genomics appearing as part of the series on "omics." Genomics pertains to all components of an organism's genes, whereas genetics involves analysis of a specific gene or genes in the context of heredity. The paper provides introductory comments,

  15. Genetics and Genomics of Single-Gene Cardiovascular Diseases : Common Hereditary Cardiomyopathies as Prototypes of Single-Gene Disorders

    NARCIS (Netherlands)

    Marian, Ali J.; van Rooij, Eva; Roberts, Robert

    2016-01-01

    This is the first of 2 review papers on genetics and genomics appearing as part of the series on “omics.” Genomics pertains to all components of an organism's genes, whereas genetics involves analysis of a specific gene or genes in the context of heredity. The paper provides introductory comments,

  16. Genetics of skin color variation in Europeans: genome-wide association studies with functional follow-up

    NARCIS (Netherlands)

    F. Liu; M. Visser (Mijke); D.L. Duffy (David); P.G. Hysi (Pirro); L.C. Jacobs (Leonie); O. Lao Grueso (Oscar); K. Zhong (Kaiyin); S. Walsh (Susan); L. Chaitanya (Lakshmi); A. Wollstein (Andreas); G. Zhu (Gu); G.W. Montgomery (Grant); A.K. Henders (Anjali); M. Mangino (Massimo); D. Glass (Daniel); V. Bataille (Veronique); R.A. Sturm (Richard A.); F. Rivadeneira Ramirez (Fernando); A. Hofman (Albert); W.F.J. van IJcken (Wilfred); A.G. Uitterlinden (André); R.-J.T.S. Palstra (Robert-Jan); T.D. Spector (Timothy); N.G. Martin (Nicholas); T.E.C. Nijsten (Tamar); M.H. Kayser (Manfred)

    2015-01-01

    textabstractIn the International Visible Trait Genetics (VisiGen) Consortium, we investigated the genetics of human skin color by combining a series of genome-wide association studies (GWAS) in a total of 17,262 Europeans with functional follow-up of discovered loci. Our GWAS provide the first genom

  17. Natural biased coin encoded in the genome determines cell strategy.

    Science.gov (United States)

    Dorri, Faezeh; Mahini, Hamid; Sharifi-Zarchi, Ali; Totonchi, Mehdi; Tusserkani, Ruzbeh; Pezeshk, Hamid; Sadeghi, Mehdi

    2014-01-01

    Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.

  18. Natural biased coin encoded in the genome determines cell strategy.

    Directory of Open Access Journals (Sweden)

    Faezeh Dorri

    Full Text Available Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.

  19. Genetics and genomics of pseudoexfoliation syndrome/glaucoma

    Directory of Open Access Journals (Sweden)

    Ursula Schlotzer-Schrehardt

    2011-01-01

    Full Text Available Pseudoexfoliation (PEX syndrome, one of the most common causes of glaucoma, represents a complex, multifactorial, late-onset disease of worldwide significance. The etiopathogenesis involves both genetic and non-genetic factors. The PEX-specific tissue alterations are caused by a generalized fibrotic matrix process, which has been characterized as a stress-induced elastosis associated with the excessive production and abnormal cross-linking of elastic microfibrils into fibrillar PEX aggregates. The identification of lysyl oxidase-like 1 (LOXL1 as a major genetic risk factor for PEX syndrome and PEX glaucoma further supports a role of elastogenesis and elastosis in the pathophysiology of PEX, as LOXL1 is a pivotal cross-linking enzyme in elastic fiber formation and stabilization. The available data suggest that LOXL1 is markedly dysregulated depending on the stage of the fibrotic process. While transient upregulation of LOXL1 during the early stages of PEX fibrogenesis participates in the formation and aggregation of abnormal PEX fiber deposits, the decreased expression of LOXL1 during the advanced stages of the disease may affect elastin metabolism and promote elastotic processes, e.g. in the lamina cribrosa, predisposing to glaucoma development. However, in view of the low penetrance of the PEX-associated risk variants of LOXL1, other genetic and/or environmental factors must contribute to the risk of developing the PEX phenotype. Some evidence exists for the contribution of additional genes with relatively small effects, e.g. clusterin (CLU, contactin-associated protein-like 2 (CNTNAP2, apolipoprotein E (APOE, glutathione S-transferases (GSTs, and tumor necrosis factor-alpha (TNFA, in certain study populations. Several environmental conditions associated with PEX, such as oxidative stress as well as pro-fibrotic cytokines and growth factors, can regulate expression of LOXL1 and elastic proteins in vitro and may therefore act as co

  20. Disproportionate Contributions of Select Genomic Compartments and Cell Types to Genetic Risk for Coronary Artery Disease.

    Directory of Open Access Journals (Sweden)

    Hong-Hee Won

    2015-10-01

    Full Text Available Large genome-wide association studies (GWAS have identified many genetic loci associated with risk for myocardial infarction (MI and coronary artery disease (CAD. Concurrently, efforts such as the National Institutes of Health (NIH Roadmap Epigenomics Project and the Encyclopedia of DNA Elements (ENCODE Consortium have provided unprecedented data on functional elements of the human genome. In the present study, we systematically investigate the biological link between genetic variants associated with this complex disease and their impacts on gene function. First, we examined the heritability of MI/CAD according to genomic compartments. We observed that single nucleotide polymorphisms (SNPs residing within nearby regulatory regions show significant polygenicity and contribute between 59-71% of the heritability for MI/CAD. Second, we showed that the polygenicity and heritability explained by these SNPs are enriched in histone modification marks in specific cell types. Third, we found that a statistically higher number of 45 MI/CAD-associated SNPs that have been identified from large-scale GWAS studies reside within certain functional elements of the genome, particularly in active enhancer and promoter regions. Finally, we observed significant heterogeneity of this signal across cell types, with strong signals observed within adipose nuclei, as well as brain and spleen cell types. These results suggest that the genetic etiology of MI/CAD is largely explained by tissue-specific regulatory perturbation within the human genome.

  1. Phased whole-genome genetic risk in a family quartet using a major allele reference sequence.

    Directory of Open Access Journals (Sweden)

    Frederick E Dewey

    2011-09-01

    Full Text Available Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (< 1,000 base pairs. We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.

  2. The humankind genome: from genetic diversity to the origin of human diseases.

    Science.gov (United States)

    Belizário, Jose E

    2013-12-01

    Genome-wide association studies have failed to establish common variant risk for the majority of common human diseases. The underlying reasons for this failure are explained by recent studies of resequencing and comparison of over 1200 human genomes and 10 000 exomes, together with the delineation of DNA methylation patterns (epigenome) and full characterization of coding and noncoding RNAs (transcriptome) being transcribed. These studies have provided the most comprehensive catalogues of functional elements and genetic variants that are now available for global integrative analysis and experimental validation in prospective cohort studies. With these datasets, researchers will have unparalleled opportunities for the alignment, mining, and testing of hypotheses for the roles of specific genetic variants, including copy number variations, single nucleotide polymorphisms, and indels as the cause of specific phenotypes and diseases. Through the use of next-generation sequencing technologies for genotyping and standardized ontological annotation to systematically analyze the effects of genomic variation on humans and model organism phenotypes, we will be able to find candidate genes and new clues for disease's etiology and treatment. This article describes essential concepts in genetics and genomic technologies as well as the emerging computational framework to comprehensively search websites and platforms available for the analysis and interpretation of genomic data.

  3. A high-definition view of functional genetic variation from natural yeast genomes.

    Science.gov (United States)

    Bergström, Anders; Simpson, Jared T; Salinas, Francisco; Barré, Benjamin; Parts, Leopold; Zia, Amin; Nguyen Ba, Alex N; Moses, Alan M; Louis, Edward J; Mustonen, Ville; Warringer, Jonas; Durbin, Richard; Liti, Gianni

    2014-04-01

    The question of how genetic variation in a population influences phenotypic variation and evolution is of major importance in modern biology. Yet much is still unknown about the relative functional importance of different forms of genome variation and how they are shaped by evolutionary processes. Here we address these questions by population level sequencing of 42 strains from the budding yeast Saccharomyces cerevisiae and its closest relative S. paradoxus. We find that genome content variation, in the form of presence or absence as well as copy number of genetic material, is higher within S. cerevisiae than within S. paradoxus, despite genetic distances as measured in single-nucleotide polymorphisms being vastly smaller within the former species. This genome content variation, as well as loss-of-function variation in the form of premature stop codons and frameshifting indels, is heavily enriched in the subtelomeres, strongly reinforcing the relevance of these regions to functional evolution. Genes affected by these likely functional forms of variation are enriched for functions mediating interaction with the external environment (sugar transport and metabolism, flocculation, metal transport, and metabolism). Our results and analyses provide a comprehensive view of genomic diversity in budding yeast and expose surprising and pronounced differences between the variation within S. cerevisiae and that within S. paradoxus. We also believe that the sequence data and de novo assemblies will constitute a useful resource for further evolutionary and population genomics studies.

  4. Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

    Science.gov (United States)

    Pope, Welkin H; Bowman, Charles A; Russell, Daniel A; Jacobs-Sera, Deborah; Asai, David J; Cresawn, Steven G; Jacobs, William R; Hendrix, Roger W; Lawrence, Jeffrey G; Hatfull, Graham F; Abbazia, Patrick; Ababio, Amma; Adam, Naazneen

    2015-01-01

    The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery. DOI: http://dx.doi.org/10.7554/eLife.06416.001 PMID:25919952

  5. A high resolution genetic map anchoring scaffolds of the sequenced watermelon genome.

    Science.gov (United States)

    Ren, Yi; Zhao, Hong; Kou, Qinghe; Jiang, Jiao; Guo, Shaogui; Zhang, Haiying; Hou, Wenju; Zou, Xiaohua; Sun, Honghe; Gong, Guoyi; Levi, Amnon; Xu, Yong

    2012-01-01

    As part of our ongoing efforts to sequence and map the watermelon (Citrullus spp.) genome, we have constructed a high density genetic linkage map. The map positioned 234 watermelon genome sequence scaffolds (an average size of 1.41 Mb) that cover about 330 Mb and account for 93.5% of the 353 Mb of the assembled genomic sequences of the elite Chinese watermelon line 97103 (Citrullus lanatus var. lanatus). The genetic map was constructed using an F(8) population of 103 recombinant inbred lines (RILs). The RILs are derived from a cross between the line 97103 and the United States Plant Introduction (PI) 296341-FR (C. lanatus var. citroides) that contains resistance to fusarium wilt (races 0, 1, and 2). The genetic map consists of eleven linkage groups that include 698 simple sequence repeat (SSR), 219 insertion-deletion (InDel) and 36 structure variation (SV) markers and spans ∼800 cM with a mean marker interval of 0.8 cM. Using fluorescent in situ hybridization (FISH) with 11 BACs that produced chromosome-specifc signals, we have depicted watermelon chromosomes that correspond to the eleven linkage groups constructed in this study. The high resolution genetic map developed here should be a useful platform for the assembly of the watermelon genome, for the development of sequence-based markers used in breeding programs, and for the identification of genes associated with important agricultural traits.

  6. Genetic variation architecture of mitochondrial genome reveals the differentiation in Korean landrace and weedy rice.

    Science.gov (United States)

    Tong, Wei; He, Qiang; Park, Yong-Jin

    2017-03-03

    Mitochondrial genome variations have been detected despite the overall conservation of this gene content, which has been valuable for plant population genetics and evolutionary studies. Here, we describe mitochondrial variation architecture and our performance of a phylogenetic dissection of Korean landrace and weedy rice. A total of 4,717 variations across the mitochondrial genome were identified adjunct with 10 wild rice. Genetic diversity assessment revealed that wild rice has higher nucleotide diversity than landrace and/or weedy, and landrace rice has higher diversity than weedy rice. Genetic distance was suggestive of a high level of breeding between landrace and weedy rice, and the landrace showing a closer association with wild rice than weedy rice. Population structure and principal component analyses showed no obvious difference in the genetic backgrounds of landrace and weedy rice in mitochondrial genome level. Phylogenetic, population split, and haplotype network evaluations were suggestive of independent origins of the indica and japonica varieties. The origin of weedy rice is supposed to be more likely from cultivated rice rather than from wild rice in mitochondrial genome level.

  7. Findings from an Independent Evaluation of the AMNH's Online Seminars on Science Course: "Genetics, Genomics, Genethics"

    Science.gov (United States)

    Inverness Research, 2008

    2008-01-01

    Inverness Research studied the American Museum of Natural History (AMNH) Seminars on Science program for eight years, from its inception in 1998 to 2006. This paper presents teacher survey ratings for "Genetics, Genomics, Genethics", along with profiles of three teachers who took the course. Course takers report on the annual follow-up…

  8. Genetic variation architecture of mitochondrial genome reveals the differentiation in Korean landrace and weedy rice

    Science.gov (United States)

    Tong, Wei; He, Qiang; Park, Yong-Jin

    2017-01-01

    Mitochondrial genome variations have been detected despite the overall conservation of this gene content, which has been valuable for plant population genetics and evolutionary studies. Here, we describe mitochondrial variation architecture and our performance of a phylogenetic dissection of Korean landrace and weedy rice. A total of 4,717 variations across the mitochondrial genome were identified adjunct with 10 wild rice. Genetic diversity assessment revealed that wild rice has higher nucleotide diversity than landrace and/or weedy, and landrace rice has higher diversity than weedy rice. Genetic distance was suggestive of a high level of breeding between landrace and weedy rice, and the landrace showing a closer association with wild rice than weedy rice. Population structure and principal component analyses showed no obvious difference in the genetic backgrounds of landrace and weedy rice in mitochondrial genome level. Phylogenetic, population split, and haplotype network evaluations were suggestive of independent origins of the indica and japonica varieties. The origin of weedy rice is supposed to be more likely from cultivated rice rather than from wild rice in mitochondrial genome level. PMID:28256554

  9. Prediction of total genetic value using genome-wide dense marker maps

    NARCIS (Netherlands)

    Meuwissen, T.H.; Hayes, B.J.; Goddard, M.E.

