WorldWideScience

Sample records for gene genetical genomics

  1. 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,

  2. 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,

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Identification of a strawberry flavor gene candidate using an integrated genetic-genomic-analytical chemistry approach.

    Science.gov (United States)

    Chambers, Alan H; Pillet, Jeremy; Plotto, Anne; Bai, Jinhe; Whitaker, Vance M; Folta, Kevin M

    2014-04-17

    There is interest in improving the flavor of commercial strawberry (Fragaria × ananassa) varieties. Fruit flavor is shaped by combinations of sugars, acids and volatile compounds. Many efforts seek to use genomics-based strategies to identify genes controlling flavor, and then designing durable molecular markers to follow these genes in breeding populations. In this report, fruit from two cultivars, varying for presence-absence of volatile compounds, along with segregating progeny, were analyzed using GC/MS and RNAseq. Expression data were bulked in silico according to presence/absence of a given volatile compound, in this case γ-decalactone, a compound conferring a peach flavor note to fruits. Computationally sorting reads in segregating progeny based on γ-decalactone presence eliminated transcripts not directly relevant to the volatile, revealing transcripts possibly imparting quantitative contributions. One candidate encodes an omega-6 fatty acid desaturase, an enzyme known to participate in lactone production in fungi, noted here as FaFAD1. This candidate was induced by ripening, was detected in certain harvests, and correlated with γ-decalactone presence. The FaFAD1 gene is present in every genotype where γ-decalactone has been detected, and it was invariably missing in non-producers. A functional, PCR-based molecular marker was developed that cosegregates with the phenotype in F1 and BC1 populations, as well as in many other cultivars and wild Fragaria accessions. Genetic, genomic and analytical chemistry techniques were combined to identify FaFAD1, a gene likely controlling a key flavor volatile in strawberry. The same data may now be re-sorted based on presence/absence of any other volatile to identify other flavor-affecting candidates, leading to rapid generation of gene-specific markers.

  10. A statistical multiprobe model for analyzing cis and trans genes in genetical genomics experiments with short-oligonucleotide arrays

    NARCIS (Netherlands)

    Alberts, Rudi; Terpstra, Peter; Bystrykh, Leonid V.; Haan, Gerald de; Jansen, Ritsert C.

    2005-01-01

    Short-oligonucleotide arrays typically contain multiple probes per gene. In genetical genomics applications a statistical model for the individual probe signals can help in separating ‘‘true’’ differential mRNA expression from ‘‘ghost’’ effects caused by polymorphisms, misdesigned probes, and batch

  11. Brief Guide to Genomics: DNA, Genes and Genomes

    Science.gov (United States)

    ... Breve guía de genómica A Brief Guide to Genomics DNA, Genes and Genomes Deoxyribonucleic acid (DNA) is ... genetic basis for health and disease. Implications of Genomics for Medical Science Virtually every human ailment has ...

  12. Gene set analyses of genome-wide association studies on 49 quantitative traits measured in a single genetic epidemiology dataset.

    Science.gov (United States)

    Kim, Jihye; Kwon, Ji-Sun; Kim, Sangsoo

    2013-09-01

    Gene set analysis is a powerful tool for interpreting a genome-wide association study result and is gaining popularity these days. Comparison of the gene sets obtained for a variety of traits measured from a single genetic epidemiology dataset may give insights into the biological mechanisms underlying these traits. Based on the previously published single nucleotide polymorphism (SNP) genotype data on 8,842 individuals enrolled in the Korea Association Resource project, we performed a series of systematic genome-wide association analyses for 49 quantitative traits of basic epidemiological, anthropometric, or blood chemistry parameters. Each analysis result was subjected to subsequent gene set analyses based on Gene Ontology (GO) terms using gene set analysis software, GSA-SNP, identifying a set of GO terms significantly associated to each trait (pcorr neuronal or nerve systems.

  13. Genetics and Genomics

    Science.gov (United States)

    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...

  14. Identification of a strawberry flavor gene candidate using an integrated genetic-genomic-analytical chemistry approach

    Science.gov (United States)

    Background: There is interest in improving the flavor of commercial strawberry (Fragaria × ananassa) varieties. Fruit flavor is shaped by combinations of sugars, acids and volatile compounds. Many efforts seek to use genomics-based strategies to identify genes controlling flavor, and then designing ...

  15. Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in beta-Catenin-Active Cancers | Office of Cancer Genomics

    Science.gov (United States)

    Genome-scale expression studies and comprehensive loss-of-function genetic screens have focused almost exclusively on the highest confidence candidate genes. Here, we describe a strategy for characterizing the lower confidence candidates identified by such approaches.

  16. Gene arrangement convergence, diverse intron content, and genetic code modifications in mitochondrial genomes of sphaeropleales (chlorophyta).

    Science.gov (United States)

    Fučíková, Karolina; Lewis, Paul O; González-Halphen, Diego; Lewis, Louise A

    2014-08-08

    The majority of our knowledge about mitochondrial genomes of Viridiplantae comes from land plants, but much less is known about their green algal relatives. In the green algal order Sphaeropleales (Chlorophyta), only one representative mitochondrial genome is currently available-that of Acutodesmus obliquus. Our study adds nine completely sequenced and three partially sequenced mitochondrial genomes spanning the phylogenetic diversity of Sphaeropleales. We show not only a size range of 25-53 kb and variation in intron content (0-11) and gene order but also conservation of 13 core respiratory genes and fragmented ribosomal RNA genes. We also report an unusual case of gene arrangement convergence in Neochloris aquatica, where the two rns fragments were secondarily placed in close proximity. Finally, we report the unprecedented usage of UCG as stop codon in Pseudomuriella schumacherensis. In addition, phylogenetic analyses of the mitochondrial protein-coding genes yield a fully resolved, well-supported phylogeny, showing promise for addressing systematic challenges in green algae. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Quantitative Trait Locus and Genetical Genomics Analysis Identifies Putatively Causal Genes for Fecundity and Brooding in the Chicken

    Directory of Open Access Journals (Sweden)

    Martin Johnsson

    2016-02-01

    Full Text Available Life history traits such as fecundity are important to evolution because they make up components of lifetime fitness. Due to their polygenic architectures, such traits are difficult to investigate with genetic mapping. Therefore, little is known about their molecular basis. One possible way toward finding the underlying genes is to map intermediary molecular phenotypes, such as gene expression traits. We set out to map candidate quantitative trait genes for egg fecundity in the chicken by combining quantitative trait locus mapping in an advanced intercross of wild by domestic chickens with expression quantitative trait locus mapping in the same birds. We measured individual egg fecundity in 232 intercross chickens in two consecutive trials, the second one aimed at measuring brooding. We found 12 loci for different aspects of egg fecundity. We then combined the genomic confidence intervals of these loci with expression quantitative trait loci from bone and hypothalamus in the same intercross. Overlaps between egg loci and expression loci, and trait–gene expression correlations identify 29 candidates from bone and five from hypothalamus. The candidate quantitative trait genes include fibroblast growth factor 1, and mitochondrial ribosomal proteins L42 and L32. In summary, we found putative quantitative trait genes for egg traits in the chicken that may have been affected by regulatory variants under chicken domestication. These represent, to the best of our knowledge, some of the first candidate genes identified by genome-wide mapping for life history traits in an avian species.

  18. Quantitative Trait Locus and Genetical Genomics Analysis Identifies Putatively Causal Genes for Fecundity and Brooding in the Chicken.

    Science.gov (United States)

    Johnsson, Martin; Jonsson, Kenneth B; Andersson, Leif; Jensen, Per; Wright, Dominic

    2015-12-04

    Life history traits such as fecundity are important to evolution because they make up components of lifetime fitness. Due to their polygenic architectures, such traits are difficult to investigate with genetic mapping. Therefore, little is known about their molecular basis. One possible way toward finding the underlying genes is to map intermediary molecular phenotypes, such as gene expression traits. We set out to map candidate quantitative trait genes for egg fecundity in the chicken by combining quantitative trait locus mapping in an advanced intercross of wild by domestic chickens with expression quantitative trait locus mapping in the same birds. We measured individual egg fecundity in 232 intercross chickens in two consecutive trials, the second one aimed at measuring brooding. We found 12 loci for different aspects of egg fecundity. We then combined the genomic confidence intervals of these loci with expression quantitative trait loci from bone and hypothalamus in the same intercross. Overlaps between egg loci and expression loci, and trait-gene expression correlations identify 29 candidates from bone and five from hypothalamus. The candidate quantitative trait genes include fibroblast growth factor 1, and mitochondrial ribosomal proteins L42 and L32. In summary, we found putative quantitative trait genes for egg traits in the chicken that may have been affected by regulatory variants under chicken domestication. These represent, to the best of our knowledge, some of the first candidate genes identified by genome-wide mapping for life history traits in an avian species.

  19. The mouse genome displays highly dynamic populations of KRAB-zinc finger protein genes and related genetic units.

    Science.gov (United States)

    Kauzlaric, Annamaria; Ecco, Gabriela; Cassano, Marco; Duc, Julien; Imbeault, Michael; Trono, Didier

    2017-01-01

    KRAB-containing poly-zinc finger proteins (KZFPs) constitute the largest family of transcription factors encoded by mammalian genomes, and growing evidence indicates that they fulfill functions critical to both embryonic development and maintenance of adult homeostasis. KZFP genes underwent broad and independent waves of expansion in many higher vertebrates lineages, yet comprehensive studies of members harbored by a given species are scarce. Here we present a thorough analysis of KZFP genes and related units in the murine genome. We first identified about twice as many elements than previously annotated as either KZFP genes or pseudogenes, notably by assigning to this family an entity formerly considered as a large group of Satellite repeats. We then could delineate an organization in clusters distributed throughout the genome, with signs of recombination, translocation, duplication and seeding of new sites by retrotransposition of KZFP genes and related genetic units (KZFP/rGUs). Moreover, we harvested evidence indicating that closely related paralogs had evolved through both drifting and shifting of sequences encoding for zinc finger arrays. Finally, we could demonstrate that the KAP1-SETDB1 repressor complex tames the expression of KZFP/rGUs within clusters, yet that the primary targets of this regulation are not the KZFP/rGUs themselves but enhancers contained in neighboring endogenous retroelements and that, underneath, KZFPs conserve highly individualized patterns of expression.

  20. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

    Science.gov (United States)

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.

  1. Genetic screening of new genes responsible for cellular adaptation to hypoxia using a genome-wide shRNA library.

    Science.gov (United States)

    Yoshino, Seiko; Hara, Toshiro; Weng, Jane S; Takahashi, Yuka; Seiki, Motoharu; Sakamoto, Takeharu

    2012-01-01

    Oxygen is a vital requirement for multi-cellular organisms to generate energy and cells have developed multiple compensatory mechanisms to adapt to stressful hypoxic conditions. Such adaptive mechanisms are intricately interconnected with other signaling pathways that regulate cellular functions such as cell growth. However, our understanding of the overall system governing the cellular response to the availability of oxygen remains limited. To identify new genes involved in the response to hypoxic stress, we have performed a genome-wide gene knockdown analysis in human lung carcinoma PC8 cells using an shRNA library carried by a lentiviral vector. The knockdown analysis was performed under both normoxic and hypoxic conditions to identify shRNA sequences enriched or lost in the resulting selected cell populations. Consequently, we identified 56 candidate genes that might contribute to the cellular response to hypoxia. Subsequent individual knockdown of each gene demonstrated that 13 of these have a significant effect upon oxygen-sensitive cell growth. The identification of BCL2L1, which encodes a Bcl-2 family protein that plays a role in cell survival by preventing apoptosis, validates the successful design of our screen. The other selected genes have not previously been directly implicated in the cellular response to hypoxia. Interestingly, hypoxia did not directly enhance the expression of any of the identified genes, suggesting that we have identified a new class of genes that have been missed by conventional gene expression analyses to identify hypoxia response genes. Thus, our genetic screening method using a genome-wide shRNA library and the newly-identified genes represent useful tools to analyze the cellular systems that respond to hypoxic stress.

  2. Molecular Genetics of Charcot-Marie-Tooth Disease: From Genes to Genomes

    Science.gov (United States)

    Azzedine, H.; Senderek, J.; Rivolta, C.; Chrast, R.

    2012-01-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders of the peripheral nervous system, mainly characterized by distal muscle weakness and atrophy leading to motor handicap. With an estimated prevalence of 1 in 2,500, this condition is one of the most commonly inherited neurological disorders. Mutations in more than 30 genes affecting glial and/or neuronal functions have been associated with different forms of CMT leading to a substantial improvement in diagnostics of the disease and in the understanding of implicated pathophysiological mechanisms. However, recent data from systematic genetic screening performed in large cohorts of CMT patients indicated that molecular diagnosis could be established only in ∼50–70% of them, suggesting that additional genes are involved in this disease. In addition to providing an overview of genetic and functional data concerning various CMT forms, this review focuses on recent data generated through the use of highly parallel genetic technologies (SNP chips, sequence capture and next-generation DNA sequencing) in CMT families, and the current and future impact of these technologies on gene discovery and diagnostics of CMTs. PMID:23293578

  3. 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

  4. A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches

    Science.gov (United States)

    Bartolomé, Nerea; Segarra, Sergi; Artieda, Marta; Francino, Olga; Sánchez, Elisenda; Szczypiorska, Magdalena; Casellas, Joaquim; Tejedor, Diego; Cerdeira, Joaquín; Martínez, Antonio; Velasco, Alfonso; Sánchez, Armand

    2015-01-01

    Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors’ opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds. PMID:25874693

  5. A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS and candidate gene approaches.

    Directory of Open Access Journals (Sweden)

    Nerea Bartolomé

    Full Text Available Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B and case (D/E. C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85 and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.

  6. A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS) and candidate gene approaches.

    Science.gov (United States)

    Bartolomé, Nerea; Segarra, Sergi; Artieda, Marta; Francino, Olga; Sánchez, Elisenda; Szczypiorska, Magdalena; Casellas, Joaquim; Tejedor, Diego; Cerdeira, Joaquín; Martínez, Antonio; Velasco, Alfonso; Sánchez, Armand

    2015-01-01

    Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.

  7. 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.

  8. Genomic analysis of Meckel-Gruber syndrome in Arabs reveals marked genetic heterogeneity and novel candidate genes.

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Alshammari, Muneera J; Swaid, Abdulrahman; Al-Gazali, Lihadh; Mardawi, Elham; Ansari, Shinu; Sogaty, Sameera; Seidahmed, Mohammed Z; AlMotairi, Muhammed I; Farra, Chantal; Kurdi, Wesam; Al-Rasheed, Shatha; Alkuraya, Fowzan S

    2013-07-01

    Meckel-Gruber syndrome (MKS, OMIM #249000) is a multiple congenital malformation syndrome that represents the severe end of the ciliopathy phenotypic spectrum. Despite the relatively common occurrence of this syndrome among Arabs, little is known about its genetic architecture in this population. This is a series of 18 Arab families with MKS, who were evaluated clinically and studied using autozygome-guided mutation analysis and exome sequencing. We show that autozygome-guided candidate gene analysis identified the underlying mutation in the majority (n=12, 71%). Exome sequencing revealed a likely pathogenic mutation in three novel candidate MKS disease genes. These include C5orf42, Ellis-van-Creveld disease gene EVC2 and SEC8 (also known as EXOC4), which encodes an exocyst protein with an established role in ciliogenesis. This is the largest and most comprehensive genomic study on MKS in Arabs and the results, in addition to revealing genetic and allelic heterogeneity, suggest that previously reported disease genes and the novel candidates uncovered by this study account for the overwhelming majority of MKS patients in our population.

  9. Genomic analysis of Meckel–Gruber syndrome in Arabs reveals marked genetic heterogeneity and novel candidate genes

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Alshammari, Muneera J; Swaid, Abdulrahman; Al-Gazali, Lihadh; Mardawi, Elham; Ansari, Shinu; Sogaty, Sameera; Seidahmed, Mohammed Z; AlMotairi, Muhammed I; Farra, Chantal; Kurdi, Wesam; Al-Rasheed, Shatha; Alkuraya, Fowzan S

    2013-01-01

    Meckel–Gruber syndrome (MKS, OMIM #249000) is a multiple congenital malformation syndrome that represents the severe end of the ciliopathy phenotypic spectrum. Despite the relatively common occurrence of this syndrome among Arabs, little is known about its genetic architecture in this population. This is a series of 18 Arab families with MKS, who were evaluated clinically and studied using autozygome-guided mutation analysis and exome sequencing. We show that autozygome-guided candidate gene analysis identified the underlying mutation in the majority (n=12, 71%). Exome sequencing revealed a likely pathogenic mutation in three novel candidate MKS disease genes. These include C5orf42, Ellis–van-Creveld disease gene EVC2 and SEC8 (also known as EXOC4), which encodes an exocyst protein with an established role in ciliogenesis. This is the largest and most comprehensive genomic study on MKS in Arabs and the results, in addition to revealing genetic and allelic heterogeneity, suggest that previously reported disease genes and the novel candidates uncovered by this study account for the overwhelming majority of MKS patients in our population. PMID:23169490

  10. A genome-wide search for genes involved in type 2 diabetes in a recently genetically isolated population from the Netherlands

    NARCIS (Netherlands)

    Y.S. Aulchenko (Yurii); N. Vaessen (Norbert); P. Heutink (Peter); J. Pullen (Jan); P.J.L.M. Snijders (Pieter); A. Hofman (Albert); L.A. Sandkuijl (Lodewijk); J.J. Houwing-Duistermaat (Jeanine); S. Bennett (Simon); B.A. Oostra (Ben); C.M. van Duijn (Cock); M. Edwards (Mark)

    2003-01-01

    textabstractMultiple genes, interacting with the environment, contribute to the susceptibility to type 2 diabetes. We performed a genome-wide search to localize type 2 diabetes susceptibility genes in a recently genetically isolated population in the Netherlands. We identified 79 nuclear families wi

  11. An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer Metastasis Susceptibility Genes.

    Directory of Open Access Journals (Sweden)

    Ling Bai

    2016-04-01

    Full Text Available Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways in breast cancer metastasis. This analysis implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease.

  12. 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.

  13. Genetic variation in Micro-RNA genes of host genome affects clinical manifestation of symptomatic Human Cytomegalovirus infection.

    Science.gov (United States)

    Misra, Maneesh Kumar; Mishra, Aditi; Pandey, Shashi Kant; Kapoor, Rakesh; Sharma, Raj Kumar; Agrawal, Suraksha

    2015-10-01

    Micro-RNAs are implicated in various physiological and pathologic processes. In this study, we tested whether Micro-RNA gene variants of host-genome affect clinical manifestation of symptomatic HCMV infection. HCMV infection was detected by fluorescent PCR and immuno-histochemistry. The detection of genetic variants of four studied Micro-RNA tag-SNPs was done through PCR-RFLP assay and validated with DNA sequencing. We observed an increased risk ranged from 3-folds to 5-folds among symptomatic HCMV cases for mutant genotype of rs2910164 (crude OR=3.11, p=0.009 and adjusted OR=3.25, p=0.007), rs11614913 (crude OR=3.20, p=0.006 and adjusted OR=3.48, p=0.004) and rs3746444 (crude OR=4.91, p=0.002 and adjusted OR=5.28, p=0.002) tag-SNPs. Interestingly, all the tag-SNPs that were significant after multiple comparisons at a FDR of 5% in symptomatic HCMV cases remained significant even after bootstrap analysis, providing internal validation to these results. Multifactor Dimensionality Reduction (MDR) analysis revealed 5-folds increased risk for symptomatic HCMV cases under the four-factor model (rs2910164, rs2292832, rs11614913 and rs3746444). These results suggest that Micro-RNA gene variants of host-genome may affect clinical manifestation of symptomatic HCMV infection. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  14. 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.

  15. 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.

  16. Genetic variations related to maternal whole blood mitochondrial DNA copy number: a genome-wide and candidate gene study.

    Science.gov (United States)

    Workalemahu, Tsegaselassie; Enquobahrie, Daniel A; Tadesse, Mahlet G; Hevner, Karin; Gelaye, Bizu; Sanchez, Sixto E; Williams, Michelle A

    2017-10-01

    We conducted genome-wide (GWAS) and candidate gene association studies of maternal mitochondrial DNA copy number. Maternal peripheral blood was collected during labor and delivery admission from 471 participants of a placental abruption case-control study conducted in Lima, Peru. Single nucleotide polymorphism (SNP) genotyping was performed using the Illumina Cardio-Metabo Chip. Whole blood mitochondrial DNA (mtDNA) copy number was measured using qRT-PCR techniques. We evaluated 119,629 SNPs in the GWAS and 161 SNPs (in 29 mitochondrial biogenesis and oxidative phosphorylation genes) in the candidate association study. Top hits from GWAS and the candidate gene study were selected to compute weighted genetic risk scores (wGRS). Linear regression models were used to calculate effect size estimates and related nominal p values. The top hit in our GWAS was chr19:51063065 in FOXA3 (empirical p values = 2.20e - 6). A total of 134 SNPs had p values copy number (p values copy number was significantly associated with wGRS based on top GWAS hits (β = 0.49, 95% CI:0.38-0.60, p copy number.

  17. 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.

  18. Generalised Anxiety Disorder--A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression.

    Directory of Open Access Journals (Sweden)

    Matthew N Davies

    Full Text Available Generalised Anxiety Disorder (GAD is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS, a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS.

  19. Generalised Anxiety Disorder--A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression.

    Science.gov (United States)

    Davies, Matthew N; Verdi, Serena; Burri, Andrea; Trzaskowski, Maciej; Lee, Minyoung; Hettema, John M; Jansen, Rick; Boomsma, Dorret I; Spector, Tim D

    2015-01-01

    Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS.

  20. Remnants of the Legume Ancestral Genome Preserved in Gene-Rich Regions: Insights from Lupinus angustifolius Physical, Genetic, and Comparative Mapping.

    Science.gov (United States)

    Książkiewicz, Michał; Zielezinski, Andrzej; Wyrwa, Katarzyna; Szczepaniak, Anna; Rychel, Sandra; Karlowski, Wojciech; Wolko, Bogdan; Naganowska, Barbara

    The narrow-leafed lupin (Lupinus angustifolius) was recently considered as a legume reference species. Genetic resources have been developed, including a draft genome sequence, linkage maps, nuclear DNA libraries, and cytogenetic chromosome-specific landmarks. Here, we used a complex approach, involving DNA fingerprinting, sequencing, genetic mapping, and molecular cytogenetics, to localize and analyze L. angustifolius gene-rich regions (GRRs). A L. angustifolius genomic bacterial artificial chromosome (BAC) library was screened with short sequence repeat (SSR)-based probes. Selected BACs were fingerprinted and assembled into contigs. BAC-end sequence (BES) annotation allowed us to choose clones for sequencing, targeting GRRs. Additionally, BESs were aligned to the scaffolds of the genome sequence. The genetic map was supplemented with 35 BES-derived markers, distributed in 14 linkage groups and tagging 37 scaffolds. The identified GRRs had an average gene density of 19.6 genes/100 kb and physical-to-genetic distance ratios of 11 to 109 kb/cM. Physical and genetic mapping was supported by multi-BAC-fluorescence in situ hybridization (FISH), and five new linkage groups were assigned to the chromosomes. Syntenic links to the genome sequences of five legume species (Medicago truncatula, Glycine max, Lotus japonicus, Phaseolus vulgaris, and Cajanus cajan) were identified. The comparative mapping of the two largest lupin GRRs provides novel evidence for ancient duplications in all of the studied species. These regions are conserved among representatives of the main clades of Papilionoideae. Furthermore, despite the complex evolution of legumes, some segments of the nuclear genome were not substantially modified and retained their quasi-ancestral structures. Cytogenetic markers anchored in these regions constitute a platform for heterologous mapping of legume genomes.

  1. Application of DETECTER, an evolutionary genomic tool to analyze genetic variation, to the cystic fibrosis gene family

    Directory of Open Access Journals (Sweden)

    De Kee Danny W

    2006-03-01

    Full Text Available Abstract Background The medical community requires computational tools that distinguish missense genetic differences having phenotypic impact within the vast number of sense mutations that do not. Tools that do this will become increasingly important for those seeking to use human genome sequence data to predict disease, make prognoses, and customize therapy to individual patients. Results An approach, termed DETECTER, is proposed to identify sites in a protein sequence where amino acid replacements are likely to have a significant effect on phenotype, including causing genetic disease. This approach uses a model-dependent tool to estimate the normalized replacement rate at individual sites in a protein sequence, based on a history of those sites extracted from an evolutionary analysis of the corresponding protein family. This tool identifies sites that have higher-than-average, average, or lower-than-average rates of change in the lineage leading to the sequence in the population of interest. The rates are then combined with sequence data to determine the likelihoods that particular amino acids were present at individual sites in the evolutionary history of the gene family. These likelihoods are used to predict whether any specific amino acid replacements, if introduced at the site in a modern human population, would have a significant impact on fitness. The DETECTER tool is used to analyze the cystic fibrosis transmembrane conductance regulator (CFTR gene family. Conclusion In this system, DETECTER retrodicts amino acid replacements associated with the cystic fibrosis disease with greater accuracy than alternative approaches. While this result validates this approach for this particular family of proteins only, the approach may be applicable to the analysis of polymorphisms generally, including SNPs in a human population.

  2. Palaeohexaploid ancestry for Caryophyllales inferred from extensive gene-based physical and genetic mapping of the sugar beet genome (Beta vulgaris).

    Science.gov (United States)

    Dohm, Juliane C; Lange, Cornelia; Holtgräwe, Daniela; Sörensen, Thomas Rosleff; Borchardt, Dietrich; Schulz, Britta; Lehrach, Hans; Weisshaar, Bernd; Himmelbauer, Heinz

    2012-05-01

    Sugar beet (Beta vulgaris) is an important crop plant that accounts for 30% of the world's sugar production annually. The genus Beta is a distant relative of currently sequenced taxa within the core eudicotyledons; the genomic characterization of sugar beet is essential to make its genome accessible to molecular dissection. Here, we present comprehensive genomic information in genetic and physical maps that cover all nine chromosomes. Based on this information we identified the proposed ancestral linkage groups of rosids and asterids within the sugar beet genome. We generated an extended genetic map that comprises 1127 single nucleotide polymorphism markers prepared from expressed sequence tags and bacterial artificial chromosome (BAC) end sequences. To construct a genome-wide physical map, we hybridized gene-derived oligomer probes against two BAC libraries with 9.5-fold cumulative coverage of the 758 Mbp genome. More than 2500 probes and clones were integrated both in genetic maps and the physical data. The final physical map encompasses 535 chromosomally anchored contigs that contains 8361 probes and 22 815 BAC clones. By using the gene order established with the physical map, we detected regions of synteny between sugar beet (order Caryophyllales) and rosid species that involves 1400-2700 genes in the sequenced genomes of Arabidopsis, poplar, grapevine, and cacao. The data suggest that Caryophyllales share the palaeohexaploid ancestor proposed for rosids and asterids. Taken together, we here provide extensive molecular resources for sugar beet and enable future high-resolution trait mapping, gene identification, and cross-referencing to regions sequenced in other plant species.

  3. Exploring the gene: Interactive exhibits on genetics and the human genome. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1994-05-01

    Under funding by the United States Department of Energy, the Exploratorium has substantially completed the prototype development of four exhibits on the nature of DNA and genetics, and substantially completed the production of ed exhibits based on these prototypes. Individually these genetic exhibits have been designed to elucidate specific themes, such as, the molecular properties of DNA, the encoding of genetic information, the expression of genetic information, and technological manipulation. The exhibits are titled Dancing DNA, Marching Bands, Protein Production Line, and Genetic Playbook. Specific exhibit projects are detailed below. In all the exhibits we have sought to draw a relationship between the nature of DNA and its expression in organisms. For most visitors, DNA exists as an invisible abstract molecule with marginal connections to their lives, while organisms exist as a familiar tangible entities. Inclusion of this broad thematic connection provides the crucial bridge between the abstract principles and the real world, and serves to underpin scientific, medical, and public interest in the topic.

  4. Genomics of local adaptation with gene flow.

    Science.gov (United States)

    Tigano, Anna; Friesen, Vicki L

    2016-05-01

    Gene flow is a fundamental evolutionary force in adaptation that is especially important to understand as humans are rapidly changing both the natural environment and natural levels of gene flow. Theory proposes a multifaceted role for gene flow in adaptation, but it focuses mainly on the disruptive effect that gene flow has on adaptation when selection is not strong enough to prevent the loss of locally adapted alleles. The role of gene flow in adaptation is now better understood due to the recent development of both genomic models of adaptive evolution and genomic techniques, which both point to the importance of genetic architecture in the origin and maintenance of adaptation with gene flow. In this review, we discuss three main topics on the genomics of adaptation with gene flow. First, we investigate selection on migration and gene flow. Second, we discuss the three potential sources of adaptive variation in relation to the role of gene flow in the origin of adaptation. Third, we explain how local adaptation is maintained despite gene flow: we provide a synthesis of recent genomic models of adaptation, discuss the genomic mechanisms and review empirical studies on the genomics of adaptation with gene flow. Despite predictions on the disruptive effect of gene flow in adaptation, an increasing number of studies show that gene flow can promote adaptation, that local adaptations can be maintained despite high gene flow, and that genetic architecture plays a fundamental role in the origin and maintenance of local adaptation with gene flow.

  5. A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage

    DEFF Research Database (Denmark)

    Andersen, Jannik N; Jansen, Peter G; Echwald, Søren M;

    2004-01-01

    and provide predicted amino acid sequences for four human PTPs that are currently defined by fragments only. Finally, we correlated each PTP locus with genetic disease markers and identified 4 PTPs that map to known susceptibility loci for type 2 diabetes and 19 PTPs that map to regions frequently deleted...

  6. Genetic and genomic dissection of resistance genes to the rice sheath blight pathogen

    Science.gov (United States)

    Rice sheath blight disease caused by the anastomosis group AG1-IA of the fungal pathogen Rhizoctonia solani is one of the most serious rice diseases in the southern US and the world. The use of fungicides is a popular but costly method to control this disease worldwide. Genetic analysis of host re...

  7. Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma.

    Science.gov (United States)

    Zhang, Mingfeng; Liang, Liming; Morar, Nilesh; Dixon, Anna L; Lathrop, G Mark; Ding, Jun; Moffatt, Miriam F; Cookson, William O C; Kraft, Peter; Qureshi, Abrar A; Han, Jiali

    2012-04-01

    Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value <0.05 and false discovery rate (FDR) <0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis.

  8. 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.

  9. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine.

    Science.gov (United States)

    Stenson, Peter D; Mort, Matthew; Ball, Edward V; Shaw, Katy; Phillips, Andrew; Cooper, David N

    2014-01-01

    The Human Gene Mutation Database (HGMD®) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum. HGMD was originally established in 1996 for the scientific study of mutational mechanisms in human genes. However, it has since acquired a much broader utility as a central unified disease-oriented mutation repository utilized by human molecular geneticists, genome scientists, molecular biologists, clinicians and genetic counsellors as well as by those specializing in biopharmaceuticals, bioinformatics and personalized genomics. The public version of HGMD (http://www.hgmd.org) is freely available to registered users from academic institutions/non-profit organizations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via BIOBASE GmbH.

  10. Assembly of the Genome of the Disease Vector Aedes aegypti onto a Genetic Linkage Map Allows Mapping of Genes Affecting Disease Transmission

    KAUST Repository

    Juneja, Punita

    2014-01-30

    The mosquito Aedes aegypti transmits some of the most important human arboviruses, including dengue, yellow fever and chikungunya viruses. It has a large genome containing many repetitive sequences, which has resulted in the genome being poorly assembled - there are 4,758 scaffolds, few of which have been assigned to a chromosome. To allow the mapping of genes affecting disease transmission, we have improved the genome assembly by scoring a large number of SNPs in recombinant progeny from a cross between two strains of Ae. aegypti, and used these to generate a genetic map. This revealed a high rate of misassemblies in the current genome, where, for example, sequences from different chromosomes were found on the same scaffold. Once these were corrected, we were able to assign 60% of the genome sequence to chromosomes and approximately order the scaffolds along the chromosome. We found that there are very large regions of suppressed recombination around the centromeres, which can extend to as much as 47% of the chromosome. To illustrate the utility of this new genome assembly, we mapped a gene that makes Ae. aegypti resistant to the human parasite Brugia malayi, and generated a list of candidate genes that could be affecting the trait. © 2014 Juneja et al.

  11. 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

  12. Comparative genomic analysis of sixty mycobacteriophage genomes: Genome clustering, gene acquisition and gene size

    Science.gov (United States)

    Hatfull, Graham F.; Jacobs-Sera, Deborah; Lawrence, Jeffrey G.; Pope, Welkin H.; Russell, Daniel A.; Ko, Ching-Chung; Weber, Rebecca J.; Patel, Manisha C.; Germane, Katherine L.; Edgar, Robert H.; Hoyte, Natasha N.; Bowman, Charles A.; Tantoco, Anthony T.; Paladin, Elizabeth C.; Myers, Marlana S.; Smith, Alexis L.; Grace, Molly S.; Pham, Thuy T.; O'Brien, Matthew B.; Vogelsberger, Amy M.; Hryckowian, Andrew J.; Wynalek, Jessica L.; Donis-Keller, Helen; Bogel, Matt W.; Peebles, Craig L.; Cresawn, Steve G.; Hendrix, Roger W.

    2010-01-01

    Mycobacteriophages are viruses that infect mycobacterial hosts. Expansion of a collection of sequenced phage genomes to a total of sixty – all infecting a common bacterial host – provides further insight into their diversity and evolution. Of the sixty phage genomes, 55 can be grouped into nine clusters according to their nucleotide sequence similarities, five of which can be further divided into subclusters; five genomes do not cluster with other phages. The sequence diversity between genomes within a cluster varies greatly; for example, the six genomes in cluster D share more than 97.5% average nucleotide similarity with each other. In contrast, similarity between the two genomes in Cluster I is barely detectable by diagonal plot analysis. The total of 6,858 predicted ORFs have been grouped into 1523 phamilies (phams) of related sequences, 46% of which possess only a single member. Only 18.8% of the phams have sequence similarity to non-mycobacteriophage database entries and fewer than 10% of all phams can be assigned functions based on database searching or synteny. Genome clustering facilitates the identification of genes that are in greatest genetic flux and are more likely to have been exchanged horizontally in relatively recent evolutionary time. Although mycobacteriophage genes exhibit smaller average size than genes of their host (205 residues compared to 315), phage genes in higher flux average only ∼100 amino acids, suggesting that the primary units of genetic exchange correspond to single protein domains. PMID:20064525

  13. 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.

  14. Application of DETECTER, an evolutionary genomic tool to analyze genetic variation, to the cystic fibrosis gene family

    OpenAIRE

    2006-01-01

    Abstract Background The medical community requires computational tools that distinguish missense genetic differences having phenotypic impact within the vast number of sense mutations that do not. Tools that do this will become increasingly important for those seeking to use human genome sequence data to predict disease, make prognoses, and customize therapy to individual patients. Results An approach, termed DETECTER, is proposed to identify sites in a protein sequence where amino acid repla...

  15. Identification of candidate genes for drought stress tolerance in rice by the integration of a genetic (QTL) map with the rice genome physical map

    Institute of Scientific and Technical Information of China (English)

    WANG Xu-sheng; ZHU Jun; MANSUETO Locedie; BRUSKIEWICH Richard

    2005-01-01

    Genetic improvement for drought stress tolerance in rice involves the quantitative nature of the trait, which reflects the additive effects of several genetic loci throughout the genome. Yield components and related traits under stressed and well-water conditions were assayed in mapping populations derived from crosses of Azucena×IR64 and Azucena×Bala. To find the candidate rice genes underlying Quantitative Trait Loci (QTL) in these populations, we conducted in silico analysis of a candidate region flanked by the genetic markers RM212 and RM319on chromosome 1, proximal to the semi-dwarf (sd1) locus. A total of 175annotated genes were identified from this region. These included 48 genes annotated by functional homology to known genes, 23pseudogenes, 24 ab initio predicted genes supported by an alignment match to an EST (Expressed sequence tag) of unknown function, and 80 hypothetical genes predicted solely by ab initio means. Among these, 16 candidate genes could potentially be involved in drought stress response.

  16. Genetics, genomics and fertility

    Science.gov (United States)

    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...

  17. Genome-wide linkage scan identifies two novel genetic loci for coronary artery disease: in GeneQuest families.

    Science.gov (United States)

    Gao, Hanxiang; Li, Lin; Rao, Shaoqi; Shen, Gongqing; Xi, Quansheng; Chen, Shenghan; Zhang, Zheng; Wang, Kai; Ellis, Stephen G; Chen, Qiuyun; Topol, Eric J; Wang, Qing K

    2014-01-01

    Coronary artery disease (CAD) is the leading cause of death worldwide. Recent genome-wide association studies (GWAS) identified >50 common variants associated with CAD or its complication myocardial infarction (MI), but collectively they account for missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL) analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49) and 3q29 (NPL  = 6.84). We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07). These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

  18. Genetics of hybrid inviability and sterility in Drosophila: dissection of introgression of D. simulans genes in D. melanogaster genome.

    Science.gov (United States)

    Sawamura, Kyoichi; Karr, Timothy L; Yamamoto, Masa-Toshi

    2004-03-01

    Interspecific crosses between Drosophila melanogaster and Drosophila simulans usually produce sterile unisexual hybrids. The barrier preventing genetic analysis of hybrid inviability and sterility has been taken away by the discovery of a D. simulans strain which produces fertile female hybrids. D. simulans genes in the cytological locations of 21A1 to 22C1-23B1 and 30F3-31C5 to 36A2-7 have been introgressed into the D. melanogaster genetic background by consecutive backcrosses. Flies heterozygous for the introgression are fertile, while homozygotes are sterile both in females and males. The genes responsible for the sterility have been mapped in the introgression. The male sterility is caused by the synergistic effect of multiple genes, while the female sterility genes have been localized to a 170 kb region (32D2 to 32E4) containing 20 open reading frames. Thus, the female sterility might be attributed to a single gene with a large effect. We have also found that the Lethal hybrid rescue mutation which prevents the inviability of male hybrids from the cross of D. melanogaster females and D. simulans males cannot rescue those carrying the introgression, suggesting that D. simulans genes maybe non-functional in this hybrid genotype. The genes responsible for the inviability have not been separated from the female sterility genes by recombination.

  19. Gene conversion in the rice genome

    DEFF Research Database (Denmark)

    Xu, Shuqing; Clark, Terry; Zheng, Hongkun;

    2008-01-01

    BACKGROUND: Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes...... is not tightly linked to natural selection in the rice genome. To assess the contribution of segmental duplication on gene conversion statistics, we determined locations of conversion partners with respect to inter-chromosomal segment duplication. The number of conversions associated with segmentation is less...

  20. 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.

  1. 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

  2. Influence of Genetic Variants in EGF and Other Genes on Hematological Traits in Korean Populations by a Genome-Wide Approach

    Directory of Open Access Journals (Sweden)

    Yun Kyoung Kim

    2015-01-01

    Full Text Available Hematological traits are important health indicators and are used as diagnostic clinical parameters for human disorders. Recently, genome-wide association studies (GWAS identified many genetic loci associated with hematological traits in diverse ethnic groups. However, additional GWAS are necessary to elucidate the breadth of genetic variation and the underlying genetic architecture represented by hematological metrics. To identify additional genetic loci influencing hematological traits (such as hematocrit, hemoglobin concentration, white blood cell count, red blood cell count, and platelet count, we conducted GWAS and meta-analyses on data from 12,509 Korean individuals grouped into population-based cohorts. Of interest is EGF, a factor plays a role in the proliferation and differentiation of hematopoietic progenitor cells. We identified a novel EGF variant, which associated with platelet count in our study (Pcombined=2.44×10-15. Our study also replicated 16 genetic associations related to five hematological traits with genome-wide significance (P<5×10-8 that were previously established in other ethnic groups. Of these, variants influencing platelet count are distributed across several genes and have pleiotropic effects in coronary artery disease and dyslipidemia. Our findings may aid in elucidating molecular mechanisms underlying not only hematopoiesis but also inflammatory and cardiovascular diseases.

  3. Genetically based location from triploid populations and gene ontology of a 3.3-mb genome region linked to Alternaria brown spot resistance in citrus reveal clusters of resistance genes.

    Directory of Open Access Journals (Sweden)

    José Cuenca

    Full Text Available Genetic analysis of phenotypical traits and marker-trait association in polyploid species is generally considered as a challenge. In the present work, different approaches were combined taking advantage of the particular genetic structures of 2n gametes resulting from second division restitution (SDR to map a genome region linked to Alternaria brown spot (ABS resistance in triploid citrus progeny. ABS in citrus is a serious disease caused by the tangerine pathotype of the fungus Alternaria alternata. This pathogen produces ACT-toxin, which induces necrotic lesions on fruit and young leaves, defoliation and fruit drop in susceptible genotypes. It is a strong concern for triploid breeding programs aiming to produce seedless mandarin cultivars. The monolocus dominant inheritance of susceptibility, proposed on the basis of diploid population studies, was corroborated in triploid progeny. Bulk segregant analysis coupled with genome scan using a large set of genetically mapped SNP markers and targeted genetic mapping by half tetrad analysis, using SSR and SNP markers, allowed locating a 3.3 Mb genomic region linked to ABS resistance near the centromere of chromosome III. Clusters of resistance genes were identified by gene ontology analysis of this genomic region. Some of these genes are good candidates to control the dominant susceptibility to the ACT-toxin. SSR and SNP markers were developed for efficient early marker-assisted selection of ABS resistant hybrids.

  4. Genetically based location from triploid populations and gene ontology of a 3.3-mb genome region linked to Alternaria brown spot resistance in citrus reveal clusters of resistance genes.

    Science.gov (United States)

    Cuenca, José; Aleza, Pablo; Vicent, Antonio; Brunel, Dominique; Ollitrault, Patrick; Navarro, Luis

    2013-01-01

    Genetic analysis of phenotypical traits and marker-trait association in polyploid species is generally considered as a challenge. In the present work, different approaches were combined taking advantage of the particular genetic structures of 2n gametes resulting from second division restitution (SDR) to map a genome region linked to Alternaria brown spot (ABS) resistance in triploid citrus progeny. ABS in citrus is a serious disease caused by the tangerine pathotype of the fungus Alternaria alternata. This pathogen produces ACT-toxin, which induces necrotic lesions on fruit and young leaves, defoliation and fruit drop in susceptible genotypes. It is a strong concern for triploid breeding programs aiming to produce seedless mandarin cultivars. The monolocus dominant inheritance of susceptibility, proposed on the basis of diploid population studies, was corroborated in triploid progeny. Bulk segregant analysis coupled with genome scan using a large set of genetically mapped SNP markers and targeted genetic mapping by half tetrad analysis, using SSR and SNP markers, allowed locating a 3.3 Mb genomic region linked to ABS resistance near the centromere of chromosome III. Clusters of resistance genes were identified by gene ontology analysis of this genomic region. Some of these genes are good candidates to control the dominant susceptibility to the ACT-toxin. SSR and SNP markers were developed for efficient early marker-assisted selection of ABS resistant hybrids.

  5. Genetically Based Location from Triploid Populations and Gene Ontology of a 3.3-Mb Genome Region Linked to Alternaria Brown Spot Resistance in Citrus Reveal Clusters of Resistance Genes

    Science.gov (United States)

    Cuenca, José; Aleza, Pablo; Vicent, Antonio; Brunel, Dominique; Ollitrault, Patrick; Navarro, Luis

    2013-01-01

    Genetic analysis of phenotypical traits and marker-trait association in polyploid species is generally considered as a challenge. In the present work, different approaches were combined taking advantage of the particular genetic structures of 2n gametes resulting from second division restitution (SDR) to map a genome region linked to Alternaria brown spot (ABS) resistance in triploid citrus progeny. ABS in citrus is a serious disease caused by the tangerine pathotype of the fungus Alternaria alternata. This pathogen produces ACT-toxin, which induces necrotic lesions on fruit and young leaves, defoliation and fruit drop in susceptible genotypes. It is a strong concern for triploid breeding programs aiming to produce seedless mandarin cultivars. The monolocus dominant inheritance of susceptibility, proposed on the basis of diploid population studies, was corroborated in triploid progeny. Bulk segregant analysis coupled with genome scan using a large set of genetically mapped SNP markers and targeted genetic mapping by half tetrad analysis, using SSR and SNP markers, allowed locating a 3.3 Mb genomic region linked to ABS resistance near the centromere of chromosome III. Clusters of resistance genes were identified by gene ontology analysis of this genomic region. Some of these genes are good candidates to control the dominant susceptibility to the ACT-toxin. SSR and SNP markers were developed for efficient early marker-assisted selection of ABS resistant hybrids. PMID:24116149

  6. Gene set analysis for interpreting genetic studies

    DEFF Research Database (Denmark)

    Pers, Tune H

    2016-01-01

    Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways and func......Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...

  7. Genome-wide linkage scan identifies two novel genetic loci for coronary artery disease: in GeneQuest families.

    Directory of Open Access Journals (Sweden)

    Hanxiang Gao

    Full Text Available Coronary artery disease (CAD is the leading cause of death worldwide. Recent genome-wide association studies (GWAS identified >50 common variants associated with CAD or its complication myocardial infarction (MI, but collectively they account for <20% of heritability, generating a phenomena of "missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49 and 3q29 (NPL  = 6.84. We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07. These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

  8. The genomes of closely related Pantoea ananatis maize seed endophytes having different effects on the host plant differ in secretion system genes and mobile genetic elements.

    Science.gov (United States)

    Sheibani-Tezerji, Raheleh; Naveed, Muhammad; Jehl, Marc-André; Sessitsch, Angela; Rattei, Thomas; Mitter, Birgit

    2015-01-01

    The seed as a habitat for microorganisms is as yet under-explored and has quite distinct characteristics as compared to other vegetative plant tissues. In this study, we investigated three closely related P. ananatis strains (named S6, S7, and S8), which were isolated from maize seeds of healthy plants. Plant inoculation experiments revealed that each of these strains exhibited a different phenotype ranging from weak pathogenic (S7), commensal (S8), to a beneficial, growth-promoting effect (S6) in maize. We performed a comparative genomics analysis in order to find genetic determinants responsible for the differences observed. Recent studies provided exciting insight into the genetic drivers of niche adaption and functional diversification of the genus Pantoea. However, we report here for the first time on the analysis of P. ananatis strains colonizing the same ecological niche but showing distinct interaction strategies with the host plant. Our comparative analysis revealed that genomes of these three strains are highly similar. However, genomic differences in genes encoding protein secretion systems and putative effectors, and transposase/integrases/phage related genes could be observed.

  9. The genomes of closely related Pantoea ananatis maize seed endophytes having different effects on the host plant differ in secretion system genes and mobile genetic elements

    Directory of Open Access Journals (Sweden)

    Raheleh eSheibani-Tezerji

    2015-05-01

    Full Text Available The seed as a habitat for microorganisms is as yet under-explored and has quite distinct characteristics as compared to other vegetative plant tissues. In this study, we investigated three closely related P. ananatis strains (named S6, S7 and S8, which were isolated from maize seeds of healthy plants. Plant inoculation experiments revealed that each of these strains exhibited a different phenotype ranging from weak pathogenic (S7, commensal (S8, to a beneficial, growth-promoting effect (S6 in maize. We performed a comparative genomics analysis in order to find genetic determinants responsible for the differences observed. Recent studies provided exciting insight into the genetic drivers of niche adaption and functional diversification of the genus Pantoea. However, we report here for the first time on the analysis of P. ananatis strains colonizing the same ecological niche but showing distinct interaction strategies with the host plant. Our comparative analysis revealed that genomes of these three strains are highly similar. However, genomic differences in genes encoding protein secretion systems and putative effectors, and transposase/integrases/phage related genes could be observed.

  10. Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.

    Directory of Open Access Journals (Sweden)

    Maxime Rotival

    2011-12-01

    Full Text Available One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739, previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1 is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178, which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644 was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the

  11. From QTL to candidate gene: Genetical genomics of simple and complex traits in potato using a pooling strategy

    Directory of Open Access Journals (Sweden)

    de Vos Ric

    2010-03-01

    Full Text Available Abstract Background Utilization of the natural genetic variation in traditional breeding programs remains a major challenge in crop plants. The identification of candidate genes underlying, or associated with, phenotypic trait QTLs is desired for effective marker assisted breeding. With the advent of high throughput -omics technologies, screening of entire populations for association of gene expression with targeted traits is becoming feasible but remains costly. Here we present the identification of novel candidate genes for different potato tuber quality traits by employing a pooling approach reducing the number of hybridizations needed. Extreme genotypes for a quantitative trait are collected and the RNA from contrasting bulks is then profiled with the aim of finding differentially expressed genes. Results We have successfully implemented the pooling strategy for potato quality traits and identified candidate genes associated with potato tuber flesh color and tuber cooking type. Elevated expression level of a dominant allele of the β-carotene hydroxylase (bch gene was associated with yellow flesh color through mapping of the gene under a major QTL for flesh color on chromosome 3. For a second trait, a candidate gene with homology to a tyrosine-lysine rich protein (TLRP was identified based on allele specificity of the probe on the microarray. TLRP was mapped on chromosome 9 in close proximity to a QTL for potato cooking type strengthening its significance as a candidate gene. Furthermore, we have performed a profiling experiment targeting a polygenic trait, by pooling individual genotypes based both on phenotypic and marker data, allowing the identification of candidate genes associated with the two different linkage groups. Conclusions A pooling approach for RNA-profiling with the aim of identifying novel candidate genes associated with tuber quality traits was successfully implemented. The identified candidate genes for tuber flesh color

  12. Differential Cotton leaf crumple virus-VIGS-mediated gene silencing and viral genome localization in different Gossypium hirsutum genetic backgrounds

    KAUST Repository

    Idris, Ali

    2010-12-01

    A Cotton leaf crumple virus (CLCrV)-based gene silencing vector containing a fragment of the Gossypium hirsutum Magnesium chelatase subunit I was used to establish endogenous gene silencing in cotton of varied genetic backgrounds. Biolistic inoculation resulted in systemic and persistent photo-bleaching of the leaves and bolls of the seven cultivars tested, however, the intensity of silencing was variable. CLCrV-VIGS-mediated expression of green fluorescent protein was used to monitor the in planta distribution of the vector, indicating successful phloem invasion in all cultivars tested. Acala SJ-1, one of the cotton cultivars, was identified as a particularly optimal candidate for CLCrV-VIGS-based cotton reverse-genetics. © 2010 Elsevier Ltd.

  13. 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...

  14. 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...

  15. GeneEd -- A Genetics Educational Resource

    Science.gov (United States)

    ... Javascript on. Feature: Genetics 101 GeneEd — A Genetics Educational Resource Past Issues / Summer 2013 Table of Contents Science ... The Hereditary Material of Life / GeneEd — A Genetics Educational Resource / Using The Genetics Home Reference Website / Understanding the ...

  16. 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.

  17. Combination of genomic approaches with functional genetic experiments reveals two modes of repression of yeast middle-phase meiosis genes

    Science.gov (United States)

    2010-01-01

    Background Regulation of meiosis and sporulation in Saccharomyces cerevisiae is a model for a highly regulated developmental process. Meiosis middle phase transcriptional regulation is governed by two transcription factors: the activator Ndt80 and the repressor Sum1. It has been suggested that the competition between Ndt80 and Sum1 determines the temporal expression of their targets during middle meiosis. Results Using a combination of ChIP-on-chip and expression profiling, we characterized a middle phase transcriptional network and studied the relationship between Ndt80 and Sum1 during middle and late meiosis. While finding a group of genes regulated by both factors in a feed forward loop regulatory motif, our data also revealed a large group of genes regulated solely by Ndt80. Measuring the expression of all Ndt80 target genes in various genetic backgrounds (WT, sum1Δ and MK-ER-Ndt80 strains), allowed us to dissect the exact transcriptional network regulating each gene, which was frequently different than the one inferred from the binding data alone. Conclusion These results highlight the need to perform detailed genetic experiments to determine the relative contribution of interactions in transcriptional regulatory networks. PMID:20716365

  18. The molecular genetic linkage map of the model legume Medicago truncatula: an essential tool for comparative legume genomics and the isolation of agronomically important genes

    Directory of Open Access Journals (Sweden)

    Ané Jean-Michel

    2002-01-01

    Full Text Available Abstract Background The legume Medicago truncatula has emerged as a model plant for the molecular and genetic dissection of various plant processes involved in rhizobial, mycorrhizal and pathogenic plant-microbe interactions. Aiming to develop essential tools for such genetic approaches, we have established the first genetic map of this species. Two parental homozygous lines were selected from the cultivar Jemalong and from the Algerian natural population (DZA315 on the basis of their molecular and phenotypic polymorphism. Results An F2 segregating population of 124 individuals between these two lines was obtained using an efficient manual crossing technique established for M. truncatula and was used to construct a genetic map. This map spans 1225 cM (average 470 kb/cM and comprises 289 markers including RAPD, AFLP, known genes and isoenzymes arranged in 8 linkage groups (2n = 16. Markers are uniformly distributed throughout the map and segregation distortion is limited to only 3 linkage groups. By mapping a number of common markers, the eight linkage groups are shown to be homologous to those of diploid alfalfa (M. sativa, implying a good level of macrosynteny between the two genomes. Using this M. truncatula map and the derived F3 populations, we were able to map the Mtsym6 symbiotic gene on linkage group 8 and the SPC gene, responsible for the direction of pod coiling, on linkage group 7. Conclusions These results demonstrate that Medicago truncatula is amenable to diploid genetic analysis and they open the way to map-based cloning of symbiotic or other agronomically-important genes using this model plant.

  19. 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.

  20. An RNA Phage Lab: MS2 in Walter Fiers' laboratory of molecular biology in Ghent, from genetic code to gene and genome, 1963-1976.

    Science.gov (United States)

    Pierrel, Jérôme

    2012-01-01

    The importance of viruses as model organisms is well-established in molecular biology and Max Delbrück's phage group set standards in the DNA phage field. In this paper, I argue that RNA phages, discovered in the 1960s, were also instrumental in the making of molecular biology. As part of experimental systems, RNA phages stood for messenger RNA (mRNA), genes and genome. RNA was thought to mediate information transfers between DNA and proteins. Furthermore, RNA was more manageable at the bench than DNA due to the availability of specific RNases, enzymes used as chemical tools to analyse RNA. Finally, RNA phages provided scientists with a pure source of mRNA to investigate the genetic code, genes and even a genome sequence. This paper focuses on Walter Fiers' laboratory at Ghent University (Belgium) and their work on the RNA phage MS2. When setting up his Laboratory of Molecular Biology, Fiers planned a comprehensive study of the virus with a strong emphasis on the issue of structure. In his lab, RNA sequencing, now a little-known technique, evolved gradually from a means to solve the genetic code, to a tool for completing the first genome sequence. Thus, I follow the research pathway of Fiers and his 'RNA phage lab' with their evolving experimental system from 1960 to the late 1970s. This study illuminates two decisive shifts in post-war biology: the emergence of molecular biology as a discipline in the 1960s in Europe and of genomics in the 1990s.

  1. Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

    Directory of Open Access Journals (Sweden)

    David H. Dreyfus

    2017-01-01

    Full Text Available Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame termed BART (BamHI A right transcripts are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBα that regulate host NF-κB. BALF-2 (BamHI A left frame transcript, a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1, may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.

  2. 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.

  3. Whole genome sequencing of Guzerá cattle reveals genetic variants in candidate genes for production, disease resistance, and heat tolerance.

    Science.gov (United States)

    Rosse, Izinara C; Assis, Juliana G; Oliveira, Francislon S; Leite, Laura R; Araujo, Flávio; Zerlotini, Adhemar; Volpini, Angela; Dominitini, Anderson J; Lopes, Beatriz C; Arbex, Wagner A; Machado, Marco A; Peixoto, Maria G C D; Verneque, Rui S; Martins, Marta F; Coimbra, Roney S; Silva, Marcos V G B; Oliveira, Guilherme; Carvalho, Maria Raquel S

    2017-02-01

    In bovines, artificial selection has produced a large number of breeds which differ in production, environmental adaptation, and health characteristics. To investigate the genetic basis of these phenotypical differences, several bovine breeds have been sequenced. Millions of new SNVs were described at every new breed sequenced, suggesting that every breed should be sequenced. Guzerat or Guzerá is an indicine breed resistant to drought and parasites that has been the base for some important breeds such as Brahman. Here, we describe the sequence of the Guzerá genome and the in silico functional analyses of intragenic breed-specific variations. Mate-paired libraries were generated using the ABI SOLiD system. Sequences were mapped to the Bos taurus reference genome (UMD 3.1) and 87% of the reference genome was covered at a 26X. Among the variants identified, 2,676,067 SNVs and 463,158 INDELs were homozygous, not found in any database searched, and may represent true differences between Guzerá and B. taurus. Functional analyses investigated with the NGS-SNP package focused on 1069 new, non-synonymous SNVs, splice-site variants (including acceptor and donor sites, and the conserved regions at both intron borders, referred to here as splice regions) and coding INDELs (NS/SS/I). These NS/SS/I map to 935 genes belonging to cell communication, environmental adaptation, signal transduction, sensory, and immune systems pathways. These pathways have been involved in phenotypes related to health, adaptation to the environment and behavior, and particularly, disease resistance and heat tolerance. Indeed, 105 of these genes are known QTLs for milk, meat and carcass, production, reproduction, and health traits. Therefore, in addition to describing new genetic variants, our approach provided groundwork for unraveling key candidate genes and mutations.

  4. A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits

    DEFF Research Database (Denmark)

    Volkov, Petr; Olsson, Anders H; Gillberg, Linn

    2016-01-01

    mediate their effects on metabolic traits (e.g. BMI, cholesterol, high-density lipoprotein (HDL), hemoglobin A1c (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR)) via altered DNA methylation in human adipose tissue. This study identifies genome-wide interactions between genetic......Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL) analysis in human adipose tissue of 119 men......, where 592,794 single nucleotide polymorphisms (SNPs) were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs) in cis and 5...

  5. 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.

  6. Genomic evidence for adaptation by gene duplication.

    Science.gov (United States)

    Qian, Wenfeng; Zhang, Jianzhi

    2014-08-01

    Gene duplication is widely believed to facilitate adaptation, but unambiguous evidence for this hypothesis has been found in only a small number of cases. Although gene duplication may increase the fitness of the involved organisms by doubling gene dosage or neofunctionalization, it may also result in a simple division of ancestral functions into daughter genes, which need not promote adaptation. Hence, the general validity of the adaptation by gene duplication hypothesis remains uncertain. Indeed, a genome-scale experiment found similar fitness effects of deleting pairs of duplicate genes and deleting individual singleton genes from the yeast genome, leading to the conclusion that duplication rarely results in adaptation. Here we contend that the above comparison is unfair because of a known duplication bias among genes with different fitness contributions. To rectify this problem, we compare homologous genes from the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. We discover that simultaneously deleting a duplicate gene pair in S. cerevisiae reduces fitness significantly more than deleting their singleton counterpart in S. pombe, revealing post-duplication adaptation. The duplicates-singleton difference in fitness effect is not attributable to a potential increase in gene dose after duplication, suggesting that the adaptation is owing to neofunctionalization, which we find to be explicable by acquisitions of binary protein-protein interactions rather than gene expression changes. These results provide genomic evidence for the role of gene duplication in organismal adaptation and are important for understanding the genetic mechanisms of evolutionary innovation.

  7. Gene finding in novel genomes

    Directory of Open Access Journals (Sweden)

    Korf Ian

    2004-05-01

    Full Text Available Abstract Background Computational gene prediction continues to be an important problem, especially for genomes with little experimental data. Results I introduce the SNAP gene finder which has been designed to be easily adaptable to a variety of genomes. In novel genomes without an appropriate gene finder, I demonstrate that employing a foreign gene finder can produce highly inaccurate results, and that the most compatible parameters may not come from the nearest phylogenetic neighbor. I find that foreign gene finders are more usefully employed to bootstrap parameter estimation and that the resulting parameters can be highly accurate. Conclusion Since gene prediction is sensitive to species-specific parameters, every genome needs a dedicated gene finder.

  8. Integration of novel SSR and gene-based SNP marker loci in the chickpea genetic map and establishment of new anchor points with Medicago truncatula genome

    Science.gov (United States)

    Nayak, Spurthi N.; Zhu, Hongyan; Varghese, Nicy; Datta, Subhojit; Choi, Hong-Kyu; Horres, Ralf; Jüngling, Ruth; Singh, Jagbir; Kavi Kishor, P. B.; Sivaramakrishnan, S.; Hoisington, Dave A.; Kahl, Günter; Winter, Peter; Cook, Douglas R.

    2010-01-01

    This study presents the development and mapping of simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers in chickpea. The mapping population is based on an inter-specific cross between domesticated and non-domesticated genotypes of chickpea (Cicer arietinum ICC 4958 × C. reticulatum PI 489777). This same population has been the focus of previous studies, permitting integration of new and legacy genetic markers into a single genetic map. We report a set of 311 novel SSR markers (designated ICCM—ICRISAT chickpea microsatellite), obtained from an SSR-enriched genomic library of ICC 4958. Screening of these SSR markers on a diverse panel of 48 chickpea accessions provided 147 polymorphic markers with 2–21 alleles and polymorphic information content value 0.04–0.92. Fifty-two of these markers were polymorphic between parental genotypes of the inter-specific population. We also analyzed 233 previously published (H-series) SSR markers that provided another set of 52 polymorphic markers. An additional 71 gene-based SNP markers were developed from transcript sequences that are highly conserved between chickpea and its near relative Medicago truncatula. By using these three approaches, 175 new marker loci along with 407 previously reported marker loci were integrated to yield an improved genetic map of chickpea. The integrated map contains 521 loci organized into eight linkage groups that span 2,602 cM, with an average inter-marker distance of 4.99 cM. Gene-based markers provide anchor points for comparing the genomes of Medicago and chickpea, and reveal extended synteny between these two species. The combined set of genetic markers and their integration into an improved genetic map should facilitate chickpea genetics and breeding, as well as translational studies between chickpea and Medicago. Electronic supplementary material The online version of this article (doi:10.1007/s00122-010-1265-1) contains supplementary material, which is

  9. 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.

  10. Genetic dissection of drought and heat tolerance in chickpea through genome-wide and candidate gene-based association mapping approaches.

    Directory of Open Access Journals (Sweden)

    Mahendar Thudi

    Full Text Available To understand the genetic basis of tolerance to drought and heat stresses in chickpea, a comprehensive association mapping approach has been undertaken. Phenotypic data were generated on the reference set (300 accessions, including 211 mini-core collection accessions for drought tolerance related root traits, heat tolerance, yield and yield component traits from 1-7 seasons and 1-3 locations in India (Patancheru, Kanpur, Bangalore and three locations in Africa (Nairobi, Egerton in Kenya and Debre Zeit in Ethiopia. Diversity Array Technology (DArT markers equally distributed across chickpea genome were used to determine population structure and three sub-populations were identified using admixture model in STRUCTURE. The pairwise linkage disequilibrium (LD estimated using the squared-allele frequency correlations (r2; when r2<0.20 was found to decay rapidly with the genetic distance of 5 cM. For establishing marker-trait associations (MTAs, both genome-wide and candidate gene-sequencing based association mapping approaches were conducted using 1,872 markers (1,072 DArTs, 651 single nucleotide polymorphisms [SNPs], 113 gene-based SNPs and 36 simple sequence repeats [SSRs] and phenotyping data mentioned above employing mixed linear model (MLM analysis with optimum compression with P3D method and kinship matrix. As a result, 312 significant MTAs were identified and a maximum number of MTAs (70 was identified for 100-seed weight. A total of 18 SNPs from 5 genes (ERECTA, 11 SNPs; ASR, 4 SNPs; DREB, 1 SNP; CAP2 promoter, 1 SNP and AMDH, 1SNP were significantly associated with different traits. This study provides significant MTAs for drought and heat tolerance in chickpea that can be used, after validation, in molecular breeding for developing superior varieties with enhanced drought and heat tolerance.

  11. Genome-wide Analysis of Gene Regulation

    DEFF Research Database (Denmark)

    Chen, Yun

    cells are capable of regulating their gene expression, so that each cell can only express a particular set of genes yielding limited numbers of proteins with specialized functions. Therefore a rigid control of differential gene expression is necessary for cellular diversity. On the other hand, aberrant...... gene regulation will disrupt the cell’s fundamental processes, which in turn can cause disease. Hence, understanding gene regulation is essential for deciphering the code of life. Along with the development of high throughput sequencing (HTS) technology and the subsequent large-scale data analysis......, genome-wide assays have increased our understanding of gene regulation significantly. This thesis describes the integration and analysis of HTS data across different important aspects of gene regulation. Gene expression can be regulated at different stages when the genetic information is passed from gene...

  12. A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits.

    Directory of Open Access Journals (Sweden)

    Petr Volkov

    Full Text Available Little is known about the extent to which interactions between genetics and epigenetics may affect the risk of complex metabolic diseases and/or their intermediary phenotypes. We performed a genome-wide DNA methylation quantitative trait locus (mQTL analysis in human adipose tissue of 119 men, where 592,794 single nucleotide polymorphisms (SNPs were related to DNA methylation of 477,891 CpG sites, covering 99% of RefSeq genes. SNPs in significant mQTLs were further related to gene expression in adipose tissue and obesity related traits. We found 101,911 SNP-CpG pairs (mQTLs in cis and 5,342 SNP-CpG pairs in trans showing significant associations between genotype and DNA methylation in adipose tissue after correction for multiple testing, where cis is defined as distance less than 500 kb between a SNP and CpG site. These mQTLs include reported obesity, lipid and type 2 diabetes loci, e.g. ADCY3/POMC, APOA5, CETP, FADS2, GCKR, SORT1 and LEPR. Significant mQTLs were overrepresented in intergenic regions meanwhile underrepresented in promoter regions and CpG islands. We further identified 635 SNPs in significant cis-mQTLs associated with expression of 86 genes in adipose tissue including CHRNA5, G6PC2, GPX7, RPL27A, THNSL2 and ZFP57. SNPs in significant mQTLs were also associated with body mass index (BMI, lipid traits and glucose and insulin levels in our study cohort and public available consortia data. Importantly, the Causal Inference Test (CIT demonstrates how genetic variants mediate their effects on metabolic traits (e.g. BMI, cholesterol, high-density lipoprotein (HDL, hemoglobin A1c (HbA1c and homeostatic model assessment of insulin resistance (HOMA-IR via altered DNA methylation in human adipose tissue. This study identifies genome-wide interactions between genetic and epigenetic variation in both cis and trans positions influencing gene expression in adipose tissue and in vivo (dysmetabolic traits associated with the development of

  13. 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.

  14. 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.

  15. Genomic disorders: A window into human gene and genome evolution

    Science.gov (United States)

    Carvalho, Claudia M. B.; Zhang, Feng; Lupski, James R.

    2010-01-01

    Gene duplications alter the genetic constitution of organisms and can be a driving force of molecular evolution in humans and the great apes. In this context, the study of genomic disorders has uncovered the essential role played by the genomic architecture, especially low copy repeats (LCRs) or segmental duplications (SDs). In fact, regardless of the mechanism, LCRs can mediate or stimulate rearrangements, inciting genomic instability and generating dynamic and unstable regions prone to rapid molecular evolution. In humans, copy-number variation (CNV) has been implicated in common traits such as neuropathy, hypertension, color blindness, infertility, and behavioral traits including autism and schizophrenia, as well as disease susceptibility to HIV, lupus nephritis, and psoriasis among many other clinical phenotypes. The same mechanisms implicated in the origin of genomic disorders may also play a role in the emergence of segmental duplications and the evolution of new genes by means of genomic and gene duplication and triplication, exon shuffling, exon accretion, and fusion/fission events. PMID:20080665

  16. 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.

  17. Genome-wide association mapping in dogs enables identification of the homeobox gene, NKX2-8, as a genetic component of neural tube defects in humans.

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    Noa Safra

    Full Text Available Neural tube defects (NTDs is a general term for central nervous system malformations secondary to a failure of closure or development of the neural tube. The resulting pathologies may involve the brain, spinal cord and/or vertebral column, in addition to associated structures such as soft tissue or skin. The condition is reported among the more common birth defects in humans, leading to significant infant morbidity and mortality. The etiology remains poorly understood but genetic, nutritional, environmental factors, or a combination of these, are known to play a role in the development of NTDs. The variable conditions associated with NTDs occur naturally in dogs, and have been previously reported in the Weimaraner breed. Taking advantage of the strong linkage-disequilibrium within dog breeds we performed genome-wide association analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using 4 affected and 96 unaffected Weimaraners. The associated region on canine chromosome 8 (pgenome  =3.0 × 10(-5, after 100,000 permutations, encodes 18 genes, including NKX2-8, a homeobox gene which is expressed in the developing neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA frameshift mutation within exon 2 of the gene, resulting in a premature stop codon that is predicted to produce a truncated protein. The exons of NKX2-8 were sequenced in human patients with spina bifida and rare variants (rs61755040 and rs10135525 were found to be significantly over-represented (p=0.036. This is the first documentation of a potential role for NKX2-8 in the etiology of NTDs, made possible by investigating the molecular basis of naturally occurring mutations in dogs.

  18. Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits.

    Science.gov (United States)

    Kristiansson, Kati; Perola, Markus; Tikkanen, Emmi; Kettunen, Johannes; Surakka, Ida; Havulinna, Aki S; Stancáková, Alena; Barnes, Chris; Widen, Elisabeth; Kajantie, Eero; Eriksson, Johan G; Viikari, Jorma; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Hartikainen, Anna-Liisa; Ruokonen, Aimo; Pouta, Anneli; Jula, Antti; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Männistö, Satu; Jousilahti, Pekka; Bonnycastle, Lori L; Järvelin, Marjo-Riitta; Kuusisto, Johanna; Collins, Francis S; Laakso, Markku; Hurles, Matthew E; Palotie, Aarno; Peltonen, Leena; Ripatti, Samuli; Salomaa, Veikko

    2012-04-01

    Genome-wide association (GWA) studies have identified several susceptibility loci for metabolic syndrome (MetS) component traits, but have had variable success in identifying susceptibility loci to the syndrome as an entity. We conducted a GWA study on MetS and its component traits in 4 Finnish cohorts consisting of 2637 MetS cases and 7927 controls, both free of diabetes, and followed the top loci in an independent sample with transcriptome and nuclear magnetic resonance-based metabonomics data. Furthermore, we tested for loci associated with multiple MetS component traits using factor analysis, and built a genetic risk score for MetS. A previously known lipid locus, APOA1/C3/A4/A5 gene cluster region (SNP rs964184), was associated with MetS in all 4 study samples (P=7.23×10(-9) in meta-analysis). The association was further supported by serum metabolite analysis, where rs964184 was associated with various very low density lipoprotein, triglyceride, and high-density lipoprotein metabolites (P=0.024-1.88×10(-5)). Twenty-two previously identified susceptibility loci for individual MetS component traits were replicated in our GWA and factor analysis. Most of these were associated with lipid phenotypes, and none with 2 or more uncorrelated MetS components. A genetic risk score, calculated as the number of risk alleles in loci associated with individual MetS traits, was strongly associated with MetS status. Our findings suggest that genes from lipid metabolism pathways have the key role in the genetic background of MetS. We found little evidence for pleiotropy linking dyslipidemia and obesity to the other MetS component traits, such as hypertension and glucose intolerance.