    2001-01-01

    Recent advances in molecular genetic techniques will make dense marker maps available and genotyping many individuals for these markers feasible. Here we attempted to estimate the effects of ∼50,000 marker haplotypes simultaneously from a limited number of phenotypic records. A genome of 1000 cM was

  10. Can Genetics and Genomics Nursing Competencies Be Successfully Taught in a Prenursing Microbiology Course?

    Science.gov (United States)

    Shuster, Michele

    2011-01-01

    In recognition of the entry into the era of personalized medicine, a new set of genetics and genomics competencies for nurses was introduced in 2006. Since then, there have been a number of reports about the critical importance of these competencies for nursing practices and about the challenges of addressing these competencies in the preservice…

  11. Grand challenges in evolutionary and population genetics: The importance of integrating epigenetics, genomics, modeling, and experimentation

    Science.gov (United States)

    Samuel A. Cushman

    2014-01-01

    This is a time of explosive growth in the fields of evolutionary and population genetics, with whole genome sequencing and bioinformatics driving a transformative paradigm shift (Morozova and Marra, 2008). At the same time, advances in epigenetics are thoroughly transforming our understanding of evolutionary processes and their implications for populations, species and...

  12. Can Genetics and Genomics Nursing Competencies Be Successfully Taught in a Prenursing Microbiology Course?

    Science.gov (United States)

    Shuster, Michele

    2011-01-01

    In recognition of the entry into the era of personalized medicine, a new set of genetics and genomics competencies for nurses was introduced in 2006. Since then, there have been a number of reports about the critical importance of these competencies for nursing practices and about the challenges of addressing these competencies in the preservice…

  13. High-resolution genetic mapping of maize pan-genome sequence anchors

    Science.gov (United States)

    In addition to single-nucleotide polymorphisms, structural variation is abundant in many plant genomes. The structural variation across a species can be represented by a ‘pan-genome’, which is essential to fully understand the genetic control of phenotypes. However, the pan-genome’s complexity hinde...

  14. Strategy for incorporating newly discovered causative genetic variants into genomic evaluations

    Science.gov (United States)

    With sequence data available for an increasing number of dairy cattle, discovery of causative genetic variants is expected to be frequent. Current genomic evaluation systems require genotypes for all markers that contribute to an evaluation. A minimum number of animals with an observation for a new ...

  15. Mitochondrial Genomics and Northwestern Atlantic Population Genetics of Marine Annelids

    Science.gov (United States)

    2005-09-01

    pulmonate gastropods Albinaria caerulea and Cepaea nemoralis because they were more easily aligned than other gastropods, and the cephalopod Loligo...disease clustering and a generalized regression approach. Cancer Research, 27, 209-220. Marko PB (2004) ’What’s larvae got to do with it?’ Disparate...The detection of disease clustering and a generalized regression approach. Cancer Research, 27, 209-220. Moberg PE, Burton RS (2000) Genetic

  16. The Genetics and the Genomics of Primary Congenital Glaucoma

    Directory of Open Access Journals (Sweden)

    Raffaella Cascella

    2015-01-01

    Full Text Available The sight is one of the five senses allowing an autonomous and high-quality life, so that alterations of any ocular component may result in several clinical phenotypes (from conjunctivitis to severe vision loss and irreversible blindness. Most parts of clinical phenotypes have been significantly associated with mutations in genes regulating the normal formation and maturation of the anterior segments of the eye. Among the eye anterior segment disorders, special attention is given to Glaucoma as it represents one of the major causes of bilateral blindness in the world, with an onset due to Mendelian or multifactorial genetic-causative traits. This review will point out the attention on the Primary Congenital Glaucoma (PCG, which is usually transmitted according to an autosomal-recessive inheritance pattern. Taking into consideration the genetic component of the PCG, it is possible to observe a strong heterogeneity concerning the disease-associated loci (GLC3, penetrance defects, and expressivity of the disease. Given the strong PGC heterogeneity, pre- and posttest genetic counseling plays an essential role in the achievement of an appropriate management of PCG, in terms of medical, social, and psychological impact of the disease.

  17. The Genetics and the Genomics of Primary Congenital Glaucoma.

    Science.gov (United States)

    Cascella, Raffaella; Strafella, Claudia; Germani, Chiara; Novelli, Giuseppe; Ricci, Federico; Zampatti, Stefania; Giardina, Emiliano

    2015-01-01

    The sight is one of the five senses allowing an autonomous and high-quality life, so that alterations of any ocular component may result in several clinical phenotypes (from conjunctivitis to severe vision loss and irreversible blindness). Most parts of clinical phenotypes have been significantly associated with mutations in genes regulating the normal formation and maturation of the anterior segments of the eye. Among the eye anterior segment disorders, special attention is given to Glaucoma as it represents one of the major causes of bilateral blindness in the world, with an onset due to Mendelian or multifactorial genetic-causative traits. This review will point out the attention on the Primary Congenital Glaucoma (PCG), which is usually transmitted according to an autosomal-recessive inheritance pattern. Taking into consideration the genetic component of the PCG, it is possible to observe a strong heterogeneity concerning the disease-associated loci (GLC3), penetrance defects, and expressivity of the disease. Given the strong PGC heterogeneity, pre- and posttest genetic counseling plays an essential role in the achievement of an appropriate management of PCG, in terms of medical, social, and psychological impact of the disease.

  18. Intelligence and Race, Gender, Class: The Fallacy of Genetic Determinism.

    Science.gov (United States)

    Belkhir, Jean Ait; Duyme, Michael

    1998-01-01

    Biological determinism represents a pseudo-scientific inquiry that is ultimately used to foster a scientific rationale for the maintenance of classism, racism, and sexism in general. Genetic diversity is an inescapable fact, but it is cultures that human brains have created that most severely limit potential. (SLD)

  19. Genetic link between family socioeconomic status and children's educational achievement estimated from genome-wide SNPs.

    Science.gov (United States)

    Krapohl, E; Plomin, R

    2016-03-01

    One of the best predictors of children's educational achievement is their family's socioeconomic status (SES), but the degree to which this association is genetically mediated remains unclear. For 3000 UK-representative unrelated children we found that genome-wide single-nucleotide polymorphisms could explain a third of the variance of scores on an age-16 UK national examination of educational achievement and half of the correlation between their scores and family SES. Moreover, genome-wide polygenic scores based on a previously published genome-wide association meta-analysis of total number of years in education accounted for ~3.0% variance in educational achievement and ~2.5% in family SES. This study provides the first molecular evidence for substantial genetic influence on differences in children's educational achievement and its association with family SES.

  20. The Molecular Genetics of Autism Spectrum Disorders: Genomic Mechanisms, Neuroimmunopathology, and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Daniel J. Guerra

    2011-01-01

    Full Text Available Autism spectrum disorders (ASDs have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD.

  1. The molecular genetics of autism spectrum disorders: genomic mechanisms, neuroimmunopathology, and clinical implications.

    Science.gov (United States)

    Guerra, Daniel J

    2011-01-01

    Autism spectrum disorders (ASDs) have become increasingly common in recent years. The discovery of single-nucleotide polymorphisms and accompanying copy number variations within the genome has increased our understanding of the architecture of the disease. These genetic and genomic alterations coupled with epigenetic phenomena have pointed to a neuroimmunopathological mechanism for ASD. Model animal studies, developmental biology, and affective neuroscience laid a foundation for dissecting the neural pathways impacted by these disease-generating mechanisms. The goal of current autism research is directed toward a systems biological approach to find the most basic genetic and environmental causes to this severe developmental disease. It is hoped that future genomic and neuroimmunological research will be directed toward finding the road toward prevention, treatment, and cure of ASD.

  2. Genetic adaptation associated with genome-doubling in autotetraploid Arabidopsis arenosa.

    Directory of Open Access Journals (Sweden)

    Jesse D Hollister

    Full Text Available Genome duplication, which results in polyploidy, is disruptive to fundamental biological processes. Genome duplications occur spontaneously in a range of taxa and problems such as sterility, aneuploidy, and gene expression aberrations are common in newly formed polyploids. In mammals, genome duplication is associated with cancer and spontaneous abortion of embryos. Nevertheless, stable polyploid species occur in both plants and animals. Understanding how natural selection enabled these species to overcome early challenges can provide important insights into the mechanisms by which core cellular functions can adapt to perturbations of the genomic environment. Arabidopsis arenosa includes stable tetraploid populations and is related to well-characterized diploids A. lyrata and A. thaliana. It thus provides a rare opportunity to leverage genomic tools to investigate the genetic basis of polyploid stabilization. We sequenced the genomes of twelve A. arenosa individuals and found signatures suggestive of recent and ongoing selective sweeps throughout the genome. Many of these are at genes implicated in genome maintenance functions, including chromosome cohesion and segregation, DNA repair, homologous recombination, transcriptional regulation, and chromatin structure. Numerous encoded proteins are predicted to interact with one another. For a critical meiosis gene, ASYNAPSIS1, we identified a non-synonymous mutation that is highly differentiated by cytotype, but present as a rare variant in diploid A. arenosa, indicating selection may have acted on standing variation already present in the diploid. Several genes we identified that are implicated in sister chromatid cohesion and segregation are homologous to genes identified in a yeast mutant screen as necessary for survival of polyploid cells, and also implicated in genome instability in human diseases including cancer. This points to commonalities across kingdoms and supports the hypothesis that

  3. Genetic adaptation associated with genome-doubling in autotetraploid Arabidopsis arenosa.

    Science.gov (United States)

    Hollister, Jesse D; Arnold, Brian J; Svedin, Elisabeth; Xue, Katherine S; Dilkes, Brian P; Bomblies, Kirsten

    2012-01-01

    Genome duplication, which results in polyploidy, is disruptive to fundamental biological processes. Genome duplications occur spontaneously in a range of taxa and problems such as sterility, aneuploidy, and gene expression aberrations are common in newly formed polyploids. In mammals, genome duplication is associated with cancer and spontaneous abortion of embryos. Nevertheless, stable polyploid species occur in both plants and animals. Understanding how natural selection enabled these species to overcome early challenges can provide important insights into the mechanisms by which core cellular functions can adapt to perturbations of the genomic environment. Arabidopsis arenosa includes stable tetraploid populations and is related to well-characterized diploids A. lyrata and A. thaliana. It thus provides a rare opportunity to leverage genomic tools to investigate the genetic basis of polyploid stabilization. We sequenced the genomes of twelve A. arenosa individuals and found signatures suggestive of recent and ongoing selective sweeps throughout the genome. Many of these are at genes implicated in genome maintenance functions, including chromosome cohesion and segregation, DNA repair, homologous recombination, transcriptional regulation, and chromatin structure. Numerous encoded proteins are predicted to interact with one another. For a critical meiosis gene, ASYNAPSIS1, we identified a non-synonymous mutation that is highly differentiated by cytotype, but present as a rare variant in diploid A. arenosa, indicating selection may have acted on standing variation already present in the diploid. Several genes we identified that are implicated in sister chromatid cohesion and segregation are homologous to genes identified in a yeast mutant screen as necessary for survival of polyploid cells, and also implicated in genome instability in human diseases including cancer. This points to commonalities across kingdoms and supports the hypothesis that selection has acted on

  4. The law of genomic sovereignty and the protection of "Mexican genetic patrimony".

    Science.gov (United States)

    Schwartz-Marín, Ernesto; Méndez, Alberto Arellano

    2012-06-01

    We present a socio-legal analysis of the policy agenda known as genomic sovereignty in Mexico--in which the notion was first coined--and its translation into a national law of health aimed at regulating population genomics research in the country. Based in more than 2 years of participant observation we sustain that the notion of genomic sovereignty, aimed at protecting the "unique" genetic patterns of populations needs to be critically reassessed. The main problem with such notion is that there are no scientifically sound ways to delimit the genetic "uniqueness" of any population in the world. Arising from this dilemma it becomes increasingly clear that the patrimonial doctrines that have been used to regulate population genomics in Mexico are inoperative, and rather than creating a legal environment in which medical genomics can become a national public good, it has created a law that has been used to monopolise human genomic research in the country; making blood samples and data tool for dispute amongst scientific elites.

  5. Meeting review. Uncovering the genetic basis of adaptive change: on the intersection of landscape genomics and theoretical population genetics.

    Science.gov (United States)

    Joost, Stéphane; Vuilleumier, Séverine; Jensen, Jeffrey D; Schoville, Sean; Leempoel, Kevin; Stucki, Sylvie; Widmer, Ivo; Melodelima, Christelle; Rolland, Jonathan; Manel, Stéphanie

    2013-07-01

    A workshop recently held at the École Polytechnique Fédérale de Lausanne (EPFL, Switzerland) was dedicated to understanding the genetic basis of adaptive change, taking stock of the different approaches developed in theoretical population genetics and landscape genomics and bringing together knowledge accumulated in both research fields. Indeed, an important challenge in theoretical population genetics is to incorporate effects of demographic history and population structure. But important design problems (e.g. focus on populations as units, focus on hard selective sweeps, no hypothesis-based framework in the design of the statistical tests) reduce their capability of detecting adaptive genetic variation. In parallel, landscape genomics offers a solution to several of these problems and provides a number of advantages (e.g. fast computation, landscape heterogeneity integration). But the approach makes several implicit assumptions that should be carefully considered (e.g. selection has had enough time to create a functional relationship between the allele distribution and the environmental variable, or this functional relationship is assumed to be constant). To address the respective strengths and weaknesses mentioned above, the workshop brought together a panel of experts from both disciplines to present their work and discuss the relevance of combining these approaches, possibly resulting in a joint software solution in the future.