  19. Genome editing for human gene therapy.

    Science.gov (United States)

    Meissner, Torsten B; Mandal, Pankaj K; Ferreira, Leonardo M R; Rossi, Derrick J; Cowan, Chad A

    2014-01-01

    The rapid advancement of genome-editing techniques holds much promise for the field of human gene therapy. From bacteria to model organisms and human cells, genome editing tools such as zinc-finger nucleases (ZNFs), TALENs, and CRISPR/Cas9 have been successfully used to manipulate the respective genomes with unprecedented precision. With regard to human gene therapy, it is of great interest to test the feasibility of genome editing in primary human hematopoietic cells that could potentially be used to treat a variety of human genetic disorders such as hemoglobinopathies, primary immunodeficiencies, and cancer. In this chapter, we explore the use of the CRISPR/Cas9 system for the efficient ablation of genes in two clinically relevant primary human cell types, CD4+ T cells and CD34+ hematopoietic stem and progenitor cells. By using two guide RNAs directed at a single locus, we achieve highly efficient and predictable deletions that ablate gene function. The use of a Cas9-2A-GFP fusion protein allows FACS-based enrichment of the transfected cells. The ease of designing, constructing, and testing guide RNAs makes this dual guide strategy an attractive approach for the efficient deletion of clinically relevant genes in primary human hematopoietic stem and effector cells and enables the use of CRISPR/Cas9 for gene therapy.

  20. 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.

  1. 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.

  2. 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.

  3. 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/.

  4. 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.

  5. 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.

  6. From the genome to the phenome and back: linking genes with human brain function and structure using genetically informed neuroimaging

    DEFF Research Database (Denmark)

    Siebner, H R; Callicott, J H; Sommer, T

    2009-01-01

    In recent years, an array of brain mapping techniques has been successfully employed to link individual differences in circuit function or structure in the living human brain with individual variations in the human genome. Several proof-of-principle studies provided converging evidence that brain...

  7. Genetically engineering adenoviral vectors for gene therapy.

    Science.gov (United States)

    Coughlan, Lynda

    2014-01-01

    Adenoviral (Ad) vectors are commonly used for various gene therapy applications. Significant advances in the genetic engineering of Ad vectors in recent years has highlighted their potential for the treatment of metastatic disease. There are several methods to genetically modify the Ad genome to incorporate retargeting peptides which will redirect the natural tropism of the viruses, including homologous recombination in bacteria or yeast. However, homologous recombination in yeast is highly efficient and can be achieved without the need for extensive cloning strategies. In addition, the method does not rely on the presence of unique restriction sites within the Ad genome and the reagents required for this method are widely available and inexpensive. Large plasmids containing the entire adenoviral genome (~36 kbp) can be modified within Saccharomyces cerevisiae yeast and genomes easily rescued in Escherichia coli hosts for analysis or amplification. A method for two-step homologous recombination in yeast is described in this chapter.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Ilja M Nolte

    Full Text Available To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1x10(-6. To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842 and QTGEN (n = 13,685. Analysis confirmed the association between common variants near NOS1AP (P = 1.4x10(-83 and the phospholamban (PLN gene (P = 1.9x10(-29. The most associated SNP near NOS1AP (rs12143842 explains 0.82% variance; the SNP near PLN (rs11153730 explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99. PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death.

  14. Genetic environment of the KPC gene in Acinetobacter baumannii ST2 clone from Puerto Rico and genomic insights into its drug resistance.

    Science.gov (United States)

    Martinez, Teresa; Martinez, Idali; Vazquez, Guillermo J; Aquino, Edna E; Robledo, Iraida E

    2016-08-01

    Carbapenems are considered the last-resort antibiotics to treat infections caused by multidrug-resistant Gram-negative bacilli. The Klebsiella pneumoniae carbapenemase (KPC) enzyme hydrolyses β-lactam antibiotics including the carbapenems. KPC has been detected worldwide in Enterobacteriaceae and Pseudomonas aeruginosa isolates associated with transposon Tn4401 commonly located in plasmids. Acinetobacter baumannii has become an important multidrug-resistant nosocomial pathogen. KPC-producing A. baumannii has been reported to date only in Puerto Rico. The objective of this study was to determine the whole genomic sequence of a KPC-producing A. baumannii in order to (i) define its allelic diversity, (ii) identify the location and genetic environment of the blaKPC and (iii) detect additional mechanisms of antimicrobial resistance. Next-generation sequencing, Southern blot, PFGE, multilocus sequence typing and bioinformatics analysis were performed. The organism was assigned to the international ST2 clone. The blaKPC-2 was identified on a novel truncated version of Tn4401e (tentatively named Tn4401h), located in the chromosome within an IncA/C plasmid fragment derived from an Enterobacteriaceae, probably owing to insertion sequence IS26. A chromosomally located truncated Tn1 transposon harbouring a blaTEM-1 was found in a novel genetic environment within an antimicrobial resistance cluster. Additional resistance mechanisms included efflux pumps, non-β-lactam antibiotic inactivating enzymes within and outside a resistance island, two class 1 integrons, In439 and the novel In1252, as well as mutations in the topoisomerase and DNA gyrase genes which confer resistance to quinolones. The presence of the blaKPC in an already globally disseminated A. baumannii ST2 presents a serious threat of further dissemination.

  15. 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.

  16. eQTL mapping of candidate genes for flower colour as a model for genetical genomics in Azalea

    NARCIS (Netherlands)

    Keyser, de E.; Smulders, M.J.M.; Bockstaele, van E.; Riek, de J.

    2012-01-01

    Flower colour in azalea is inherited as a semi-qualitative trait and is mainly determined by differences in anthocyanins and flavonols. A two-gene model is used to explain the phenotypic variation between white, brick red and carmine red colour: W in case the flower petals contain anthocyanins and Q

  17. Evolution of genes and genomes on the Drosophila phylogeny.

    Science.gov (United States)

    Clark, Andrew G; Eisen, Michael B; Smith, Douglas R; Bergman, Casey M; Oliver, Brian; Markow, Therese A; Kaufman, Thomas C; Kellis, Manolis; Gelbart, William; Iyer, Venky N; Pollard, Daniel A; Sackton, Timothy B; Larracuente, Amanda M; Singh, Nadia D; Abad, Jose P; Abt, Dawn N; Adryan, Boris; Aguade, Montserrat; Akashi, Hiroshi; Anderson, Wyatt W; Aquadro, Charles F; Ardell, David H; Arguello, Roman; Artieri, Carlo G; Barbash, Daniel A; Barker, Daniel; Barsanti, Paolo; Batterham, Phil; Batzoglou, Serafim; Begun, Dave; Bhutkar, Arjun; Blanco, Enrico; Bosak, Stephanie A; Bradley, Robert K; Brand, Adrianne D; Brent, Michael R; Brooks, Angela N; Brown, Randall H; Butlin, Roger K; Caggese, Corrado; Calvi, Brian R; Bernardo de Carvalho, A; Caspi, Anat; Castrezana, Sergio; Celniker, Susan E; Chang, Jean L; Chapple, Charles; Chatterji, Sourav; Chinwalla, Asif; Civetta, Alberto; Clifton, Sandra W; Comeron, Josep M; Costello, James C; Coyne, Jerry A; Daub, Jennifer; David, Robert G; Delcher, Arthur L; Delehaunty, Kim; Do, Chuong B; Ebling, Heather; Edwards, Kevin; Eickbush, Thomas; Evans, Jay D; Filipski, Alan; Findeiss, Sven; Freyhult, Eva; Fulton, Lucinda; Fulton, Robert; Garcia, Ana C L; Gardiner, Anastasia; Garfield, David A; Garvin, Barry E; Gibson, Greg; Gilbert, Don; Gnerre, Sante; Godfrey, Jennifer; Good, Robert; Gotea, Valer; Gravely, Brenton; Greenberg, Anthony J; Griffiths-Jones, Sam; Gross, Samuel; Guigo, Roderic; Gustafson, Erik A; Haerty, Wilfried; Hahn, Matthew W; Halligan, Daniel L; Halpern, Aaron L; Halter, Gillian M; Han, Mira V; Heger, Andreas; Hillier, LaDeana; Hinrichs, Angie S; Holmes, Ian; Hoskins, Roger A; Hubisz, Melissa J; Hultmark, Dan; Huntley, Melanie A; Jaffe, David B; Jagadeeshan, Santosh; Jeck, William R; Johnson, Justin; Jones, Corbin D; Jordan, William C; Karpen, Gary H; Kataoka, Eiko; Keightley, Peter D; Kheradpour, Pouya; Kirkness, Ewen F; Koerich, Leonardo B; Kristiansen, Karsten; Kudrna, Dave; Kulathinal, Rob J; Kumar, Sudhir; Kwok, Roberta; Lander, Eric; Langley, Charles H; Lapoint, Richard; Lazzaro, Brian P; Lee, So-Jeong; Levesque, Lisa; Li, Ruiqiang; Lin, Chiao-Feng; Lin, Michael F; Lindblad-Toh, Kerstin; Llopart, Ana; Long, Manyuan; Low, Lloyd; Lozovsky, Elena; Lu, Jian; Luo, Meizhong; Machado, Carlos A; Makalowski, Wojciech; Marzo, Mar; Matsuda, Muneo; Matzkin, Luciano; McAllister, Bryant; McBride, Carolyn S; McKernan, Brendan; McKernan, Kevin; Mendez-Lago, Maria; Minx, Patrick; Mollenhauer, Michael U; Montooth, Kristi; Mount, Stephen M; Mu, Xu; Myers, Eugene; Negre, Barbara; Newfeld, Stuart; Nielsen, Rasmus; Noor, Mohamed A F; O'Grady, Patrick; Pachter, Lior; Papaceit, Montserrat; Parisi, Matthew J; Parisi, Michael; Parts, Leopold; Pedersen, Jakob S; Pesole, Graziano; Phillippy, Adam M; Ponting, Chris P; Pop, Mihai; Porcelli, Damiano; Powell, Jeffrey R; Prohaska, Sonja; Pruitt, Kim; Puig, Marta; Quesneville, Hadi; Ram, Kristipati Ravi; Rand, David; Rasmussen, Matthew D; Reed, Laura K; Reenan, Robert; Reily, Amy; Remington, Karin A; Rieger, Tania T; Ritchie, Michael G; Robin, Charles; Rogers, Yu-Hui; Rohde, Claudia; Rozas, Julio; Rubenfield, Marc J; Ruiz, Alfredo; Russo, Susan; Salzberg, Steven L; Sanchez-Gracia, Alejandro; Saranga, David J; Sato, Hajime; Schaeffer, Stephen W; Schatz, Michael C; Schlenke, Todd; Schwartz, Russell; Segarra, Carmen; Singh, Rama S; Sirot, Laura; Sirota, Marina; Sisneros, Nicholas B; Smith, Chris D; Smith, Temple F; Spieth, John; Stage, Deborah E; Stark, Alexander; Stephan, Wolfgang; Strausberg, Robert L; Strempel, Sebastian; Sturgill, David; Sutton, Granger; Sutton, Granger G; Tao, Wei; Teichmann, Sarah; Tobari, Yoshiko N; Tomimura, Yoshihiko; Tsolas, Jason M; Valente, Vera L S; Venter, Eli; Venter, J Craig; Vicario, Saverio; Vieira, Filipe G; Vilella, Albert J; Villasante, Alfredo; Walenz, Brian; Wang, Jun; Wasserman, Marvin; Watts, Thomas; Wilson, Derek; Wilson, Richard K; Wing, Rod A; Wolfner, Mariana F; Wong, Alex; Wong, Gane Ka-Shu; Wu, Chung-I; Wu, Gabriel; Yamamoto, Daisuke; Yang, Hsiao-Pei; Yang, Shiaw-Pyng; Yorke, James A; Yoshida, Kiyohito; Zdobnov, Evgeny; Zhang, Peili; Zhang, Yu; Zimin, Aleksey V; Baldwin, Jennifer; Abdouelleil, Amr; Abdulkadir, Jamal; Abebe, Adal; Abera, Brikti; Abreu, Justin; Acer, St Christophe; Aftuck, Lynne; Alexander, Allen; An, Peter; Anderson, Erica; Anderson, Scott; Arachi, Harindra; Azer, Marc; Bachantsang, Pasang; Barry, Andrew; Bayul, Tashi; Berlin, Aaron; Bessette, Daniel; Bloom, Toby; Blye, Jason; Boguslavskiy, Leonid; Bonnet, Claude; Boukhgalter, Boris; Bourzgui, Imane; Brown, Adam; Cahill, Patrick; Channer, Sheridon; Cheshatsang, Yama; Chuda, Lisa; Citroen, Mieke; Collymore, Alville; Cooke, Patrick; Costello, Maura; D'Aco, Katie; Daza, Riza; De Haan, Georgius; DeGray, Stuart; DeMaso, Christina; Dhargay, Norbu; Dooley, Kimberly; Dooley, Erin; Doricent, Missole; Dorje, Passang; Dorjee, Kunsang; Dupes, Alan; Elong, Richard; Falk, Jill; Farina, Abderrahim; Faro, Susan; Ferguson, Diallo; Fisher, Sheila; Foley, Chelsea D; Franke, Alicia; Friedrich, Dennis; Gadbois, Loryn; Gearin, Gary; Gearin, Christina R; Giannoukos, Georgia; Goode, Tina; Graham, Joseph; Grandbois, Edward; Grewal, Sharleen; Gyaltsen, Kunsang; Hafez, Nabil; Hagos, Birhane; Hall, Jennifer; Henson, Charlotte; Hollinger, Andrew; Honan, Tracey; Huard, Monika D; Hughes, Leanne; Hurhula, Brian; Husby, M Erii; Kamat, Asha; Kanga, Ben; Kashin, Seva; Khazanovich, Dmitry; Kisner, Peter; Lance, Krista; Lara, Marcia; Lee, William; Lennon, Niall; Letendre, Frances; LeVine, Rosie; Lipovsky, Alex; Liu, Xiaohong; Liu, Jinlei; Liu, Shangtao; Lokyitsang, Tashi; Lokyitsang, Yeshi; Lubonja, Rakela; Lui, Annie; MacDonald, Pen; Magnisalis, Vasilia; Maru, Kebede; Matthews, Charles; McCusker, William; McDonough, Susan; Mehta, Teena; Meldrim, James; Meneus, Louis; Mihai, Oana; Mihalev, Atanas; Mihova, Tanya; Mittelman, Rachel; Mlenga, Valentine; Montmayeur, Anna; Mulrain, Leonidas; Navidi, Adam; Naylor, Jerome; Negash, Tamrat; Nguyen, Thu; Nguyen, Nga; Nicol, Robert; Norbu, Choe; Norbu, Nyima; Novod, Nathaniel; O'Neill, Barry; Osman, Sahal; Markiewicz, Eva; Oyono, Otero L; Patti, Christopher; Phunkhang, Pema; Pierre, Fritz; Priest, Margaret; Raghuraman, Sujaa; Rege, Filip; Reyes, Rebecca; Rise, Cecil; Rogov, Peter; Ross, Keenan; Ryan, Elizabeth; Settipalli, Sampath; Shea, Terry; Sherpa, Ngawang; Shi, Lu; Shih, Diana; Sparrow, Todd; Spaulding, Jessica; Stalker, John; Stange-Thomann, Nicole; Stavropoulos, Sharon; Stone, Catherine; Strader, Christopher; Tesfaye, Senait; Thomson, Talene; Thoulutsang, Yama; Thoulutsang, Dawa; Topham, Kerri; Topping, Ira; Tsamla, Tsamla; Vassiliev, Helen; Vo, Andy; Wangchuk, Tsering; Wangdi, Tsering; Weiand, Michael; Wilkinson, Jane; Wilson, Adam; Yadav, Shailendra; Young, Geneva; Yu, Qing; Zembek, Lisa; Zhong, Danni; Zimmer, Andrew; Zwirko, Zac; Jaffe, David B; Alvarez, Pablo; Brockman, Will; Butler, Jonathan; Chin, CheeWhye; Gnerre, Sante; Grabherr, Manfred; Kleber, Michael; Mauceli, Evan; MacCallum, Iain

    2007-11-08

    Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

  18. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

    NARCIS (Netherlands)

    G. Schumann (Gunter); L. Coin (Lachlan); A. Lourdusamy (Anbarasu); P. Charoen (Pimphen); K.H. Berger (Karen); D. Stacey (David); S. Desrivières (Sylvane); F.A. Aliev (Fazil); A.A. Khan (Anokhi); N. Amin (Najaf); G. Bakalkin (Georgy); B. Balkau (Beverley); J.W.J. Beulens (Joline); A. Bilbao (Ainhoa); R.A. de Boer (Rudolf); D. Beury (Delphine); M.L. Bots (Michiel); E.J. Breetvelt (Elemi); S. Cauchi (Stephane); C. Cavalcanti-Proença (Christine); J.C. Chambers (John); T.-K. Clarke; N. Dahmen (N.); E.J.C. de Geus (Eco); D. Dick (Danielle); F. Ducci (Francesca); A. Easton (Alanna); H.J. Edenberg (Howard); T. Esk (Tõnu); A. Fernández-Medarde (Alberto); T. Foroud (Tatiana); N.B. Freimer (Nelson); J.-A. Girault; D.E. Grobbee (Diederick); S. Guarrera (Simonetta); D.F. Gudbjartsson (Daniel); A.L. Hartikainen; A.C. Heath (Andrew); V. Hesselbrock (Victor); A. Hofman (Albert); J.J. Hottenga (Jouke Jan); M.K. Isohanni (Matti); J. Kaprio (Jaakko); K-T. Khaw (Kay-Tee); B. Kuehnel (Brigitte); J. Laitinen (Jaana); S. Lobbens (Stéphane); J. Luan; M. Mangino (Massimo); M. Maroteaux (Matthieu); G. Matullo (Giuseppe); M.I. McCarthy (Mark); C. Mueller (Christian); G. Navis (Gerjan); M.E. Numans (Mattijs); A.M. Núñez (Alejandro); D.R. Nyholt (Dale); C.N. Onland-Moret (Charlotte); B.A. Oostra (Ben); P.F. O'Reilly (Paul); M. Palkovits (Miklos); B.W.J.H. Penninx (Brenda); S. Polidoro (Silvia); A. Pouta (Anneli); I. Prokopenko (Inga); F. Ricceri (Fulvio); E. Santos (Eugenio); J.H. Smit (Johannes); N. Soranzo (Nicole); K. Song (Kijoung); U. Sovio (Ulla); M. Stumvoll (Michael); I. Surakk (Ida); T.E. Thorgeirsson (Thorgeir); U. Thorsteinsdottir (Unnur); C. Troakes (Claire); T. Tyrfingsson (Thorarinn); A. Tönjes (Anke); C.S.P.M. Uiterwaal (Cuno); A.G. Uitterlinden (André); P. van der Harst (Pim); Y.T. van der Schouw (Yvonne); O. Staehlin (Oliver); N. Vogelzangs (Nicole); P. Vollenweider (Peter); G. Waeber (Gérard); N.J. Wareham (Nick); D. Waterworth (Dawn); J.B. Whitfield (John); E.H. Wichmann (Erich); G.A.H.M. Willemsen (Gonneke); J.C.M. Witteman (Jacqueline); X. Yuan (Xin); G. Zhai (Guangju); J.H. Zhao (Jing); W. Zhang (Weihua); N.G. Martin (Nicholas); A. Metspalu (Andres); A. Doering (Angela); J. Scott (James); T.D. Spector (Timothy); R.J.F. Loos (Ruth); D.I. Boomsma (Dorret); V. Mooser (Vincent); L. Peltonen (Leena Johanna); K. Stefansson (Kari); P. Tikka-Kleemola (Päivi); P. Vineis (Paolo); W.H. Sommer (Wolfgang); J.S. Kooner (Jaspal); R. Spanagel (Rainer); U.A. Heberlein (Ulrike); M.R. Järvelin; P. Elliott (Paul); Y.S. Aulchenko (Yurii); S.J.L. Bakker (Stephan)

    2011-01-01

    textabstractAlcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram

  19. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

    NARCIS (Netherlands)

    Schumann, Gunter; Coin, Lachlan J.; Lourdusamy, Anbarasu; Charoen, Pimphen; Berger, Karen H.; Stacey, David; Desrivieres, Sylvane; Aliev, Fazil A.; Khan, Anokhi A.; Amin, Najaf; Aulchenko, Yurii S.; Bakalkin, Georgy; Bakker, Stephan J.; Balkau, Beverley; Beulens, Joline W.; Bilbao, Ainhoa; de Boer, Rudolf A.; Beury, Delphine; Bots, Michiel L.; Breetvelt, Elemi J.; Cauchi, Stephane; Cavalcanti-Proenca, Christine; Chambers, John C.; Clarke, Toni-Kim; Dahmen, Norbert; de Geus, Eco J.; Dick, Danielle; Ducci, Francesca; Easton, Alanna; Edenberg, Howard J.; Esk, Tonu; Fernandez-Medarde, Alberto; Foroud, Tatiana; Freimer, Nelson B.; Girault, Jean-Antoine; Grobbee, Diederick E.; Guarrera, Simonetta; Gudbjartsson, Daniel F.; Hartikainen, Anna-Liisa; Heath, Andrew C.; Hesselbrock, Victor; Hofman, Albert; Hottenga, Jouke-Jan; Isohanni, Matti K.; Kaprio, Jaakko; Khaw, Kay-Tee; Kuehnel, Brigitte; Laitinen, Jaana; Lobbens, Stephane; Luan, Jian'an; Mangino, Massimo; Maroteaux, Matthieu; Matullo, Giuseppe; McCarthy, Mark I.; Mueller, Christian; Navis, Gerjan; Numans, Mattijs E.; Nunez, Alejandro; Nyholt, Dale R.; Onland-Moret, Charlotte N.; Oostra, Ben A.; O'Reilly, Paul F.; Palkovits, Miklos; Penninx, Brenda W.; Polidoro, Silvia; Pouta, Anneli; Prokopenko, Inga; Ricceri, Fulvio; Santos, Eugenio; Smit, Johannes H.; Soranzo, Nicole; Song, Kijoung; Sovio, Ulla; Stumvoll, Michael; Surakk, Ida; Thorgeirsson, Thorgeir E.; Thorsteinsdottir, Unnur; Troakes, Claire; Tyrfingsson, Thorarinn; Toenjes, Anke; Uiterwaal, Cuno S.; Uitterlinden, Andre G.; van der Harst, Pim; van der Schouw, Yvonne T.; Staehlin, Oliver; Vogelzangs, Nicole; Vollenweider, Peter; Waeber, Gerard; Wareham, Nicholas J.; Waterworth, Dawn M.; Whitfield, John B.; Wichmann, Erich H.; Willemsen, Gonneke; Witteman, Jacqueline C.; Yuan, Xin; Zhai, Guangju; Zhao, Jing H.; Zhang, Weihua; Martin, Nicholas G.; Metspalu, Andres; Doering, Angela; Scott, James; Spector, Tim D.; Loos, Ruth J.; Boomsma, Dorret I.; Mooser, Vincent; Peltonen, Leena; Stefansson, Kari; van Duijn, Cornelia M.; Vineis, Paolo; Sommer, Wolfgang H.; Kooner, Jaspal S.; Spanagel, Rainer; Heberlein, Ulrike A.; Jarvelin, Marjo-Riitta; Elliott, Paul

    2011-01-01

    Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of similar to 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram p

  20. 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.

  1. Molecular genetics of Psoriasis (Principles, technology, gene location, genetic polymorphism and gene expression).

    Science.gov (United States)

    Al Robaee, Ahmad A

    2010-11-01

    Psoriasis is a common inflammatory skin disease with an etiology bases on both environmental and genetic factors. As is the case of many autoimmune diseases its real cause remains poorly defined. However, it is known that genetic factors contribute to disease susceptibility. The linkage analysis has been used to identify multiple loci and alleles that confer risk of the disease. Some other studies have focused upon single nucleotide polymorphisms (SNPs) for mapping of probable causal variants. Other studies, using genome-wide analytical techniques, tried to link the disease to copy number variants (CNVs) that are segments of DNA ranging in size from kilobases to megabases that vary in copy number. CNVs represent an important element of genomic polymorphism in humans and harboring dosage-sensitive genes may cause or predispose to a variety of human genetic diseases. The mechanisms giving rise to SNPs and CNVs can be considered as fundamental processes underlying gene duplications, deletions, insertions, inversions and complex combinations of rearrangements. The duplicated genes being the results of 'successful' copies are fixed and maintained in the population. Conversely, many 'unsuccessful' duplicates remain in the genome as pseudogenes. There is another form of genetic variations termed copy-neutral loss of heterozygosity (LOH) with less information about their potential impact on complex diseases. Additional studies would include associated gene expression variations with either SNPs or CNVs. Now many genetic techniques such as PCR, real time PCR, microarray and restriction fragment length analysis are available for detecting genetic polymorphisms, gene mapping and estimation of gene expression. Recently, the scientists have used these tools to define genetic signatures of disease, to understand genetic causes of disease and to characterize the effects of certain drugs on gene expression. This review highlights the principles, technology and applications on

  2. 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.

  3. Re-Examining the Gene in Personalized Genomics

    Science.gov (United States)

    Bartol, Jordan

    2013-01-01

    Personalized genomics companies (PG; also called "direct-to-consumer genetics") are businesses marketing genetic testing to consumers over the Internet. While much has been written about these new businesses, little attention has been given to their roles in science communication. This paper provides an analysis of the gene concept…

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

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

    Science.gov (United States)

    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.

  10. Whole genome homology-based identification of candidate genes ...

    African Journals Online (AJOL)

    Josephine Erhiakporeh

    2016-07-06

    Jul 6, 2016 ... identification of a set of 75 candidate genes (42, 22 and 11 from Arabidopsis, potato and tomato, ... understanding on the genetic basis of drought tolerance by using the .... Comparative genomics and genes expression assay ... Primer code ... physiological and molecular responses to drought stress.

  11. 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.

  12. 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.

  13. Genes but not genomes reveal bacterial domestication of Lactococcus lactis.

    Directory of Open Access Journals (Sweden)

    Delphine Passerini

    Full Text Available BACKGROUND: The population structure and diversity of Lactococcus lactis subsp. lactis, a major industrial bacterium involved in milk fermentation, was determined at both gene and genome level. Seventy-six lactococcal isolates of various origins were studied by different genotyping methods and thirty-six strains displaying unique macrorestriction fingerprints were analyzed by a new multilocus sequence typing (MLST scheme. This gene-based analysis was compared to genomic characteristics determined by pulsed-field gel electrophoresis (PFGE. METHODOLOGY/PRINCIPAL FINDINGS: The MLST analysis revealed that L. lactis subsp. lactis is essentially clonal with infrequent intra- and intergenic recombination; also, despite its taxonomical classification as a subspecies, it displays a genetic diversity as substantial as that within several other bacterial species. Genome-based analysis revealed a genome size variability of 20%, a value typical of bacteria inhabiting different ecological niches, and that suggests a large pan-genome for this subspecies. However, the genomic characteristics (macrorestriction pattern, genome or chromosome size, plasmid content did not correlate to the MLST-based phylogeny, with strains from the same sequence type (ST differing by up to 230 kb in genome size. CONCLUSION/SIGNIFICANCE: The gene-based phylogeny was not fully consistent with the traditional classification into dairy and non-dairy strains but supported a new classification based on ecological separation between "environmental" strains, the main contributors to the genetic diversity within the subspecies, and "domesticated" strains, subject to recent genetic bottlenecks. Comparison between gene- and genome-based analyses revealed little relationship between core and dispensable genome phylogenies, indicating that clonal diversification and phenotypic variability of the "domesticated" strains essentially arose through substantial genomic flux within the dispensable

  14. 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.

  15. 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.

  16. Genetic and comparative genomics mapping reveals that a powdery mildew resistance gene Ml3D232 originating from wild emmer co-segregates with an NBS-LRR analog in common wheat (Triticum aestivum L.).

    Science.gov (United States)

    Zhang, Hongtao; Guan, Haiying; Li, Jingting; Zhu, Jie; Xie, Chaojie; Zhou, Yilin; Duan, Xiayu; Yang, Tsomin; Sun, Qixin; Liu, Zhiyong

    2010-11-01

    Powdery mildew caused by Blumeria graminis f. sp. tritici is one of the most important wheat diseases worldwide and breeding for resistance using diversified disease resistance genes is the most promising approach to prevent outbreaks of powdery mildew. A powdery mildew resistance gene, originating from wild emmer wheat (Triticum turgidum var. dicoccoides) accessions collected from Israel, has been transferred into the hexaploid wheat line 3D232 through crossing and backcrossing. Inoculation results with 21 B. graminis f. sp. tritici races indicated that 3D232 is resistant to all of the powdery mildew isolates tested. Genetic analyses of 3D232 using an F(2) segregating population and F(3) families indicated that a single dominant gene, Ml3D232, confers resistance in the host seedling stage. By applying molecular markers and bulked segregant analysis (BSA), we have identified polymorphic simple sequence repeats (SSR), expressed sequence tags (EST) and derived sequence tagged site (STS) markers to determine that the Ml3D232 is located on chromosome 5BL bin 0.59-0.76. Comparative genetic analyses using mapped EST markers and genome sequences of rice and Brachypodium established co-linearity of the Ml3D232 genomic region with a 1.4 Mb genomic region on Brachypodium distachyon chromosome 4, and a 1.2 Mb contig located on the Oryza sativa chromosome 9. Our comparative approach enabled us to develop new EST-STS markers and to delimit the genomic region carrying Ml3D232 to a 0.8 cM segment that is collinear with a 558 kb region on B. distachyon. Eight EST markers, including an NBS-LRR analog, co-segregated with Ml3D232 to provide a target site for fine genetic mapping, chromosome landing and map-based cloning of the powdery mildew resistance gene. This newly developed common wheat germplasm provides broad-spectrum resistance to powdery mildew and a valuable resource for wheat breeding programs.

  17. The cavefish genome reveals candidate genes for eye loss

    Science.gov (United States)

    McGaugh, Suzanne E.; Gross, Joshua B.; Aken, Bronwen; Blin, Maryline; Borowsky, Richard; Chalopin, Domitille; Hinaux, Hélène; Jeffery, William R.; Keene, Alex; Ma, Li; Minx, Patrick; Murphy, Daniel; O’Quin, Kelly E.; Rétaux, Sylvie; Rohner, Nicolas; Searle, Steve M. J.; Stahl, Bethany A.; Tabin, Cliff; Volff, Jean-Nicolas; Yoshizawa, Masato; Warren, Wesley C.

    2014-01-01

    Natural populations subjected to strong environmental selection pressures offer a window into the genetic underpinnings of evolutionary change. Cavefish populations, Astyanax mexicanus (Teleostei: Characiphysi), exhibit repeated, independent evolution for a variety of traits including eye degeneration, pigment loss, increased size and number of taste buds and mechanosensory organs, and shifts in many behavioural traits. Surface and cave forms are interfertile making this system amenable to genetic interrogation; however, lack of a reference genome has hampered efforts to identify genes responsible for changes in cave forms of A. mexicanus. Here we present the first de novo genome assembly for Astyanax mexicanus cavefish, contrast repeat elements to other teleost genomes, identify candidate genes underlying quantitative trait loci (QTL), and assay these candidate genes for potential functional and expression differences. We expect the cavefish genome to advance understanding of the evolutionary process, as well as, analogous human disease including retinal dysfunction. PMID:25329095

  18. A Method for Identification of Selenoprotein Genes in Archaeal Genomes

    Institute of Scientific and Technical Information of China (English)

    Mingfeng Li; Yanzhao Huang; Yi Xiao

    2009-01-01

    The genetic codon UGA has a dual function: serving as a terminator and encoding selenocysteine. However, most popular gene annotation programs only take it as a stop signal, resulting in misannotation or completely missing selenoprotein genes. We developed a computational method named Asec-Prediction that is specific for the prediction of archaeal selenoprotein genes. To evaluate its effectiveness, we first applied it to 14 archaeal genomes with previously known selenoprotein genes, and Asec-Prediction identified all reported selenoprotein genes without redundant results. When we applied it to 12 archaeal genomes that had not been researched for selenoprotein genes, Asec-Prediction detected a novel selenoprotein gene in Methanosarcina acetivorans. Further evidence was also collected to support that the predicted gene should be a real selenoprotein gene. The result shows that Asec-Prediction is effective for the prediction of archaeal selenoprotein genes.

  19. 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.

  20. Genetic correction using engineered nucleases for gene therapy applications.

    Science.gov (United States)

    Li, Hongmei Lisa; Nakano, Takao; Hotta, Akitsu

    2014-01-01

    Genetic mutations in humans are associated with congenital disorders and phenotypic traits. Gene therapy holds the promise to cure such genetic disorders, although it has suffered from several technical limitations for decades. Recent progress in gene editing technology using tailor-made nucleases, such as meganucleases (MNs), zinc finger nucleases (ZFNs), TAL effector nucleases (TALENs) and, more recently, CRISPR/Cas9, has significantly broadened our ability to precisely modify target sites in the human genome. In this review, we summarize recent progress in gene correction approaches of the human genome, with a particular emphasis on the clinical applications of gene therapy.

  1. 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

  2. Genes, genetics, and Class III malocclusion.

    Science.gov (United States)

    Xue, F; Wong, R W K; Rabie, A B M

    2010-05-01

    To present current views that are pertinent to the investigation of the genetic etiology of Class III malocclusion. Class III malocclusion is thought to be a polygenic disorder that results from an interaction between susceptibility genes and environmental factors. However, research on family pedigrees has indicated that Class III malocclusion might also be a monogenic dominant phenotype. Recent studies have reported that genes that encode specific growth factors or other signaling molecules are involved in condylar growth under mechanical strain. These genes, which include Indian hedgehog homolog (IHH), parathyroid-hormone like hormone (PTHLH), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF), and variations in their levels of expression play an important role in the etiology of Class III malocclusion. In addition, genome-wide scans have revealed chromosomal loci that are associated with Class III malocclusion. It is likely that chromosomal loci 1p36, 12q23, and 12q13 harbor genes that confer susceptibility to Class III malocclusion. In a case-control association study, we identified erythrocyte membrane protein band 4.1 (EPB41) to be a new positional candidate gene that might be involved in susceptibility to mandibular prognathism. Most of the earlier studies on the genetic etiology of Class III malocclusion have focused on the patterns of inheritance of this phenotype. Recent investigations have focused on understanding the genetic variables that affect Class III malocclusion and might provide new approaches to uncovering the genetic etiology of this phenotype.

  3. Identification and Categorization of Horizontally Transferred Genes in Prokaryotic Genomes

    Institute of Scientific and Technical Information of China (English)

    Shuo-Yong SHI; Xiao-Hui CAI; Da-fu DING

    2005-01-01

    Horizontal gene transfer (HGT), a process through which genomes acquire genetic materials from distantly related organisms, is believed to be one of the major forces in prokaryotic genome evolution.However, systematic investigation is still scarce to clarify two basic issues about HGT: (1) what types of genes are transferred; and (2) what influence HGT events over the organization and evolution of biological pathways. Genome-scale investigations of these two issues will advance the systematical understanding of HGT in the context of prokaryotic genome evolution. Having investigated 82 genomes, we constructed an HGT database across broad evolutionary timescales. We identified four function categories containing a high proportion of horizontally transferred genes: cell envelope, energy metabolism, regulatory functions, and transport/binding proteins. Such biased function distribution indicates that HGT is not completely random;instead, it is under high selective pressure, required by function restraints in organisms. Furthermore, we mapped the transferred genes onto the connectivity structure map of organism-specific pathways listed in Kyoto Encyclopedia of Genes and Genomes (KEGG). Our results suggest that recruitment of transferred genes into pathways is also selectively constrained because of the tuned interaction between original pathway members. Pathway organization structures still conserve well through evolution even with the recruitment of horizontally transferred genes. Interestingly, in pathways whose organization were significantly affected by HGT events, the operon-like arrangement of transferred genes was found to be prevalent. Such results suggest that operon plays an essential and directional role in the integration of alien genes into pathways.

  4. Comparative genomic analysis of eutherian kallikrein genes

    Directory of Open Access Journals (Sweden)

    Marko Premzl

    2017-03-01

    Full Text Available The present study made attempts to update and revise eutherian kallikrein genes implicated in major physiological and pathological processes and in medical molecular diagnostics. Using eutherian comparative genomic analysis protocol and free available genomic sequence assemblies, the tests of reliability of eutherian public genomic sequences annotated most comprehensive curated third party data gene data set of eutherian kallikrein genes including 121 complete coding sequences among 335 potential coding sequences. The present analysis first described 13 major gene clusters of eutherian kallikrein genes, and explained their differential gene expansion patterns. One updated classification and nomenclature of eutherian kallikrein genes was proposed, as new framework of future experiments.

  5. 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.

  6. From trees to the forest: genes to genomics.

    Science.gov (United States)

    Mullighan, Charles; Petersdorf, Effie; Davies, Stella M; DiPersio, John

    2011-01-01

    Crick, Watson, and colleagues revealed the genetic code in 1953, and since that time, remarkable progress has been made in understanding what makes each of us who we are. Identification of single genes important in disease, and the development of a mechanistic understanding of genetic elements that regulate gene function, have cast light on the pathophysiology of many heritable and acquired disorders. In 1990, the human genome project commenced, with the goal of sequencing the entire human genome, and a "first draft" was published with astonishing speed in 2001. The first draft, although an extraordinary achievement, reported essentially an imaginary haploid mix of alleles rather than a true diploid genome. In the years since 2001, technology has further improved, and efforts have been focused on filling in the gaps in the initial genome and starting the huge task of looking at normal variation in the human genome. This work is the beginning of understanding human genetics in the context of the structure of the genome as a complete entity, and as more than simply the sum of a series of genes. We present 3 studies in this review that apply genomic approaches to leukemia and to transplantation to improve and extend therapies.

  7. 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.

  8. Recent Achievement in Gene Cloning and Functional Genomics in Soybean

    Directory of Open Access Journals (Sweden)

    Zhengjun Xia

    2013-01-01

    Full Text Available Soybean is a model plant for photoperiodism as well as for symbiotic nitrogen fixation. However, a rather low efficiency in soybean transformation hampers functional analysis of genes isolated from soybean. In comparison, rapid development and progress in flowering time and photoperiodic response have been achieved in Arabidopsis and rice. As the soybean genomic information has been released since 2008, gene cloning and functional genomic studies have been revived as indicated by successfully characterizing genes involved in maturity and nematode resistance. Here, we review some major achievements in the cloning of some important genes and some specific features at genetic or genomic levels revealed by the analysis of functional genomics of soybean.

  9. Uses of antimicrobial genes from microbial genome

    Science.gov (United States)

    Sorek, Rotem; Rubin, Edward M.

    2013-08-20

    We describe a method for mining microbial genomes to discover antimicrobial genes and proteins having broad spectrum of activity. Also described are antimicrobial genes and their expression products from various microbial genomes that were found using this method. The products of such genes can be used as antimicrobial agents or as tools for molecular biology.

  10. Genome-based genetic tool development for Bacillus methanolicus: theta- and rolling circle-replicating plasmids for inducible gene expression and application to methanol-based cadaverine production

    Directory of Open Access Journals (Sweden)

    Marta Irla

    2016-09-01

    Full Text Available Bacillus methanolicus is a thermophilic methylotroph able to overproduce amino acids from methanol, a substrate not used for human or animal nutrition. Based on our previous RNA-seq analysis a mannitol inducible promoter and a putative mannitol activator gene mtlR were identified. The mannitol inducible promoter was applied for controlled gene expression using fluorescent reporter proteins and a flow cytometry analysis, and improved by changing the -35 promoter region and by co-expression of the mtlR regulator gene. For independent complementary gene expression control, the heterologous xylose-inducible system from B. megaterium was employed and a two-plasmid gene expression system was developed. Four different replicons for expression vectors were compared with respect to their copy number and stability. As an application example, methanol-based production of cadaverine was shown to be improved from 11.3 g/L to 17.5 g/L when a heterologous lysine decarboxylase gene cadA was expressed from a theta-replicating rather than a rolling-circle replicating vector. The current work on inducible promoter systems and compatible theta- or rolling circle-replicating vectors is an important extension of the poorly developed B. methanolicus genetic toolbox, valuable for genetic engineering and further exploration of this bacterium.

  11. 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.

  12. 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.

  13. Building phylogenetic trees by using gene Nucleotide Genomic Signals.

    Science.gov (United States)

    Cristea, Paul Dan

    2012-01-01

    Nucleotide genomic signal (NuGS) methodology allows a molecular level approach to determine distances between homologous genes or between conserved equivalent non-coding genome regions in various species or individuals of the same species. Therefore, distances between the genes of species or individuals can be computed and phylogenetic trees can be built. The paper illustrates the use of the nucleotide imbalance (N) and nucleotide pair imbalance (P) signals to determine the distances between the genes of several Hominidae. The results are in accordance with those of other genetic or phylogenetic approaches to establish distances between Hominidae species.

  14. 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.

  15. 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.

  16. Regulation of methane genes and genome expression

    Energy Technology Data Exchange (ETDEWEB)

    John N. Reeve

    2009-09-09

    At the start of this project, it was known that methanogens were Archaeabacteria (now Archaea) and were therefore predicted to have gene expression and regulatory systems different from Bacteria, but few of the molecular biology details were established. The goals were then to establish the structures and organizations of genes in methanogens, and to develop the genetic technologies needed to investigate and dissect methanogen gene expression and regulation in vivo. By cloning and sequencing, we established the gene and operon structures of all of the “methane” genes that encode the enzymes that catalyze methane biosynthesis from carbon dioxide and hydrogen. This work identified unique sequences in the methane gene that we designated mcrA, that encodes the largest subunit of methyl-coenzyme M reductase, that could be used to identify methanogen DNA and establish methanogen phylogenetic relationships. McrA sequences are now the accepted standard and used extensively as hybridization probes to identify and quantify methanogens in environmental research. With the methane genes in hand, we used northern blot and then later whole-genome microarray hybridization analyses to establish how growth phase and substrate availability regulated methane gene expression in Methanobacterium thermautotrophicus ΔH (now Methanothermobacter thermautotrophicus). Isoenzymes or pairs of functionally equivalent enzymes catalyze several steps in the hydrogen-dependent reduction of carbon dioxide to methane. We established that hydrogen availability determine which of these pairs of methane genes is expressed and therefore which of the alternative enzymes is employed to catalyze methane biosynthesis under different environmental conditions. As were unable to establish a reliable genetic system for M. thermautotrophicus, we developed in vitro transcription as an alternative system to investigate methanogen gene expression and regulation. This led to the discovery that an archaeal protein

  17. Regulation of methane genes and genome expression

    Energy Technology Data Exchange (ETDEWEB)

    John N. Reeve

    2009-09-09

    At the start of this project, it was known that methanogens were Archaeabacteria (now Archaea) and were therefore predicted to have gene expression and regulatory systems different from Bacteria, but few of the molecular biology details were established. The goals were then to establish the structures and organizations of genes in methanogens, and to develop the genetic technologies needed to investigate and dissect methanogen gene expression and regulation in vivo. By cloning and sequencing, we established the gene and operon structures of all of the “methane” genes that encode the enzymes that catalyze methane biosynthesis from carbon dioxide and hydrogen. This work identified unique sequences in the methane gene that we designated mcrA, that encodes the largest subunit of methyl-coenzyme M reductase, that could be used to identify methanogen DNA and establish methanogen phylogenetic relationships. McrA sequences are now the accepted standard and used extensively as hybridization probes to identify and quantify methanogens in environmental research. With the methane genes in hand, we used northern blot and then later whole-genome microarray hybridization analyses to establish how growth phase and substrate availability regulated methane gene expression in Methanobacterium thermautotrophicus ΔH (now Methanothermobacter thermautotrophicus). Isoenzymes or pairs of functionally equivalent enzymes catalyze several steps in the hydrogen-dependent reduction of carbon dioxide to methane. We established that hydrogen availability determine which of these pairs of methane genes is expressed and therefore which of the alternative enzymes is employed to catalyze methane biosynthesis under different environmental conditions. As were unable to establish a reliable genetic system for M. thermautotrophicus, we developed in vitro transcription as an alternative system to investigate methanogen gene expression and regulation. This led to the discovery that an archaeal protein

  18. 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.

  19. Comparative genetic mapping revealed powdery mildew resistance gene MlWE4 derived from wild emmer is located in same genomic region of Pm36 and Ml3D232 on chromosome 5BL

    Institute of Scientific and Technical Information of China (English)

    ZHANG Dong; WANG Yong; CHEN Yong-xing; LIU Zhi-yong; OUYANG Shu-hong; WANG Li-li; CUI Yu; WU Qiu-hong; LIANG Yong; WANG Zhen-zhong; XIE Jing-zhong; ZHANG De-yun

    2015-01-01

    Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most devastating wheat diseases. Wild emmer wheat (Triticum turgidum ssp. dicoccoides) is a promising source of disease resistance for wheat. A powdery mildew resistance gene conferring resistance to B. graminis f. sp. tritici isolate E09, originating from wild emmer wheat, has been transferred into the hexaploid wheat line WE4 through crossing and backcrossing. Genetic analyses indicated that the powdery mildew resistance was control ed by a single dominant gene, temporarily designated MlWE4. By mean of comparative genomics and bulked segregant analysis, a genetic linkage map of MlWE4 was constructed, and MlWE4 was mapped on the distal region of chromosome arm 5BL. Comparative genetic linkage maps showed that genes MlWE4, Pm36 and Ml3D232 were co-segregated with markers XBD37670 and XBD37680, indicating they are likely the same gene or al eles in the same locus. The co-segregated markers provide a starting point for chromosome landing and map-based cloning of MlWE4, Pm36 and Ml3D232.

  20. 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.

  1. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia

    Science.gov (United States)

    Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D'Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C.; Maletta, Raffaele G.; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, Massimo; Puca, Annibale A.; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew; Cusi, Daniele; Hardy, John; Momeni, Parastoo

    2015-01-01

    Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10−7 and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of –cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD–genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis. PMID:26154020

  2. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia.

    Science.gov (United States)

    Ferrari, Raffaele; Grassi, Mario; Salvi, Erika; Borroni, Barbara; Palluzzi, Fernando; Pepe, Daniele; D'Avila, Francesca; Padovani, Alessandro; Archetti, Silvana; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Galimberti, Daniela; Scarpini, Elio; Serpente, Maria; Rossi, Giacomina; Giaccone, Giorgio; Tagliavini, Fabrizio; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Bruni, Amalia C; Maletta, Raffaele G; Bernardi, Livia; Postiglione, Alfredo; Milan, Graziella; Franceschi, Massimo; Puca, Annibale A; Novelli, Valeria; Barlassina, Cristina; Glorioso, Nicola; Manunta, Paolo; Singleton, Andrew; Cusi, Daniele; Hardy, John; Momeni, Parastoo

    2015-10-01

    Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10(-7) and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis.

  3. Genome classification by gene distribution: An overlapping subspace clustering approach

    Directory of Open Access Journals (Sweden)

    Halgamuge Saman K

    2008-04-01

    , Clostridium phi3626, Geobacillus GBSV1, and Listeria monocytogenes PSA. Conclusion The method described in this paper can assist evolutionary study through objectively classifying genomes based on their resemblance in gene order, gene content and gene positions. The method is suitable for application to genomes with high genetic exchange and various conserved gene arrangement, as demonstrated through our application on phages.

  4. 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.

  5. 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.

  6. Whole genome phylogeny of Prochlorococcus marinus group of cyanobacteria: genome alignment and overlapping gene approach.

    Science.gov (United States)

    Prabha, Ratna; Singh, Dhananjaya P; Gupta, Shailendra K; Rai, Anil

    2014-06-01

    Prochlorococcus is the smallest known oxygenic phototrophic marine cyanobacterium dominating the mid-latitude oceans. Physiologically and genetically distinct P. marinus isolates from many oceans in the world were assigned two different groups, a tightly clustered high-light (HL)-adapted and a divergent low-light (LL-) adapted clade. Phylogenetic analysis of this cyanobacterium on the basis of 16S rRNA and other conserved genes did not show consistency with its phenotypic behavior. We analyzed phylogeny of this genus on the basis of complete genome sequences through genome alignment, overlapping-gene content and gene-order approach. Phylogenetic tree of P. marinus obtained by comparing whole genome sequences in contrast to that based on 16S rRNA gene, corresponded well with the HL/LL ecotypic distinction of twelve strains and showed consistency with phenotypic classification of P. marinus. Evidence for the horizontal descent and acquisition of genes within and across the genus was observed. Many genes involved in metabolic functions were found to be conserved across these genomes and many were continuously gained by different strains as per their needs during the course of their evolution. Consistency in the physiological and genetic phylogeny based on whole genome sequence is established. These observations improve our understanding about the adaptation and diversification of these organisms under evolutionary pressure.

  7. Pichia stipitis genomics, transcriptomics, and gene clusters

    Science.gov (United States)

    Thomas W. Jeffries; Jennifer R. Headman Van Vleet

    2009-01-01

    Genome sequencing and subsequent global gene expression studies have advanced our understanding of the lignocellulose-fermenting yeast Pichia stipitis. These studies have provided an insight into its central carbon metabolism, and analysis of its genome has revealed numerous functional gene clusters and tandem repeats. Specialized physiological traits are often the...

  8. Evidence for mitochondrial genetic control of autosomal gene expression.

    Science.gov (United States)

    Kassam, Irfahan; Qi, Tuan; Lloyd-Jones, Luke; Holloway, Alexander; Jan Bonder, Marc; Henders, Anjali K; Martin, Nicholas G; Powell, Joseph E; Franke, Lude; Montgomery, Grant W; Visscher, Peter M; McRae, Allan F

    2016-10-18

    The mitochondrial and nuclear genomes coordinate and co-evolve in eukaryotes in order to adapt to environmental changes. Variation in the mitochondrial genome is capable of affecting expression of genes on the nuclear genome. Sex-specific mitochondrial genetic control of gene expression has been demonstrated in Drosophila melanogaster, where males were found to drive most of the total variation in gene expression. This has potential implications for male-related health and disease resulting from variation in mtDNA solely inherited from the mother. We used a family-based study comprised of 47,323 gene expression probes and 78 mitochondrial SNPs (mtSNPs) from n = 846 individuals to examine the extent of mitochondrial genetic control of gene expression in humans. This identified 15 significant probe-mtSNP associations (P[Formula: see text]) corresponding to 5 unique genes on the mitochondrial and nuclear genomes, with three of these genes corresponding to mitochondrial genetic control of gene expression in the nuclear genome. The associated mtSNPs for three genes (one cis and two trans associations) were replicated (P expression in any of these five probes. Sex-specific effects were examined by applying our analysis to males and females separately and testing for differences in effect size. The MEST gene was identified as having the most significantly different effect sizes across the sexes (P [Formula: see text]). MEST was similarly expressed in males and females with the G allele; however, males with the C allele are highly expressed for MEST, while females show no expression of the gene. This study provides evidence for the mitochondrial genetic control of expression of several genes in humans, with little evidence found for sex-specific effects.

  9. 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.

  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. Genetical genomic determinants of alcohol consumption in rats and humans

    Directory of Open Access Journals (Sweden)

    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

  12. KEGG: kyoto encyclopedia of genes and genomes.

    Science.gov (United States)

    Kanehisa, M; Goto, S

    2000-01-01

    KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).

  13. Genome-wide patterns of Arabidopsis gene expression in nature.

    Directory of Open Access Journals (Sweden)

    Christina L Richards

    Full Text Available Organisms in the wild are subject to multiple, fluctuating environmental factors, and it is in complex natural environments that genetic regulatory networks actually function and evolve. We assessed genome-wide gene expression patterns in the wild in two natural accessions of the model plant Arabidopsis thaliana and examined the nature of transcriptional variation throughout its life cycle and gene expression correlations with natural environmental fluctuations. We grew plants in a natural field environment and measured genome-wide time-series gene expression from the plant shoot every three days, spanning the seedling to reproductive stages. We find that 15,352 genes were expressed in the A. thaliana shoot in the field, and accession and flowering status (vegetative versus flowering were strong components of transcriptional variation in this plant. We identified between ∼110 and 190 time-varying gene expression clusters in the field, many of which were significantly overrepresented by genes regulated by abiotic and biotic environmental stresses. The two main principal components of vegetative shoot gene expression (PC(veg correlate to temperature and precipitation occurrence in the field. The largest PC(veg axes included thermoregulatory genes while the second major PC(veg was associated with precipitation and contained drought-responsive genes. By exposing A. thaliana to natural environments in an open field, we provide a framework for further understanding the genetic networks that are deployed in natural environments, and we connect plant molecular genetics in the laboratory to plant organismal ecology in the wild.

  14. Biased distribution of DNA uptake sequences towards genome maintenance genes

    DEFF Research Database (Denmark)

    Davidsen, T.; Rodland, E.A.; Lagesen, K.

    2004-01-01

    coding regions are the DNA uptake sequences (DUS) required for natural genetic transformation. More importantly, we found a significantly higher density of DUS within genes involved in DNA repair, recombination, restriction-modification and replication than in any other annotated gene group......Repeated sequence signatures are characteristic features of all genomic DNA. We have made a rigorous search for repeat genomic sequences in the human pathogens Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae and found that by far the most frequent 9-10mers residing within...

  15. 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/.

  16. 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.

  17. 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.

  18. Gene enrichment in plant genomic shotgun libraries.

    Science.gov (United States)

    Rabinowicz, Pablo D; McCombie, W Richard; Martienssen, Robert A

    2003-04-01

    The Arabidopsis genome (about 130 Mbp) has been completely sequenced; whereas a draft sequence of the rice genome (about 430 Mbp) is now available and the sequencing of this genome will be completed in the near future. The much larger genomes of several important crop species, such as wheat (about 16,000 Mbp) or maize (about 2500 Mbp), may not be fully sequenced with current technology. Instead, sequencing-analysis strategies are being developed to obtain sequencing and mapping information selectively for the genic fraction (gene space) of complex plant genomes.

  19. 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.

  20. 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.

  1. 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.

  2. Clustering of gene ontology terms in genomes.

    Science.gov (United States)

    Tiirikka, Timo; Siermala, Markku; Vihinen, Mauno

    2014-10-25

    Although protein coding genes occupy only a small fraction of genomes in higher species, they are not randomly distributed within or between chromosomes. Clustering of genes with related function(s) and/or characteristics has been evident at several different levels. To study how common the clustering of functionally related genes is and what kind of functions the end products of these genes are involved, we collected gene ontology (GO) terms for complete genomes and developed a method to detect previously undefined gene clustering. Exhaustive analysis was performed for seven widely studied species ranging from human to Escherichia coli. To overcome problems related to varying gene lengths and densities, a novel method was developed and a fixed number of genes were analyzed irrespective of the genome span covered. Statistically very significant GO term clustering was apparent in all the investigated genomes. The analysis window, which ranged from 5 to 50 consecutive genes, revealed extensive GO term clusters for genes with widely varying functions. Here, the most interesting and significant results are discussed and the complete dataset for each analyzed species is available at the GOme database at http://bioinf.uta.fi/GOme. The results indicated that clusters of genes with related functions are very common, not only in bacteria, in which operons are frequent, but also in all the studied species irrespective of how complex they are. There are some differences between species but in all of them GO term clusters are common and of widely differing sizes. The presented method can be applied to analyze any genome or part of a genome for which descriptive features are available, and thus is not restricted to ontology terms. This method can also be applied to investigate gene and protein expression patterns. The results pave a way for further studies of mechanisms that shape genome structure and evolutionary forces related to them. Copyright © 2014 Elsevier B.V. All

  3. 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.

  4. 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.

  5. Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches.

    Science.gov (United States)

    Middleton, Frank A; Pato, Carlos N; Gentile, Karen L; McGann, Lindsay; Brown, Andrea M; Trauzzi, Marco; Diab, Heba; Morley, Christopher P; Medeiros, Helena; Macedo, Antonio; Azevedo, M Helena; Pato, Michele T

    2005-07-05

    We performed global RNA transcript analysis and comprehensive gene group analysis of peripheral blood leukocyte (PBL) RNA from two groups of matched sib-pairs that were discordant for either schizophrenia (n = 33 sib-pairs) or bipolar disorder (n = 5 sib-pairs). The pairs chosen for these analyses were selected from families with known patterns of genetic linkage (5q for schizophrenia and 6q for bipolar disorder). At the single gene level, we obtained lists of the transcripts with the most significant changes in expression and from these lists determined those with the highest degree of predictive power for classifying subjects according to diagnosis in these samples. At the gene group level, we comprehensively analyzed pairwise expression changes of more than 4,000 functional groups and cytogenetic locations, and present a novel method of displaying these data that we term "cytogenomic" mapping. Verification of selected changes in expression was performed using quantitative real-time RT-PCR. Our results provide compelling evidence for the utility of analyzing PBL RNA for changes in expression in neuropsychiatric disorders. Copyright 2005 Wiley-Liss, Inc.

  6. 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.

  7. 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

  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.

  9. The Aspergillus Genome Database, a curated comparative genomics resource for gene, protein and sequence information for the Aspergillus research community.

    Science.gov (United States)

    Arnaud, Martha B; Chibucos, Marcus C; Costanzo, Maria C; Crabtree, Jonathan; Inglis, Diane O; Lotia, Adil; Orvis, Joshua; Shah, Prachi; Skrzypek, Marek S; Binkley, Gail; Miyasato, Stuart R; Wortman, Jennifer R; Sherlock, Gavin

    2010-01-01

    The Aspergillus Genome Database (AspGD) is an online genomics resource for researchers studying the genetics and molecular biology of the Aspergilli. AspGD combines high-quality manual curation of the experimental scientific literature examining the genetics and molecular biology of Aspergilli, cutting-edge comparative genomics approaches to iteratively refine and improve structural gene annotations across multiple Aspergillus species, and web-based research tools for accessing and exploring the data. All of these data are freely available at http://www.aspgd.org. We welcome feedback from users and the research community at aspergillus-curator@genome.stanford.edu.

  10. Genetics in PSC: what do the "risk genes" teach us?

    Science.gov (United States)

    Folseraas, Trine; Liaskou, Evaggelia; Anderson, Carl A; Karlsen, Tom H

    2015-06-01

    A role of genetics in primary sclerosing cholangitis (PSC) development is now firmly established. A total of 16 risk genes have been reported at highly robust ("genome-wide") significance levels, and ongoing efforts suggest that the list will ultimately be considerably longer. Importantly, this genetic risk pool so far accounts for less than 10 % of an estimated overall PSC susceptibility. The relative importance of genetic versus environmental factors (including gene-gene and gene-environment interactions) in remaining aspects of PSC pathogenesis is unknown, and other study designs than genome-wide association studies are needed to explore these aspects. For some of the loci, e.g. HLA and FUT2, distinct interacting environmental factors may exist, and working from the genetic associations may prove one valid path for determining the specific nature of environmental triggers. So far the biological implications for PSC risk genes are typically merely hypothesized based on previously published literature, and there is therefore a strong need for dedicated translational studies to determine their roles within the specific disease context of PSC. Apparently, most risk loci seem to involve in a subset of biological pathways for which genetic associations exist in a multitude of immune-mediated diseases, accounting for both inflammatory bowel disease as well as prototypical autoimmunity. In the present article, we will survey the current knowledge on PSC genetics with a particular emphasis on the pathophysiological insight potentially gained from genetic risk loci involving in this profound immunogenetic pleiotropy.

  11. 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.

  12. Comparative genomics of the bacterial genus Listeria: Genome evolution is characterized by limited gene acquisition and limited gene loss.

    Science.gov (United States)

    den Bakker, Henk C; Cummings, Craig A; Ferreira, Vania; Vatta, Paolo; Orsi, Renato H; Degoricija, Lovorka; Barker, Melissa; Petrauskene, Olga; Furtado, Manohar R; Wiedmann, Martin

    2010-12-02

    The bacterial genus Listeria contains pathogenic and non-pathogenic species, including the pathogens L. monocytogenes and L. ivanovii, both of which carry homologous virulence gene clusters such as the prfA cluster and clusters of internalin genes. Initial evidence for multiple deletions of the prfA cluster during the evolution of Listeria indicates that this genus provides an interesting model for studying the evolution of virulence and also presents practical challenges with regard to definition of pathogenic strains. To better understand genome evolution and evolution of virulence characteristics in Listeria, we used a next generation sequencing approach to generate draft genomes for seven strains representing Listeria species or clades for which genome sequences were not available. Comparative analyses of these draft genomes and six publicly available genomes, which together represent the main Listeria species, showed evidence for (i) a pangenome with 2,032 core and 2,918 accessory genes identified to date, (ii) a critical role of gene loss events in transition of Listeria species from facultative pathogen to saprotroph, even though a consistent pattern of gene loss seemed to be absent, and a number of isolates representing non-pathogenic species still carried some virulence associated genes, and (iii) divergence of modern pathogenic and non-pathogenic Listeria species and strains, most likely circa 47 million years ago, from a pathogenic common ancestor that contained key virulence genes. Genome evolution in Listeria involved limited gene loss and acquisition as supported by (i) a relatively high coverage of the predicted pan-genome by the observed pan-genome, (ii) conserved genome size (between 2.8 and 3.2 Mb), and (iii) a highly syntenic genome. Limited gene loss in Listeria did include loss of virulence associated genes, likely associated with multiple transitions to a saprotrophic lifestyle. The genus Listeria thus provides an example of a group of

  13. Comparative genomics of the bacterial genus Listeria: Genome evolution is characterized by limited gene acquisition and limited gene loss

    Directory of Open Access Journals (Sweden)

    Barker Melissa

    2010-12-01

    Full Text Available Abstract Background The bacterial genus Listeria contains pathogenic and non-pathogenic species, including the pathogens L. monocytogenes and L. ivanovii, both of which carry homologous virulence gene clusters such as the prfA cluster and clusters of internalin genes. Initial evidence for multiple deletions of the prfA cluster during the evolution of Listeria indicates that this genus provides an interesting model for studying the evolution of virulence and also presents practical challenges with regard to definition of pathogenic strains. Results To better understand genome evolution and evolution of virulence characteristics in Listeria, we used a next generation sequencing approach to generate draft genomes for seven strains representing Listeria species or clades for which genome sequences were not available. Comparative analyses of these draft genomes and six publicly available genomes, which together represent the main Listeria species, showed evidence for (i a pangenome with 2,032 core and 2,918 accessory genes identified to date, (ii a critical role of gene loss events in transition of Listeria species from facultative pathogen to saprotroph, even though a consistent pattern of gene loss seemed to be absent, and a number of isolates representing non-pathogenic species still carried some virulence associated genes, and (iii divergence of modern pathogenic and non-pathogenic Listeria species and strains, most likely circa 47 million years ago, from a pathogenic common ancestor that contained key virulence genes. Conclusions Genome evolution in Listeria involved limited gene loss and acquisition as supported by (i a relatively high coverage of the predicted pan-genome by the observed pan-genome, (ii conserved genome size (between 2.8 and 3.2 Mb, and (iii a highly syntenic genome. Limited gene loss in Listeria did include loss of virulence associated genes, likely associated with multiple transitions to a saprotrophic lifestyle. The genus

  14. JGI Plant Genomics Gene Annotation Pipeline

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Shengqiang; Rokhsar, Dan; Goodstein, David; Hayes, David; Mitros, Therese

    2014-07-14

    Plant genomes vary in size and are highly complex with a high amount of repeats, genome duplication and tandem duplication. Gene encodes a wealth of information useful in studying organism and it is critical to have high quality and stable gene annotation. Thanks to advancement of sequencing technology, many plant species genomes have been sequenced and transcriptomes are also sequenced. To use these vastly large amounts of sequence data to make gene annotation or re-annotation in a timely fashion, an automatic pipeline is needed. JGI plant genomics gene annotation pipeline, called integrated gene call (IGC), is our effort toward this aim with aid of a RNA-seq transcriptome assembly pipeline. It utilizes several gene predictors based on homolog peptides and transcript ORFs. See Methods for detail. Here we present genome annotation of JGI flagship green plants produced by this pipeline plus Arabidopsis and rice except for chlamy which is done by a third party. The genome annotations of these species and others are used in our gene family build pipeline and accessible via JGI Phytozome portal whose URL and front page snapshot are shown below.

  15. 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...

  16. 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.

  17. Gene finding in the chicken genome

    Directory of Open Access Journals (Sweden)

    Antonarakis Stylianos E

    2005-05-01

    Full Text Available Abstract Background Despite the continuous production of genome sequence for a number of organisms, reliable, comprehensive, and cost effective gene prediction remains problematic. This is particularly true for genomes for which there is not a large collection of known gene sequences, such as the recently published chicken genome. We used the chicken sequence to test comparative and homology-based gene-finding methods followed by experimental validation as an effective genome annotation method. Results We performed experimental evaluation by RT-PCR of three different computational gene finders, Ensembl, SGP2 and TWINSCAN, applied to the chicken genome. A Venn diagram was computed and each component of it was evaluated. The results showed that de novo comparative methods can identify up to about 700 chicken genes with no previous evidence of expression, and can correctly extend about 40% of homology-based predictions at the 5' end. Conclusions De novo comparative gene prediction followed by experimental verification is effective at enhancing the annotation of the newly sequenced genomes provided by standard homology-based methods.

  18. 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

  19. Impact of genetic polymorphisms of four cytokine genes on treatment ...

    African Journals Online (AJOL)

    Manar Obada

    2016-04-25

    Apr 25, 2016 ... genes on treatment induced viral clearance in HCV infected Egyptian .... shown to influence TNF-a expression [11]. Interferon gamma ... has been carried out in accordance with The Code of Ethics of the World ... Molecular testing. Genomic DNA ..... Our findings could be explained on the basis that genetic.

  20. 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

  1. 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.

  2. Comparative genomic analysis of soybean flowering genes.

    Directory of Open Access Journals (Sweden)

    Chol-Hee Jung

    Full Text Available Flowering is an important agronomic trait that determines crop yield. Soybean is a major oilseed legume crop used for human and animal feed. Legumes have unique vegetative and floral complexities. Our understanding of the molecular basis of flower initiation and development in legumes is limited. Here, we address this by using a computational approach to examine flowering regulatory genes in the soybean genome in comparison to the most studied model plant, Arabidopsis. For this comparison, a genome-wide analysis of orthologue groups was performed, followed by an in silico gene expression analysis of the identified soybean flowering genes. Phylogenetic analyses of the gene families highlighted the evolutionary relationships among these candidates. Our study identified key flowering genes in soybean and indicates that the vernalisation and the ambient-temperature pathways seem to be the most variant in soybean. A comparison of the orthologue groups containing flowering genes indicated that, on average, each Arabidopsis flowering gene has 2-3 orthologous copies in soybean. Our analysis highlighted that the CDF3, VRN1, SVP, AP3 and PIF3 genes are paralogue-rich genes in soybean. Furthermore, the genome mapping of the soybean flowering genes showed that these genes are scattered randomly across the genome. A paralogue comparison indicated that the soybean genes comprising the largest orthologue group are clustered in a 1.4 Mb region on chromosome 16 of soybean. Furthermore, a comparison with the undomesticated soybean (Glycine soja revealed that there are hundreds of SNPs that are associated with putative soybean flowering genes and that there are structural variants that may affect the genes of the light-signalling and ambient-temperature pathways in soybean. Our study provides a framework for the soybean flowering pathway and insights into the relationship and evolution of flowering genes between a short-day soybean and the long-day plant

  3. 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.

  4. Integrase-directed recovery of functional genes from genomic libraries.

    Science.gov (United States)

    Rowe-Magnus, Dean A

    2009-09-01

    Large population sizes, rapid growth and 3.8 billion years of evolution firmly establish microorganisms as a major source of the planet's biological and genetic diversity. However, up to 99% of the microorganisms in a given environment cannot be cultured. Culture-independent methods that directly access the genetic potential of an environmental sample can unveil new proteins with diverse functions, but the sequencing of random DNA can generate enormous amounts of extraneous data. Integrons are recombination systems that accumulate open reading frames (gene cassettes), many of which code for functional proteins with enormous adaptive potential. Some integrons harbor hundreds of gene cassettes and evidence suggests that the gene cassette pool may be limitless in size. Accessing this genetic pool has been hampered since sequence-based techniques, such as hybridization or PCR, often recover only partial genes or a small subset of those present in the sample. Here, a three-plasmid genetic strategy for the sequence-independent recovery of gene cassettes from genomic libraries is described and its use by retrieving functional gene cassettes from the chromosomal integron of Vibrio vulnificus ATCC 27562 is demonstrated. By manipulating the natural activity of integrons, we can gain access to the caches of functional genes amassed by these structures.

  5. 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.

  6. 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

  7. 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

  8. Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting | Office of Cancer Genomics

    Science.gov (United States)

    The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell-cycle arrest.

  9. Metabolic Genes within Cyanophage Genomes: Implications for Diversity and Evolution

    Directory of Open Access Journals (Sweden)

    E-Bin Gao

    2016-09-01

    Full Text Available Cyanophages, a group of viruses specifically infecting cyanobacteria, are genetically diverse and extensively abundant in water environments. As a result of selective pressure, cyanophages often acquire a range of metabolic genes from host genomes. The host-derived genes make a significant contribution to the ecological success of cyanophages. In this review, we summarize the host-derived metabolic genes, as well as their origin and roles in cyanophage evolution and important host metabolic pathways, such as the light-dependent reactions of photosynthesis, the pentose phosphate pathway, nutrient acquisition and nucleotide biosynthesis. We also discuss the suitability of the host-derived metabolic genes as potential diagnostic markers for the detection of genetic diversity of cyanophages in natural environments.

  10. 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.

  11. A genome-wide 20 K citrus microarray for gene expression analysis

    OpenAIRE

    Gadea Jose; Forment Javier; Santiago Julia; Marques M Carmen; Juarez Jose; Mauri Nuria; Martinez-Godoy M Angeles

    2008-01-01

    Abstract Background Understanding of genetic elements that contribute to key aspects of citrus biology will impact future improvements in this economically important crop. Global gene expression analysis demands microarray platforms with a high genome coverage. In the last years, genome-wide EST collections have been generated in citrus, opening the possibility to create new tools for functional genomics in this crop plant. Results We have designed and constructed a publicly available genome-...

  12. A genome-wide 20 K citrus microarray for gene expression analysis

    OpenAIRE

    Martinez-Godoy, M Angeles; Mauri, Nuria; Juarez, Jose; Marques, M Carmen; Santiago, Julia; Forment, Javier; Gadea, Jose

    2008-01-01

    Background Understanding of genetic elements that contribute to key aspects of citrus biology will impact future improvements in this economically important crop. Global gene expression analysis demands microarray platforms with a high genome coverage. In the last years, genome-wide EST collections have been generated in citrus, opening the possibility to create new tools for functional genomics in this crop plant. Results We have designed and constructed a publicly available genome-wide cDNA...