  6. Genome-wide distribution of genetic diversity and linkage disequilibrium in elite sugar beet germplasm

    Directory of Open Access Journals (Sweden)

    Weißleder Knuth

    2011-10-01

    Full Text Available Abstract Background Characterization of population structure and genetic diversity of germplasm is essential for the efficient organization and utilization of breeding material. The objectives of this study were to (i explore the patterns of population structure in the pollen parent heterotic pool using different methods, (ii investigate the genome-wide distribution of genetic diversity, and (iii assess the extent and genome-wide distribution of linkage disequilibrium (LD in elite sugar beet germplasm. Results A total of 264 and 238 inbred lines from the yield type and sugar type inbreds of the pollen parent heterotic gene pools, respectively, which had been genotyped with 328 SNP markers, were used in this study. Two distinct subgroups were detected based on different statistical methods within the elite sugar beet germplasm set, which was in accordance with its breeding history. MCLUST based on principal components, principal coordinates, or lapvectors had high correspondence with the germplasm type information as well as the assignment by STRUCTURE, which indicated that these methods might be alternatives to STRUCTURE for population structure analysis. Gene diversity and modified Roger's distance between the examined germplasm types varied considerably across the genome, which might be due to artificial selection. This observation indicates that population genetic approaches could be used to identify candidate genes for the traits under selection. Due to the fact that r2 >0.8 is required to detect marker-phenotype association explaining less than 1% of the phenotypic variance, our observation of a low proportion of SNP loci pairs showing such levels of LD suggests that the number of markers has to be dramatically increased for powerful genome-wide association mapping. Conclusions We provided a genome-wide distribution map of genetic diversity and linkage disequilibrium for the elite sugar beet germplasm, which is useful for the application of

  7. A genetic linkage map and comparative mapping of the prairie vole (Microtus ochrogaster genome

    Directory of Open Access Journals (Sweden)

    Young Larry J

    2011-07-01

    Full Text Available Abstract Background The prairie vole (Microtus ochrogaster is an emerging rodent model for investigating the genetics, evolution and molecular mechanisms of social behavior. Though a karyotype for the prairie vole has been reported and low-resolution comparative cytogenetic analyses have been done in this species, other basic genetic resources for this species, such as a genetic linkage map, are lacking. Results Here we report the construction of a genome-wide linkage map of the prairie vole. The linkage map consists of 406 markers that are spaced on average every 7 Mb and span an estimated ~90% of the genome. The sex average length of the linkage map is 1707 cM, which, like other Muroid rodent linkage maps, is on the lower end of the length distribution of linkage maps reported to date for placental mammals. Linkage groups were assigned to 19 out of the 26 prairie vole autosomes as well as the X chromosome. Comparative analyses of the prairie vole linkage map based on the location of 387 Type I markers identified 61 large blocks of synteny with the mouse genome. In addition, the results of the comparative analyses revealed a potential elevated rate of inversions in the prairie vole lineage compared to the laboratory mouse and rat. Conclusions A genetic linkage map of the prairie vole has been constructed and represents the fourth genome-wide high-resolution linkage map reported for Muroid rodents and the first for a member of the Arvicolinae sub-family. This resource will advance studies designed to dissect the genetic basis of a variety of social behaviors and other traits in the prairie vole as well as our understanding of genome evolution in the genus Microtus.

  8. Ecological genomics in Xanthomonas: the nature of genetic adaptation with homologous recombination and host shifts.

    Science.gov (United States)

    Huang, Chao-Li; Pu, Pei-Hua; Huang, Hao-Jen; Sung, Huang-Mo; Liaw, Hung-Jiun; Chen, Yi-Min; Chen, Chien-Ming; Huang, Ming-Ban; Osada, Naoki; Gojobori, Takashi; Pai, Tun-Wen; Chen, Yu-Tin; Hwang, Chi-Chuan; Chiang, Tzen-Yuh

    2015-03-15

    Comparative genomics provides insights into the diversification of bacterial species. Bacterial speciation usually takes place with lasting homologous recombination, which not only acts as a cohering force between diverging lineages but brings advantageous alleles favored by natural selection, and results in ecologically distinct species, e.g., frequent host shift in Xanthomonas pathogenic to various plants. Using whole-genome sequences, we examined the genetic divergence in Xanthomonas campestris that infected Brassicaceae, and X. citri, pathogenic to a wider host range. Genetic differentiation between two incipient races of X. citri pv. mangiferaeindicae was attributable to a DNA fragment introduced by phages. In contrast to most portions of the genome that had nearly equivalent levels of genetic divergence between subspecies as a result of the accumulation of point mutations, 10% of the core genome involving with homologous recombination contributed to the diversification in Xanthomonas, as revealed by the correlation between homologous recombination and genomic divergence. Interestingly, 179 genes were under positive selection; 98 (54.7%) of these genes were involved in homologous recombination, indicating that foreign genetic fragments may have caused the adaptive diversification, especially in lineages with nutritional transitions. Homologous recombination may have provided genetic materials for the natural selection, and host shifts likely triggered ecological adaptation in Xanthomonas. To a certain extent, we observed positive selection nevertheless contributed to ecological divergence beyond host shifting. Altogether, mediated with lasting gene flow, species formation in Xanthomonas was likely governed by natural selection that played a key role in helping the deviating populations to explore novel niches (hosts) or respond to environmental cues, subsequently triggering species diversification.

  9. Ecological genomics in Xanthomonas: the nature of genetic adaptation with homologous recombination and host shifts

    KAUST Repository

    Huang, Chao-Li

    2015-03-15

    Background: Comparative genomics provides insights into the diversification of bacterial species. Bacterial speciation usually takes place with lasting homologous recombination, which not only acts as a cohering force between diverging lineages but brings advantageous alleles favored by natural selection, and results in ecologically distinct species, e.g., frequent host shift in Xanthomonas pathogenic to various plants. Results: Using whole-genome sequences, we examined the genetic divergence in Xanthomonas campestris that infected Brassicaceae, and X. citri, pathogenic to a wider host range. Genetic differentiation between two incipient races of X. citri pv. mangiferaeindicae was attributable to a DNA fragment introduced by phages. In contrast to most portions of the genome that had nearly equivalent levels of genetic divergence between subspecies as a result of the accumulation of point mutations, 10% of the core genome involving with homologous recombination contributed to the diversification in Xanthomonas, as revealed by the correlation between homologous recombination and genomic divergence. Interestingly, 179 genes were under positive selection; 98 (54.7%) of these genes were involved in homologous recombination, indicating that foreign genetic fragments may have caused the adaptive diversification, especially in lineages with nutritional transitions. Homologous recombination may have provided genetic materials for the natural selection, and host shifts likely triggered ecological adaptation in Xanthomonas. To a certain extent, we observed positive selection nevertheless contributed to ecological divergence beyond host shifting. Conclusion: Altogether, mediated with lasting gene flow, species formation in Xanthomonas was likely governed by natural selection that played a key role in helping the deviating populations to explore novel niches (hosts) or respond to environmental cues, subsequently triggering species diversification. © Huang et al.

  10. Building capacity for human genetics and genomics research in Trinidad and Tobago

    Science.gov (United States)

    Roach, Allana; Warner, Wayne A.; Llanos, Adana A. M.

    2016-01-01

    Advances in human genetics and genomic sciences and the corresponding explosion of biomedical technologies have deepened current understanding of human health and revolutionized medicine. In developed nations, this has led to marked improvements in disease risk stratification and diagnosis. These advances have also led to targeted intervention strategies aimed at promoting disease prevention, prolonging disease onset, and mitigating symptoms, as in the well-known case of breast cancer and the BRCA1 gene. In contrast, in the developing nation of Trinidad and Tobago, this scientific revolution has not translated into the development and application of effective genomics-based interventions for improving public health. While the reasons for this are multifactorial, the underlying basis may be rooted in the lack of pertinence of internationally driven genomics research to the local public health needs in the country, as well as a lack of relevance of internationally conducted genetics research to the genetic and environmental contexts of the population. Indeed, if Trinidad and Tobago is able to harness substantial public health benefit from genetics/genomics research, then there is a dire need, in the near future, to build local capacity for the conduct and translation of such research. Specifically, it is essential to establish a national human genetics/genomics research agenda in order to build sustainable human capacity through education and knowledge transfer and to generate public policies that will provide the basis for the creation of a mutually beneficial framework (including partnerships with more developed nations) that is informed by public health needs and contextual realities of the nation. PMID:26837529

  11. Draft genome of the sea cucumber Apostichopus japonicus and genetic polymorphism among color variants.

    Science.gov (United States)

    Jo, Jihoon; Oh, Jooseong; Lee, Hyun-Gwan; Hong, Hyun-Hee; Lee, Sung-Gwon; Cheon, Seongmin; Kern, Elizabeth M A; Jin, Soyeong; Cho, Sung-Jin; Park, Joong-Ki; Park, Chungoo

    2017-01-01

    The Japanese sea cucumber (Apostichopus japonicus Selenka 1867) is an economically important species as a source of seafood and ingredient in traditional medicine. It is mainly found off the coasts of northeast Asia. Recently, substantial exploitation and widespread biotic diseases in A. japonicus have generated increasing conservation concern. However, the genomic knowledge base and resources available for researchers to use in managing this natural resource and to establish genetically based breeding systems for sea cucumber aquaculture are still in a nascent stage. A total of 312 Gb of raw sequences were generated using the Illumina HiSeq 2000 platform and assembled to a final size of 0.66 Gb, which is about 80.5% of the estimated genome size (0.82 Gb). We observed nucleotide-level heterozygosity within the assembled genome to be 0.986%. The resulting draft genome assembly comprising 132 607 scaffolds with an N50 value of 10.5 kb contains a total of 21 771 predicted protein-coding genes. We identified 6.6-14.5 million heterozygous single nucleotide polymorphisms in the assembled genome of the three natural color variants (green, red, and black), resulting in an estimated nucleotide diversity of 0.00146. We report the first draft genome of A. japonicus and provide a general overview of the genetic variation in the three major color variants of A. japonicus. These data will help provide a comprehensive view of the genetic, physiological, and evolutionary relationships among color variants in A. japonicus, and will be invaluable resources for sea cucumber genomic research. © The Author 2017. Published by Oxford University Press.

  12. A unique genetic code change in the mitochondrial genome of the parasitic nematode Radopholus similis

    Directory of Open Access Journals (Sweden)

    Van Leeuwen Thomas

    2009-09-01

    Full Text Available Abstract Background Mitochondria (mt contain their own autonomously replicating DNA, constituted as a small circular genome encoding essential subunits of the respiratory chain. Mt DNA is characterized by a genetic code which differs from the standard one. Interestingly, the mt genome of nematodes share some peculiar features, such as small transfer RNAs, truncated ribosomal RNAs and - in the class of Chromadorean nematodes - unidirectional transcription. Findings We present the complete mt genomic sequence (16,791 bp of the plant-parasitic nematode Radopholus similis (class Chromadorea. Although it has a gene content similar to most other nematodes, many idiosyncrasies characterize the extremely AT-rich mt genome of R. similis (85.4% AT. The secondary structure of the large (16S rRNA is further reduced, the gene order is unique, the large non-coding region contains two large repeats, and most interestingly, the UAA codon is reassigned from translation termination to tyrosine. In addition, 7 out of 12 protein-coding genes lack a canonical stop codon and analysis of transcriptional data showed the absence of polyadenylation. Northern blot analysis confirmed that only one strand is transcribed and processed. Furthermore, using nucleotide content bias methods, regions for the origin of replication are suggested. Conclusion The extraordinary mt genome of R. similis with its unique genetic code appears to contain exceptional features correlated to DNA decoding. Therefore the genome may provide an incentive to further elucidate these barely understood processes in nematodes. This comprehension may eventually lead to parasitic nematode-specific control targets as healthy mitochondria are imperative for organism survival. In addition, the presented genome is an interesting exceptional event in genetic code evolution.

  13. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes

    DEFF Research Database (Denmark)

    Nielsen, Henrik Bjørn; Almeida, Mathieu; Juncker, Agnieszka

    2014-01-01

    , such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly...... affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples....

  14. Genetics of immune-mediated disorders: from genome-wide association to molecular mechanism

    Science.gov (United States)

    Kumar, Vinod; Wijmenga, Cisca; Xavier, Ramnik J.

    2016-01-01

    Genetic association studies have identified not only hundreds of susceptibility loci to immune-mediated diseases but also pinpointed causal amino-acid variants of HLA genes that contribute to many autoimmune reactions. Majority of non-HLA genetic variants are located within non-coding regulatory region. Expression QTL studies have shown that these variants affect disease mainly by regulating gene expression. We discuss recent findings on shared genetic loci between infectious and immune-mediated diseases and provide potential clues to explore genetic associations in the context of these infectious agents. We propose that the interdisciplinary studies (genetics-genomics-immunology-infection-bioinformatics) are the future post-GWAS approaches to advance our understanding of the pathogenesis of immune-mediated diseases. PMID:25458995

  15. Genetic Algorithm for Initial Orbit Determination with Too Short Arc

    Science.gov (United States)

    Xin-ran, Li; Xin, Wang

    2017-01-01

    A huge quantity of too-short-arc (TSA) observational data have been obtained in sky surveys of space objects. However, reasonable results for the TSAs can hardly be obtained with the classical methods of initial orbit determination (IOD). In this paper, the IOD is reduced to a two-stage hierarchical optimization problem containing three variables for each stage. Using the genetic algorithm, a new method of the IOD for TSAs is established, through the selections of the optimized variables and the corresponding genetic operators for specific problems. Numerical experiments based on the real measurements show that the method can provide valid initial values for the follow-up work.