  13. [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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. Identification of neural outgrowth genes using genome-wide RNAi.

    Directory of Open Access Journals (Sweden)

    Katharine J Sepp

    2008-07-01

    Full Text Available While genetic screens have identified many genes essential for neurite outgrowth, they have been limited in their ability to identify neural genes that also have earlier critical roles in the gastrula, or neural genes for which maternally contributed RNA compensates for gene mutations in the zygote. To address this, we developed methods to screen the Drosophila genome using RNA-interference (RNAi on primary neural cells and present the results of the first full-genome RNAi screen in neurons. We used live-cell imaging and quantitative image analysis to characterize the morphological phenotypes of fluorescently labelled primary neurons and glia in response to RNAi-mediated gene knockdown. From the full genome screen, we focused our analysis on 104 evolutionarily conserved genes that when downregulated by RNAi, have morphological defects such as reduced axon extension, excessive branching, loss of fasciculation, and blebbing. To assist in the phenotypic analysis of the large data sets, we generated image analysis algorithms that could assess the statistical significance of the mutant phenotypes. The algorithms were essential for the analysis of the thousands of images generated by the screening process and will become a valuable tool for future genome-wide screens in primary neurons. Our analysis revealed unexpected, essential roles in neurite outgrowth for genes representing a wide range of functional categories including signalling molecules, enzymes, channels, receptors, and cytoskeletal proteins. We also found that genes known to be involved in protein and vesicle trafficking showed similar RNAi phenotypes. We confirmed phenotypes of the protein trafficking genes Sec61alpha and Ran GTPase using Drosophila embryo and mouse embryonic cerebral cortical neurons, respectively. Collectively, our results showed that RNAi phenotypes in primary neural culture can parallel in vivo phenotypes, and the screening technique can be used to identify many new

  19. The "one-step" Bean pod mottle virus (BPMV)-derived vector is a functional genomics tool for efficient overexpression of heterologous protein, virus-induced gene silencing and genetic mapping of BPMV R-gene in common bean (Phaseolus vulgaris L.).

    Science.gov (United States)

    Pflieger, Stéphanie; Blanchet, Sophie; Meziadi, Chouaib; Richard, Manon M S; Thareau, Vincent; Mary, Fanny; Mazoyer, Céline; Geffroy, Valérie

    2014-08-29

    Over the last two years, considerable advances have been made in common bean (Phaseolus vulgaris L.) genomics, especially with the completion of the genome sequence and the availability of RNAseq data. However, as common bean is recalcitrant to stable genetic transformation, much work remains to be done for the development of functional genomics tools adapted to large-scale studies. Here we report the successful implementation of an efficient viral vector system for foreign gene expression, virus-induced gene silencing (VIGS) and genetic mapping of a BPMV resistance gene in common bean, using a "one-step" BPMV vector originally developed in soybean. With the goal of developing this vector for high-throughput VIGS studies in common bean, we optimized the conditions for rub-inoculation of infectious BPMV-derived plasmids in common bean cv. Black Valentine. We then tested the susceptibility to BPMV of six cultivars, and found that only Black Valentine and JaloEEP558 were susceptible to BPMV. We used a BPMV-GFP construct to detect the spatial and temporal infection patterns of BPMV in vegetative and reproductive tissues. VIGS of the PHYTOENE DESATURASE (PvPDS) marker gene was successfully achieved with recombinant BPMV vectors carrying fragments ranging from 132 to 391 bp. Finally, we mapped a gene for resistance to BPMV (R-BPMV) at one end of linkage group 2, in the vicinity of a locus (I locus) previously shown to be involved in virus resistance. The "one-step" BPMV vector system therefore enables rapid and simple functional studies in common bean, and could be suitable for large-scale analyses. In the post-genomic era, these advances are timely for the common bean research community.

  20. Comparative genomics of Neisseria meningitidis: core genome, islands of horizontal transfer and pathogen-specific genes.

    Science.gov (United States)

    Dunning Hotopp, Julie C; Grifantini, Renata; Kumar, Nikhil; Tzeng, Yih Ling; Fouts, Derrick; Frigimelica, Elisabetta; Draghi, Monia; Giuliani, Marzia Monica; Rappuoli, Rino; Stephens, David S; Grandi, Guido; Tettelin, Hervé

    2006-12-01

    To better understand Neisseria meningitidis genomes and virulence, microarray comparative genome hybridization (mCGH) data were collected from one Neisseria cinerea, two Neisseria lactamica, two Neisseria gonorrhoeae and 48 Neisseria meningitidis isolates. For N. meningitidis, these isolates are from diverse clonal complexes, invasive and carriage strains, and all major serogroups. The microarray platform represented N. meningitidis strains MC58, Z2491 and FAM18, and N. gonorrhoeae FA1090. By comparing hybridization data to genome sequences, the core N. meningitidis genome and insertions/deletions (e.g. capsule locus, type I secretion system) related to pathogenicity were identified, including further characterization of the capsule locus, bioinformatics analysis of a type I secretion system, and identification of some metabolic pathways associated with intracellular survival in pathogens. Hybridization data clustered meningococcal isolates from similar clonal complexes that were distinguished by the differential presence of six distinct islands of horizontal transfer. Several of these islands contained prophage or other mobile elements, including a novel prophage and a transposon carrying portions of a type I secretion system. Acquisition of some genetic islands appears to have occurred in multiple lineages, including transfer between N. lactamica and N. meningitidis. However, island acquisition occurs infrequently, such that the genomic-level relationship is not obscured within clonal complexes. The N. meningitidis genome is characterized by the horizontal acquisition of multiple genetic islands; the study of these islands reveals important sets of genes varying between isolates and likely to be related to pathogenicity.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. [The application of genome editing in identification of plant gene function and crop breeding].

    Science.gov (United States)

    Xiangchun, Zhou; Yongzhong, Xing

    2016-03-01

    Plant genome can be modified via current biotechnology with high specificity and excellent efficiency. Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system are the key engineered nucleases used in the genome editing. Genome editing techniques enable gene targeted mutagenesis, gene knock-out, gene insertion or replacement at the target sites during the endogenous DNA repair process, including non-homologous end joining (NHEJ) and homologous recombination (HR), triggered by the induction of DNA double-strand break (DSB). Genome editing has been successfully applied in the genome modification of diverse plant species, such as Arabidopsis thaliana, Oryza sativa, and Nicotiana tabacum. In this review, we summarize the application of genome editing in identification of plant gene function and crop breeding. Moreover, we also discuss the improving points of genome editing in crop precision genetic improvement for further study.

  6. 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.

  7. 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.

  8. 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.

  9. Gene discovery in the Entamoeba invadens genome.

    Science.gov (United States)

    Wang, Zheng; Samuelson, John; Clark, C Graham; Eichinger, Daniel; Paul, Jaishree; Van Dellen, Katrina; Hall, Neil; Anderson, Iain; Loftus, Brendan

    2003-06-01

    Entamoeba invadens, a parasite of reptiles, is a model for the study of encystation by the human enteric pathogen Entamoeba histolytica, because E. invadens form cysts in axenic culture. With approximately 0.5-fold sequence coverage of the genome, we were able to get insights into E. invadens gene and genome features. Overall, the E. invadens genome displays many of the features that are emerging from ongoing genome sequencing efforts in E. histolytica. At the nucleotide level the E. invadens genome has on average 60% sequence identity with that of E. histolytica. The presence of introns in E. invadens was predicted with similar consensus (GTTTGT em leader A/TAG) sequences to those identified in E. histolytica and Entamoeba dispar. Sequences highly repeated in the genome of E. histolytica (rRNAs, tRNAs, CXXC-rich proteins, and Leu-rich repeat proteins) were found to be highly repeated in the E. invadens genome. Numerous proteins homologous to those implicated in amoebic virulence, (Gal/GalNAc lectins, amoebapores, and cysteine proteinases) and drug resistance (p-glycoproteins) were identified. Homologs of proteins involved in cell cycle, vesicular trafficking and signal transduction were identified, which may be involved in en/excystation and cell growth of E. invadens. Finally, multiple copies of a number of E. invadens genes coding for predicted enzymes involved in core metabolism and the targets of anti-amoebic drugs were identified.

  10. In-silico human genomics with GeneCards

    Directory of Open Access Journals (Sweden)

    Stelzer Gil

    2011-10-01

    Full Text Available Abstract Since 1998, the bioinformatics, systems biology, genomics and medical communities have enjoyed a synergistic relationship with the GeneCards database of human genes (http://www.genecards.org. This human gene compendium was created to help to introduce order into the increasing chaos of information flow. As a consequence of viewing details and deep links related to specific genes, users have often requested enhanced capabilities, such that, over time, GeneCards has blossomed into a suite of tools (including GeneDecks, GeneALaCart, GeneLoc, GeneNote and GeneAnnot for a variety of analyses of both single human genes and sets thereof. In this paper, we focus on inhouse and external research activities which have been enabled, enhanced, complemented and, in some cases, motivated by GeneCards. In turn, such interactions have often inspired and propelled improvements in GeneCards. We describe here the evolution and architecture of this project, including examples of synergistic applications in diverse areas such as synthetic lethality in cancer, the annotation of genetic variations in disease, omics integration in a systems biology approach to kidney disease, and bioinformatics tools.

  11. Evaluation of the utility of gene expression and metabolic information for genomic prediction in maize.

    Science.gov (United States)

    Guo, Zhigang; Magwire, Michael M; Basten, Christopher J; Xu, Zhanyou; Wang, Daolong

    2016-12-01

    Predictive ability derived from gene expression and metabolic information was evaluated using genomic prediction methods based on datasets from a public maize panel. With the rapid development of high throughput biological technologies, information from gene expression and metabolites has received growing attention in plant genetics and breeding. In this study, we evaluated the utility of gene expression and metabolic information for genomic prediction using data obtained from a maize diversity panel. Our results show that, when used as predictor variables, gene expression levels and metabolite abundances provided reasonable predictive abilities relative to those based on genetic markers, although these values were not as large as those with genetic markers. Integrating gene expression levels and metabolite abundances with genetic markers significantly improved predictive abilities in comparison to the benchmark genomic best linear unbiased prediction model using genome-wide markers only. Predictive abilities based on gene expression and metabolites were trait-specific and were affected by the time of measurement and tissue samples as well as the number of genes and metabolites included in the model. In general, our results suggest that, rather than being conventionally used as intermediate phenotypes, gene expression and metabolic information can be used as predictors for genomic prediction and help improve genetic gains for complex traits in breeding programs.

  12. 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.

  13. Genome origin, historical hybridization and genetic differentiation in Anthosachne australasica (Triticeae; Poaceae), inferred from chloroplast rbcL, trnH-psbA and nuclear Acc1 gene sequences.

    Science.gov (United States)

    Sha, Li-Na; Fan, Xing; Wang, Xiao-Li; Dong, Zhen-Zhen; Zeng, Jian; Zhang, Hai-Qin; Kang, Hou-Yang; Wang, Yi; Liao, Jin-Qiu; Zhou, Yong-Hong

    2017-01-01

    Anthosachne Steudel is a group of allopolyploid species that was derived from hexaploidization between the Asian StY genome Roegneria entity and the Australasia W genome Australopyrum species. Polyploidization and apomixis contribute to taxonomic complexity in Anthosachne Here, a study is presented on the phylogeny and evolutionary history of Anthosachne australasica The aims are to demonstrate the process of polyploidization events and to explore the differentiation patterns of the St genome following geographic isolation. Chloroplast rbcL and trnH-psbA and nuclear Acc1 gene sequences of 60 Anthosachne taxa and nine Roegneria species were analysed with those of 33 diploid taxa representing 20 basic genomes in Triticeae. The phylogenetic relationships were reconstructed. A time-calibrated phylogeny was generated to estimate the evolutionary history of A. australasica Nucleotide diversity patterns were used to assess the divergence within A. australasica and between Anthosachne and its putative progenitors. Three homoeologous copies of the Acc1 sequences from Anthosachne were grouped with the Acc1 sequences from Roegneria, Pseudoroegneria, Australopyrum, Dasypyrum and Peridictyon The chloroplast sequences of Anthosachne were clustered with those from Roegneria and Pseudoroegneria Divergence time for Anthosachne was dated to 4·66 million years ago (MYA). The level of nucleotide diversity in Australasian Anthosachne was higher than that in continental Roegneria A low level of genetic differentiation within the A. australasica complex was found. Anthosachne originated from historical hybridization between Australopyrum species and a Roegneria entity colonized from Asia to Australasia via South-east Asia during the late Miocene. The St lineage served as the maternal donor during the speciation of Anthosachne A contrasting pattern of population genetic structure exists in the A. australasica complex. Greater diversity in island Anthosachne compared with continental

  14. 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.

  15. Gene-Environment Interactions in Asthma: Genetic and Epigenetic Effects.

    Science.gov (United States)

    Lee, Jong-Uk; Kim, Jeong Dong; Park, Choon-Sik

    2015-07-01

    Over the past three decades, a large number of genetic studies have been aimed at finding genetic variants associated with the risk of asthma, applying various genetic and genomic approaches including linkage analysis, candidate gene polymorphism studies, and genome-wide association studies (GWAS). However, contrary to general expectation, even single nucleotide polymorphisms (SNPs) discovered by GWAS failed to fully explain the heritability of asthma. Thus, application of rare allele polymorphisms in well defined phenotypes and clarification of environmental factors have been suggested to overcome the problem of 'missing' heritability. Such factors include allergens, cigarette smoke, air pollutants, and infectious agents during pre- and post-natal periods. The first and simplest interaction between a gene and the environment is a candidate interaction of both a well known gene and environmental factor in a direct physical or chemical interaction such as between CD14 and endotoxin or between HLA and allergens. Several GWAS have found environmental interactions with occupational asthma, aspirin exacerbated respiratory disease, tobacco smoke-related airway dysfunction, and farm-related atopic diseases. As one of the mechanisms behind gene-environment interaction is epigenetics, a few studies on DNA CpG methylation have been reported on subphenotypes of asthma, pitching the exciting idea that it may be possible to intervene at the junction between the genome and the environment. Epigenetic studies are starting to include data from clinical samples, which will make them another powerful tool for re-search on gene-environment interactions in asthma.

  16. Genome-Wide Associations of Gene Expression Variation in Humans.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis- to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

  17. Genome-wide associations of gene expression variation in humans.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    2005-12-01

    Full Text Available The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis- to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

  18. 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.

  19. A Candida albicans CRISPR system permits genetic engineering of essential genes and gene families.

    Science.gov (United States)

    Vyas, Valmik K; Barrasa, M Inmaculada; Fink, Gerald R

    Candida albicans is a pathogenic yeast that causes mucosal and systematic infections with high mortality. The absence of facile molecular genetics has been a major impediment to analysis of pathogenesis. The lack of meiosis coupled with the absence of plasmids makes genetic engineering cumbersome, especially for essential functions and gene families. We describe a C. albicans CRISPR system that overcomes many of the obstacles to genetic engineering in this organism. The high frequency with which CRISPR-induced mutations can be directed to target genes enables easy isolation of homozygous gene knockouts, even without selection. Moreover, the system permits the creation of strains with mutations in multiple genes, gene families, and genes that encode essential functions. This CRISPR system is also effective in a fresh clinical isolate of undetermined ploidy. Our method transforms the ability to manipulate the genome of Candida and provides a new window into the biology of this pathogen.

  20. 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..

  1. Tandemly Arrayed Genes in Vertebrate Genomes

    Directory of Open Access Journals (Sweden)

    Deng Pan

    2008-01-01

    Full Text Available Tandemly arrayed genes (TAGs are duplicated genes that are linked as neighbors on a chromosome, many of which have important physiological and biochemical functions. Here we performed a survey of these genes in 11 available vertebrate genomes. TAGs account for an average of about 14% of all genes in these vertebrate genomes, and about 25% of all duplications. The majority of TAGs (72–94% have parallel transcription orientation (i.e., they are encoded on the same strand in contrast to the genome, which has about 50% of its genes in parallel transcription orientation. The majority of tandem arrays have only two members. In all species, the proportion of genes that belong to TAGs tends to be higher in large gene families than in small ones; together with our recent finding that tandem duplication played a more important role than retroposition in large families, this fact suggests that among all types of duplication mechanisms, tandem duplication is the predominant mechanism of duplication, especially in large families. Finally, several species have a higher proportion of large tandem arrays that are species-specific than random expectation.

  2. From risk genes to psychiatric phenotypes - Studies of fibroblast growth factor-related and genome-wide genetic variants in humans and mice

    NARCIS (Netherlands)

    Terwisscha van Scheltinga, A.F.

    2013-01-01

    Schizophrenia is a severe mental disorder with a high heritability. This thesis describes studies on the association between genetic variants and phenotypes related to schizophrenia, such as brain volume and IQ, in order to learn about which processes are affected by schizophrenia-associated genetic

  3. 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.

  4. Comparative Genomic Analysis Reveals Organization, Function and Evolution of ars Genes in Pantoea spp.

    OpenAIRE

    Wang, Liying; Wang, Jin; Jing, Chuanyong

    2017-01-01

    Numerous genes are involved in various strategies to resist toxic arsenic (As). However, the As resistance strategy in genus Pantoea is poorly understood. In this study, a comparative genome analysis of 23 Pantoea genomes was conducted. Two vertical genetic arsC-like genes without any contribution to As resistance were found to exist in the 23 Pantoea strains. Besides the two arsC-like genes, As resistance gene clusters arsRBC or arsRBCH were found in 15 Pantoea genomes. These ars clusters we...

  5. Genome-wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stress.

    LENUS (Irish Health Repository)

    Enjalbert, Brice

    2009-04-01

    Candida albicans is more pathogenic than Candida dubliniensis. However, this disparity in virulence is surprising given the high level of sequence conservation and the wide range of phenotypic traits shared by these two species. Increased sensitivity to environmental stresses has been suggested to be a possible contributory factor to the lower virulence of C. dubliniensis. In this study, we investigated, in the first comparison of C. albicans and C. dubliniensis by transcriptional profiling, global gene expression in each species when grown under conditions in which the two species exhibit differential stress tolerance. The profiles revealed similar core responses to stresses in both species, but differences in the amplitude of the general transcriptional responses to thermal, salt and oxidative stress. Differences in the regulation of specific stress genes were observed between the two species. In particular, ENA21, encoding a sodium ion transporter, was strongly induced in C. albicans but not in C. dubliniensis. In addition, ENA21 was identified in a forward genetic screen for C. albicans genomic sequences that increase salt tolerance in C. dubliniensis. Introduction of a single copy of CaENA21 was subsequently shown to be sufficient to confer salt tolerance upon C. dubliniensis.

  6. 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...

  7. 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.

  8. Synaptotagmin gene content of the sequenced genomes

    Directory of Open Access Journals (Sweden)

    Craxton Molly

    2004-07-01

    Full Text Available Abstract Background Synaptotagmins exist as a large gene family in mammals. There is much interest in the function of certain family members which act crucially in the regulated synaptic vesicle exocytosis required for efficient neurotransmission. Knowledge of the functions of other family members is relatively poor and the presence of Synaptotagmin genes in plants indicates a role for the family as a whole which is wider than neurotransmission. Identification of the Synaptotagmin genes within completely sequenced genomes can provide the entire Synaptotagmin gene complement of each sequenced organism. Defining the detailed structures of all the Synaptotagmin genes and their encoded products can provide a useful resource for functional studies and a deeper understanding of the evolution of the gene family. The current rapid increase in the number of sequenced genomes from different branches of the tree of life, together with the public deposition of evolutionarily diverse transcript sequences make such studies worthwhile. Results I have compiled a detailed list of the Synaptotagmin genes of Caenorhabditis, Anopheles, Drosophila, Ciona, Danio, Fugu, Mus, Homo, Arabidopsis and Oryza by examining genomic and transcript sequences from public sequence databases together with some transcript sequences obtained by cDNA library screening and RT-PCR. I have compared all of the genes and investigated the relationship between plant Synaptotagmins and their non-Synaptotagmin counterparts. Conclusions I have identified and compared 98 Synaptotagmin genes from 10 sequenced genomes. Detailed comparison of transcript sequences reveals abundant and complex variation in Synaptotagmin gene expression and indicates the presence of Synaptotagmin genes in all animals and land plants. Amino acid sequence comparisons indicate patterns of conservation and diversity in function. Phylogenetic analysis shows the origin of Synaptotagmins in multicellular eukaryotes and their

  9. Construction of the BAC Library of Small Abalone (Haliotis diversicolor) for Gene Screening and Genome Characterization.

    Science.gov (United States)

    Jiang, Likun; You, Weiwei; Zhang, Xiaojun; Xu, Jian; Jiang, Yanliang; Wang, Kai; Zhao, Zixia; Chen, Baohua; Zhao, Yunfeng; Mahboob, Shahid; Al-Ghanim, Khalid A; Ke, Caihuan; Xu, Peng

    2016-02-01

    The small abalone (Haliotis diversicolor) is one of the most important aquaculture species in East Asia. To facilitate gene cloning and characterization, genome analysis, and genetic breeding of it, we constructed a large-insert bacterial artificial chromosome (BAC) library, which is an important genetic tool for advanced genetics and genomics research. The small abalone BAC library includes 92,610 clones with an average insert size of 120 Kb, equivalent to approximately 7.6× of the small abalone genome. We set up three-dimensional pools and super pools of 18,432 BAC clones for target gene screening using PCR method. To assess the approach, we screened 12 target genes in these 18,432 BAC clones and identified 16 positive BAC clones. Eight positive BAC clones were then sequenced and assembled with the next generation sequencing platform. The assembled contigs representing these 8 BAC clones spanned 928 Kb of the small abalone genome, providing the first batch of genome sequences for genome evaluation and characterization. The average GC content of small abalone genome was estimated as 40.33%. A total of 21 protein-coding genes, including 7 target genes, were annotated into the 8 BACs, which proved the feasibility of PCR screening approach with three-dimensional pools in small abalone BAC library. One hundred fifty microsatellite loci were also identified from the sequences for marker development in the future. The BAC library and clone pools provided valuable resources and tools for genetic breeding and conservation of H. diversicolor.

  10. Genomics of the human carnitine acyltransferase genes

    NARCIS (Netherlands)

    van der Leij, FR; Huijkman, NCA; Boomsma, C; Kuipers, JRG; Bartelds, B

    2000-01-01

    Five genes in the human genome are known to encode different active forms of related carnitine acyltransferases: CPT1A for liver-type carnitine palmitoyltransferase I, CPT1B for muscle-type carnitine palmitoyltransferase I, CPT2 for carnitine palmitoyltransferase II, CROT for carnitine octanoyltrans

  11. 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

  12. 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

  13. Common genetic variation near the phospholamban gene is associated with cardiac repolarisation : Meta-analysis of three genome-wide association studies

    NARCIS (Netherlands)

    I.M. Nolte (Ilja); C. Wallace (Chris); S.J. Newhouse (Stephen); D. Waggott (Daryl); J. Fu (Jingyuan); N. Soranzo (Nicole); R. Gwilliam (Rhian); S. Demissie (Serkalem); I. Savelieva (Irina); D. Zheng (Dongling); C. Dalageorgou (Chrysoula); M. Farrall (Martin); N.J. Samani (Nilesh); J. Connell (John); M.J. Brown (Morris); A. Dominiczak (Anna); M. Lathrop (Mark); E. Zeggini (Eleftheria); L.V. Wain (Louise); C. Newton-Cheh (Christopher); M. Eijgelsheim (Mark); K. Rice (Kenneth); P.I.W. de Bakker (Paul); A. Pfeufer (Arne); S. Sanna (Serena); D.E. Arking (Dan); F.W. Asselbergs (Folkert); T.D. Spector (Tim); N.D. Carter (Nicholas); S. Jeffery (Steve); M. Tobin (Martin); M. Caulfield (Mark); H. Snieder (Harold); A.D. Paterson (Andrew); P. Munroe (Patricia); Y. Jamshidi (Yalda)

    2009-01-01

    textabstractTo identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the Tw

  14. Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation : Meta-Analysis of Three Genome-Wide Association Studies

    NARCIS (Netherlands)

    Nolte, Ilja M.; Wallace, Chris; Newhouse, Stephen J.; Waggott, Daryl; Fu, Jingyuan; Soranzo, Nicole; Gwilliam, Rhian; Deloukas, Panos; Savelieva, Irina; Zheng, Dongling; Dalageorgou, Chrysoula; Farrall, Martin; Samani, Nilesh J.; Connell, John; Brown, Morris; Dominiczak, Anna; Lathrop, Mark; Zeggini, Eleftheria; Wain, Louise V.; Newton-Cheh, Christopher; Eijgelsheim, Mark; Rice, Kenneth; de Bakker, Paul I. W.; Pfeufer, Arne; Sanna, Serena; Arking, Dan E.; Asselbergs, Folkert W.; Spector, Tim D.; Carter, Nicholas D.; Jeffery, Steve; Tobin, Martin; Caulfield, Mark; Snieder, Harold; Paterson, Andrew D.; Munroe, Patricia B.; Jamshidi, Yalda

    2009-01-01

    To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BR

  15. Common genetic variation near the phospholamban gene is associated with cardiac repolarisation : Meta-analysis of three genome-wide association studies

    NARCIS (Netherlands)

    I.M. Nolte (Ilja); C. Wallace (Chris); S.J. Newhouse (Stephen); D. Waggott (Daryl); J. Fu (Jingyuan); N. Soranzo (Nicole); R. Gwilliam (Rhian); S. Demissie (Serkalem); I. Savelieva (Irina); D. Zheng (Dongling); C. Dalageorgou (Chrysoula); M. Farrall (Martin); N.J. Samani (Nilesh); J. Connell (John); M.J. Brown (Morris); A. Dominiczak (Anna); M. Lathrop (Mark); E. Zeggini (Eleftheria); L.V. Wain (Louise); C. Newton-Cheh (Christopher); M. Eijgelsheim (Mark); K. Rice (Kenneth); P.I.W. de Bakker (Paul); A. Pfeufer (Arne); S. Sanna (Serena); D.E. Arking (Dan); F.W. Asselbergs (Folkert); T.D. Spector (Tim); N.D. Carter (Nicholas); S. Jeffery (Steve); M. Tobin (Martin); M. Caulfield (Mark); H. Snieder (Harold); A.D. Paterson (Andrew); P. Munroe (Patricia); Y. Jamshidi (Yalda)

    2009-01-01

    textabstractTo identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the

  16. Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation : Meta-Analysis of Three Genome-Wide Association Studies

    NARCIS (Netherlands)

    Nolte, Ilja M.; Wallace, Chris; Newhouse, Stephen J.; Waggott, Daryl; Fu, Jingyuan; Soranzo, Nicole; Gwilliam, Rhian; Deloukas, Panos; Savelieva, Irina; Zheng, Dongling; Dalageorgou, Chrysoula; Farrall, Martin; Samani, Nilesh J.; Connell, John; Brown, Morris; Dominiczak, Anna; Lathrop, Mark; Zeggini, Eleftheria; Wain, Louise V.; Newton-Cheh, Christopher; Eijgelsheim, Mark; Rice, Kenneth; de Bakker, Paul I. W.; Pfeufer, Arne; Sanna, Serena; Arking, Dan E.; Asselbergs, Folkert W.; Spector, Tim D.; Carter, Nicholas D.; Jeffery, Steve; Tobin, Martin; Caulfield, Mark; Snieder, Harold; Paterson, Andrew D.; Munroe, Patricia B.; Jamshidi, Yalda

    2009-01-01

    To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and

  17. 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

  18. 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

  19. Genomic discovery of potent chromatin insulators for human gene therapy.

    Science.gov (United States)

    Liu, Mingdong; Maurano, Matthew T; Wang, Hao; Qi, Heyuan; Song, Chao-Zhong; Navas, Patrick A; Emery, David W; Stamatoyannopoulos, John A; Stamatoyannopoulos, George

    2015-02-01

    Insertional mutagenesis and genotoxicity, which usually manifest as hematopoietic malignancy, represent major barriers to realizing the promise of gene therapy. Although insulator sequences that block transcriptional enhancers could mitigate or eliminate these risks, so far no human insulators with high functional potency have been identified. Here we describe a genomic approach for the identification of compact sequence elements that function as insulators. These elements are highly occupied by the insulator protein CTCF, are DNase I hypersensitive and represent only a small minority of the CTCF recognition sequences in the human genome. We show that the elements identified acted as potent enhancer blockers and substantially decreased the risk of tumor formation in a cancer-prone animal model. The elements are small, can be efficiently accommodated by viral vectors and have no detrimental effects on viral titers. The insulators we describe here are expected to increase the safety of gene therapy for genetic diseases.

  20. 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...

  1. 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...

  2. 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.

  3. 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.

  4. The complete mitochondrial genome sequence and gene organization of Tridentiger trigonocephalus (Gobiidae: Gobionellinae) with phylogenetic consideration.

    Science.gov (United States)

    Wei, Hongqing; Ma, Hongyu; Ma, Chunyan; Zhang, Fengying; Wang, Wei; Chen, Wei; Ma, Lingbo

    2016-09-01

    The complete mitochondrial genome plays an important role in studies of genome-level characteristics and phylogenetic relationships. Here we determined the complete mitogenome sequence of Tridentiger trigonocephalus (Perciformes, Gobiidae), and discovered its phylogenetic relationship. This circular genome was 16 662 bp in length, and consisted of 37 typical genes, including 13 protein-coding genes, 22 tRNA genes, and two rRNA genes. The gene order of T. trigonocephalus mitochondrial genome was identical to those observed in most other vertebrates. Of 37 genes, 28 were encoded by heavy strand, while the others were encoded by light strand. The phylogenetic tree constructed by 13 concatenated protein-coding genes showed that T. trigonocephalus was closest to T. bifasciatus, and then to T. barbatus among the 20 species within suborder Gobioidei. This work should facilitate the studies on population genetic diversity, and molecular evolution in Gobioidei fishes.

  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. 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.

  8. 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.

  9. 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 ...

  10. Multidimensional gene set analysis of genomic data.

    Directory of Open Access Journals (Sweden)

    David Montaner

    Full Text Available Understanding the functional implications of changes in gene expression, mutations, etc., is the aim of most genomic experiments. To achieve this, several functional profiling methods have been proposed. Such methods study the behaviour of different gene modules (e.g. gene ontology terms in response to one particular variable (e.g. differential gene expression. In spite to the wealth of information provided by functional profiling methods, a common limitation to all of them is their inherent unidimensional nature. In order to overcome this restriction we present a multidimensional logistic model that allows studying the relationship of gene modules with different genome-scale measurements (e.g. differential expression, genotyping association, methylation, copy number alterations, heterozygosity, etc. simultaneously. Moreover, the relationship of such functional modules with the interactions among the variables can also be studied, which produces novel results impossible to be derived from the conventional unidimensional functional profiling methods. We report sound results of gene sets associations that remained undetected by the conventional one-dimensional gene set analysis in several examples. Our findings demonstrate the potential of the proposed approach for the discovery of new cell functionalities with complex dependences on more than one variable.

  11. From biophysics to evolutionary genetics: statistical aspects of gene regulation

    Directory of Open Access Journals (Sweden)

    Lässig Michael

    2007-09-01

    Full Text Available Abstract This is an introductory review on how genes interact to produce biological functions. Transcriptional interactions involve the binding of proteins to regulatory DNA. Specific binding sites can be identified by genomic analysis, and these undergo a stochastic evolution process governed by selection, mutations, and genetic drift. We focus on the links between the biophysical function and the evolution of regulatory elements. In particular, we infer fitness landscapes of binding sites from genomic data, leading to a quantitative evolutionary picture of regulation.

  12. 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.

  13. Mobile genetic elements and cancer. From mutations to gene therapy.

    Science.gov (United States)

    Kozeretska, I A; Demydov, S V; Ostapchenko, L I

    2011-12-01

    In the present review, an association between cancer and the activity of the non-LTR retroelements L1, Alu, and SVA, as well as endogenous retroviruses, in the human genome, is analyzed. Data suggesting that transposons have been involved in embryogenesis and malignization processes, are presented. Events that lead to the activation of mobile elements in mammalian somatic cells, as well as the use of mobile elements in genetic screening and cancer gene therapy, are reviewed.

  14. Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome.

    Science.gov (United States)

    Kim, Woonsu; Park, Hyesun; Seo, Seongwon

    2016-01-01

    The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle.

  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. Gene targeting, genome editing: from Dolly to editors.

    Science.gov (United States)

    Tan, Wenfang; Proudfoot, Chris; Lillico, Simon G; Whitelaw, C Bruce A

    2016-06-01

    One of the most powerful strategies to investigate biology we have as scientists, is the ability to transfer genetic material in a controlled and deliberate manner between organisms. When applied to livestock, applications worthy of commercial venture can be devised. Although initial methods used to generate transgenic livestock resulted in random transgene insertion, the development of SCNT technology enabled homologous recombination gene targeting strategies to be used in livestock. Much has been accomplished using this approach. However, now we have the ability to change a specific base in the genome without leaving any other DNA mark, with no need for a transgene. With the advent of the genome editors this is now possible and like other significant technological leaps, the result is an even greater diversity of possible applications. Indeed, in merely 5 years, these 'molecular scissors' have enabled the production of more than 300 differently edited pigs, cattle, sheep and goats. The advent of genome editors has brought genetic engineering of livestock to a position where industry, the public and politicians are all eager to see real use of genetically engineered livestock to address societal needs. Since the first transgenic livestock reported just over three decades ago the field of livestock biotechnology has come a long way-but the most exciting period is just starting.

  17. A Global Genomic and Genetic Strategy to Identify, Validate and Use Gene Signatures of Xenobiotic-Responsive Transcription Factors in Prediction of Pathway Activation in the Mouse Liver

    Science.gov (United States)

    Many drugs and environmentally-relevant chemicals activate xenobiotic-responsive transcription factors. Identification of target genes of these factors would be useful in predicting pathway activation in in vitro chemical screening as well as their involvement in disease states. ...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Translating human genetics into mouse: the impact of ultra-rapid in vivo genome editing.

    Science.gov (United States)

    Aida, Tomomi; Imahashi, Risa; Tanaka, Kohichi

    2014-01-01

    Gene-targeted mutant animals, such as knockout or knockin mice, have dramatically improved our understanding of the functions of genes in vivo and the genetic diversity that characterizes health and disease. However, the generation of targeted mice relies on gene targeting in embryonic stem (ES) cells, which is a time-consuming, laborious, and expensive process. The recent groundbreaking development of several genome editing technologies has enabled the targeted alteration of almost any sequence in any cell or organism. These technologies have now been applied to mouse zygotes (in vivo genome editing), thereby providing new avenues for simple, convenient, and ultra-rapid production of knockout or knockin mice without the need for ES cells. Here, we review recent achievements in the production of gene-targeted mice by in vivo genome editing. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  3. 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

  4. RiceGeneThresher: a web-based application for mining genes underlying QTL in rice genome.

    Science.gov (United States)

    Thongjuea, Supat; Ruanjaichon, Vinitchan; Bruskiewich, Richard; Vanavichit, Apichart

    2009-01-01

    RiceGeneThresher is a public online resource for mining genes underlying genome regions of interest or quantitative trait loci (QTL) in rice genome. It is a compendium of rice genomic resources consisting of genetic markers, genome annotation, expressed sequence tags (ESTs), protein domains, gene ontology, plant stress-responsive genes, metabolic pathways and prediction of protein-protein interactions. RiceGeneThresher system integrates these diverse data sources and provides powerful web-based applications, and flexible tools for delivering customized set of biological data on rice. Its system supports whole-genome gene mining for QTL by querying using DNA marker intervals or genomic loci. RiceGeneThresher provides biologically supported evidences that are essential for targeting groups or networks of genes involved in controlling traits underlying QTL. Users can use it to discover and to assign the most promising candidate genes in preparation for the further gene function validation analysis. The web-based application is freely available at http://rice.kps.ku.ac.th.

  5. Effect of Duplicate Genes on Mouse Genetic Robustness: An Update

    Directory of Open Access Journals (Sweden)

    Zhixi Su

    2014-01-01

    Full Text Available In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (PE between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD. Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity.

  6. 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.

  7. Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes.

    Science.gov (United States)

    Singh, Param Priya; Arora, Jatin; Isambert, Hervé

    2015-07-01

    Whole genome duplications (WGD) have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs, which amount to about 20 to 35% of genes in the human genome, have also been shown to be prone to dominant deleterious mutations and frequently implicated in cancer and genetic diseases. Hence, identifying ohnologs is central to better understand the evolution of vertebrates and their susceptibility to genetic diseases. Early computational analyses to identify vertebrate ohnologs relied on content-based synteny comparisons between the human genome and a single invertebrate outgroup genome or within the human genome itself. These approaches are thus limited by lineage specific rearrangements in individual genomes. We report, in this study, the identification of vertebrate ohnologs based on the quantitative assessment and integration of synteny conservation between six amniote vertebrates and six invertebrate outgroups. Such a synteny comparison across multiple genomes is shown to enhance the statistical power of ohnolog identification in vertebrates compared to earlier approaches, by overcoming lineage specific genome rearrangements. Ohnolog gene families can be browsed and downloaded for three statistical confidence levels or recompiled for specific, user-defined, significance criteria at http://ohnologs.curie.fr/. In the light of the importance of WGD on the genetic makeup of vertebrates, our analysis provides a useful resource for researchers interested in gaining further insights on vertebrate evolution and genetic diseases.

  8. Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes.

    Directory of Open Access Journals (Sweden)

    Param Priya Singh

    2015-07-01

    Full Text Available Whole genome duplications (WGD have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs, which amount to about 20 to 35% of genes in the human genome, have also been shown to be prone to dominant deleterious mutations and frequently implicated in cancer and genetic diseases. Hence, identifying ohnologs is central to better understand the evolution of vertebrates and their susceptibility to genetic diseases. Early computational analyses to identify vertebrate ohnologs relied on content-based synteny comparisons between the human genome and a single invertebrate outgroup genome or within the human genome itself. These approaches are thus limited by lineage specific rearrangements in individual genomes. We report, in this study, the identification of vertebrate ohnologs based on the quantitative assessment and integration of synteny conservation between six amniote vertebrates and six invertebrate outgroups. Such a synteny comparison across multiple genomes is shown to enhance the statistical power of ohnolog identification in vertebrates compared to earlier approaches, by overcoming lineage specific genome rearrangements. Ohnolog gene families can be browsed and downloaded for three statistical confidence levels or recompiled for specific, user-defined, significance criteria at http://ohnologs.curie.fr/. In the light of the importance of WGD on the genetic makeup of vertebrates, our analysis provides a useful resource for researchers interested in gaining further insights on vertebrate evolution and genetic diseases.

  9. GENE MUTATIONS, GENETIC DISEASE AND PHARMACOGENETIC GENES DISORDER

    OpenAIRE

    Ishak

    2010-01-01

    Somatic cell mutation is able to create genetic variance in a cell population and can induce cancer and tumor when gene mutations took place at repressor gene in controlling cell cycles such as p53 gene. Whereas germline cell mutation can cause genetic disease such as sickle cell anemia, breast cancer, thalassemia, parkinson’s as well as defect of biochemical pathway that influence drug-receptor interaction, which has negative effect and lead to hospitalized of patient. Most of reports mentio...

  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. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

    OpenAIRE

    Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wid...

  12. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

    OpenAIRE

    Chang eShen; Jing eGao; Yu Jun Sheng; Jinfa eDou; Fusheng eZhou; Xiaodong eZheng; Randy eKo; Xianfa eTang; Caihong Hong Zhu; Xianyong Yong Yin; Liangdan Dan Sun; Yong eCui; Xue Jun Zhang

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association stud...

  13. 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.

  14. Comparative genomics of rhizobia nodulating soybean suggests extensive recruitment of lineage-specific genes in adaptations.

    Science.gov (United States)

    Tian, Chang Fu; Zhou, Yuan Jie; Zhang, Yan Ming; Li, Qin Qin; Zhang, Yun Zeng; Li, Dong Fang; Wang, Shuang; Wang, Jun; Gilbert, Luz B; Li, Ying Rui; Chen, Wen Xin

    2012-05-29

    The rhizobium-legume symbiosis has been widely studied as the model of mutualistic evolution and the essential component of sustainable agriculture. Extensive genetic and recent genomic studies have led to the hypothesis that many distinct strategies, regardless of rhizobial phylogeny, contributed to the varied rhizobium-legume symbiosis. We sequenced 26 genomes of Sinorhizobium and Bradyrhizobium nodulating soybean to test this hypothesis. The Bradyrhizobium core genome is disproportionally enriched in lipid and secondary metabolism, whereas several gene clusters known to be involved in osmoprotection and adaptation to alkaline pH are specific to the Sinorhizobium core genome. These features are consistent with biogeographic patterns of these bacteria. Surprisingly, no genes are specifically shared by these soybean microsymbionts compared with other legume microsymbionts. On the other hand, phyletic patterns of 561 known symbiosis genes of rhizobia reflected the species phylogeny of these soybean microsymbionts and other rhizobia. Similar analyses with 887 known functional genes or the whole pan genome of rhizobia revealed that only the phyletic distribution of functional genes was consistent with the species tree of rhizobia. Further evolutionary genetics revealed that recombination dominated the evolution of core genome. Taken together, our results suggested that faithfully vertical genes were rare compared with those with history of recombination including lateral gene transfer, although rhizobial adaptations to symbiotic interactions and other environmental conditions extensively recruited lineage-specific shell genes under direct or indirect control through the speciation process.

  15. 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.

  16. A large-scale zebrafish gene knockout resource for the genome-wide study of gene function.

    Science.gov (United States)

    Varshney, Gaurav K; Lu, Jing; Gildea, Derek E; Huang, Haigen; Pei, Wuhong; Yang, Zhongan; Huang, Sunny C; Schoenfeld, David; Pho, Nam H; Casero, David; Hirase, Takashi; Mosbrook-Davis, Deborah; Zhang, Suiyuan; Jao, Li-En; Zhang, Bo; Woods, Ian G; Zimmerman, Steven; Schier, Alexander F; Wolfsberg, Tyra G; Pellegrini, Matteo; Burgess, Shawn M; Lin, Shuo

    2013-04-01

    With the completion of the zebrafish genome sequencing project, it becomes possible to analyze the function of zebrafish genes in a systematic way. The first step in such an analysis is to inactivate each protein-coding gene by targeted or random mutation. Here we describe a streamlined pipeline using proviral insertions coupled with high-throughput sequencing and mapping technologies to widely mutagenize genes in the zebrafish genome. We also report the first 6144 mutagenized and archived F1's predicted to carry up to 3776 mutations in annotated genes. Using in vitro fertilization, we have rescued and characterized ~0.5% of the predicted mutations, showing mutation efficacy and a variety of phenotypes relevant to both developmental processes and human genetic diseases. Mutagenized fish lines are being made freely available to the public through the Zebrafish International Resource Center. These fish lines establish an important milestone for zebrafish genetics research and should greatly facilitate systematic functional studies of the vertebrate genome.

  17. Hypertension and genetic variation in endothelial-specific genes.

    Directory of Open Access Journals (Sweden)

    Erik Larsson

    Full Text Available Genome-wide association (GWA studies usually detect common genetic variants with low-to-medium effect sizes. Many contributing variants are not revealed, since they fail to reach significance after strong correction for multiple comparisons. The WTCCC study for hypertension, for example, failed to identify genome-wide significant associations. We hypothesized that genetic variation in genes expressed specifically in the endothelium may be important for hypertension development. Results from the WTCCC study were combined with previously published gene expression data from mice to specifically investigate SNPs located within endothelial-specific genes, bypassing the requirement for genome-wide significance. Six SNPs from the WTCCC study were selected for independent replication in 5205 hypertensive patients and 5320 population-based controls, and successively in a cohort of 16,537 individuals. A common variant (rs10860812 in the DRAM (damage-regulated autophagy modulator locus showed association with hypertension (P = 0.008 in the replication study. The minor allele (A had a protective effect (OR = 0.93; 95% CI 0.88-0.98 per A-allele, which replicates the association in the WTCCC GWA study. However, a second follow-up, in the larger cohort, failed to reveal an association with blood pressure. We further tested the endothelial-specific genes for co-localization with a panel of newly discovered SNPs from large meta-GWAS on hypertension or blood pressure. There was no significant overlap between those genes and hypertension or blood pressure loci. The result does not support the hypothesis that genetic variation in genes expressed in endothelium plays an important role for hypertension development. Moreover, the discordant association of rs10860812 with blood pressure in the case control study versus the larger Malmö Preventive Project-study highlights the importance of rigorous replication in multiple large independent studies.

  18. A Probabilistic Genome-Wide Gene Reading Frame Sequence Model

    DEFF Research Database (Denmark)

    Have, Christian Theil; Mørk, Søren

    We introduce a new type of probabilistic sequence model, that model the sequential composition of reading frames of genes in a genome. Our approach extends gene finders with a model of the sequential composition of genes at the genome-level -- effectively producing a sequential genome annotation...... and are evaluated by the effect on prediction performance. Since bacterial gene finding to a large extent is a solved problem it forms an ideal proving ground for evaluating the explicit modeling of larger scale gene sequence composition of genomes. We conclude that the sequential composition of gene reading frames...... as output. The model can be used to obtain the most probable genome annotation based on a combination of i: a gene finder score of each gene candidate and ii: the sequence of the reading frames of gene candidates through a genome. The model --- as well as a higher order variant --- is developed and tested...

  19. 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

  20. A genomic survey of the fish parasite Spironucleus salmonicida indicates genomic plasticity among diplomonads and significant lateral gene transfer in eukaryote genome evolution

    Directory of Open Access Journals (Sweden)

    Logsdon John M

    2007-02-01

    Full Text Available Abstract Background Comparative genomic studies of the mitochondrion-lacking protist group Diplomonadida (diplomonads has been lacking, although Giardia lamblia has been intensively studied. We have performed a sequence survey project resulting in 2341 expressed sequence tags (EST corresponding to 853 unique clones, 5275 genome survey sequences (GSS, and eleven finished contigs from the diplomonad fish parasite Spironucleus salmonicida (previously described as S. barkhanus. Results The analyses revealed a compact genome with few, if any, introns and very short 3' untranslated regions. Strikingly different patterns of codon usage were observed in genes corresponding to frequently sampled ESTs versus genes poorly sampled, indicating that translational selection is influencing the codon usage of highly expressed genes. Rigorous phylogenomic analyses identified 84 genes – mostly encoding metabolic proteins – that have been acquired by diplomonads or their relatively close ancestors via lateral gene transfer (LGT. Although most acquisitions were from prokaryotes, more than a dozen represent likely transfers of genes between eukaryotic lineages. Many genes that provide novel insights into the genetic basis of the biology and pathogenicity of this parasitic protist were identified including 149 that putatively encode variant-surface cysteine-rich proteins which are candidate virulence factors. A number of genomic properties that distinguish S. salmonicida from its human parasitic relative G. lamblia were identified such as nineteen putative lineage-specific gene acquisitions, distinct mutational biases and codon usage and distinct polyadenylation signals. Conclusion Our results highlight the power of comparative genomic studies to yield insights into the biology of parasitic protists and the evolution of their genomes, and suggest that genetic exchange between distantly-related protist lineages may be occurring at an appreciable rate in eukaryote

  1. Identification of genetic elements associated with EPSPs gene amplification.

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    Todd A Gaines

    Full Text Available Weed populations can have high genetic plasticity and rapid responses to environmental selection pressures. For example, 100-fold amplification of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS gene evolved in the weed species Amaranthus palmeri to confer resistance to glyphosate, the world's most important herbicide. However, the gene amplification mechanism is unknown. We sequenced the EPSPS gene and genomic regions flanking EPSPS loci in A. palmeri, and searched for mobile genetic elements or repetitive sequences. The EPSPS gene was 10,229 bp, containing 8 exons and 7 introns. The gene amplification likely proceeded through a DNA-mediated mechanism, as introns exist in the amplified gene copies and the entire amplified sequence is at least 30 kb in length. Our data support the presence of two EPSPS loci in susceptible (S A. palmeri, and that only one of these was amplified in glyphosate-resistant (R A. palmeri. The EPSPS gene amplification event likely occurred recently, as no sequence polymorphisms were found within introns of amplified EPSPS copies from R individuals. Sequences with homology to miniature inverted-repeat transposable elements (MITEs were identified next to EPSPS gene copies only in R individuals. Additionally, a putative Activator (Ac transposase and a repetitive sequence region were associated with amplified EPSPS genes. The mechanism controlling this DNA-mediated amplification remains unknown. Further investigation is necessary to determine if the gene amplification may have proceeded via DNA transposon-mediated replication, and/or unequal recombination between different genomic regions resulting in replication of the EPSPS gene.

  2. Gene finding in genetically isolated populations

    NARCIS (Netherlands)

    P. Heutink (Peter); B.A. Oostra (Ben)

    2002-01-01

    textabstractThe struggle to identify susceptibility genes for complex disorders has stimulated geneticists to develop new approaches. One approach that has gained considerable interest is to focus on genetically isolated populations rather than on the general population. There rema

  3. 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

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

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    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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

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

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    Eric E Schadt

    2008-05-01

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

  11. Mapping and annotating obesity-related genes in pig and human genomes.

    Science.gov (United States)

    Martelli, Pier Luigi; Fontanesi, Luca; Piovesan, Damiano; Fariselli, Piero; Casadio, Rita

    2014-01-01

    Background. Obesity is a major health problem in both developed and emerging countries. Obesity is a complex disease whose etiology involves genetic factors in strong interplay with environmental determinants and lifestyle. The discovery of genetic factors and biological pathways underlying human obesity is hampered by the difficulty in controlling the genetic background of human cohorts. Animal models are then necessary to further dissect the genetics of obesity. Pig has emerged as one of the most attractive models, because of the similarity with humans in the mechanisms regulating the fat deposition. Results. We collected the genes related to obesity in humans and to fat deposition traits in pig. We localized them on both human and pig genomes, building a map useful to interpret comparative studies on obesity. We characterized the collected genes structurally and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein interaction network. Conclusions. The collected set consists of 361 obesity related genes in human and pig genomes. All genes were mapped on the human genome, and 54 could not be localized on the pig genome (release 2012). Only for 3 human genes there is no counterpart in pig, confirming that this animal is a good model for human obesity studies. Obesity related genes are mostly involved in regulation and signaling processes/pathways and relevant connection emerges between obesity-related genes and diseases such as cancer and infectious diseases.

  12. 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.

  13. 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.

  14. Psoriasis-Associated Genetic Polymorphism in North Indian Population in the CCHCR1 Gene and in a Genomic Segment Flanking the HLA-C Region

    Directory of Open Access Journals (Sweden)

    G. Gandhi

    2011-01-01

    Full Text Available Psoriasis is a common, chronic, recurrent, inflammatory, hyper proliferative disorder of the skin, which has a relatively high prevalence in the general population (0.6–4.8%. Linkage and association analyses in various populations have revealed a major locus for psoriasis susceptibility, PSORS1, at 6p21.3. Association of the disease with human leukocyte antigen (HLA Cw6, corneodesmosin (CDSN and the coiled-coil alpha-helical rod protein-1 (CCHCR1 has also been reported. Though the PSORS1 locus accounts for 30–50% of familial psoriasis in various global population groups, yet no studies have been published from the North Indian population. Some of the SNPs in HLA-C and CCHCR1 genes have been reported as markers for disease susceptibility. Therefore in the present study, DNA samples from psoriasis patients from North India were genotyped for polymorphisms in CCHCR1 and HLA-C genes. The allele frequencies were calculated for patients and controls, and were compared for odds ratio and confidence interval values. SNPn.7*22222 (rs12208888, SNPn.7*22333 (rs12216025, SNPn.9*24118 (rs10456057, CCHCR1_386 (rs130065, CCHCR1_404 (rs130076 and CCHCR1_1364 (rs130071 were found to be significant in psoriasis patients. Linkage disequilibrium analysis revealed two haplotypes (rs12208888, rs2844608, rs12216025, rs10456057, rs130065, rs130066, rs130068, rs130269, and rs12208888, rs2844608, rs12216025, rs130076, rs130066, rs130068, rs130269, rs130071 as highly susceptible haplotypes for psoriasis in the cohort studied. Preliminary analysis of the data also suggests the possibilities of ethnic group specific disease related polymorphisms, pending validation in future studies.

  15. 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

  16. EcoGene: a genome sequence database for Escherichia coli K-12.

    Science.gov (United States)

    Rudd, K E

    2000-01-01

    The EcoGene database provides a set of gene and protein sequences derived from the genome sequence of Escherichia coli K-12. EcoGene is a source of re-annotated sequences for the SWISS-PROT and Colibri databases. EcoGene is used for genetic and physical map compilations in collaboration with the Coli Genetic Stock Center. The EcoGene12 release includes 4293 genes. EcoGene12 differs from the GenBank annotation of the complete genome sequence in several ways, including (i) the revision of 706 predicted or confirmed gene start sites, (ii) the correction or hypothetical reconstruction of 61 frame-shifts caused by either sequence error or mutation, (iii) the reconstruction of 14 protein sequences interrupted by the insertion of IS elements, and (iv) pre-dictions that 92 genes are partially deleted gene fragments. A literature survey identified 717 proteins whose N-terminal amino acids have been verified by sequencing. 12 446 cross-references to 6835 literature citations and s are provided. EcoGene is accessible at a new website: http://bmb.med.miami.edu/EcoGene/EcoWeb. Users can search and retrieve individual EcoGene GenePages or they can download large datasets for incorporation into database management systems, facilitating various genome-scale computational and functional analyses.

  17. 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.

  18. 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

  19. 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.

  20. Genomic analysis of primordial dwarfism reveals novel disease genes.

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S

    2014-02-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.

  1. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  2. Bioinformatics Assisted Gene Discovery and Annotation of Human Genome

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    As the sequencing stage of human genome project is near the end, the work has begun for discovering novel genes from genome sequences and annotating their biological functions. Here are reviewed current major bioinformatics tools and technologies available for large scale gene discovery and annotation from human genome sequences. Some ideas about possible future development are also provided.

  3. The genetics of alcoholism: identifying specific genes through family studies.

    Science.gov (United States)

    Edenberg, Howard J; Foroud, Tatiana

    2006-09-01

    Alcoholism is a complex disorder with both genetic and environmental risk factors. Studies in humans have begun to elucidate the genetic underpinnings of the risk for alcoholism. Here we briefly review strategies for identifying individual genes in which variations affect the risk for alcoholism and related phenotypes, in the context of one large study that has successfully identified such genes. The Collaborative Study on the Genetics of Alcoholism (COGA) is a family-based study that has collected detailed phenotypic data on individuals in families with multiple alcoholic members. A genome-wide linkage approach led to the identification of chromosomal regions containing genes that influenced alcoholism risk and related phenotypes. Subsequently, single nucleotide polymorphisms (SNPs) were genotyped in positional candidate genes located within the linked chromosomal regions, and analyzed for association with these phenotypes. Using this sequential approach, COGA has detected association with GABRA2, CHRM2 and ADH4; these associations have all been replicated by other researchers. COGA has detected association to additional genes including GABRG3, TAS2R16, SNCA, OPRK1 and PDYN, results that are awaiting confirmation. These successes demonstrate that genes contributing to the risk for alcoholism can be reliably identified using human subjects.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. APPLICATION OF GENETIC DEAFNESS GENE CHIP FOR DETECTION OF GENE MUTATION OF DEAFNESS IN PREGNANT WOMEN

    Institute of Scientific and Technical Information of China (English)

    CHANG Liang; ZHONG Su; ZHAO Nan; LIU Ping; ZHAO Yangyu; QIAO Jie

    2014-01-01

    Objective The study is to identify the carrier rate of common deafness mutation in Chinese pregnant women via detecting deafness gene mutations with gene chip. Methods The pregnant women in obstetric clinic without hearing impairment and hearing disorders family history were selected. The informed consent was signed. Peripheral blood was taken to extract genom-ic DNA. Application of genetic deafness gene chip for detecting 9 mutational hot spot of the most common 4 Chinese deafness genes, namely GJB2 (35delG,176del16bp, 235delC, 299delAT), GJB3 (C538T) ,SLC26A4 ( IVS72A>G, A2168G) and mito-chondrial DNA 12S rRNA (A1555G, C1494T) . Further genetic testing were provided to the spouses and newborns of the screened carriers. Results Peripheral blood of 430 pregnant women were detected,detection of deafness gene mutation carri-ers in 24 cases(4.2%), including 13 cases of the GJB2 heterozygous mutation, 3 cases of SLC26A4 heterozygous mutation, 1 cases of GJB3 heterozygous mutation, and 1 case of mitochondrial 12S rRNA mutation. 18 spouses and 17 newborns took fur-ther genetic tests, and 6 newborns inherited the mutation from their mother. Conclusion The common deafness genes muta-tion has a high carrier rate in pregnant women group,235delC and IVS7-2A>G heterozygous mutations are common.

  9. 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.

  10. 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.

  11. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success

    Science.gov (United States)

    Timmerman, Vincent; Strickland, Alleene V.; Züchner, Stephan

    2014-01-01

    Charcot-Marie-Tooth (CMT) neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs. PMID:24705285

  12. Genetics of Charcot-Marie-Tooth (CMT Disease within the Frame of the Human Genome Project Success

    Directory of Open Access Journals (Sweden)

    Vincent Timmerman

    2014-01-01

    Full Text Available Charcot-Marie-Tooth (CMT neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs.

  13. 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

  14. 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.

  15. Genetic Innovation in Vertebrates: Gypsy Integrase Genes and Other Genes Derived from Transposable Elements

    Directory of Open Access Journals (Sweden)

    Domitille Chalopin

    2012-01-01

    Full Text Available Due to their ability to drive DNA rearrangements and to serve as a source of new coding and regulatory sequences, transposable elements (TEs are considered as powerful evolutionary agents within genomes. In this paper, we review the mechanism of molecular domestication, which corresponds to the formation of new genes derived from TE sequences. Many genes derived from retroelements and DNA transposons have been identified in mammals and other vertebrates, some of them fulfilling essential functions for the development and survival of their host organisms. We will particularly focus on the evolution and expression of Gypsy integrase (GIN genes, which have been formed from ancient event(s of molecular domestication and have evolved differentially in some vertebrate sublineages. What we describe here is probably only the tip of the evolutionary iceberg, and future genome analyses will certainly uncover new TE-derived genes and biological functions driving genetic innovation in vertebrates and other organisms.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Meta-analysis and genome-wide interpretation of genetic susceptibility to drug addiction

    Directory of Open Access Journals (Sweden)

    Johnson Catherine

    2011-10-01

    Full Text Available Abstract Background Classical genetic studies provide strong evidence for heritable contributions to susceptibility to developing dependence on addictive substances. Candidate gene and genome-wide association studies (GWAS have sought genes, chromosomal regions and allelic variants likely to contribute to susceptibility to drug addiction. Results Here, we performed a meta-analysis of addiction candidate gene association studies and GWAS to investigate possible functional mechanisms associated with addiction susceptibility. From meta-data retrieved from 212 publications on candidate gene association studies and 5 GWAS reports, we linked a total of 843 haplotypes to addiction susceptibility. We mapped the SNPs in these haplotypes to functional and regulatory elements in the genome and estimated the magnitude of the contributions of different molecular mechanisms to their effects on addiction susceptibility. In addition to SNPs in coding regions, these data suggest that haplotypes in gene regulatory regions may also contribute to addiction susceptibility. When we compared the lists of genes identified by association studies and those identified by molecular biological studies of drug-regulated genes, we observed significantly higher participation in the same gene interaction networks than expected by chance, despite little overlap between the two gene lists. Conclusions These results appear to offer new insights into the genetic factors underlying drug addiction.

  2. Reframed Genome-Scale Metabolic Model to Facilitate Genetic Design and Integration with Expression Data.

    Science.gov (United States)

    Gu, Deqing; Jian, Xingxing; Zhang, Cheng; Hua, Qiang

    2016-06-08

    Genome-scale metabolic network models (GEMs) have played important roles in the design of genetically engineered strains and helped biologists to decipher metabolism. However, due to the complex gene-reaction relationships that exist in model systems, most algorithms have limited capabilities with respect to directly predicting accurate genetic design for metabolic engineering. In particular, methods that predict reaction knockout strategies leading to overproduction are often impractical in terms of gene manipulations. Recently, we proposed a method named LTM (logical transformation of model) to simplify the gene-reaction associations by introducing intermediate pseudo reactions, which makes it possible to generate genetic design. Here, we propose an alternative method to relieve researchers from deciphering complex gene-reactions by adding pseudo gene controlling reactions. In comparison to LTM, this new method introduces fewer pseudo reactions and generates a much smaller model system named as gModel. We showed that gModel allows two seldom reported applications: identification of minimal genomes and design of minimal cell factories within a modified OptKnock framework. In addition, gModel could be used to integrate expression data directly and improve the performance of the E-Fmin method for predicting fluxes. In conclusion, the model transformation procedure will facilitate genetic research based on GEMs, extending their applications.

  3. 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.

  4. Sampling Daphnia's expressed genes: preservation, expansion and invention of crustacean genes with reference to insect genomes

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    Bauer Darren J

    2007-07-01

    Full Text Available Abstract Background Functional and comparative studies of insect genomes have shed light on the complement of genes, which in part, account for shared morphologies, developmental programs and life-histories. Contrasting the gene inventories of insects to those of the nematodes provides insight into the genomic changes responsible for their diversification. However, nematodes have weak relationships to insects, as each belongs to separate animal phyla. A better outgroup to distinguish lineage specific novelties would include other members of Arthropoda. For example, crustaceans are close allies to the insects (together forming Pancrustacea and their fascinating aquatic lifestyle provides an important comparison for understanding the genetic basis of adaptations to life on land versus life in water. Results This study reports on the first characterization of cDNA libraries and sequences for the model crustacean Daphnia pulex. We analyzed 1,546 ESTs of which 1,414 represent approximately 787 nuclear genes, by measuring their sequence similarities with insect and nematode proteomes. The provisional annotation of genes is supported by expression data from microarray studies described in companion papers. Loci expected to be shared between crustaceans and insects because of their mutual biological features are identified, including genes for reproduction, regulation and cellular processes. We identify genes that are likely derived within Pancrustacea or lost within the nematodes. Moreover, lineage specific gene family expansions are identified, which suggest certain biological demands associated with their ecological setting. In particular, up to seven distinct ferritin loci are found in Daphnia compared to three in most insects. Finally, a substantial fraction of the sampled gene transcripts shares no sequence similarity with those from other arthropods. Genes functioning during development and reproduction are comparatively well conserved between

  5. Evolution of a microbial nitrilase gene family: a comparative and environmental genomics study

    Directory of Open Access Journals (Sweden)

    Eads Jonathan R

    2005-08-01

    Full Text Available Abstract Background Completed genomes and environmental genomic sequences are bringing a significant contribution to understanding the evolution of gene families, microbial metabolism and community eco-physiology. Here, we used comparative genomics and phylogenetic analyses in conjunction with enzymatic data to probe the evolution and functions of a microbial nitrilase gene family. Nitrilases are relatively rare in bacterial genomes, their biological function being unclear. Results We examined the genetic neighborhood of the different subfamily genes and discovered conserved gene clusters or operons associated with specific nitrilase clades. The inferred evolutionary transitions that separate nitrilases which belong to different gene clusters correlated with changes in their enzymatic properties. We present evidence that Darwinian adaptation acted during one of those transitions and identified sites in the enzyme that may have been under positive selection. Conclusion Changes in the observed biochemical properties of the nitrilases associated with the different gene clusters are consistent with a hypothesis that those enzymes have been recruited to a novel metabolic pathway following gene duplication and neofunctionalization. These results demonstrate the benefits of combining environmental genomic sampling and completed genomes data with evolutionary and biochemical analyses in the study of gene families. They also open new directions for studying the functions of nitrilases and the genes they are associated with.

  6. Genomic variation in Salmonella enterica core genes for epidemiological typing

    DEFF Research Database (Denmark)

    Leekitcharoenphon, Pimlapas; Lukjancenko, Oksana; Rundsten, Carsten Friis

    2012-01-01

    Background: Technological advances in high throughput genome sequencing are making whole genome sequencing (WGS) available as a routine tool for bacterial typing. Standardized procedures for identification of relevant genes and of variation are needed to enable comparison between studies and over...... genomes and evaluate their value as typing targets, comparing whole genome typing and traditional methods such as 16S and MLST. A consensus tree based on variation of core genes gives much better resolution than 16S and MLST; the pan-genome family tree is similar to the consensus tree, but with higher...... that there is a positive selection towards mutations leading to amino acid changes. Conclusions: Genomic variation within the core genome is useful for investigating molecular evolution and providing candidate genes for bacterial genome typing. Identification of genes with different degrees of variation is important...

  7. 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...

  8. Genomic variation in Salmonella enterica core genes for epidemiological typing

    Directory of Open Access Journals (Sweden)

    Leekitcharoenphon Pimlapas

    2012-03-01

    Full Text Available Abstract Background Technological advances in high throughput genome sequencing are making whole genome sequencing (WGS available as a routine tool for bacterial typing. Standardized procedures for identification of relevant genes and of variation are needed to enable comparison between studies and over time. The core genes--the genes that are conserved in all (or most members of a genus or species--are potentially good candidates for investigating genomic variation in phylogeny and epidemiology. Results We identify a set of 2,882 core genes clusters based on 73 publicly available Salmonella enterica genomes and evaluate their value as typing targets, comparing whole genome typing and traditional methods such as 16S and MLST. A consensus tree based on variation of core genes gives much better resolution than 16S and MLST; the pan-genome family tree is similar to the consensus tree, but with higher confidence. The core genes can be divided into two categories: a few highly variable genes and a larger set of conserved core genes, with low variance. For the most variable core genes, the variance in amino acid sequences is higher than for the corresponding nucleotide sequences, suggesting that there is a positive selection towards mutations leading to amino acid changes. Conclusions Genomic variation within the core genome is useful for investigating molecular evolution and providing candidate genes for bacterial genome typing. Identification of genes with different degrees of variation is important especially in trend analysis.

  9. Amplification of Whole Tumor Genomes and Gene-by-Gene Mapping of Genomic Aberrations from Limited Sources of Fresh-Frozen and Paraffin-Embedded DNA

    Science.gov (United States)

    Bredel, Markus; Bredel, Claudia; Juric, Dejan; Kim, Young; Vogel, Hannes; Harsh, Griffith R.; Recht, Lawrence D.; Pollack, Jonathan R.; Sikic, Branimir I.

    2005-01-01

    Sufficient quantity of genomic DNA can be a bottleneck in genome-wide analysis of clinical tissue samples. DNA polymerase Phi29 can be used for the random-primed amplification of whole genomes, although the amplification may introduce bias in gene dosage. We have performed a detailed investigation of this technique in archival fresh-frozen and formalin-fixed/paraffin-embedded tumor DNA by using cDNA microarray-based comparative genomic hybridization. Phi29 amplified DNA from matched pairs of fresh-frozen and formalin-fixed/paraffin-embedded tumor samples with similar efficiency. The distortion in gene dosage representation in the amplified DNA was nonrandom and reproducibly involved distinct genomic loci. Regional amplification efficiency was significantly linked to regional GC content of the template genome. The biased gene representation in amplified tumor DNA could be effectively normalized by using amplified reference DNA. Our data suggest that genome-wide gene dosage alterations in clinical tumor samples can be reliably assessed from a few hundred tumor cells. Therefore, this amplification method should lend itself to high-throughput genetic analyses of limited sources of tumor, such as fine-needle biopsies, laser-microdissected tissue, and small paraffin-embedded specimens. PMID:15858140

  10. 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.

  11. 遗传基因组学方法对Myoc基因调控网络的研究%Analysis of Myocilin gene regulatory network using a genetic genomics approach

    Institute of Scientific and Technical Information of China (English)

    陆宏; 陆璐; 管怀进; 陈辉; 张俊芳; 胡楠; 帅捷

    2013-01-01

    Background The pathogenesis of primary open angle glaucoma(POAG) and high myopia are very complex.To construct the regulatory network of virulence genes and relevant genes that involved in pathogenicity are helpful for reveal of the pathogenesis.Objective The aim of this study was to investigate myocilin(Myoc),a gene that contributes to POAG and high myopia in eyes of BXD Recombinant Inbred(BXD RI)mice and construct the regulatory network of Myoc.Methods The affymetrix microarray system was used to detect the differential expression of Myoc in the eyes of C57BL/6J(B6),DBA/2J(D2) and BXD RI mice.Expression quantitative trait loci (eQTL) mapping was performed to construct the regulatory network of Myoc gene.Results The average expression level of the Myoc gene in the BXD strains was 10.83,and the gene exhibited expression levels ranging from 8.39 in BXD55 mice tol 1.43 in B6 mice.The eQTL mapping for the Myoc gene showed a significant likelihood ratio statistic (LRS) of 21.78.The QTL was mapped in chromosome 2,and Myoc was located on chromosome 1,indicating that the Myoc gene was a trans-acting QTL.Olfml2a was identified to be a candidate upstream gene of Myoc by analysis of bioinformatics.Genetic regulatory network analysis demonstrated that a series of genes associated with Myoc probably played roles in the pathogenesis and development of POAG and high myopia.Conclusions The genetical genomics approach provides a powerful tool for constructing pathways that contribute to complex traits,such as POAG and high myopia.%背景 原发性开角型青光眼(POAG)和高度近视的发病机制复杂,可能有较多致病基因及致病相关基因参与,构建基因调控网络有助于揭示发病机制.目的 采用遗传基因组学方法研究Myoc基因的调控网络,探索其在POAG中的可能作用机制.方法 Affymetrix基因芯片用于检测确定68个品系的BXD重组近交系(BXD RI)小鼠及其亲本C57 BL/6J(B6)小鼠和DBA/2J(D2)小鼠、F1代小鼠眼组

  12. Genomics of crop wild relatives: expanding the gene pool for crop improvement.

    Science.gov (United States)

    Brozynska, Marta; Furtado, Agnelo; Henry, Robert J

    2016-04-01

    Plant breeders require access to new genetic diversity to satisfy the demands of a growing human population for more food that can be produced in a variable or changing climate and to deliver the high-quality food with nutritional and health benefits demanded by consumers. The close relatives of domesticated plants, crop wild relatives (CWRs), represent a practical gene pool for use by plant breeders. Genomics of CWR generates data that support the use of CWR to expand the genetic diversity of crop plants. Advances in DNA sequencing technology are enabling the efficient sequencing of CWR and their increased use in crop improvement. As the sequencing of genomes of major crop species is completed, attention has shifted to analysis of the wider gene pool of major crops including CWR. A combination of de novo sequencing and resequencing is required to efficiently explore useful genetic variation in CWR. Analysis of the nuclear genome, transcriptome and maternal (chloroplast and mitochondrial) genome of CWR is facilitating their use in crop improvement. Genome analysis results in discovery of useful alleles in CWR and identification of regions of the genome in which diversity has been lost in domestication bottlenecks. Targeting of high priority CWR for sequencing will maximize the contribution of genome sequencing of CWR. Coordination of global efforts to apply genomics has the potential to accelerate access to and conservation of the biodiversity essential to the sustainability of agriculture and food production.