  16. Novel PCR assay for determining the genetic sex of mice.

    Science.gov (United States)

    McFarlane, L; Truong, V; Palmer, J S; Wilhelm, D

    2013-01-01

    A number of studies require the determination of the genetic sex of mouse embryos before sexual differentiation and/or of mutant mice that display partial or complete sex reversal. The majority of current methods for sexing by PCR involve multiplexing of 2 primer pairs. We have developed a novel sexing PCR using a single primer pair that amplifies fragments from the X and the Y chromosome with a clear size difference between the respective amplicons. This assay provides a rapid and reliable method to identify the genetic sex of mice across different mouse strains.

  17. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes

    NARCIS (Netherlands)

    Nielsen, H.B.; Almeida, M.; Sierakowska Juncker, A.; Rasmussen, S.; Li, J.; Sunagawa, S.; Plichta, D.R.; Gautier, L.; Pedersen, A.G.; Chatelier, Le E.; Pelletier, E.; Bonde, I.; Nielsen, T.; Manichanh, C.; Arumugam, M.; Batto, J.M.; Quintanilha dos Santos, M.B.; Blom, N.; Borruel, N.; Burgdorf, K.S.; Boumezbeur, F.; Casellas, F.; Doré, J.; Dworzynski, P.; Guarner, F.; Hansen, T.; Hildebrand, F.; Kaas, R.S.; Kennedy, S.; Kristiansen, K.; Kultima, J.R.; Leonard, P.; Levenez, F.; Lund, O.; Moumen, B.; Paslier, Le D.; Pons, N.; Pedersen, O.; Prifti, E.; Qin, J.; Raes, J.; Sørensen, S.; Tap, J.; Tims, S.; Ussery, D.W.; Yamada, T.; Jamet, A.; Mérieux, A.; Cultrone, A.; Torrejon, A.; Quinquis, B.; Brechot, C.; Delorme, C.; M'Rini, C.; Vos, de W.M.; Maguin, E.; Varela, E.; Guedon, E.; Gwen, F.; Haimet, F.; Artiguenave, F.; Vandemeulebrouck, G.; Denariaz, G.; Khaci, G.; Blottière, H.; Knol, J.; Weissenbach, J.; Hylckama Vlieg, van J.E.; Torben, J.; Parkhil, J.; Turner, K.; Guchte, van de M.; Antolin, M.; Rescigno, M.; Kleerebezem, M.; Derrien, M.; Galleron, N.; Sanchez, N.; Grarup, N.; Veiga, P.; Oozeer, R.; Dervyn, R.; Layec, S.; Bruls, T.; Winogradski, Y.; Zoetendal, E.G.; Renault, D.; Sicheritz-Ponten,; Bork, P.; Wang, J.; Brunak, S.; Ehrlich, S.D.

    2014-01-01

    Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as part

  18. Whole genome sequence analysis of unidentified genetically modified papaya for development of a specific detection method.

    Science.gov (United States)

    Nakamura, Kosuke; Kondo, Kazunari; Akiyama, Hiroshi; Ishigaki, Takumi; Noguchi, Akio; Katsumata, Hiroshi; Takasaki, Kazuto; Futo, Satoshi; Sakata, Kozue; Fukuda, Nozomi; Mano, Junichi; Kitta, Kazumi; Tanaka, Hidenori; Akashi, Ryo; Nishimaki-Mogami, Tomoko

    2016-08-15

    Identification of transgenic sequences in an unknown genetically modified (GM) papaya (Carica papaya L.) by whole genome sequence analysis was demonstrated. Whole genome sequence data were generated for a GM-positive fresh papaya fruit commodity detected in monitoring using real-time polymerase chain reaction (PCR). The sequences obtained were mapped against an open database for papaya genome sequence. Transgenic construct- and event-specific sequences were identified as a GM papaya developed to resist infection from a Papaya ringspot virus. Based on the transgenic sequences, a specific real-time PCR detection method for GM papaya applicable to various food commodities was developed. Whole genome sequence analysis enabled identifying unknown transgenic construct- and event-specific sequences in GM papaya and development of a reliable method for detecting them in papaya food commodities.

  19. Genetic screens and functional genomics using CRISPR/Cas9 technology.

    Science.gov (United States)

    Hartenian, Ella; Doench, John G

    2015-04-01

    Functional genomics attempts to understand the genome by perturbing the flow of information from DNA to RNA to protein, in order to learn how gene dysfunction leads to disease. CRISPR/Cas9 technology is the newest tool in the geneticist's toolbox, allowing researchers to edit DNA with unprecedented ease, speed and accuracy, and representing a novel means to perform genome-wide genetic screens to discover gene function. In this review, we first summarize the discovery and characterization of CRISPR/Cas9, and then compare it to other genome engineering technologies. We discuss its initial use in screening applications, with a focus on optimizing on-target activity and minimizing off-target effects. Finally, we comment on future challenges and opportunities afforded by this technology.

  20. Next-generation sequencing technology for genetics and genomics of sorghum

    DEFF Research Database (Denmark)

    Luo, Hong; Mocoeur, Anne Raymonde Joelle; Jing, Hai-Chun

    2014-01-01

    NGS platforms, comparing their working theories and reveiwing their advantages and disavantages. We also discuss the future of NGS development and point out that single molecular sequencing would push the technology to the next level for biological sciences. Much of the chapter focuses on the use......The invention and application of Next-Generation Sequencing (NGS) technologies have revolutionized the study of genetics and genomics. Much research which would not even be considered are nowdays being excuted in many laboratories as routine. In this chapter, we introduce the currently available...... of NGS technologies in sorghum. Although the acquisition of the first whole-genome sequence in sorghum was carried out primarily using Sanger sequencing, the use of NGS for examining the genome-wide variation was almost synchronized with other work. Interesting genomic variation was found between sweet...

  1. Whole genome SNP discovery and analysis of genetic diversity in Turkey (Meleagris gallopavo

    Directory of Open Access Journals (Sweden)

    Aslam Muhammad L

    2012-08-01

    Full Text Available Abstract Background The turkey (Meleagris gallopavo is an important agricultural species and the second largest contributor to the world’s poultry meat production. Genetic improvement is attributed largely to selective breeding programs that rely on highly heritable phenotypic traits, such as body size and breast muscle development. Commercial breeding with small effective population sizes and epistasis can result in loss of genetic diversity, which in turn can lead to reduced individual fitness and reduced response to selection. The presence of genomic diversity in domestic livestock species therefore, is of great importance and a prerequisite for rapid and accurate genetic improvement of selected breeds in various environments, as well as to facilitate rapid adaptation to potential changes in breeding goals. Genomic selection requires a large number of genetic markers such as e.g. single nucleotide polymorphisms (SNPs the most abundant source of genetic variation within the genome. Results Alignment of next generation sequencing data of 32 individual turkeys from different populations was used for the discovery of 5.49 million SNPs, which subsequently were used for the analysis of genetic diversity among the different populations. All of the commercial lines branched from a single node relative to the heritage varieties and the South Mexican turkey population. Heterozygosity of all individuals from the different turkey populations ranged from 0.17-2.73 SNPs/Kb, while heterozygosity of populations ranged from 0.73-1.64 SNPs/Kb. The average frequency of heterozygous SNPs in individual turkeys was 1.07 SNPs/Kb. Five genomic regions with very low nucleotide variation were identified in domestic turkeys that showed state of fixation towards alleles different than wild alleles. Conclusion The turkey genome is much less diverse with a relatively low frequency of heterozygous SNPs as compared to other livestock species like chicken and pig. The

  2. Potential benefits of genomic selection on genetic gain of small ruminant breeding programs.

    Science.gov (United States)

    Shumbusho, F; Raoul, J; Astruc, J M; Palhiere, I; Elsen, J M

    2013-08-01

    In conventional small ruminant breeding programs, only pedigree and phenotype records are used to make selection decisions but prospects of including genomic information are now under consideration. The objective of this study was to assess the potential benefits of genomic selection on the genetic gain in French sheep and goat breeding designs of today. Traditional and genomic scenarios were modeled with deterministic methods for 3 breeding programs. The models included decisional variables related to male selection candidates, progeny testing capacity, and economic weights that were optimized to maximize annual genetic gain (AGG) of i) a meat sheep breeding program that improved a meat trait of heritability (h(2)) = 0.30 and a maternal trait of h(2) = 0.09 and ii) dairy sheep and goat breeding programs that improved a milk trait of h(2) = 0.30. Values of ±0.20 of genetic correlation between meat and maternal traits were considered to study their effects on AGG. The Bulmer effect was accounted for and the results presented here are the averages of AGG after 10 generations of selection. Results showed that current traditional breeding programs provide an AGG of 0.095 genetic standard deviation (σa) for meat and 0.061 σa for maternal trait in meat breed and 0.147 σa and 0.120 σa in sheep and goat dairy breeds, respectively. By optimizing decisional variables, the AGG with traditional selection methods increased to 0.139 σa for meat and 0.096 σa for maternal traits in meat breeding programs and to 0.174 σa and 0.183 σa in dairy sheep and goat breeding programs, respectively. With a medium-sized reference population (nref) of 2,000 individuals, the best genomic scenarios gave an AGG that was 17.9% greater than with traditional selection methods with optimized values of decisional variables for combined meat and maternal traits in meat sheep, 51.7% in dairy sheep, and 26.2% in dairy goats. The superiority of genomic schemes increased with the size of the

  3. Comparative genomic analysis of 45 type strains of the genus Bifidobacterium: a snapshot of its genetic diversity and evolution.

    Directory of Open Access Journals (Sweden)

    Zhihong Sun

    Full Text Available Bifidobacteria are well known for their human health-promoting effects and are therefore widely applied in the food industry. Members of the Bifidobacterium genus were first identified from the human gastrointestinal tract and were then found to be widely distributed across various ecological niches. Although the genetic diversity of Bifidobacterium has been determined based on several marker genes or a few genomes, the global diversity and evolution scenario for the entire genus remain unresolved. The present study comparatively analyzed the genomes of 45 type strains. We built a robust genealogy for Bifidobacterium based on 402 core genes and defined its root according to the phylogeny of the tree of bacteria. Our results support that all human isolates are of younger lineages, and although species isolated from bees dominate the more ancient lineages, the bee was not necessarily the original host for bifidobacteria. Moreover, the species isolated from different hosts are enriched with specific gene sets, suggesting host-specific adaptation. Notably, bee-specific genes are strongly associated with respiratory metabolism and are potential in helping those bacteria adapt to the oxygen-rich gut environment in bees. This study provides a snapshot of the genetic diversity and evolution of Bifidobacterium, paving the way for future studies on the taxonomy and functional genomics of the genus.

  4. Genetic determinants of serum testosterone concentrations in men.

    Directory of Open Access Journals (Sweden)

    Claes Ohlsson

    2011-10-01

    Full Text Available Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871 and two de novo replication cohorts (n = 4,620 to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG locus (17p13-p12 were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10(-41 and rs6258, p = 2.3×10(-22. Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10(-16. The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01. Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.

  5. 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.

  6. 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.

  7. DNA secondary structures and epigenetic determinants of cancer genome evolution

    OpenAIRE

    2010-01-01

    An unstable genome is a hallmark of many cancers. It is unclear, however, whether some mutagenic features driving somatic alterations in cancer are encoded in the genome sequence and whether they can operate in a tissue-specific manner. We performed a genome-wide analysis of 663,446 DNA breakpoints associated with somatic copy-number alterations (SCNAs) from 2,792 cancer samples classified into 26 cancer types. Many SCNA breakpoints are spatially clustered in cancer genomes. We observed a sig...

  8. Genetic and perinatal determinants of structural brain deficits in schizophrenia.

    Science.gov (United States)

    Cannon, T D; Mednick, S A; Parnas, J

    1989-10-01

    Using a subsample from the Copenhagen schizophrenia high-risk project, we examined the contributions of schizophrenic genetic liability and perinatal complications to computed tomographic (CT) measurements of ventricular enlargement and cortical and cerebellar abnormalities. A factor analysis of six CT measurements yielded two significant factors. One factor reflected multisite neural deficits as evidenced by abnormality of the cerebellar vermis and widening of the sylvian and interhemispheric fissures and cortical sulci. The other factor reflected periventricular damage as evidenced by enlargement of the third and lateral ventricles. Because all of the subjects had schizophrenic mothers, the major source of genetic variation is contributed by the diagnostic status of their fathers. In a stepwise multiple-regression analysis, it was determined that the multisite neural deficits factor was significantly related to genetic risk for schizophrenia (as measured by schizophrenia spectrum illness in the subjects' fathers) but was unrelated to pregnancy or delivery complications or to weight at birth. Periventricular damage was highly and significantly correlated with the number of complications suffered at delivery, but only among subjects with an elevated genetic risk. Although limited by a small sample size, these results suggest that the two types of CT abnormalities in schizophrenia may reflect partially independent processes based on different combinations of genetic and perinatal influences.

  9. Key questions in the genetics and genomics of eco-evolutionary dynamics.

    Science.gov (United States)

    Hendry, A P

    2013-12-01

    Increasing acceptance that evolution can be 'rapid' (or 'contemporary') has generated growing interest in the consequences for ecology. The genetics and genomics of these 'eco-evolutionary dynamics' will be--to a large extent--the genetics and genomics of organismal phenotypes. In the hope of stimulating research in this area, I review empirical data from natural populations and draw the following conclusions. (1) Considerable additive genetic variance is present for most traits in most populations. (2) Trait correlations do not consistently oppose selection. (3) Adaptive differences between populations often involve dominance and epistasis. (4) Most adaptation is the result of genes of small-to-modest effect, although (5) some genes certainly have larger effects than the others. (6) Adaptation by independent lineages to similar environments is mostly driven by different alleles/genes. (7) Adaptation to new environments is mostly driven by standing genetic variation, although new mutations can be important in some instances. (8) Adaptation is driven by both structural and regulatory genetic variation, with recent studies emphasizing the latter. (9) The ecological effects of organisms, considered as extended phenotypes, are often heritable. Overall, the study of eco-evolutionary dynamics will benefit from perspectives and approaches that emphasize standing genetic variation in many genes of small-to-modest effect acting across multiple traits and that analyze overall adaptation or 'fitness'. In addition, increasing attention should be paid to dominance, epistasis and regulatory variation.

  10. Obesity and genomics: role of technology in unraveling the complex genetic architecture of obesity.

    Science.gov (United States)

    Apalasamy, Yamunah Devi; Mohamed, Zahurin

    2015-04-01

    Obesity is a complex and multifactorial disease that occurs as a result of the interaction between "obesogenic" environmental factors and genetic components. Although the genetic component of obesity is clear from the heritability studies, the genetic basis remains largely elusive. Successes have been achieved in identifying the causal genes for monogenic obesity using animal models and linkage studies, but these approaches are not fruitful for polygenic obesity. The developments of genome-wide association approach have brought breakthrough discovery of genetic variants for polygenic obesity where tens of new susceptibility loci were identified. However, the common SNPs only accounted for a proportion of heritability. The arrival of NGS technologies and completion of 1000 Genomes Project have brought other new methods to dissect the genetic architecture of obesity, for example, the use of exome genotyping arrays and deep sequencing of candidate loci identified from GWAS to study rare variants. In this review, we summarize and discuss the developments of these genetic approaches in human obesity.

  11. Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthmag

    NARCIS (Netherlands)

    McGeachie, Michael J.; Yates, Katherine P.; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L.; Van Natta, Mark L.; Wise, Robert A.; Szefler, Stanley J.; Sharma, Sunita; Kho, Alvin T.; Cho, Michael H.; Croteau-Chonka, Damien C.; Castaldi, Peter J.; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R.; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A.; Zeiger, Robert S.; Adkinson, N. Franklin; Williams, Paul V.; Kelly, H. William; Grasemann, Hartmut; Vonk, Judith M.; Koppelman, Gerard H.; Postma, Dirkje S.; Raby, Benjamin A.; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Silverman, Edwin K.; Tonascia, James; Strunk, Robert C.; Weiss, Scott T.

    2016-01-01

    Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. Objectives: To determine the genetic underpinni

  12. MicroRNAs: Tiny Genetic Switches in Our Genome

    Indian Academy of Sciences (India)

    Venkatesan Sundaresan

    2017-02-01

    Gary Ruvkun is a winner of the 2015 Breakthrough Prize in Life Sciences. He is a codiscoverer of microRNAs (with Victor Ambros, University of Massachusetts), regarded as one of the seminal discoveries of 21st century molecular biology. In addition to the Breakthrough Prize, Ruvkun and Ambros have received the Warren Triennial Prize, the Laskar Foundation Award, and numerous other awards and prizes. Professor Ruvkun obtained his PhD from Harvard University, did his postdoctoral research at MIT, and subsequently accepted a faculty position at Harvard, where he is currently Professor of Genetics. His laboratory conducts research on basic cellular processes, using the worm \\italics{C. elegans} as a model system.

  13. Gene cloning: exploring cotton functional genomics and genetic improvement

    Institute of Scientific and Technical Information of China (English)

    Diqiu LIU; Xianlong ZHANG

    2008-01-01

    Cotton is the most important natural fiber plant in the world. The genetic improvement of the quality of the cotton fiber and agricultural productivity is imperative under the situation of increasing consumption and rapid development of textile technology. Recently, the study of cotton molecular biology has progressed greatly. A lot of specifically or preferentially expressed cotton fiber genes were cloned and analyzed. On the other hand, identification of stress response genes expressed in cotton was performed by other research groups. The major stress factors were studied including the wilt pathogens Verticillium dahliae, Fusarium oxy-sporum f. sp. vasinfectum, bacterial blight, root-knot nematode, drought, and salt stress. What is more, a few genes related to the biosynthesis of gossypol, other sesquiterpene phytoalexins and the major seed oil fatty acids were isolated from cotton. In the present review, we focused on the major advances in cotton gene cloning and expression profiling in the recent years.

  14. Genetically Determined Variation in Lysis Time Variance in the Bacteriophage φX174.

    Science.gov (United States)

    Baker, Christopher W; Miller, Craig R; Thaweethai, Tanayott; Yuan, Jeffrey; Baker, Meghan Hollibaugh; Joyce, Paul; Weinreich, Daniel M

    2016-04-07

    Researchers in evolutionary genetics recently have recognized an exciting opportunity in decomposing beneficial mutations into their proximal, mechanistic determinants. The application of methods and concepts from molecular biology and life history theory to studies of lytic bacteriophages (phages) has allowed them to understand how natural selection sees mutations influencing life history. This work motivated the research presented here, in which we explored whether, under consistent experimental conditions, small differences in the genome of bacteriophage φX174 could lead to altered life history phenotypes among a panel of eight genetically distinct clones. We assessed the clones' phenotypes by applying a novel statistical framework to the results of a serially sampled parallel infection assay, in which we simultaneously inoculated each of a large number of replicate host volumes with ∼1 phage particle. We sequentially plated the volumes over the course of infection and counted the plaques that formed after incubation. These counts served as a proxy for the number of phage particles in a single volume as a function of time. From repeated assays, we inferred significant, genetically determined heterogeneity in lysis time and burst size, including lysis time variance. These findings are interesting in light of the genetic and phenotypic constraints on the single-protein lysis mechanism of φX174. We speculate briefly on the mechanisms underlying our results, and we discuss the potential importance of lysis time variance in viral evolution.

  15. Genetically Determined Variation in Lysis Time Variance in the Bacteriophage φX174

    Directory of Open Access Journals (Sweden)

    Christopher W. Baker

    2016-04-01

    Full Text Available Researchers in evolutionary genetics recently have recognized an exciting opportunity in decomposing beneficial mutations into their proximal, mechanistic determinants. The application of methods and concepts from molecular biology and life history theory to studies of lytic bacteriophages (phages has allowed them to understand how natural selection sees mutations influencing life history. This work motivated the research presented here, in which we explored whether, under consistent experimental conditions, small differences in the genome of bacteriophage φX174 could lead to altered life history phenotypes among a panel of eight genetically distinct clones. We assessed the clones’ phenotypes by applying a novel statistical framework to the results of a serially sampled parallel infection assay, in which we simultaneously inoculated each of a large number of replicate host volumes with ∼1 phage particle. We sequentially plated the volumes over the course of infection and counted the plaques that formed after incubation. These counts served as a proxy for the number of phage particles in a single volume as a function of time. From repeated assays, we inferred significant, genetically determined heterogeneity in lysis time and burst size, including lysis time variance. These findings are interesting in light of the genetic and phenotypic constraints on the single-protein lysis mechanism of φX174. We speculate briefly on the mechanisms underlying our results, and we discuss the potential importance of lysis time variance in viral evolution.

  16. Chado use case: storing genomic, genetic and breeding data of Rosaceae and Gossypium crops in Chado.

    Science.gov (United States)

    Jung, Sook; Lee, Taein; Ficklin, Stephen; Yu, Jing; Cheng, Chun-Huai; Main, Dorrie

    2016-01-01

    The Genome Database for Rosaceae (GDR) and CottonGen are comprehensive online data repositories that provide access to integrated genomic, genetic and breeding data through search, visualization and analysis tools for Rosaceae crops and Gossypium (cotton). These online databases use Chado, an open-source, generic and ontology-driven database schema for biological data, as the primary data storage platform. Chado is highly normalized and uses ontologies to indicate the 'types' of data. Therefore, Chado is flexible such that it has been used to house genomic, genetic and breeding data for GDR and CottonGen. These data include whole genome sequence and annotation, transcripts, molecular markers, genetic maps, Quantitative Trait Loci, Mendelian Trait Loci, traits, germplasm, pedigrees, large scale phenotypic and genotypic data, ontologies and publications. We provide information about how to store these types of data in Chado using GDR and CottonGen as examples sites that were converted from an older legacy infrastructure. Database URL: GDR (www.rosaceae.org), CottonGen (www.cottongen.org).

  17. Robust Inference of Genetic Exchange Communities from Microbial Genomes Using TF-IDF

    Science.gov (United States)

    Cong, Yingnan; Chan, Yao-ban; Phillips, Charles A.; Langston, Michael A.; Ragan, Mark A.

    2017-01-01

    Bacteria and archaea can exchange genetic material across lineages through processes of lateral genetic transfer (LGT). Collectively, these exchange relationships can be modeled as a network and analyzed using concepts from graph theory. In particular, densely connected regions within an LGT network have been defined as genetic exchange communities (GECs). However, it has been problematic to construct networks in which edges solely represent LGT. Here we apply term frequency-inverse document frequency (TF-IDF), an alignment-free method originating from document analysis, to infer regions of lateral origin in bacterial genomes. We examine four empirical datasets of different size (number of genomes) and phyletic breadth, varying a key parameter (word length k) within bounds established in previous work. We map the inferred lateral regions to genes in recipient genomes, and construct networks in which the nodes are groups of genomes, and the edges natively represent LGT. We then extract maximum and maximal cliques (i.e., GECs) from these graphs, and identify nodes that belong to GECs across a wide range of k. Most surviving lateral transfer has happened within these GECs. Using Gene Ontology enrichment tests we demonstrate that biological processes associated with metabolism, regulation and transport are often over-represented among the genes affected by LGT within these communities. These enrichments are largely robust to change of k. PMID:28154557

  18. Genetic parameters for predicted methane production and potential for reducing enteric emissions through genomic selection.

    Science.gov (United States)

    Haas, Y de; Windig, J J; Calus, M P L; Dijkstra, J; Haan, M de; Bannink, A; Veerkamp, R F

    2011-12-01

    Mitigation of enteric methane (CH₄) emission in ruminants has become an important area of research because accumulation of CH₄ is linked to global warming. Nutritional and microbial opportunities to reduce CH₄ emissions have been extensively researched, but little is known about using natural variation to breed animals with lower CH₄ yield. Measuring CH₄ emission rates directly from animals is difficult and hinders direct selection on reduced CH₄ emission. However, improvements can be made through selection on associated traits (e.g., residual feed intake, RFI) or through selection on CH₄ predicted from feed intake and diet composition. The objective was to establish phenotypic and genetic variation in predicted CH₄ output, and to determine the potential of genetics to reduce methane emissions in dairy cattle. Experimental data were used and records on daily feed intake, weekly body weights, and weekly milk production were available from 548 heifers. Residual feed intake (MJ/d) is the difference between net energy intake and calculated net energy requirements for maintenance as a function of body weight and for fat- and protein-corrected milk production. Predicted methane emission (PME; g/d) is 6% of gross energy intake (Intergovernmental Panel on Climate Change methodology) corrected for energy content of methane (55.65 kJ/g). The estimated heritabilities for PME and RFI were 0.35 and 0.40, respectively. The positive genetic correlation between RFI and PME indicated that cows with lower RFI have lower PME (estimates ranging from 0.18 to 0.84). Hence, it is possible to decrease the methane production of a cow by selecting more-efficient cows, and the genetic variation suggests that reductions in the order of 11 to 26% in 10 yr are theoretically possible, and could be even higher in a genomic selection program. However, several uncertainties are discussed; for example, the lack of true methane measurements (and the key assumption that methane

  19. Genetic Resources, Genome Mapping and Evolutionary Genomics of the Pig (Sus scrofa)

    OpenAIRE

    Chen, K.; Baxter, T.; Muir, W. M.; Groenen, M.A.M.; Schook, L B

    2007-01-01

    The pig, a representative of the artiodactyla clade, is one of the first animals domesticated, and has become an important agriculture animal as one of the major human nutritional sources of animal based protein. The pig is also a valuable biomedical model organism for human health. The pig's importance to human health and nutrition is reflected in the decision to sequence its genome (3X). As an animal species with its wild ancestors present in the world, the pig provides a unique opportunity...

  20. A genome-wide analysis of genetic diversity in Trypanosoma cruzi intergenic regions.

    Directory of Open Access Journals (Sweden)

    Leonardo G Panunzi

    2014-05-01

    Full Text Available BACKGROUND: Trypanosoma cruzi is the causal agent of Chagas Disease. Recently, the genomes of representative strains from two major evolutionary lineages were sequenced, allowing the construction of a detailed genetic diversity map for this important parasite. However this map is focused on coding regions of the genome, leaving a vast space of regulatory regions uncharacterized in terms of their evolutionary conservation and/or divergence. METHODOLOGY: Using data from the hybrid CL Brener and Sylvio X10 genomes (from the TcVI and TcI Discrete Typing Units, respectively, we identified intergenic regions that share a common evolutionary ancestry, and are present in both CL Brener haplotypes (TcII-like and TcIII-like and in the TcI genome; as well as intergenic regions that were conserved in only two of the three genomes/haplotypes analyzed. The genetic diversity in these regions was characterized in terms of the accumulation of indels and nucleotide changes. PRINCIPAL FINDINGS: Based on this analysis we have identified i a core of highly conserved intergenic regions, which remained essentially unchanged in independently evolving lineages; ii intergenic regions that show high diversity in spite of still retaining their corresponding upstream and downstream coding sequences; iii a number of defined sequence motifs that are shared by a number of unrelated intergenic regions. A fraction of indels explains the diversification of some intergenic regions by the expansion/contraction of microsatellite-like repeats.