  13. Genomic and network patterns of schizophrenia genetic variation in human evolutionary accelerated regions.

    Science.gov (United States)

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

    2015-05-01

    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-specific evolution. Our results suggest that schizophrenia-associated loci enrich in genes near previously identified human accelerated regions (HARs). Specifically, we find that genes near HARs conserved in nonhuman primates (pHARs) are enriched for schizophrenia-associated loci, and that pHAR-associated schizophrenia genes are under stronger selective pressure than other schizophrenia genes and other pHAR-associated genes. We further evaluate pHAR-associated schizophrenia genes in regulatory network contexts to investigate associated molecular functions and mechanisms. We find that pHAR-associated schizophrenia genes significantly enrich in a GABA-related coexpression module that was previously found to be differentially regulated in schizophrenia affected individuals versus healthy controls. In another two independent networks constructed from gene expression profiles from prefrontal cortex samples, we find that pHAR-associated schizophrenia genes are located in more central positions and their average path lengths to the other nodes are significantly shorter than those of other schizophrenia genes. Together, our results suggest that HARs are associated with potentially important functional roles in the genetic architecture of schizophrenia.

  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. Putative essential and core-essential genes in Mycoplasma genomes.

    Science.gov (United States)

    Lin, Yan; Zhang, Randy Ren

    2011-01-01

    Mycoplasma, which was used to create the first "synthetic life", has been an important species in the emerging field, synthetic biology. However, essential genes, an important concept of synthetic biology, for both M. mycoides and M. capricolum, as well as 14 other Mycoplasma with available genomes, are still unknown. We have developed a gene essentiality prediction algorithm that incorporates information of biased gene strand distribution, homologous search and codon adaptation index. The algorithm, which achieved an accuracy of 80.8% and 78.9% in self-consistence and cross-validation tests, respectively, predicted 5880 essential genes in the 16 Mycoplasma genomes. The intersection set of essential genes in available Mycoplasma genomes consists of 153 core essential genes. The predicted essential genes (available from pDEG, tubic.tju.edu.cn/pdeg) and the proposed algorithm can be helpful for studying minimal Mycoplasma genomes as well as essential genes in other genomes.

  16. Powerful tools for genetic modification: Advances in gene editing.

    Science.gov (United States)

    Roesch, Erica A; Drumm, Mitchell L

    2017-09-27

    Recent discoveries and technical advances in genetic engineering, methods called gene or genome editing, provide hope for repairing genes that cause diseases like cystic fibrosis (CF) or otherwise altering a gene for therapeutic benefit. There are both hopes and hurdles with these technologies, with new ideas emerging almost daily. Initial studies using intestinal organoid cultures carrying the common, F508del mutation have shown that gene editing by CRISPR/Cas9 can convert cells lacking CFTR function to cells with normal channel function, providing a precedent that this technology can be harnessed for CF. While this is an important precedent, the challenges that remain are not trivial. A logistical issue for this and many other genetic diseases is genetic heterogeneity. Approximately, 2000 mutations associated with CF have been found in CFTR, the gene responsible for CF, and thus a feasible strategy that would encompass all individuals affected by the disease is particularly difficult to envision. However, single strategies that would be applicable to all subjects affected by CF have been conceived and are being investigated. With all of these approaches, efficiency (the proportion of cells edited), accuracy (how often other sites in the genome are affected), and delivery of the gene editing components to the desired cells are perhaps the most significant, impending hurdles. Our understanding of each of these areas is increasing rapidly, and while it is impossible to predict when a successful strategy will reach the clinic, there is every reason to believe it is a question of "when" and not "if." © 2017 Wiley Periodicals, Inc.

  17. Gene and genome parameters of mammalian liver circadian genes (LCGs.

    Directory of Open Access Journals (Sweden)

    Gang Wu

    Full Text Available The mammalian circadian system controls various physiology processes and behavior responses by regulating thousands of circadian genes with rhythmic expressions. In this study, we redefined circadian-regulated genes based on published results in the mouse liver and compared them with other gene groups defined relative to circadian regulations, especially the non-circadian-regulated genes expressed in liver at multiple molecular levels from gene position to protein expression based on integrative analyses of different datasets from the literature. Based on the intra-tissue analysis, the liver circadian genes or LCGs show unique features when compared to other gene groups. First, LCGs in general have less neighboring genes and larger in both genomic and 3'-UTR lengths but shorter in CDS (coding sequence lengths. Second, LCGs have higher mRNA and protein abundance, higher temporal expression variations, and shorter mRNA half-life. Third, more than 60% of LCGs form major co-expression clusters centered in four temporal windows: dawn, day, dusk, and night. In addition, larger and smaller LCGs are found mainly expressed in the day and night temporal windows, respectively, and we believe that LCGs are well-partitioned into the gene expression regulatory network that takes advantage of gene size, expression constraint, and chromosomal architecture. Based on inter-tissue analysis, more than half of LCGs are ubiquitously expressed in multiple tissues but only show rhythmical expression in one or limited number of tissues. LCGs show at least three-fold lower expression variations across the temporal windows than those among different tissues, and this observation suggests that temporal expression variations regulated by the circadian system is relatively subtle as compared with the tissue expression variations formed during development. Taken together, we suggest that the circadian system selects gene parameters in a cost effective way to improve tissue

  18. Co-regulation of pluripotency and genetic integrity at the genomic level

    Directory of Open Access Journals (Sweden)

    Daniel J. Cooper

    2014-11-01

    Full Text Available The Disposable Soma Theory holds that genetic integrity will be maintained at more pristine levels in germ cells than in somatic cells because of the unique role germ cells play in perpetuating the species. We tested the hypothesis that the same concept applies to pluripotent cells compared to differentiated cells. Analyses of transcriptome and cistrome databases, along with canonical pathway analysis and chromatin immunoprecipitation confirmed differential expression of DNA repair and cell death genes in embryonic stem cells and induced pluripotent stem cells relative to fibroblasts, and predicted extensive direct and indirect interactions between the pluripotency and genetic integrity gene networks in pluripotent cells. These data suggest that enhanced maintenance of genetic integrity is fundamentally linked to the epigenetic state of pluripotency at the genomic level. In addition, these findings demonstrate how a small number of key pluripotency factors can regulate large numbers of downstream genes in a pathway-specific manner.

  19. Comparative Inference of Duplicated Genes Produced by Polyploidization in Soybean Genome

    Directory of Open Access Journals (Sweden)

    Yanmei Yang

    2013-01-01

    Full Text Available Soybean (Glycine max is one of the most important crop plants for providing protein and oil. It is important to investigate soybean genome for its economic and scientific value. Polyploidy is a widespread and recursive phenomenon during plant evolution, and it could generate massive duplicated genes which is an important resource for genetic innovation. Improved sequence alignment criteria and statistical analysis are used to identify and characterize duplicated genes produced by polyploidization in soybean. Based on the collinearity method, duplicated genes by whole genome duplication account for 70.3% in soybean. From the statistical analysis of the molecular distances between duplicated genes, our study indicates that the whole genome duplication event occurred more than once in the genome evolution of soybean, which is often distributed near the ends of chromosomes.

  20. In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Bekim Sadikovic

    Full Text Available Genetic and epigenetic changes contribute to deregulation of gene expression and development of human cancer. Changes in DNA methylation are key epigenetic factors regulating gene expression and genomic stability. Recent progress in microarray technologies resulted in developments of high resolution platforms for profiling of genetic, epigenetic and gene expression changes. OS is a pediatric bone tumor with characteristically high level of numerical and structural chromosomal changes. Furthermore, little is known about DNA methylation changes in OS. Our objective was to develop an integrative approach for analysis of high-resolution epigenomic, genomic, and gene expression profiles in order to identify functional epi/genomic differences between OS cell lines and normal human osteoblasts. A combination of Affymetrix Promoter Tilling Arrays for DNA methylation, Agilent array-CGH platform for genomic imbalance and Affymetrix Gene 1.0 platform for gene expression analysis was used. As a result, an integrative high-resolution approach for interrogation of genome-wide tumour-specific changes in DNA methylation was developed. This approach was used to provide the first genomic DNA methylation maps, and to identify and validate genes with aberrant DNA methylation in OS cell lines. This first integrative analysis of global cancer-related changes in DNA methylation, genomic imbalance, and gene expression has provided comprehensive evidence of the cumulative roles of epigenetic and genetic mechanisms in deregulation of gene expression networks.

  1. Perceptions and understanding of genetics and genetic eye disease and attitudes to genetic testing and gene therapy in a primary eye care setting.

    Science.gov (United States)

    Ganne, Pratyusha; Garrioch, Robert; Votruba, Marcela

    2015-03-01

    Genetic eye pathology represents a significant percentage of the causes of blindness in industrialized countries. This study explores the level of understanding and perceptions of genetics and inherited eye diseases and the attitudes to genetic testing and gene therapy. The study was conducted in two parts. Participant groups included were: undergraduate students of optometry, primary eye care professionals and members of the general public. A preliminary study aimed to understand perceptions and to explore the level of knowledge about genetics in general, eye genetics and gene therapy. A second survey was designed to explore attitudes to genetic testing and gene therapy. The majority of participants (82%) perceived genetics as an important science. However, none of them showed a high level of understanding of genetics and inherited eye diseases. Undergraduate students and primary eye care professionals were better informed about inherited eye diseases than the general public (p = 0.001). The majority (80%) across all three groups had a positive attitude to genetic testing and gene therapy. There was a lack of knowledge about the genetic services available among all groups of participants. This calls for serious thinking about the level of dissemination of information about genetics and inherited eye diseases. It shows a broadly supportive attitude to genomic medicine among the public. Improving public awareness and education in inherited eye diseases can improve the utility of genetic testing and therapy.

  2. 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

  3. Development of an ultra-dense genetic map of the sunflower genome based on single-feature polymorphisms.

    Directory of Open Access Journals (Sweden)

    John E Bowers

    Full Text Available The development of ultra-dense genetic maps has the potential to facilitate detailed comparative genomic analyses and whole genome sequence assemblies. Here we describe the use of a custom Affymetrix GeneChip containing nearly 2.4 million features (25 bp sequences targeting 86,023 unigenes from sunflower (Helianthus annuus L. and related species to test for single-feature polymorphisms (SFPs in a recombinant inbred line (RIL mapping population derived from a cross between confectionery and oilseed sunflower lines (RHA280×RHA801. We then employed an existing genetic map derived from this same population to rigorously filter out low quality data and place 67,486 features corresponding to 22,481 unigenes on the sunflower genetic map. The resulting map contains a substantial fraction of all sunflower genes and will thus facilitate a number of downstream applications, including genome assembly and the identification of candidate genes underlying QTL or traits of interest.

  4. 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.

  5. Gene Prioritization for Imaging Genetics Studies Using Gene Ontology and a Stratified False Discovery Rate Approach.

    Science.gov (United States)

    Patel, Sejal; Park, Min Tae M; Chakravarty, M Mallar; Knight, Jo

    2016-01-01

    Imaging genetics is an emerging field in which the association between genes and neuroimaging-based quantitative phenotypes are used to explore the functional role of genes in neuroanatomy and neurophysiology in the context of healthy function and neuropsychiatric disorders. The main obstacle for researchers in the field is the high dimensionality of the data in both the imaging phenotypes and the genetic variants commonly typed. In this article, we develop a novel method that utilizes Gene Ontology, an online database, to select and prioritize certain genes, employing a stratified false discovery rate (sFDR) approach to investigate their associations with imaging phenotypes. sFDR has the potential to increase power in genome wide association studies (GWAS), and is quickly gaining traction as a method for multiple testing correction. Our novel approach addresses both the pressing need in genetic research to move beyond candidate gene studies, while not being overburdened with a loss of power due to multiple testing. As an example of our methodology, we perform a GWAS of hippocampal volume using both the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA2) and the Alzheimer's Disease Neuroimaging Initiative datasets. The analysis of ENIGMA2 data yielded a set of SNPs with sFDR values between 10 and 20%. Our approach demonstrates a potential method to prioritize genes based on biological systems impaired in a disease.

  6. 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.

  7. Whole-Genome Duplications Spurred the Functional Diversification of the Globin Gene Superfamily in Vertebrates

    OpenAIRE

    Hoffmann, Federico G.; Opazo, Juan C; Storz, Jay F.

    2011-01-01

    It has been hypothesized that two successive rounds of whole-genome duplication (WGD) in the stem lineage of vertebrates provided genetic raw materials for the evolutionary innovation of many vertebrate-specific features. However, it has seldom been possible to trace such innovations to specific functional differences between paralogous gene products that derive from a WGD event. Here, we report genomic evidence for a direct link between WGD and key physiological innovations in the vertebrate...

  8. A genome-wide 20 K citrus microarray for gene expression analysis

    OpenAIRE

    Martínez-Godoy, M. Ángeles; Mauri, Nuria; Juárez, José; Marqués, M. Carmen; Santiago, Julia; Forment, Javier; Gadea Vacas, José

    2008-01-01

    Background: Understanding of genetic elements that contribute to key aspects of citrus biology will impact future improvements in this economically important crop. Global gene expression analysis demands microarray platforms with a high genome coverage. In the last years, genomewide EST collections have been generated in citrus, opening the possibility to create new tools for functional genomics in this crop plant. Results: We have designed and constructed a publicly available ...

  9. Assessing Genetic Diversity among Brettanomyces Yeasts by DNA Fingerprinting and Whole-Genome Sequencing

    Science.gov (United States)

    Crauwels, Sam; Zhu, Bo; Steensels, Jan; Busschaert, Pieter; De Samblanx, Gorik; Marchal, Kathleen; Willems, Kris A.

    2014-01-01

    Brettanomyces yeasts, with the species Brettanomyces (Dekkera) bruxellensis being the most important one, are generally reported to be spoilage yeasts in the beer and wine industry due to the production of phenolic off flavors. However, B. bruxellensis is also known to be a beneficial contributor in certain fermentation processes, such as the production of certain specialty beers. Nevertheless, despite its economic importance, Brettanomyces yeasts remain poorly understood at the genetic and genomic levels. In this study, the genetic relationship between more than 50 Brettanomyces strains from all presently known species and from several sources was studied using a combination of DNA fingerprinting techniques. This revealed an intriguing correlation between the B. bruxellensis fingerprints and the respective isolation source. To further explore this relationship, we sequenced a (beneficial) beer isolate of B. bruxellensis (VIB X9085; ST05.12/22) and compared its genome sequence with the genome sequences of two wine spoilage strains (AWRI 1499 and CBS 2499). ST05.12/22 was found to be substantially different from both wine strains, especially at the level of single nucleotide polymorphisms (SNPs). In addition, there were major differences in the genome structures between the strains investigated, including the presence of large duplications and deletions. Gene content analysis revealed the presence of 20 genes which were present in both wine strains but absent in the beer strain, including many genes involved in carbon and nitrogen metabolism, and vice versa, no genes that were missing in both AWRI 1499 and CBS 2499 were found in ST05.12/22. Together, this study provides tools to discriminate Brettanomyces strains and provides a first glimpse at the genetic diversity and genome plasticity of B. bruxellensis. PMID:24814796

  10. Assessing genetic diversity among Brettanomyces yeasts by DNA fingerprinting and whole-genome sequencing.

    Science.gov (United States)

    Crauwels, Sam; Zhu, Bo; Steensels, Jan; Busschaert, Pieter; De Samblanx, Gorik; Marchal, Kathleen; Willems, Kris A; Verstrepen, Kevin J; Lievens, Bart

    2014-07-01

    Brettanomyces yeasts, with the species Brettanomyces (Dekkera) bruxellensis being the most important one, are generally reported to be spoilage yeasts in the beer and wine industry due to the production of phenolic off flavors. However, B. bruxellensis is also known to be a beneficial contributor in certain fermentation processes, such as the production of certain specialty beers. Nevertheless, despite its economic importance, Brettanomyces yeasts remain poorly understood at the genetic and genomic levels. In this study, the genetic relationship between more than 50 Brettanomyces strains from all presently known species and from several sources was studied using a combination of DNA fingerprinting techniques. This revealed an intriguing correlation between the B. bruxellensis fingerprints and the respective isolation source. To further explore this relationship, we sequenced a (beneficial) beer isolate of B. bruxellensis (VIB X9085; ST05.12/22) and compared its genome sequence with the genome sequences of two wine spoilage strains (AWRI 1499 and CBS 2499). ST05.12/22 was found to be substantially different from both wine strains, especially at the level of single nucleotide polymorphisms (SNPs). In addition, there were major differences in the genome structures between the strains investigated, including the presence of large duplications and deletions. Gene content analysis revealed the presence of 20 genes which were present in both wine strains but absent in the beer strain, including many genes involved in carbon and nitrogen metabolism, and vice versa, no genes that were missing in both AWRI 1499 and CBS 2499 were found in ST05.12/22. Together, this study provides tools to discriminate Brettanomyces strains and provides a first glimpse at the genetic diversity and genome plasticity of B. bruxellensis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  11. Genes and genetic testing in hereditary ataxias.

    Science.gov (United States)

    Sandford, Erin; Burmeister, Margit

    2014-07-22

    Ataxia is a neurological cerebellar disorder characterized by loss of coordination during muscle movements affecting walking, vision, and speech. Genetic ataxias are very heterogeneous, with causative variants reported in over 50 genes, which can be inherited in classical dominant, recessive, X-linked, or mitochondrial fashion. A common mechanism of dominant ataxias is repeat expansions, where increasing lengths of repeated DNA sequences result in non-functional proteins that accumulate in the body causing disease. Greater understanding of all ataxia genes has helped identify several different pathways, such as DNA repair, ubiquitination, and ion transport, which can be used to help further identify new genes and potential treatments. Testing for the most common mutations in these genes is now clinically routine to help with prognosis and treatment decisions, but next generation sequencing will revolutionize how genetic testing will be done. Despite the large number of known ataxia causing genes, however, many individuals with ataxia are unable to obtain a genetic diagnosis, suggesting that more genes need to be discovered. Utilization of next generation sequencing technologies, expression studies, and increased knowledge of ataxia pathways will aid in the identification of new ataxia genes.

  12. Genome-Wide Screening of Genes Required for Glycosylphosphatidylinositol Biosynthesis.

    Directory of Open Access Journals (Sweden)

    Yao Rong

    Full Text Available Glycosylphosphatidylinositol (GPI is synthesized and transferred to proteins in the endoplasmic reticulum (ER. GPI-anchored proteins are then transported from the ER to the plasma membrane through the Golgi apparatus. To date, at least 17 steps have been identified to be required for the GPI biosynthetic pathway. Here, we aimed to establish a comprehensive screening method to identify genes involved in GPI biosynthesis using mammalian haploid screens. Human haploid cells were mutagenized by the integration of gene trap vectors into the genome. Mutagenized cells were then treated with a bacterial pore-forming toxin, aerolysin, which binds to GPI-anchored proteins for targeting to the cell membrane. Cells that showed low surface expression of CD59, a GPI-anchored protein, were further enriched for. Gene trap insertion sites in the non-selected population and in the enriched population were determined by deep sequencing. This screening enriched 23 gene regions among the 26 known GPI biosynthetic genes, which when mutated are expected to decrease the surface expression of GPI-anchored proteins. Our results indicate that the forward genetic approach using haploid cells is a useful and powerful technique to identify factors involved in phenotypes of interest.

  13. 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.

  14. Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome

    OpenAIRE

    Zemojtel, T.; Koehler, S; Mackenroth, L; Jaeger, M.; Hecht, J.; Krawitz, P.; Graul-Neumann, L; Doelken, S.; Ehmke, N.; Spielmann, M.; Oien, N.C.; Schweiger, M R; Krueger, U; Frommer, G.; Fischer, B.

    2014-01-01

    Less than half of patients with suspected genetic disease receive a molecular diagnosis. We have therefore integrated next-generation sequencing (NGS), bioinformatics, and clinical data into an effective diagnostic workflow. We used variants in the 2741 established Mendelian disease genes [the disease-associated genome (DAG)] to develop a targeted enrichment DAG panel (7.1 Mb), which achieves a coverage of 20-fold or better for 98% of bases. Furthermore, we established a computational method ...

  15. The molecular genetic makeup of acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Abstract: Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Genomic sequence around butterfly wing development genes: annotation and comparative analysis.

    Directory of Open Access Journals (Sweden)

    Inês C Conceição

    Full Text Available BACKGROUND: Analysis of genomic sequence allows characterization of genome content and organization, and access beyond gene-coding regions for identification of functional elements. BAC libraries, where relatively large genomic regions are made readily available, are especially useful for species without a fully sequenced genome and can increase genomic coverage of phylogenetic and biological diversity. For example, no butterfly genome is yet available despite the unique genetic and biological properties of this group, such as diversified wing color patterns. The evolution and development of these patterns is being studied in a few target species, including Bicyclus anynana, where a whole-genome BAC library allows targeted access to large genomic regions. METHODOLOGY/PRINCIPAL FINDINGS: We characterize ∼1.3 Mb of genomic sequence around 11 selected genes expressed in B. anynana developing wings. Extensive manual curation of in silico predictions, also making use of a large dataset of expressed genes for this species, identified repetitive elements and protein coding sequence, and highlighted an expansion of Alcohol dehydrogenase genes. Comparative analysis with orthologous regions of the lepidopteran reference genome allowed assessment of conservation of fine-scale synteny (with detection of new inversions and translocations and of DNA sequence (with detection of high levels of conservation of non-coding regions around some, but not all, developmental genes. CONCLUSIONS: The general properties and organization of the available B. anynana genomic sequence are similar to the lepidopteran reference, despite the more than 140 MY divergence. Our results lay the groundwork for further studies of new interesting findings in relation to both coding and non-coding sequence: 1 the Alcohol dehydrogenase expansion with higher similarity between the five tandemly-repeated B. anynana paralogs than with the corresponding B. mori orthologs, and 2 the high

  5. Genome-wide experimental determination of barriers to horizontal gene transfer

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Edward; Sorek, Rotem; Zhu, Yiwen; Creevey, Christopher J.; Francino, M. Pilar; Bork, Peer; Rubin, Edward M.

    2007-09-24

    Horizontal gene transfer, in which genetic material is transferred from the genome of one organism to another, has been investigated in microbial species mainly through computational sequence analyses. To address the lack of experimental data, we studied the attempted movement of 246,045 genes from 79 prokaryotic genomes into E. coli and identified genes that consistently fail to transfer. We studied the mechanisms underlying transfer inhibition by placing coding regions from different species under the control of inducible promoters. Their toxicity to the host inhibited transfer regardless of the species of origin and our data suggest that increased gene dosage and associated increased expression is a predominant cause for transfer failure. While these experimental studies examined transfer solely into E. coli, a computational analysis of gene transfer rates across available bacterial and archaeal genomes indicates that the barriers observed in our study are general across the tree of life.

  6. Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies

    NARCIS (Netherlands)

    C. Rodriguez-Fontenla (Cristina); M. Calaza (Manuel); E. Evangelou (Evangelos); A.M. Valdes (Ana Maria); N.K. Arden (Nigel); F.J. Blanco; A.J. Carr (Andrew Jonathan); K. Chapman (Kay); P. Deloukas (Panagiotis); M. Doherty (Michael); T. Esko (Tõnu); C.M. Garcés Aletá (Carlos); J.J. Gomez-Reino Carnota (Juan); H.T. Helgadottir (Hafdis); A. Hofman (Albert); I. Jonsdottir (Ingileif); J.M. Kerkhof (Hanneke); M. Kloppenburg (Margreet); A. McCaskie (Andrew); E.E. Ntzani (Evangelia); W.E.R. Ollier (William); N. Oreiro (Natividad); K. Panoutsopoulou (Kalliope); S.H. Ralston (Stuart); Y.F.M. Ramos (Yolande); J.A. Riancho (José); F. Rivadeneira Ramirez (Fernando); P.E. Slagboom (Eline); U. Styrkarsdottir (Unnur); U. Thorsteinsdottir (Unnur); G. Thorleifsson (Gudmar); A. Tsezou (Aspasia); A.G. Uitterlinden (André); G.A. Wallis (Gillian); J.M. Wilkinson (Mark); G. Zhai (Guangju); Y. Zhu (Yanyan); D. Felson; J.P.A. Ioannidis (John); J. Loughlin (John); A. Metspalu (Andres); I. Meulenbelt (Ingrid); J-A. Zwart (John-Anker); J.B.J. van Meurs (Joyce); E. Zeggini (Eleftheria); T.D. Spector (Timothy); A. Gonzalez (Antonio)

    2014-01-01

    textabstractObjective To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. Methods A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiolog

  7. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

    Science.gov (United States)

    KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. De novo assembly of a field isolate genome reveals novel Plasmodium vivax erythrocyte invasion genes.

    Science.gov (United States)

    Hester, James; Chan, Ernest R; Menard, Didier; Mercereau-Puijalon, Odile; Barnwell, John; Zimmerman, Peter A; Serre, David

    2013-01-01

    Recent sequencing of Plasmodium vivax field isolates and monkey-adapted strains enabled characterization of SNPs throughout the genome. These analyses relied on mapping short reads onto the P. vivax reference genome that was generated using DNA from the monkey-adapted strain Salvador I. Any genomic locus deleted in this strain would be lacking in the reference genome sequence and missed in previous analyses. Here, we report de novo assembly of a P. vivax field isolate genome. Out of 2,857 assembled contigs, we identify 362 contigs, each containing more than 5 kb of contiguous DNA sequences absent from the reference genome sequence. These novel P. vivax DNA sequences account for 3.8 million nucleotides and contain 792 predicted genes. Most of these contigs contain members of multigene families and likely originate from telomeric regions. Interestingly, we identify two contigs containing predicted protein coding genes similar to known Plasmodium red blood cell invasion proteins. One gene encodes the reticulocyte-binding protein gene orthologous to P. cynomolgi RBP2e and P. knowlesi NBPXb. The second gene harbors all the hallmarks of a Plasmodium erythrocyte-binding protein, including conserved Duffy-binding like and C-terminus cysteine-rich domains. Phylogenetic analysis shows that this novel gene clusters separately from all known Plasmodium Duffy-binding protein genes. Additional analyses showing that this gene is present in most P. vivax genomes and transcribed in blood-stage parasites suggest that P. vivax red blood cell invasion mechanisms may be more complex than currently understood. The strategy employed here complements previous genomic analyses and takes full advantage of next-generation sequencing data to provide a comprehensive characterization of genetic variations in this important malaria parasite. Further analyses of the novel protein coding genes discovered through de novo assembly have the potential to identify genes that influence key aspects of P

  13. Advances in gene technology: Human genetic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Scott, W.A.; Ahmad, F.; Black, S.; Schultz, J.; Whelan, W.J.

    1984-01-01

    This book discusses the papers presented at the conference on the subject of ''advances in Gene technology: Human genetic disorders''. Molecular biology of various carcinomas and inheritance of metabolic diseases is discussed and technology advancement in diagnosis of hereditary diseases is described. Some of the titles discussed are-Immunoglobulin genes translocation and diagnosis; hemophilia; oncogenes; oncogenic transformations; experimental data on mice, hamsters, birds carcinomas and sarcomas.

  14. Genome-wide conserved non-coding microsatellite (CNMS) marker-based integrative genetical genomics for quantitative dissection of seed weight in chickpea

    Science.gov (United States)

    Bajaj, Deepak; Saxena, Maneesha S.; Kujur, Alice; Das, Shouvik; Badoni, Saurabh; Tripathi, Shailesh; Upadhyaya, Hari D.; Gowda, C. L. L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

    2015-01-01

    Phylogenetic footprinting identified 666 genome-wide paralogous and orthologous CNMS (conserved non-coding microsatellite) markers from 5′-untranslated and regulatory regions (URRs) of 603 protein-coding chickpea genes. The (CT)n and (GA)n CNMS carrying CTRMCAMV35S and GAGA8BKN3 regulatory elements, respectively, are abundant in the chickpea genome. The mapped genic CNMS markers with robust amplification efficiencies (94.7%) detected higher intraspecific polymorphic potential (37.6%) among genotypes, implying their immense utility in chickpea breeding and genetic analyses. Seventeen differentially expressed CNMS marker-associated genes showing strong preferential and seed tissue/developmental stage-specific expression in contrasting genotypes were selected to narrow down the gene targets underlying seed weight quantitative trait loci (QTLs)/eQTLs (expression QTLs) through integrative genetical genomics. The integration of transcript profiling with seed weight QTL/eQTL mapping, molecular haplotyping, and association analyses identified potential molecular tags (GAGA8BKN3 and RAV1AAT regulatory elements and alleles/haplotypes) in the LOB-domain-containing protein- and KANADI protein-encoding transcription factor genes controlling the cis-regulated expression for seed weight in the chickpea. This emphasizes the potential of CNMS marker-based integrative genetical genomics for the quantitative genetic dissection of complex seed weight in chickpea. PMID:25504138

  15. Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication.

    Science.gov (United States)

    Montague, Michael J; Li, Gang; Gandolfi, Barbara; Khan, Razib; Aken, Bronwen L; Searle, Steven M J; Minx, Patrick; Hillier, LaDeana W; Koboldt, Daniel C; Davis, Brian W; Driscoll, Carlos A; Barr, Christina S; Blackistone, Kevin; Quilez, Javier; Lorente-Galdos, Belen; Marques-Bonet, Tomas; Alkan, Can; Thomas, Gregg W C; Hahn, Matthew W; Menotti-Raymond, Marilyn; O'Brien, Stephen J; Wilson, Richard K; Lyons, Leslie A; Murphy, William J; Warren, Wesley C

    2014-12-02

    Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.

  16. 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...

  17. Comparative Genome of GK and Wistar Rats Reveals Genetic Basis of Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Tiancheng Liu

    Full Text Available The Goto-Kakizaki (GK rat, which has been developed by repeated inbreeding of glucose-intolerant Wistar rats, is the most widely studied rat model for Type 2 diabetes (T2D. However, the detailed genetic background of T2D phenotype in GK rats is still largely unknown. We report a survey of T2D susceptible variations based on high-quality whole genome sequencing of GK and Wistar rats, which have generated a list of GK-specific variations (228 structural variations, 2660 CNV amplification and 2834 CNV deletion, 1796 protein affecting SNVs or indels by comparative genome analysis and identified 192 potential T2D-associated genes. The genes with variants are further refined with prior knowledge and public resource including variant polymorphism of rat strains, protein-protein interactions and differential gene expression. Finally we have identified 15 genetic mutant genes which include seven known T2D related genes (Tnfrsf1b, Scg5, Fgb, Sell, Dpp4, Icam1, and Pkd2l1 and eight high-confidence new candidate genes (Ldlr, Ccl2, Erbb3, Akr1b1, Pik3c2a, Cd5, Eef2k, and Cpd. Our result reveals that the T2D phenotype may be caused by the accumulation of multiple variations in GK rat, and that the mutated genes may affect biological functions including adipocytokine signaling, glycerolipid metabolism, PPAR signaling, T cell receptor signaling and insulin signaling pathways. We present the genomic difference between two closely related rat strains (GK and Wistar and narrow down the scope of susceptible loci. It also requires further experimental study to understand and validate the relationship between our candidate variants and T2D phenotype. Our findings highlight the importance of sequenced-based comparative genomics for investigating disease susceptibility loci in inbreeding animal models.

  18. Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes.

    Science.gov (United States)

    Kang, Zhen; Zhang, Junli; Jin, Peng; Yang, Sen

    2015-01-01

    Owing to our limited understanding of the relationship between sequence and function and the interaction between intracellular pathways and regulatory systems, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are difficult to achieve. As an alternative approach, directed evolution has been widely used to engineer genomes and enzyme-coding genes. In particular, significant developments toward DNA synthesis, DNA assembly (in vitro or in vivo), recombination-mediated genetic engineering, and high-throughput screening techniques in the field of synthetic biology have been matured and widely adopted, enabling rapid semi-rational genome engineering to generate variants with desired properties. In this commentary, these novel tools and their corresponding applications in the directed evolution of genomes and enzymes are discussed. Moreover, the strategies for genome engineering and rapid in vitro enzyme evolution are also proposed.

  19. Insular organization of gene space in grass genomes.

    Science.gov (United States)

    Gottlieb, Andrea; Müller, Hans-Georg; Massa, Alicia N; Wanjugi, Humphrey; Deal, Karin R; You, Frank M; Xu, Xiangyang; Gu, Yong Q; Luo, Ming-Cheng; Anderson, Olin D; Chan, Agnes P; Rabinowicz, Pablo; Devos, Katrien M; Dvorak, Jan

    2013-01-01

    Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands "gene insulae" to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes.

  20. Insular organization of gene space in grass genomes.

    Directory of Open Access Journals (Sweden)

    Andrea Gottlieb

    Full Text Available Wheat and maize genes were hypothesized to be clustered into islands but the hypothesis was not statistically tested. The hypothesis is statistically tested here in four grass species differing in genome size, Brachypodium distachyon, Oryza sativa, Sorghum bicolor, and Aegilops tauschii. Density functions obtained under a model where gene locations follow a homogeneous Poisson process and thus are not clustered are compared with a model-free situation quantified through a non-parametric density estimate. A simple homogeneous Poisson model for gene locations is not rejected for the small O. sativa and B. distachyon genomes, indicating that genes are distributed largely uniformly in those species, but is rejected for the larger S. bicolor and Ae. tauschii genomes, providing evidence for clustering of genes into islands. It is proposed to call the gene islands "gene insulae" to distinguish them from other types of gene clustering that have been proposed. An average S. bicolor and Ae. tauschii insula is estimated to contain 3.7 and 3.9 genes with an average intergenic distance within an insula of 2.1 and 16.5 kb, respectively. Inter-insular distances are greater than 8 and 81 kb and average 15.1 and 205 kb, in S. bicolor and Ae. tauschii, respectively. A greater gene density observed in the distal regions of the Ae. tauschii chromosomes is shown to be primarily caused by shortening of inter-insular distances. The comparison of the four grass genomes suggests that gene locations are largely a function of a homogeneous Poisson process in small genomes. Nonrandom insertions of LTR retroelements during genome expansion creates gene insulae, which become less dense and further apart with the increase in genome size. High concordance in relative lengths of orthologous intergenic distances among the investigated genomes including the maize genome suggests functional constraints on gene distribution in the grass genomes.

  1. 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

  2. Development of an integrated genome informatics, data management and workflow infrastructure: A toolbox for the study of complex disease genetics

    Directory of Open Access Journals (Sweden)

    Burren Oliver S

    2004-01-01

    Full Text Available Abstract The genetic dissection of complex disease remains a significant challenge. Sample-tracking and the recording, processing and storage of high-throughput laboratory data with public domain data, require integration of databases, genome informatics and genetic analyses in an easily updated and scaleable format. To find genes involved in multifactorial diseases such as type 1 diabetes (T1D, chromosome regions are defined based on functional candidate gene content, linkage information from humans and animal model mapping information. For each region, genomic information is extracted from Ensembl, converted and loaded into ACeDB for manual gene annotation. Homology information is examined using ACeDB tools and the gene structure verified. Manually curated genes are extracted from ACeDB and read into the feature database, which holds relevant local genomic feature data and an audit trail of laboratory investigations. Public domain information, manually curated genes, polymorphisms, primers, linkage and association analyses, with links to our genotyping database, are shown in Gbrowse. This system scales to include genetic, statistical, quality control (QC and biological data such as expression analyses of RNA or protein, all linked from a genomics integrative display. Our system is applicable to any genetic study of complex disease, of either large or small scale.