  1. Impact of marker ascertainment bias on genomic selection accuracy and estimates of genetic diversity.

    Directory of Open Access Journals (Sweden)

    Nicolas Heslot

    Full Text Available Genome-wide molecular markers are often being used to evaluate genetic diversity in germplasm collections and for making genomic selections in breeding programs. To accurately predict phenotypes and assay genetic diversity, molecular markers should assay a representative sample of the polymorphisms in the population under study. Ascertainment bias arises when marker data is not obtained from a random sample of the polymorphisms in the population of interest. Genotyping-by-sequencing (GBS is rapidly emerging as a low-cost genotyping platform, even for the large, complex, and polyploid wheat (Triticum aestivum L. genome. With GBS, marker discovery and genotyping occur simultaneously, resulting in minimal ascertainment bias. The previous platform of choice for whole-genome genotyping in many species such as wheat was DArT (Diversity Array Technology and has formed the basis of most of our knowledge about cereals genetic diversity. This study compared GBS and DArT marker platforms for measuring genetic diversity and genomic selection (GS accuracy in elite U.S. soft winter wheat. From a set of 365 breeding lines, 38,412 single nucleotide polymorphism GBS markers were discovered and genotyped. The GBS SNPs gave a higher GS accuracy than 1,544 DArT markers on the same lines, despite 43.9% missing data. Using a bootstrap approach, we observed significantly more clustering of markers and ascertainment bias with DArT relative to GBS. The minor allele frequency distribution of GBS markers had a deficit of rare variants compared to DArT markers. Despite the ascertainment bias of the DArT markers, GS accuracy for three traits out of four was not significantly different when an equal number of markers were used for each platform. This suggests that the gain in accuracy observed using GBS compared to DArT markers was mainly due to a large increase in the number of markers available for the analysis.

  2. Genome-wide assessment for genetic variants associated with ventricular dysfunction after primary coronary artery bypass graft surgery.

    Directory of Open Access Journals (Sweden)

    Amanda A Fox

    Full Text Available BACKGROUND: Postoperative ventricular dysfunction (VnD occurs in 9-20% of coronary artery bypass graft (CABG surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery. METHODS: A genome-wide association study identified single nucleotide polymorphisms (SNPs associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for ≥2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed. RESULTS: Over 100 SNPs were associated with VnD (P2.1 of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted.

  3. Using the chicken genome sequence in the development and mapping of genetic markers in the turkey (Meleagris gallopavo).

    Science.gov (United States)

    Chaves, L D; Knutson, T P; Krueth, S B; Reed, K M

    2006-04-01

    The efficacy of employing the chicken genome sequence in developing genetic markers and in mapping the turkey genome was studied. Eighty previously uncharacterized microsatellite markers were identified for the turkey using BLAST alignment to the chicken genome. The chicken sequence was then used to develop primers for polymerase chain reaction where the turkey sequence was either unavailable or insufficient. A total of 78 primer sets were tested for amplification and polymorphism in the turkey, and informative markers were genetically mapped. Sixty-five (83%) amplified turkey genomic DNA, and 33 (42%) were polymorphic in the University of Minnesota/Nicholas Turkey Breeding Farms mapping families. All but one marker genetically mapped to the position predicted from the chicken genome sequence. These results demonstrate the usefulness of the chicken sequence for the development of genomic resources in other avian species.

  4. Applications of population genetics to animal breeding, from wright, fisher and lush to genomic prediction.

    Science.gov (United States)

    Hill, William G

    2014-01-01

    Although animal breeding was practiced long before the science of genetics and the relevant disciplines of population and quantitative genetics were known, breeding programs have mainly relied on simply selecting and mating the best individuals on their own or relatives' performance. This is based on sound quantitative genetic principles, developed and expounded by Lush, who attributed much of his understanding to Wright, and formalized in Fisher's infinitesimal model. Analysis at the level of individual loci and gene frequency distributions has had relatively little impact. Now with access to genomic data, a revolution in which molecular information is being used to enhance response with "genomic selection" is occurring. The predictions of breeding value still utilize multiple loci throughout the genome and, indeed, are largely compatible with additive and specifically infinitesimal model assumptions. I discuss some of the history and genetic issues as applied to the science of livestock improvement, which has had and continues to have major spin-offs into ideas and applications in other areas.

  5. Unraveling the genetic etiology of adult antisocial behavior: a genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Jorim J Tielbeek

    Full Text Available Crime poses a major burden for society. The heterogeneous nature of criminal behavior makes it difficult to unravel its causes. Relatively little research has been conducted on the genetic influences of criminal behavior. The few twin and adoption studies that have been undertaken suggest that about half of the variance in antisocial behavior can be explained by genetic factors. In order to identify the specific common genetic variants underlying this behavior, we conduct the first genome-wide association study (GWAS on adult antisocial behavior. Our sample comprised a community sample of 4816 individuals who had completed a self-report questionnaire. No genetic polymorphisms reached genome-wide significance for association with adult antisocial behavior. In addition, none of the traditional candidate genes can be confirmed in our study. While not genome-wide significant, the gene with the strongest association (p-value = 8.7×10(-5 was DYRK1A, a gene previously related to abnormal brain development and mental retardation. Future studies should use larger, more homogeneous samples to disentangle the etiology of antisocial behavior. Biosocial criminological research allows a more empirically grounded understanding of criminal behavior, which could ultimately inform and improve current treatment strategies.

  6. Applications of Population Genetics to Animal Breeding, from Wright, Fisher and Lush to Genomic Prediction

    Science.gov (United States)

    Hill, William G.

    2014-01-01

    Although animal breeding was practiced long before the science of genetics and the relevant disciplines of population and quantitative genetics were known, breeding programs have mainly relied on simply selecting and mating the best individuals on their own or relatives’ performance. This is based on sound quantitative genetic principles, developed and expounded by Lush, who attributed much of his understanding to Wright, and formalized in Fisher’s infinitesimal model. Analysis at the level of individual loci and gene frequency distributions has had relatively little impact. Now with access to genomic data, a revolution in which molecular information is being used to enhance response with “genomic selection” is occurring. The predictions of breeding value still utilize multiple loci throughout the genome and, indeed, are largely compatible with additive and specifically infinitesimal model assumptions. I discuss some of the history and genetic issues as applied to the science of livestock improvement, which has had and continues to have major spin-offs into ideas and applications in other areas. PMID:24395822

  7. Prehistoric genomes reveal the genetic foundation and cost of horse domestication.

    Science.gov (United States)

    Schubert, Mikkel; Jónsson, Hákon; Chang, Dan; Der Sarkissian, Clio; Ermini, Luca; Ginolhac, Aurélien; Albrechtsen, Anders; Dupanloup, Isabelle; Foucal, Adrien; Petersen, Bent; Fumagalli, Matteo; Raghavan, Maanasa; Seguin-Orlando, Andaine; Korneliussen, Thorfinn S; Velazquez, Amhed M V; Stenderup, Jesper; Hoover, Cindi A; Rubin, Carl-Johan; Alfarhan, Ahmed H; Alquraishi, Saleh A; Al-Rasheid, Khaled A S; MacHugh, David E; Kalbfleisch, Ted; MacLeod, James N; Rubin, Edward M; Sicheritz-Ponten, Thomas; Andersson, Leif; Hofreiter, Michael; Marques-Bonet, Tomas; Gilbert, M Thomas P; Nielsen, Rasmus; Excoffier, Laurent; Willerslev, Eske; Shapiro, Beth; Orlando, Ludovic

    2014-12-30

    The domestication of the horse ∼ 5.5 kya and the emergence of mounted riding, chariotry, and cavalry dramatically transformed human civilization. However, the genetics underlying horse domestication are difficult to reconstruct, given the near extinction of wild horses. We therefore sequenced two ancient horse genomes from Taymyr, Russia (at 7.4- and 24.3-fold coverage), both predating the earliest archeological evidence of domestication. We compared these genomes with genomes of domesticated horses and the wild Przewalski's horse and found genetic structure within Eurasia in the Late Pleistocene, with the ancient population contributing significantly to the genetic variation of domesticated breeds. We furthermore identified a conservative set of 125 potential domestication targets using four complementary scans for genes that have undergone positive selection. One group of genes is involved in muscular and limb development, articular junctions, and the cardiac system, and may represent physiological adaptations to human utilization. A second group consists of genes with cognitive functions, including social behavior, learning capabilities, fear response, and agreeableness, which may have been key for taming horses. We also found that domestication is associated with inbreeding and an excess of deleterious mutations. This genetic load is in line with the "cost of domestication" hypothesis also reported for rice, tomatoes, and dogs, and it is generally attributed to the relaxation of purifying selection resulting from the strong demographic bottlenecks accompanying domestication. Our work demonstrates the power of ancient genomes to reconstruct the complex genetic changes that transformed wild animals into their domesticated forms, and the population context in which this process took place.

  8. Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements.

    Directory of Open Access Journals (Sweden)

    Martin Wu

    2004-03-01

    Full Text Available The complete sequence of the 1,267,782 bp genome of Wolbachia pipientis wMel, an obligate intracellular bacteria of Drosophila melanogaster, has been determined. Wolbachia, which are found in a variety of invertebrate species, are of great interest due to their diverse interactions with different hosts, which range from many forms of reproductive parasitism to mutualistic symbioses. Analysis of the wMel genome, in particular phylogenomic comparisons with other intracellular bacteria, has revealed many insights into the biology and evolution of wMel and Wolbachia in general. For example, the wMel genome is unique among sequenced obligate intracellular species in both being highly streamlined and containing very high levels of repetitive DNA and mobile DNA elements. This observation, coupled with multiple evolutionary reconstructions, suggests that natural selection is somewhat inefficient in wMel, most likely owing to the occurrence of repeated population bottlenecks. Genome analysis predicts many metabolic differences with the closely related Rickettsia species, including the presence of intact glycolysis and purine synthesis, which may compensate for an inability to obtain ATP directly from its host, as Rickettsia can. Other discoveries include the apparent inability of wMel to synthesize lipopolysaccharide and the presence of the most genes encoding proteins with ankyrin repeat domains of any prokaryotic genome yet sequenced. Despite the ability of wMel to infect the germline of its host, we find no evidence for either recent lateral gene transfer between wMel and D. melanogaster or older transfers between Wolbachia and any host. Evolutionary analysis further supports the hypothesis that mitochondria share a common ancestor with the alpha-Proteobacteria, but shows little support for the grouping of mitochondria with species in the order Rickettsiales. With the availability of the complete genomes of both species and excellent genetic tools for

  9. Common genetic variations in the CYP2R1 and GC genes are determinants of vitamin D status in Danes

    DEFF Research Database (Denmark)

    Nissen, Ioanna

    ), after 6 months intake of vitamin D3-fortified bread and milk (paper II) and in 92 participants in the VitDgen study after artificial UVB irradiation during winter (paper III). Common genetic variations in the CYP2R1 and GC genes were found to be important determinants of vitamin D status in three out...... by genetic variation in vitamin D modulating genes. Twin and family-based studies indicate that genetic variation may have an appreciable influence on vitamin D status. Moreover, several candidate gene studies including two genome-wide association studies (GWAS) have found single nucleotide polymorphisms...... (SNPs) in CYP2R1, CYP24A1, CYP27B1, C10orf88, DHCR7/NADSYN1, GC and VDR genes to be associated with vitamin D status. The main hypothesis of this work was that genetically determined variation in vitamin D metabolism would influence the effect of vitamin D sources (vitamin D...

  10. Genetic testing and Alzheimer disease: recommendations of the Stanford Program in Genomics, Ethics, and Society.

    Science.gov (United States)

    McConnell, L M; Koenig, B A; Greely, H T; Raffin, T A

    1999-01-01

    Several genes associated with Alzheimer disease (AD) have been localized and cloned; two genetic tests are already commercially available, and new tests are being developed. Genetic testing for AD--either for disease prediction or for diagnosis--raises critical ethical concerns. The multidisciplinary Alzheimer Disease Working Group of the Stanford Program in Genomics, Ethics, and Society (PGES) presents comprehensive recommendations on genetic testing for AD. The Group concludes that under current conditions, genetic testing for AD prediction or diagnosis is only rarely appropriate. Criteria for judging the readiness of a test for introduction into routine clinical practice typically rely heavily on evaluation of technical efficacy. PGES recommends a broader and more comprehensive approach, considering: 1) the unique social and historical meanings of AD; 2) the availability of procedures to promote good surrogate decision making for incompetent patients and to safeguard confidentiality; 3) access to sophisticated genetic counselors able to communicate complex risk information and effectively convey the social costs and psychological burdens of testing, such as unintentional disclosure of predictive genetic information to family members; 4) protection from inappropriate advertising and marketing of genetic tests; and 5) recognition of the need for public education about the meaning and usefulness of predictive and diagnostic tests for AD. In this special issue of Genetic Testing, the PGES recommendations are published along with comprehensive background papers authored by Working Group members.

  11. The Bifidobacterium dentium Bd1 genome sequence reflects its genetic adaptation to the human oral cavity.

    Directory of Open Access Journals (Sweden)

    Marco Ventura

    2009-12-01

    Full Text Available Bifidobacteria, one of the relatively dominant components of the human intestinal microbiota, are considered one of the key groups of beneficial intestinal bacteria (probiotic bacteria. However, in addition to health-promoting taxa, the genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic cariogenic pathogen. The genetic basis for the ability of B. dentium to survive in the oral cavity and contribute to caries development is not understood. The genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to completion to uncover a single circular 2,636,368 base pair chromosome with 2,143 predicted open reading frames. Annotation of the genome sequence revealed multiple ways in which B. dentium has adapted to the oral environment through specialized nutrient acquisition, defences against antimicrobials, and gene products that increase fitness and competitiveness within the oral niche. B. dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent with genome-based predictions, while colonization and persistence factors implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva-derived compounds were also identified. Global transcriptome analysis demonstrated that many of the genes encoding these predicted traits are highly expressed under relevant physiological conditions. This is the first report to identify, through various genomic approaches, specific genetic adaptations of a Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a cariogenic microorganism in the oral cavity. In silico analysis and comparative genomic hybridization experiments clearly reveal a high level of genome conservation among various B. dentium strains. The data indicate that the genome of this opportunistic cariogen has evolved through a very limited number of horizontal gene acquisition events, highlighting the narrow boundaries that separate commensals from

  12. Quantitative Seq-LGS: Genome-Wide Identification of Genetic Drivers of Multiple Phenotypes in Malaria Parasites

    KAUST Repository

    Abkallo, Hussein M.

    2016-10-01

    Identifying the genetic determinants of phenotypes that impact on disease severity is of fundamental importance for the design of new interventions against malaria. Traditionally, such discovery has relied on labor-intensive approaches that require significant investments of time and resources. By combining Linkage Group Selection (LGS), quantitative whole genome population sequencing and a novel mathematical modeling approach (qSeq-LGS), we simultaneously identified multiple genes underlying two distinct phenotypes, identifying novel alleles for growth rate and strain specific immunity (SSI), while removing the need for traditionally required steps such as cloning, individual progeny phenotyping and marker generation. The detection of novel variants, verified by experimental phenotyping methods, demonstrates the remarkable potential of this approach for the identification of genes controlling selectable phenotypes in malaria and other apicomplexan parasites for which experimental genetic crosses are amenable.

  13. Ocean acidification genetics - Genetics and genomics of response to ocean acidification

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — We are applying a variety of genetic tools to assess the response of our ocean resources to ocean acidification, including gene expression techniques, identification...

  14. Looping Genomes: Diagnostic Change and the Genetic Makeup of the Autism Population.

    Science.gov (United States)

    Navon, Daniel; Eyal, Gil

    2016-03-01

    This article builds on Hacking's framework of "dynamic nominalism" to show how knowledge about biological etiology can interact with the "kinds of people" delineated by diagnostic categories in ways that "loop" or modify both over time. The authors use historical materials to show how "geneticization" played a crucial role in binding together autism as a biosocial community and how evidence from genetics research later made an important contribution to the diagnostic expansion of autism. In the second part of the article, the authors draw on quantitative and qualitative analyses of autism rates over time in several rare conditions that are delineated strictly according to genomic mutations in order to demonstrate that these changes in diagnostic practice helped to both increase autism's prevalence and create its enormous genetic heterogeneity. Thus, a looping process that began with geneticization and involved the social effects of genetics research itself transformed the autism population and its genetic makeup.

  15. Genetic Algorithm Optimization for Determining Fuzzy Measures from Fuzzy Data

    Directory of Open Access Journals (Sweden)

    Chen Li

    2013-01-01

    Full Text Available Fuzzy measures and fuzzy integrals have been successfully used in many real applications. How to determine fuzzy measures is a very difficult problem in these applications. Though there have existed some methodologies for solving this problem, such as genetic algorithms, gradient descent algorithms, neural networks, and particle swarm algorithm, it is hard to say which one is more appropriate and more feasible. Each method has its advantages. Most of the existed works can only deal with the data consisting of classic numbers which may arise limitations in practical applications. It is not reasonable to assume that all data are real data before we elicit them from practical data. Sometimes, fuzzy data may exist, such as in pharmacological, financial and sociological applications. Thus, we make an attempt to determine a more generalized type of general fuzzy measures from fuzzy data by means of genetic algorithms and Choquet integrals. In this paper, we make the first effort to define the σ-λ rules. Furthermore we define and characterize the Choquet integrals of interval-valued functions and fuzzy-number-valued functions based on σ-λ rules. In addition, we design a special genetic algorithm to determine a type of general fuzzy measures from fuzzy data.

  16. Congruence-Incongruence Patterns in Alpha-1 Antitrypsin Deficiency Couples' Genetic Determinist Beliefs and Perceived Control over Genes: Implications for Clinical and Public Health Genomic Communication.

    Science.gov (United States)

    Parrott, Roxanne L; Smith, Rachel A; Hong, Soo Jung; Worthington, Amber

    2015-06-01

    Genomics makes possible the isolation of multiple genes as co-factors that increase, but do not determine, risk for many adult-onset medical conditions, including alpha-1 antitrypsin deficiency (AATD). Those diagnosed with an adult-onset medical condition, such as AATD, are often married and make decisions about testing and care as a couple. We examined genetic essentialist and threat beliefs, focusing on beliefs about the genetic contribution to disease susceptibility and severity, as well as perceptions of control related to genes and health for married couples (N =59), in which one spouse has been tested for genetic mutations associated with AATD. The intraclass correlation for spouses' beliefs about genetic essentialism was strong and statistically significant, but the associations for their other beliefs were not. Incongruence between AATD participants and their spouses regarding genes' influence on disease severity directly related to incongruent perceptions of control and genetic contribution to disease susceptibility. Results revealed an inverse relationship to AATD participants' perceptions of behavioral control and a direct relationship to their beliefs about genes' influence on disease severity. This suggests a pattern of incongruence in which AATD participants have low levels of perceived control over genes' influence on health and high levels of perceived genetic influence on disease severity compared to spouses. With public health communication efforts lagging behind the science of genomics, insights regarding the congruence or incongruence associated with married couples' beliefs about genes' influence on disease afford pathways to guide clinical and public health communication about genomics.

  17. Genetic determinants of mate recognition in Brachionus manjavacas (Rotifera

    Directory of Open Access Journals (Sweden)

    Kubanek Julia

    2009-09-01

    Full Text Available Abstract Background Mate choice is of central importance to most animals, influencing population structure, speciation, and ultimately the survival of a species. Mating behavior of male brachionid rotifers is triggered by the product of a chemosensory gene, a glycoprotein on the body surface of females called the mate recognition pheromone. The mate recognition pheromone has been biochemically characterized, but little was known about the gene(s. We describe the isolation and characterization of the mate recognition pheromone gene through protein purification, N-terminal amino acid sequence determination, identification of the mate recognition pheromone gene from a cDNA library, sequencing, and RNAi knockdown to confirm the functional role of the mate recognition pheromone gene in rotifer mating. Results A 29 kD protein capable of eliciting rotifer male circling was isolated by high-performance liquid chromatography. Two transcript types containing the N-terminal sequence were identified in a cDNA library; further characterization by screening a genomic library and by polymerase chain reaction revealed two genes belonging to each type. Each gene begins with a signal peptide region followed by nearly perfect repeats of an 87 to 92 codon motif with no codons between repeats and the final motif prematurely terminated by the stop codon. The two Type A genes contain four and seven repeats and the two Type B genes contain three and five repeats, respectively. Only the Type B gene with three repeats encodes a peptide with a molecular weight of 29 kD. Each repeat of the Type B gene products contains three asparagines as potential sites for N-glycosylation; there are no asparagines in the Type A genes. RNAi with Type A double-stranded RNA did not result in less circling than in the phosphate-buffered saline control, but transfection with Type B double-stranded RNA significantly reduced male circling by 17%. The very low divergence between repeat units

  18. Genome editing revolutionize the creation of genetically modified pigs for modeling human diseases.

    Science.gov (United States)

    Yao, Jing; Huang, Jiaojiao; Zhao, Jianguo

    2016-09-01

    Pigs have anatomical, physiological and genomic characteristics that make them highly suitable for modeling human diseases. Genetically modified (GM) pig models of human diseases are critical for studying pathogenesis, treatment, and prevention. The emergence of nuclease-mediated genome editing technology has been successfully employed for engineering of the pig genome, which has revolutionize the creation of GM pig models with highly complex pathophysiologies and comorbidities. In this review, we summarize the progress of recently developed genome editing technologies, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9), which enable highly efficient and precise introduction of genome modifications into pigs, and tailored disease models that have been generated in various disciplines via genome editing technology. We also summarize the GM pig models that have been generated by conventional transgenic strategies. Additionally, perspectives regarding the application of GM pigs in biomedical research are discussed.

  19. Genetic recombination pathways and their application for genome modification of human embryonic stem cells.

    Science.gov (United States)

    Nieminen, Mikko; Tuuri, Timo; Savilahti, Harri

    2010-10-01

    Human embryonic stem cells are pluripotent cells derived from early human embryo and retain a potential to differentiate into all adult cell types. They provide vast opportunities in cell replacement therapies and are expected to become significant tools in drug discovery as well as in the studies of cellular and developmental functions of human genes. The progress in applying different types of DNA recombination reactions for genome modification in a variety of eukaryotic cell types has provided means to utilize recombination-based strategies also in human embryonic stem cells. Homologous recombination-based methods, particularly those utilizing extended homologous regions and those employing zinc finger nucleases to boost genomic integration, have shown their usefulness in efficient genome modification. Site-specific recombination systems are potent genome modifiers, and they can be used to integrate DNA into loci that contain an appropriate recombination signal sequence, either naturally occurring or suitably pre-engineered. Non-homologous recombination can be used to generate random integrations in genomes relatively effortlessly, albeit with a moderate efficiency and precision. DNA transposition-based strategies offer substantially more efficient random strategies and provide means to generate single-copy insertions, thus potentiating the generation of genome-wide insertion libraries applicable in genetic screens.

  20. Genomic Characterization of a Pattern D Streptococcus pyogenes emm53 Isolate Reveals a Genetic Rationale for Invasive Skin Tropicity.

    Science.gov (United States)

    Bao, Yun-Juan; Liang, Zhong; Mayfield, Jeffrey A; Donahue, Deborah L; Carothers, Katelyn E; Lee, Shaun W; Ploplis, Victoria A; Castellino, Francis J

    2016-06-15

    The genome of an invasive skin-tropic strain (AP53) of serotype M53 group A Streptococcus pyogenes (GAS) is composed of a circular chromosome of 1,860,554 bp and carries genetic markers for infection at skin locales, viz, emm gene family pattern D and FCT type 3. Through genome-scale comparisons of AP53 with other GAS genomes, we identified 596 candidate single-nucleotide polymorphisms (SNPs) that reveal a potential genetic basis for skin tropism. The genome of AP53 differed by ∼30 point mutations from a noninvasive pattern D serotype M53 strain (Alab49), 4 of which are located in virulence genes. One pseudogene, yielding an inactive sensor kinase (CovS(-)) of the two-component transcriptional regulator CovRS, a major determinant for invasiveness, severely attenuated the expression of the secreted cysteine protease SpeB and enhanced the expression of the hyaluronic acid capsule compared to the isogenic noninvasive AP53/CovS(+) strain. The collagen-binding protein transcript sclB differed in the number of 5'-pentanucleotide repeats in the signal peptides of AP53 and Alab49 (9 versus 15), translating into different lengths of their signal peptides, which nonetheless maintained a full-length translatable coding frame. Furthermore, GAS strain AP53 acquired two phages that are absent in Alab49. One such phage (ΦAP53.2) contains the known virulence factor superantigen exotoxin gene tandem speK-slaA Overall, we conclude that this bacterium has evolved in multiple ways, including mutational variations of regulatory genes, short-tandem-repeat polymorphisms, large-scale genomic alterations, and acquisition of phages, all of which may be involved in shaping the adaptation of GAS in specific infectious environments and contribute to its enhanced virulence. Infectious strains of S. pyogenes (GAS) are classified by their serotypes, relating to the surface M protein, the emm-like subfamily pattern, and their tropicity toward the nasopharynx and/or skin. It is generally agreed

  1. A genome-wide survey of transgenerational genetic effects in autism.

    Directory of Open Access Journals (Sweden)

    Kathryn M Tsang

    Full Text Available Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction. We used simple models of single locus parent-child interaction and identified suggestive results (P<10(-4 that cannot be explained by main effects, but no genome-wide significant signals. Some of these maternal and maternal-child associations were in or adjacent to autism candidate genes including: PCDH9, FOXP1, GABRB3, NRXN1, RELN, MACROD2, FHIT, RORA, CNTN4, CNTNAP2, FAM135B, LAMA1, NFIA, NLGN4X, RAPGEF4, and SDK1. We attempted validation of potential autism association under maternal-specific models using maternal-paternal comparison in family-based GWAS datasets. Our results suggest that further study of parental genetic effects and parent-child interaction in autism is warranted.