  3. Genome Analyses of Icelandic Strains of Sulfolobus islandicus, Model Organisms for Genetic and Virus-Host Interaction Studies

    DEFF Research Database (Denmark)

    Guo, Li; Brügger, Kim; Liu, Chao;

    2011-01-01

    The genomes of two Sulfolobus islandicus strains obtained from Icelandic solfataras were sequenced and analyzed. Strain REY15A is a host for a versatile genetic toolbox. It exhibits a genome of minimal size, is stable genetically, and is easy to grow and manipulate. Strain HVE10/4 shows a broad h...... conjugative plasmids, which have integrated at a few tRNA genes lacking introns. This provides a possible rationale for the presence of the introns.......The genomes of two Sulfolobus islandicus strains obtained from Icelandic solfataras were sequenced and analyzed. Strain REY15A is a host for a versatile genetic toolbox. It exhibits a genome of minimal size, is stable genetically, and is easy to grow and manipulate. Strain HVE10/4 shows a broad...... in gene content and gene order occur. These include gene clusters involved in specific metabolic pathways, multiple copies of VapBC antitoxin-toxin gene pairs, and in strain HVE10/4, a 50-kb region rich in glycosyl transferase genes. The variable region also contains most of the insertion sequence (IS...

  4. An integrative systems genetics approach reveals potential causal genes and pathways related to obesity

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Zhernakova, Daria V.; Westra, Harm-Jan

    2015-01-01

    BACKGROUND: Obesity is a multi-factorial health problem in which genetic factors play an important role. Limited results have been obtained in single-gene studies using either genomic or transcriptomic data. RNA sequencing technology has shown its potential in gaining accurate knowledge about...... the transcriptome, and may reveal novel genes affecting complex diseases. Integration of genomic and transcriptomic variation (expression quantitative trait loci [eQTL] mapping) has identified causal variants that affect complex diseases. We integrated transcriptomic data from adipose tissue and genomic data from...... a porcine model to investigate the mechanisms involved in obesity using a systems genetics approach. METHODS: Using a selective gene expression profiling approach, we selected 36 animals based on a previously created genomic Obesity Index for RNA sequencing of subcutaneous adipose tissue. Differential...

  5. 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.

  6. Regulatory Network Construction in Arabidopsis using genome-wide gene expression QTLs

    NARCIS (Netherlands)

    Keurentjes, J.J.B.; Fu, J.J.; Terpstra, I.R.; Garcia, J.M.; van den Ackerveken, G.; Snoek, L.B.; Peeters, A.J.M.; Vreugdenhil, D.; Koornreef, M.; Jansen, R.C.

    2007-01-01

    Regulatory network construction in Arabidopsis by using genome-wide gene expression quantitative trait loci.Keurentjes JJ, Fu J, Terpstra IR, Garcia JM, van den Ackerveken G, Snoek LB, Peeters AJ, Vreugdenhil D, Koornneef M, Jansen RC. Laboratory of Genetics, Wageningen University, Arboretumlaan 4,

  7. Regulatory network construction in Arabidopsis by using genome-wide gene expression quantitative trait loci

    NARCIS (Netherlands)

    Keurentjes, Joost J.B.; Fu, Jingyuan; Terpstra, Inez R.; Garcia, Juan M.; Ackerveken, Guido van den; Snoek, L. Basten; Peeters, Anton J.M.; Vreugdenhil, Dick; Koornneef, Maarten; Jansen, Ritsert C.

    2007-01-01

    Accessions of a plant species can show considerable genetic differences that are analyzed effectively by using recombinant inbred line (RIL) populations. Here we describe the results of genome-wide expression variation analysis in an RIL population of Arabidopsis thaliana. For many genes, variation

  8. 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.

  9. Early host gene expression responses to a Salmonella infection in the intestine of chickens with different genetic background

    NARCIS (Netherlands)

    Hemert, van S.; Hoekman, A.J.W.; Smith, M.A.; Rebel, J.M.J.

    2006-01-01

    So far the responses of chickens to Salmonella have not been studied in vivo on a whole genome-wide scale. Furthermore, the influence of the host genetic background on gene expression responses is unknown. In this study gene expression profiles in the chicken (Gallus gallus) intestine of two genetic

  10. The "one-step" Bean pod mottle virus (BPMV)derived vector is a functional genomics tool for efficient overexpression of heterologous protein, virus-induced gene silencing and genetic mapping of BPMV R-gene in common bean (Phaseolus vulgaris L.)

    OpenAIRE

    Pflieger, Stéphanie; Blanchet, Sophie; Meziadi, Chouaïb; Richard, Manon; Thareau, Vincent; Mary, Fanny; Mazoyer, Céline; Geffroy, Valerie

    2014-01-01

    Background Over the last two years, considerable advances have been made in common bean (Phaseolus vulgaris L.) genomics, especially with the completion of the genome sequence and the availability of RNAseq data. However, as common bean is recalcitrant to stable genetic transformation, much work remains to be done for the development of functional genomics tools adapted to large-scale studies. Results Here we report the successful implementation of an efficient viral vector system for foreign...

  11. Population genetics of fungal and oomycete effectors involved in gene-for-gene interactions.

    Science.gov (United States)

    Stukenbrock, Eva H; McDonald, Bruce A

    2009-04-01

    Antagonistic coevolution between plants and pathogens has generated a broad array of attack and defense mechanisms. In the classical avirulence (Avr) gene-for-gene model, the pathogen gene evolves to escape host recognition while the host resistance (R) gene evolves to track the evolving pathogen elicitor. In the case of host-specific toxins (HST), the evolutionary arms race may be inverted, with the gene encoding the pathogen toxin evolving to maintain recognition of the host sensitivity target while the host sensitivity gene evolves to escape binding with the toxin. Pathogen effector genes, including those encoding Avr elicitors and HST, often show elevated levels of polymorphism reflecting the coevolutionary arms race between host and pathogen. However, selection can also eliminate variation in the coevolved gene and its neighboring regions when advantageous alleles are swept to fixation. The distribution and diversity of corresponding host genes will have a major impact on the distribution and diversity of effectors in the pathogen population. Population genetic analyses including both hosts and their pathogens provide an essential tool to understand the diversity and dynamics of effector genes. Here, we summarize current knowledge about the population genetics of fungal and oomycete effector genes, focusing on recent studies that have used both spatial and temporal collections to assess the diversity and distribution of alleles and to monitor changes in allele frequencies over time. These studies illustrate that effector genes exhibit a significant degree of diversity at both small and large sampling scales, suggesting that local selection plays an important role in their evolution. They also illustrate that Avr elicitors and HST may be recognizing the same R genes in plants, leading to evolutionary outcomes that differ for necrotrophs and biotrophs while affecting the evolution of the corresponding R genes. Under this scenario, the optimal number of R genes

  12. 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.

  13. Maintenance and expression of the S. cerevisiae mitochondrial genome--from genetics to evolution and systems biology.

    Science.gov (United States)

    Lipinski, Kamil A; Kaniak-Golik, Aneta; Golik, Pawel

    2010-01-01

    As a legacy of their endosymbiotic eubacterial origin, mitochondria possess a residual genome, encoding only a few proteins and dependent on a variety of factors encoded by the nuclear genome for its maintenance and expression. As a facultative anaerobe with well understood genetics and molecular biology, Saccharomyces cerevisiae is the model system of choice for studying nucleo-mitochondrial genetic interactions. Maintenance of the mitochondrial genome is controlled by a set of nuclear-coded factors forming intricately interconnected circuits responsible for replication, recombination, repair and transmission to buds. Expression of the yeast mitochondrial genome is regulated mostly at the post-transcriptional level, and involves many general and gene-specific factors regulating splicing, RNA processing and stability and translation. A very interesting aspect of the yeast mitochondrial system is the relationship between genome maintenance and gene expression. Deletions of genes involved in many different aspects of mitochondrial gene expression, notably translation, result in an irreversible loss of functional mtDNA. The mitochondrial genetic system viewed from the systems biology perspective is therefore very fragile and lacks robustness compared to the remaining systems of the cell. This lack of robustness could be a legacy of the reductive evolution of the mitochondrial genome, but explanations involving selective advantages of increased evolvability have also been postulated. Copyright © 2009 Elsevier B.V. All rights reserved.

  14. A genomic overview of short genetic variations in a basal chordate, Ciona intestinalis

    Directory of Open Access Journals (Sweden)

    Satou Yutaka

    2012-05-01

    Full Text Available Abstract Background Although the Ciona intestinalis genome contains many allelic polymorphisms, there is only limited data analyzed systematically. Establishing a dense map of genetic variations in C. intestinalis is necessary not only for linkage analysis, but also for other experimental biology including molecular developmental and evolutionary studies, because animals from natural populations are typically used for experiments. Results Here, we identified over three million candidate short genomic variations within a 110 Mb euchromatin region among five C. intestinalis individuals. The average nucleotide diversity was approximately 1.1%. Genetic variations were found at a similar density in intergenic and gene regions. Non-synonymous and nonsense nucleotide substitutions were found in 12,493 and 1,214 genes accounting for 81.9% and 8.0% of the entire gene set, respectively, and over 60% of genes in the single animal encode non-identical proteins between maternal and paternal alleles. Conclusions Our results provide a framework for studying evolution of the animal genome, as well as a useful resource for a wide range of C. intestinalis researchers.

  15. Identification of susceptibility genes and genetic modifiers of human diseases

    Science.gov (United States)

    Abel, Kenneth; Kammerer, Stefan; Hoyal, Carolyn; Reneland, Rikard; Marnellos, George; Nelson, Matthew R.; Braun, Andreas

    2005-03-01

    The completion of the human genome sequence enables the discovery of genes involved in common human disorders. The successful identification of these genes is dependent on the availability of informative sample sets, validated marker panels, a high-throughput scoring technology, and a strategy for combining these resources. We have developed a universal platform technology based on mass spectrometry (MassARRAY) for analyzing nucleic acids with high precision and accuracy. To fuel this technology, we generated more than 100,000 validated assays for single nucleotide polymorphisms (SNPs) covering virtually all known and predicted human genes. We also established a large DNA sample bank comprised of more than 50,000 consented healthy and diseased individuals. This combination of reagents and technology allows the execution of large-scale genome-wide association studies. Taking advantage of MassARRAY"s capability for quantitative analysis of nucleic acids, allele frequencies are estimated in sample pools containing large numbers of individual DNAs. To compare pools as a first-pass "filtering" step is a tremendous advantage in throughput and cost over individual genotyping. We employed this approach in numerous genome-wide, hypothesis-free searches to identify genes associated with common complex diseases, such as breast cancer, osteoporosis, and osteoarthritis, and genes involved in quantitative traits like high density lipoproteins cholesterol (HDL-c) levels and central fat. Access to additional well-characterized patient samples through collaborations allows us to conduct replication studies that validate true disease genes. These discoveries will expand our understanding of genetic disease predisposition, and our ability for early diagnosis and determination of specific disease subtype or progression stage.

  16. Involvement of plastid, mitochondrial and nuclear genomes in plant-to-plant horizontal gene transfer

    Directory of Open Access Journals (Sweden)

    Maria Virginia Sanchez-Puerta

    2014-12-01

    Full Text Available This review focuses on plant-to-plant horizontal gene transfer (HGT involving the three DNA-containing cellular compartments. It highlights the great incidence of HGT in the mitochondrial genome (mtDNA of angiosperms, the increasing number of examples in plant nuclear genomes, and the lack of any convincing evidence for HGT in the well-studied plastid genome of land plants. Most of the foreign mitochondrial genes are non-functional, generally found as pseudogenes in the recipient plant mtDNA that maintains its functional native genes. The few exceptions involve chimeric HGT, in which foreign and native copies recombine leading to a functional and single copy of the gene. Maintenance of foreign genes in plant mitochondria is probably the result of genetic drift, but a possible evolutionary advantage may be conferred through the generation of genetic diversity by gene conversion between native and foreign copies. Conversely, a few cases of nuclear HGT in plants involve functional transfers of novel genes that resulted in adaptive evolution. Direct cell-to-cell contact between plants (e.g. host-parasite relationships or natural grafting facilitate the exchange of genetic material, in which HGT has been reported for both nuclear and mitochondrial genomes, and in the form of genomic DNA, instead of RNA. A thorough review of the literature indicates that HGT in mitochondrial and nuclear genomes of angiosperms is much more frequent than previously expected and that the evolutionary impact and mechanisms underlying plant-to-plant HGT remain to be uncovered.

  17. Strigolactone biology: genes, functional genomics, epigenetics and applications.

    Science.gov (United States)

    Makhzoum, Abdullah; Yousefzadi, Morteza; Malik, Sonia; Gantet, Pascal; Tremouillaux-Guiller, Jocelyne

    2017-03-01

    Strigolactones (SLs) represent an important new plant hormone class marked by their multifunctional role in plant and rhizosphere interactions. These compounds stimulate hyphal branching in arbuscular mycorrhizal fungi (AMF) and seed germination of root parasitic plants. In addition, they are involved in the control of plant architecture by inhibiting bud outgrowth as well as many other morphological and developmental processes together with other plant hormones such as auxins and cytokinins. The biosynthetic pathway of SLs that are derived from carotenoids was partially decrypted based on the identification of mutants from a variety of plant species. Only a few SL biosynthetic and regulated genes and related regulatory transcription factors have been identified. However, functional genomics and epigenetic studies started to give first elements on the modality of the regulation of SLs related genes. Since they control plant architecture and plant-rhizosphere interaction, SLs start to be used for agronomical and biotechnological applications. Furthermore, the genes involved in the SL biosynthetic pathway and genes regulated by SL constitute interesting targets for plant breeding. Therefore, it is necessary to decipher and better understand the genetic determinants of their regulation at different levels.

  18. Neutral Theory Predicts the Relative Abundance and Diversity of Genetic Elements in a Broad Array of Eukaryotic Genomes

    Science.gov (United States)

    Serra, François; Becher, Verónica; Dopazo, Hernán

    2013-01-01

    It is universally true in ecological communities, terrestrial or aquatic, temperate or tropical, that some species are very abundant, others are moderately common, and the majority are rare. Likewise, eukaryotic genomes also contain classes or “species” of genetic elements that vary greatly in abundance: DNA transposons, retrotransposons, satellite sequences, simple repeats and their less abundant functional sequences such as RNA or genes. Are the patterns of relative species abundance and diversity similar among ecological communities and genomes? Previous dynamical models of genomic diversity have focused on the selective forces shaping the abundance and diversity of transposable elements (TEs). However, ideally, models of genome dynamics should consider not only TEs, but also the diversity of all genetic classes or “species” populating eukaryotic genomes. Here, in an analysis of the diversity and abundance of genetic elements in >500 eukaryotic chromosomes, we show that the patterns are consistent with a neutral hypothesis of genome assembly in virtually all chromosomes tested. The distributions of relative abundance of genetic elements are quite precisely predicted by the dynamics of an ecological model for which the principle of functional equivalence is the main assumption. We hypothesize that at large temporal scales an overarching neutral or nearly neutral process governs the evolution of abundance and diversity of genetic elements in eukaryotic genomes. PMID:23798991

  19. Comparative genomics of the relationship between gene structure and expression

    NARCIS (Netherlands)

    Ren, X.

    2006-01-01

    The relationship between the structure of genes and their expression is a relatively new aspect of genome organization and regulation. With more genome sequences and expression data becoming available, bioinformatics approaches can help the further elucidation of the relationships between gene struc

  20. Weeding out the genes: the Arabidopsis genome project.

    Science.gov (United States)

    Martienssen, R A

    2000-05-01

    The Arabidopsis genome sequence is scheduled for completion at the end of this year (December 2000). It will be the first higher plant genome to be sequenced, and will allow a detailed comparison with bacterial, yeast and animal genomes. Already, two of the five chromosomes have been sequenced, and we have had our first glimpse of higher eukaryotic centromeres, and the structure of heterochromatin. The implications for understanding plant gene function, genome structure and genome organization are profound. In this review, the lessons learned for future genome projects are reviewed as well as a summary of the initial findings in Arabidopsis.

  1. The genome BLASTatlas - a GeneWiz extension for visualization of whole-genome homology

    DEFF Research Database (Denmark)

    Hallin, Peter Fischer; Binnewies, Tim Terence; Ussery, David

    2008-01-01

    the Clostridium tetani plasmid p88, where homologues for toxin genes can be easily visualized in other sequenced Clostridium genomes, and for a Clostridium botulinum genome, compared to 14 other Clostridium genomes. DNA structural information is also included in the atlas to visualize the DNA chromosomal context...

  2. 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...

  3. Ultrahigh-dimensional variable selection method for whole-genome gene-gene interaction analysis

    Directory of Open Access Journals (Sweden)

    Ueki Masao

    2012-05-01

    Full Text Available Abstract Background Genome-wide gene-gene interaction analysis using single nucleotide polymorphisms (SNPs is an attractive way for identification of genetic components that confers susceptibility of human complex diseases. Individual hypothesis testing for SNP-SNP pairs as in common genome-wide association study (GWAS however involves difficulty in setting overall p-value due to complicated correlation structure, namely, the multiple testing problem that causes unacceptable false negative results. A large number of SNP-SNP pairs than sample size, so-called the large p small n problem, precludes simultaneous analysis using multiple regression. The method that overcomes above issues is thus needed. Results We adopt an up-to-date method for ultrahigh-dimensional variable selection termed the sure independence screening (SIS for appropriate handling of numerous number of SNP-SNP interactions by including them as predictor variables in logistic regression. We propose ranking strategy using promising dummy coding methods and following variable selection procedure in the SIS method suitably modified for gene-gene interaction analysis. We also implemented the procedures in a software program, EPISIS, using the cost-effective GPGPU (General-purpose computing on graphics processing units technology. EPISIS can complete exhaustive search for SNP-SNP interactions in standard GWAS dataset within several hours. The proposed method works successfully in simulation experiments and in application to real WTCCC (Wellcome Trust Case–control Consortium data. Conclusions Based on the machine-learning principle, the proposed method gives powerful and flexible genome-wide search for various patterns of gene-gene interaction.

  4. High-Diversity Genes in the Arabidopsis Genome

    OpenAIRE

    Cork, Jennifer M.; Purugganan, Michael D.

    2005-01-01

    High-diversity genes represent an important class of loci in organismal genomes. Since elevated levels of nucleotide variation are a key component of the molecular signature for balancing selection or local adaptation, high-diversity genes may represent loci whose alleles are selectively maintained as balanced polymorphisms. Comparison of 4300 random shotgun sequence fragments of the Arabidopsis thaliana Ler ecotype genome with the whole genomic sequence of the Col-0 ecotype identified 60 gen...

  5. 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

  6. 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.

  7. Advancing Eucalyptus genomics: identification and sequencing of lignin biosynthesis genes from deep-coverage BAC libraries

    Directory of Open Access Journals (Sweden)

    Kudrna David

    2011-03-01

    Full Text Available Abstract Background Eucalyptus species are among the most planted hardwoods in the world because of their rapid growth, adaptability and valuable wood properties. The development and integration of genomic resources into breeding practice will be increasingly important in the decades to come. Bacterial artificial chromosome (BAC libraries are key genomic tools that enable positional cloning of important traits, synteny evaluation, and the development of genome framework physical maps for genetic linkage and genome sequencing. Results We describe the construction and characterization of two deep-coverage BAC libraries EG_Ba and EG_Bb obtained from nuclear DNA fragments of E. grandis (clone BRASUZ1 digested with HindIII and BstYI, respectively. Genome coverages of 17 and 15 haploid genome equivalents were estimated for EG_Ba and EG_Bb, respectively. Both libraries contained large inserts, with average sizes ranging from 135 Kb (Eg_Bb to 157 Kb (Eg_Ba, very low extra-nuclear genome contamination providing a probability of finding a single copy gene ≥ 99.99%. Libraries were screened for the presence of several genes of interest via hybridizations to high-density BAC filters followed by PCR validation. Five selected BAC clones were sequenced and assembled using the Roche GS FLX technology providing the whole sequence of the E. grandis chloroplast genome, and complete genomic sequences of important lignin biosynthesis genes. Conclusions The two E. grandis BAC libraries described in this study represent an important milestone for the advancement of Eucalyptus genomics and forest tree research. These BAC resources have a highly redundant genome coverage (> 15×, contain large average inserts and have a very low percentage of clones with organellar DNA or empty vectors. These publicly available BAC libraries are thus suitable for a broad range of applications in genetic and genomic research in Eucalyptus and possibly in related species of Myrtaceae

  8. 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.

  9. 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.

  10. Genome sequences of siphoviruses infecting marine Synechococcus unveil a diverse cyanophage group and extensive phage-host genetic exchanges.

    Science.gov (United States)

    Huang, Sijun; Wang, Kui; Jiao, Nianzhi; Chen, Feng

    2012-02-01

    Investigating the interactions between marine cyanobacteria and their viruses (phages) is important towards understanding the dynamic of ocean's primary productivity. Genome sequencing of marine cyanophages has greatly advanced our understanding about their ecology and evolution. Among 24 reported genomes of cyanophages that infect marine picocyanobacteria, 17 are from cyanomyoviruses and six from cyanopodoviruses, and only one from cyanosiphovirus (Prochlorococcus phage P-SS2). Here we present four complete genome sequences of siphoviruses (S-CBS1, S-CBS2, S-CBS3 and S-CBS4) that infect four different marine Synechococcus strains. Three distinct subtypes were recognized among the five known marine siphoviruses (including P-SS2) in terms of morphology, genome architecture, gene content and sequence similarity. Our study revealed that cyanosiphoviruses are genetically diverse with polyphyletic origin. No core genes were found across these five cyanosiphovirus genomes, and this is in contrast to the fact that many core genes have been found in cyanomyovirus or cyanopodovirus genomes. Interestingly, genes encoding three structural proteins and a lysozyme of S-CBS1 and S-CBS3 showed homology to a prophage-like genetic element in two freshwater Synechococcus elongatus genomes. Re-annotation of the prophage-like genomic region suggests that S. elongatus may contain an intact prophage. Cyanosiphovirus genes involved in DNA metabolism and replication share high sequence homology with those in cyanobacteria, and further phylogenetic analysis based on these genes suggests that ancient and selective genetic exchanges occurred, possibly due to past prophage integration. Metagenomic analysis based on the Global Ocean Sampling database showed that cyanosiphoviruses are present in relatively low abundance in the ocean surface water compared to cyanomyoviruses and cyanopodoviruses.

  11. Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics.

    Science.gov (United States)

    Linehan, W Marston

    2012-11-01

    Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease.

  12. Single gene-based distinction of individual microbial genomes from a mixed population of microbial cells

    Directory of Open Access Journals (Sweden)

    Manu Valtteri Tamminen

    2015-03-01

    Full Text Available Recent progress in environmental microbiology has revealed vast populations of microbes in any given habitat that cannot be detected by conventional culturing strategies. The use of sensitive genetic detection methods such as CARD-FISH and in situ PCR have been limited by the cell wall permeabilization requirement that cannot be performed similarly on all cell types without lysing some and leaving some unpermeabilized. Furthermore, the detection of low copy targets such as genes present in single copies in the microbial genomes, has remained problematic. We describe an emulsion-based procedure to trap individual microbial cells into picoliter-volume polyacrylamide droplets that provide a rigid support for genetic material and therefore allow complete degradation of cellular material to expose the individual genomes. The polyacrylamide droplets are subsequently converted into picoliter-scale reactors for genome amplification. The amplified genomes are labelled based on the presence of a target gene and differentiated from those that do not contain the gene by flow cytometry. Using the Escherichia coli strains XL1 and MC1061, which differ with respect to the presence (XL1 or absence (MC1061 of a single copy of a tetracycline resistance gene per genome, we demonstrate that XL1 genomes present at 0.1% of MC1061 genomes can be differentiated using this method. Using a spiked sediment microbial sample, we demonstrate that the method is applicable to highly complex environmental microbial communities as a target gene-based screen for individual microbes. The method provides a novel tool for enumerating functional cell populations in complex microbial communities. We envision that the method could be optimized for fluorescence-activated cell sorting to enrich genetic material of interest from complex environmental samples.

  13. On the relation between gene flow theory and genetic gain

    Directory of Open Access Journals (Sweden)

    Woolliams John A

    2000-01-01

    Full Text Available Abstract In conventional gene flow theory the rate of genetic gain is calculated as the summed products of genetic selection differential and asymptotic proportion of genes deriving from sex-age groups. Recent studies have shown that asymptotic proportions of genes predicted from conventional gene flow theory may deviate considerably from true proportions. However, the rate of genetic gain predicted from conventional gene flow theory was accurate. The current note shows that the connection between asymptotic proportions of genes and rate of genetic gain that is embodied in conventional gene flow theory is invalid, even though genetic gain may be predicted correctly from it.

  14. Evolution of closely linked gene pairs in vertebrate genomes

    NARCIS (Netherlands)

    Franck, E.; Hulsen, T.; Huynen, M.A.; Jong, de W.W.; Lunsen, N.H.; Madsen, O.

    2008-01-01

    The orientation of closely linked genes in mammalian genomes is not random: there are more head-to-head (h2h) gene pairs than expected. To understand the origin of this enrichment in h2h gene pairs, we have analyzed the phylogenetic distribution of gene pairs separated by less than 600 bp of interge

  15. 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.

  16. Exploring genetic variation in the tomato (Solanum section Lycopersicon) clade by whole-genome sequencing.

    Science.gov (United States)

    Aflitos, Saulo; Schijlen, Elio; de Jong, Hans; de Ridder, Dick; Smit, Sandra; Finkers, Richard; Wang, Jun; Zhang, Gengyun; Li, Ning; Mao, Likai; Bakker, Freek; Dirks, Rob; Breit, Timo; Gravendeel, Barbara; Huits, Henk; Struss, Darush; Swanson-Wagner, Ruth; van Leeuwen, Hans; van Ham, Roeland C H J; Fito, Laia; Guignier, Laëtitia; Sevilla, Myrna; Ellul, Philippe; Ganko, Eric; Kapur, Arvind; Reclus, Emannuel; de Geus, Bernard; van de Geest, Henri; Te Lintel Hekkert, Bas; van Haarst, Jan; Smits, Lars; Koops, Andries; Sanchez-Perez, Gabino; van Heusden, Adriaan W; Visser, Richard; Quan, Zhiwu; Min, Jiumeng; Liao, Li; Wang, Xiaoli; Wang, Guangbiao; Yue, Zhen; Yang, Xinhua; Xu, Na; Schranz, Eric; Smets, Erik; Vos, Rutger; Rauwerda, Johan; Ursem, Remco; Schuit, Cees; Kerns, Mike; van den Berg, Jan; Vriezen, Wim; Janssen, Antoine; Datema, Erwin; Jahrman, Torben; Moquet, Frederic; Bonnet, Julien; Peters, Sander

    2014-10-01

    We explored genetic variation by sequencing a selection of 84 tomato accessions and related wild species representative of the Lycopersicon, Arcanum, Eriopersicon and Neolycopersicon groups, which has yielded a huge amount of precious data on sequence diversity in the tomato clade. Three new reference genomes were reconstructed to support our comparative genome analyses. Comparative sequence alignment revealed group-, species- and accession-specific polymorphisms, explaining characteristic fruit traits and growth habits in the various cultivars. Using gene models from the annotated Heinz 1706 reference genome, we observed differences in the ratio between non-synonymous and synonymous SNPs (dN/dS) in fruit diversification and plant growth genes compared to a random set of genes, indicating positive selection and differences in selection pressure between crop accessions and wild species. In wild species, the number of single-nucleotide polymorphisms (SNPs) exceeds 10 million, i.e. 20-fold higher than found in most of the crop accessions, indicating dramatic genetic erosion of crop and heirloom tomatoes. In addition, the highest levels of heterozygosity were found for allogamous self-incompatible wild species, while facultative and autogamous self-compatible species display a lower heterozygosity level. Using whole-genome SNP information for maximum-likelihood analysis, we achieved complete tree resolution, whereas maximum-likelihood trees based on SNPs from ten fruit and growth genes show incomplete resolution for the crop accessions, partly due to the effect of heterozygous SNPs. Finally, results suggest that phylogenetic relationships are correlated with habitat, indicating the occurrence of geographical races within these groups, which is of practical importance for Solanum genome evolution studies.

  17. A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

    Science.gov (United States)

    Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

    2015-01-01

    Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

  18. A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types.

    Directory of Open Access Journals (Sweden)

    Feixiong Cheng

    2015-09-01

    Full Text Available Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1. The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics.

  19. Genome-wide search for gene-gene interactions in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Shuo Jiao

    Full Text Available Genome-wide association studies (GWAS have successfully identified a number of single-nucleotide polymorphisms (SNPs associated with colorectal cancer (CRC risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI. With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<10(-4. For the known locus rs10795668 (10p14, we found an interacting SNP rs367615 (5q21 with replication p = 0.01 and combined p = 4.19×10(-8. Among the top marginal SNPs after LD pruning (n = 163, we identified an interaction between rs1571218 (20p12.3 and rs10879357 (12q21.1 (nominal combined p = 2.51×10(-6; Bonferroni adjusted p = 0.03. Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC.

  20. Gene interactions in the evolution of genomic imprinting.

    Science.gov (United States)

    Wolf, J B; Brandvain, Y

    2014-08-01

    Numerous evolutionary theories have been developed to explain the epigenetic phenomenon of genomic imprinting. Here, we explore a subset of theories wherein non-additive genetic interactions can favour imprinting. In the simplest genic interaction--the case of underdominance--imprinting can be favoured to hide effectively low-fitness heterozygous genotypes; however, as there is no asymmetry between maternally and paternally inherited alleles in this model, other means of enforcing monoallelic expression may be more plausible evolutionary outcomes than genomic imprinting. By contrast, more successful interaction models of imprinting rely on an asymmetry between the maternally and paternally inherited alleles at a locus that favours the silencing of one allele as a means of coordinating the expression of high-fitness allelic combinations. For example, with interactions between autosomal loci, imprinting functionally preserves high-fitness genotypes that were favoured by selection in the previous generation. In this scenario, once a focal locus becomes imprinted, selection at interacting loci favours a matching imprint. Uniparental transmission generates similar asymmetries for sex chromosomes and cytoplasmic factors interacting with autosomal loci, with selection favouring the expression of either maternal or paternally derived autosomal alleles depending on the pattern of transmission of the uniparentally inherited factor. In a final class of models, asymmetries arise when genes expressed in offspring interact with genes expressed in one of its parents. Under such a scenario, a locus evolves to have imprinted expression in offspring to coordinate the interaction with its parent's genome. We illustrate these models and explore key links and differences using a unified framework.

  1. 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.

  2. Candidate genes revealed by a genome scan for mosquito resistance to a bacterial insecticide: sequence and gene expression variations

    Directory of Open Access Journals (Sweden)

    David Jean-Philippe

    2009-11-01

    Full Text Available Abstract Background Genome scans are becoming an increasingly popular approach to study the genetic basis of adaptation and speciation, but on their own, they are often helpless at identifying the specific gene(s or mutation(s targeted by selection. This shortcoming is hopefully bound to disappear in the near future, thanks to the wealth of new genomic resources that are currently being developed for many species. In this article, we provide a foretaste of this exciting new era by conducting a genome scan in the mosquito Aedes aegypti with the aim to look for candidate genes involved in resistance to Bacillus thuringiensis subsp. israelensis (Bti insecticidal toxins. Results The genome of a Bti-resistant and a Bti-susceptible strains was surveyed using about 500 MITE-based molecular markers, and the loci showing the highest inter-strain genetic differentiation were sequenced and mapped on the Aedes aegypti genome sequence. Several good candidate genes for Bti-resistance were identified in the vicinity of these highly differentiated markers. Two of them, coding for a cadherin and a leucine aminopeptidase, were further examined at the sequence and gene expression levels. In the resistant strain, the cadherin gene displayed patterns of nucleotide polymorphisms consistent with the action of positive selection (e.g. an excess of high compared to intermediate frequency mutations, as well as a significant under-expression compared to the susceptible strain. Conclusion Both sequence and gene expression analyses agree to suggest a role for positive selection in the evolution of this cadherin gene in the resistant strain. However, it is unlikely that resistance to Bti is conferred by this gene alone, and further investigation will be needed to characterize other genes significantly associated with Bti resistance in Ae. aegypti. Beyond these results, this article illustrates how genome scans can build on the body of new genomic information (here, full

  3. Theories of Population Variation in Genes and Genomes

    DEFF Research Database (Denmark)

    Christiansen, Freddy

    genetics, while emphasizing the close interplay between theory and empiricism. Traditional topics such as genetic and phenotypic variation, mutation, migration, and linkage are covered and advanced by contemporary coalescent theory, which describes the genealogy of genes in a population, ultimately...

  4. Missing genes in the annotation of prokaryotic genomes

    Directory of Open Access Journals (Sweden)

    Feng Wu-chun

    2010-03-01

    Full Text Available Abstract Background Protein-coding gene detection in prokaryotic genomes is considered a much simpler problem than in intron-containing eukaryotic genomes. However there have been reports that prokaryotic gene finder programs have problems with small genes (either over-predicting or under-predicting. Therefore the question arises as to whether current genome annotations have systematically missing, small genes. Results We have developed a high-performance computing methodology to investigate this problem. In this methodology we compare all ORFs larger than or equal to 33 aa from all fully-sequenced prokaryotic replicons. Based on that comparison, and using conservative criteria requiring a minimum taxonomic diversity between conserved ORFs in different genomes, we have discovered 1,153 candidate genes that are missing from current genome annotations. These missing genes are similar only to each other and do not have any strong similarity to gene sequences in public databases, with the implication that these ORFs belong to missing gene families. We also uncovered 38,895 intergenic ORFs, readily identified as putative genes by similarity to currently annotated genes (we call these absent annotations. The vast majority of the missing genes found are small (less than 100 aa. A comparison of select examples with GeneMark, EasyGene and Glimmer predictions yields evidence that some of these genes are escaping detection by these programs. Conclusions Prokaryotic gene finders and prokaryotic genome annotations require improvement for accurate prediction of small genes. The number of missing gene families found is likely a lower bound on the actual number, due to the conservative criteria used to determine whether an ORF corresponds to a real gene.

  5. Evolution of paralogous genes: Reconstruction of genome rearrangements through comparison of multiple genomes within Staphylococcus aureus.

    Science.gov (United States)

    Tsuru, Takeshi; Kawai, Mikihiko; Mizutani-Ui, Yoko; Uchiyama, Ikuo; Kobayashi, Ichizo

    2006-06-01

    Analysis of evolution of paralogous genes in a genome is central to our understanding of genome evolution. Comparison of closely related bacterial genomes, which has provided clues as to how genome sequences evolve under natural conditions, would help in such an analysis. With species Staphylococcus aureus, whole-genome sequences have been decoded for seven strains. We compared their DNA sequences to detect large genome polymorphisms and to deduce mechanisms of genome rearrangements that have formed each of them. We first compared strains N315 and Mu50, which make one of the most closely related strain pairs, at the single-nucleotide resolution to catalogue all the middle-sized (more than 10 bp) to large genome polymorphisms such as indels and substitutions. These polymorphisms include two paralogous gene sets, one in a tandem paralogue gene cluster for toxins in a genomic island and the other in a ribosomal RNA operon. We also focused on two other tandem paralogue gene clusters and type I restriction-modification (RM) genes on the genomic islands. Then we reconstructed rearrangement events responsible for these polymorphisms, in the paralogous genes and the others, with reference to the other five genomes. For the tandem paralogue gene clusters, we were able to infer sequences for homologous recombination generating the change in the repeat number. These sequences were conserved among the repeated paralogous units likely because of their functional importance. The sequence specificity (S) subunit of type I RM systems showed recombination, likely at the homology of a conserved region, between the two variable regions f