  2. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

    Science.gov (United States)

    Lee, S Hong; Ripke, Stephan; Neale, Benjamin M; Faraone, Stephen V; Purcell, Shaun M; Perlis, Roy H; Mowry, Bryan J; Thapar, Anita; Goddard, Michael E; Witte, John S; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E; Asherson, Philip; Azevedo, Maria H; Backlund, Lena; Badner, Judith A; Bailey, Anthony J; Banaschewski, Tobias; Barchas, Jack D; Barnes, Michael R; Barrett, Thomas B; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B; Black, Donald W; Blackwood, Douglas H R; Bloss, Cinnamon S; Boehnke, Michael; Boomsma, Dorret I; Breen, Gerome; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G; Buitelaar, Jan K; Bunney, William E; Buxbaum, Joseph D; Byerley, William F; Byrne, Enda M; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Cloninger, C Robert; Collier, David A; Cook, Edwin H; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H; Craig, David W; Craig, Ian W; Crosbie, Jennifer; Cuccaro, Michael L; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J; Doyle, Alysa E; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P; Edenberg, Howard J; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E; Ferrier, I Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B; Freitag, Christine M; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V; Georgieva, Lyudmila; Gershon, Elliot S; Geschwind, Daniel H; Giegling, Ina; Gill, Michael; Gordon, Scott D; Gordon-Smith, Katherine; Green, Elaine K; Greenwood, Tiffany A; Grice, Dorothy E; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P; Hamshere, Marian L; Hansen, Thomas F; Hartmann, Annette M; Hautzinger, Martin; Heath, Andrew C; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hipolito, Maria; Hoefels, Susanne; Holmans, Peter A; Holsboer, Florian; Hoogendijk, Witte J; Hottenga, Jouke-Jan; Hultman, Christina M; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K; Kahn, René S; Kandaswamy, Radhika; Keller, Matthew C; Kennedy, James L; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K; Klauck, Sabine M; Klei, Lambertus; Knowles, James A; Kohli, Martin A; Koller, Daniel L; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Långström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B; Leboyer, Marion; Ledbetter, David H; Lee, Phil H; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F; Lewis, Cathryn M; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A; Lin, Dan-Yu; Linszen, Don H; Liu, Chunyu; Lohoff, Falk W; Loo, Sandra K; Lord, Catherine; Lowe, Jennifer K; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela A F; Maestrini, Elena; Magnusson, Patrik K E; Mahon, Pamela B; Maier, Wolfgang; Malhotra, Anil K; Mane, Shrikant M; Martin, Christa L; Martin, Nicholas G; Mattheisen, Manuel; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A; McGhee, Kevin A; McGough, James J; McGrath, Patrick J; McGuffin, Peter; McInnis, Melvin G; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W; McMahon, Francis J; McMahon, William M; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P; Montgomery, Grant W; Moran, Jennifer L; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W; Morrow, Eric M; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W; Muir, Walter J; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M; Myin-Germeys, Inez; Neale, Michael C; Nelson, Stan F; Nievergelt, Caroline M; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A; Nöthen, Markus M; Nurnberger, John I; Nwulia, Evaristus A; Nyholt, Dale R; O'Dushlaine, Colm; Oades, Robert D; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A; Osby, Urban; Owen, Michael J; Palotie, Aarno; Parr, Jeremy R; Paterson, Andrew D; Pato, Carlos N; Pato, Michele T; Penninx, Brenda W; Pergadia, Michele L; Pericak-Vance, Margaret A; Pickard, Benjamin S; Pimm, Jonathan; Piven, Joseph; Posthuma, Danielle; Potash, James B; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J; Quinn, Emma M; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rossin, Lizzy; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R; Sanders, Stephan J; Santangelo, Susan L; Sergeant, Joseph A; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F; Scheftner, William A; Schellenberg, Gerard D; Scherer, Stephen W; Schork, Nicholas J; Schulze, Thomas G; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J; Shi, Jianxin; Shilling, Paul D; Shyn, Stanley I; Silverman, Jeremy M; Slager, Susan L; Smalley, Susan L; Smit, Johannes H; Smith, Erin N; Sonuga-Barke, Edmund J S; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S; Strohmaier, Jana; Stroup, T Scott; Sutcliffe, James S; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C; Todorov, Alexandre A; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M; Vieland, Veronica J; Vincent, John B; Visscher, Peter M; Walsh, Christopher A; Wassink, Thomas H; Watson, Stanley J; Weissman, Myrna M; Werge, Thomas; Wienker, Thomas F; Wijsman, Ellen M; Willemsen, Gonneke; Williams, Nigel; Willsey, A Jeremy; Witt, Stephanie H; Xu, Wei; Young, Allan H; Yu, Timothy W; Zammit, Stanley; Zandi, Peter P; Zhang, Peng; Zitman, Frans G; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R; Sklar, Pamela; Daly, Mark J; O'Donovan, Michael C; Craddock, Nicholas; Sullivan, Patrick F; Smoller, Jordan W; Kendler, Kenneth S; Wray, Naomi R

    2013-09-01

    Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

  3. A survey of application: genomics and genetic programming, a new frontier.

    Science.gov (United States)

    Khan, Mohammad Wahab; Alam, Mansaf

    2012-08-01

    The aim of this paper is to provide an introduction to the rapidly developing field of genetic programming (GP). Particular emphasis is placed on the application of GP to genomics. First, the basic methodology of GP is introduced. This is followed by a review of applications in the areas of gene network inference, gene expression data analysis, SNP analysis, epistasis analysis and gene annotation. Finally this paper concluded by suggesting potential avenues of possible future research on genetic programming, opportunities to extend the technique, and areas for possible practical applications.

  4. Improving human forensics through advances in genetics, genomics and molecular biology.

    Science.gov (United States)

    Kayser, Manfred; de Knijff, Peter

    2011-03-01

    Forensic DNA profiling currently allows the identification of persons already known to investigating authorities. Recent advances have produced new types of genetic markers with the potential to overcome some important limitations of current DNA profiling methods. Moreover, other developments are enabling completely new kinds of forensically relevant information to be extracted from biological samples. These include new molecular approaches for finding individuals previously unknown to investigators, and new molecular methods to support links between forensic sample donors and criminal acts. Such advances in genetics, genomics and molecular biology are likely to improve human forensic case work in the near future.

  5. Genetically determined patozoospermia. Literature review and research results

    Directory of Open Access Journals (Sweden)

    E. E. Bragina

    2015-01-01

    Full Text Available Genetic factors (chromosomal aberrations and point mutations are the cause of infertility in 10–15 % of men with impaired fertility. Homogeneous structural and functional defects in the sperm or the total terato-, asthenozoospermia – rare cases of genetically determined male infertility, are autosomal recessive diseases. Currently, described 4 types of «syndromic» spermopatology. 1. Primary ciliary dyskinesia (PCD in men with total asthenozoospermia. Affects axoneme structures (microtubules, dynein arms, radial spokes. It identified more than 20 chromosomal loci responsible for the development of the PCD. 2. Dysplasia of the fibrous sheath of sperm tail in men with asthenozoospermia. The shortened and thickened sperm tail observed with disorganization of vertical columns and cross ribs of the fibrous sheath. Candidate genes – genes family ACAP. 3. Globozoospermia in men with teratozoospermia characterized by the presence of sperm with round heads, primary lack of acrosome and disorganization middle part of the flagellum. Found mutations or deletions of genes SPATA16, PICK1 and DPY19L2. 4. Syndrome decapitated spermatozoa in men with teratozoospermia (microcephaly. Abnormalities in the spermiogenesis development of connecting part jf the tail and proximal (morphologically normal centrioles.In 2012–2014 years we have studied the ultrastructure of 2267 semen samples of men with impaired fertility. Globozoospermia revealed in 7 patients, dysplasia of the fibrous sheath – 13, decapitated sperm – in one. PCD was revealed in 4 patients (lack of axoneme dynein arms was found in 1 patient, absence of axoneme radial spokes – in 3 patients.The problem of genetically determined patozoospermya must be taken into account when the assisted reproductive technologies practises. There are few cases of successful assisted reproductive technologies with sperm of these patients. We don»t know the etiological factors of syndromic spermopatologe, so

  6. Genetics and Genomics of Single-Gene Cardiovascular Diseases: Common Hereditary Cardiomyopathies as Prototypes of Single-Gene Disorders.

    Science.gov (United States)

    Marian, Ali J; van Rooij, Eva; Roberts, Robert

    2016-12-27

    This is the first of 2 review papers on genetics and genomics appearing as part of the series on "omics." Genomics pertains to all components of an organism's genes, whereas genetics involves analysis of a specific gene or genes in the context of heredity. The paper provides introductory comments, describes the basis of human genetic diversity, and addresses the phenotypic consequences of genetic variants. Rare variants with large effect sizes are responsible for single-gene disorders, whereas complex polygenic diseases are typically due to multiple genetic variants, each exerting a modest effect size. To illustrate the clinical implications of genetic variants with large effect sizes, 3 common forms of hereditary cardiomyopathies are discussed as prototypic examples of single-gene disorders, including their genetics, clinical manifestations, pathogenesis, and treatment. The genetic basis of complex traits is discussed in a separate paper. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. Genetic improvement of Pacific white shrimp [Penaeus (Litopenaeus) vannamei]: perspectives for genomic selection

    Science.gov (United States)

    Castillo-Juárez, Héctor; Campos-Montes, Gabriel R.; Caballero-Zamora, Alejandra; Montaldo, Hugo H.

    2015-01-01

    The uses of breeding programs for the Pacific white shrimp [Penaeus (Litopenaeus) vannamei] based on mixed linear models with pedigreed data are described. The application of these classic breeding methods yielded continuous progress of great value to increase the profitability of the shrimp industry in several countries. Recent advances in such areas as genomics in shrimp will allow for the development of new breeding programs in the near future that will increase genetic progress. In particular, these novel techniques may help increase disease resistance to specific emerging diseases, which is today a very important component of shrimp breeding programs. Thanks to increased selection accuracy, simulated genetic advance using genomic selection for survival to a disease challenge was up to 2.6 times that of phenotypic sib selection. PMID:25852740

  8. Genetic improvement of Pacific white shrimp (Penaeus (Litopenaeus vannamei: perspectives for genomic selection

    Directory of Open Access Journals (Sweden)

    Héctor eCastillo-Juárez

    2015-03-01

    Full Text Available The use of breeding programs for the Pacific white shrimp (Penaeus (Litopenaeus vannamei based on mixed linear models with pedigreed data are described. The application of these classic breeding methods yielded continuous progress of great value to increase the profitability of the shrimp industry in several countries. Recent advances in such areas as genomics in shrimp will allow for the development of new breeding programs in the near future that will increase genetic progress. In particular, these novel techniques may help increase disease resistance to specific emerging diseases, which is today a very important component of shrimp breeding programs. Thanks to increased selection accuracy, simulated genetic advance using genomic selection for survival to a disease challenge was up to 2.6 times that of phenotypic sib selection.

  9. Kazusa Marker DataBase: a database for genomics, genetics, and molecular breeding in plants.

    Science.gov (United States)

    Shirasawa, Kenta; Isobe, Sachiko; Tabata, Satoshi; Hirakawa, Hideki

    2014-09-01

    In order to provide useful genomic information for agronomical plants, we have established a database, the Kazusa Marker DataBase (http://marker.kazusa.or.jp). This database includes information on DNA markers, e.g., SSR and SNP markers, genetic linkage maps, and physical maps, that were developed at the Kazusa DNA Research Institute. Keyword searches for the markers, sequence data used for marker development, and experimental conditions are also available through this database. Currently, 10 plant species have been targeted: tomato (Solanum lycopersicum), pepper (Capsicum annuum), strawberry (Fragaria × ananassa), radish (Raphanus sativus), Lotus japonicus, soybean (Glycine max), peanut (Arachis hypogaea), red clover (Trifolium pratense), white clover (Trifolium repens), and eucalyptus (Eucalyptus camaldulensis). In addition, the number of plant species registered in this database will be increased as our research progresses. The Kazusa Marker DataBase will be a useful tool for both basic and applied sciences, such as genomics, genetics, and molecular breeding in crops.

  10. Novel R tools for analysis of genome-wide population genetic data with emphasis on clonality

    Directory of Open Access Journals (Sweden)

    Zhian N Kamvar

    2015-06-01

    Full Text Available To gain a detailed understanding of how plant microbes evolve and adapt to hosts, pesticides, and other factors, knowledge of the population dynamics and evolutionary history of populations is crucial. Plant pathogen populations are often clonal or partially clonal which requires different analytical tools. With the advent of high throughput sequencing technologies, obtaining genome-wide population genetic data has become easier than ever before. We previously contributed the R package poppr specifically addressing issues with analysis of clonal populations. In this paper we provide several significant extensions to poppr with a focus on large, genome-wide SNP data. Specifically, we provide several new functionalities including the new function mlg.filter to define clone boundaries allowing for inspection and definition of what is a clonal lineage, minimum spanning networks with reticulation, a sliding-window analysis of the index of association, modular bootstrapping of any genetic distance, and analyses across any level of hierarchies.

  11. Structure, dynamics and function of Leishmania genome: resolving the puzzle of infection, genetics and evolution?

    Science.gov (United States)

    Dujardin, Jean-Claude

    2009-03-01

    We review and discuss here the specificity and contribution of genome (re-)arrangement studies for the exploration of genetic diversity among Leishmania. We show how the early molecular karyotyping studies generated an original perception of the genetics and evolution of these Protozoa, while providing some possible explanations on the parasite diverse phenotypes (drug resistance, pathogenicity...). We compare the results with the enormous amount of data provided by the recent genome sequencing projects, so far focused on one strain per genus/species. We highlight the relevance of parallel sequencing of different strains of a same species, now made possible by the new sequencing technologies. We recommend paying a particular attention to variation in gene copy number, a feature showed by the karyotyping studies to be extremely informative.

  12. Assessing Genetic Diversity among Brettanomyces Yeasts by DNA Fingerprinting and Whole-Genome Sequencing

    Scienc