1. Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping
- Author
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Vaysse, A., Ratnakumar, A., Derrien, T., Axelsson, E., Rosengren Pielberg, G., Sigurdsson, S., Fall, T., Seppälä, E.H., Hansen, M.S., Lawley, C.T., Karlsson, E.K., Bannasch, D.L., Vilà, C., Lohi, H., Galibert, F., Fredholm, M., Häggström, O., Hedhammar, A., André, C., Lindblad-Toh, K., Hitte, C., van Steenbeek, F.G., Fieten, H., Leegwater, P.A.J., LUPA Consortium, x, Webster, M.T., Advances in Veterinary Medicine, Tissue Repair, Geneeskunde van gezelschapsdieren, Research Programs Unit, Department of Medical and Clinical Genetics, Research Programme of Molecular Medicine, Veterinary Biosciences, Departments of Faculty of Veterinary Medicine, Broad Institute of MIT and Harvard, Sigurdsson, Snaever, Sigurdsson, Snaevar, Karlsson, Elinor K., Lindblad-Toh, Kerstin, Webster, Matthew T., Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Science for Life Laboratory, Uppsala University-Department of Medical Biochemistry and Microbiology, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Basic Veterinary Biosciences, HMNC Brain Health-Biomedicum Helsinki-Folkhälsan Institute of Genetics, Illumina, Inc., FAS Center for Systems Biology, Harvard University [Cambridge], Department of Population Health and Reproduction, University of California [Davis] (UC Davis), University of California-University of California, Department of Integrative Ecology (CSIC), Estación Biológica de Doñana (EBD), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Faculty of Life Sciences, Division of Genetics and Bioinformatics, Faculty of Life Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Swedish University of Agricultural Sciences (SLU), This research was mainly supported by The LUPA Consortium, which is a Collaborative Research Project funded by the European Commission under the 7th Research Framework Programme (www.eurolupa.org)., The LUPA Consortium, European Project: 201370,EC:FP7:HEALTH,FP7-HEALTH-2007-A,LUPA(2008), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Harvard University, University of California (UC)-University of California (UC), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), De Villemeur, Hervé, and Unravelling the molecular basis of common complex human disorders using the dog as a model system - LUPA - - EC:FP7:HEALTH2008-01-01 - 2012-06-30 - 201370 - VALID
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POSITIVE SELECTION ,Genotyping Techniques ,Genome-wide association study ,Breeding ,413 Veterinary science ,MESH: Dogs ,0302 clinical medicine ,MESH: Behavior, Animal ,MESH: Animals ,Genome Sequencing ,MESH: Genetic Variation ,mapping ,MESH: Phylogeny ,Genome Evolution ,Phylogeny ,0303 health sciences ,education.field_of_study ,Behavior, Animal ,MESH: Polymorphism, Single Nucleotide ,1184 Genetics, developmental biology, physiology ,Genomics ,Genome Scans ,selection ,dog ,identification ,genomic ,Fixation (population genetics) ,COAT COLOR ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,PERSONALITY-TRAITS ,Gene Flow ,Genetics and Breeding ,education ,Single-nucleotide polymorphism ,MESH: Breeding ,MESH: Phenotype ,03 medical and health sciences ,CANIS-FAMILIARIS ,Effective Population Size ,MESH: Genotyping Techniques ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Genome-Wide Association Studies ,Genetics ,Genetik ,Biology ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Genetic Drift ,MESH: Ear ,Computational Biology ,Genetic Variation ,MESH: Haplotypes ,Phenotypic trait ,HAPLOTYPE STRUCTURE ,variation phénotypique ,Mutation ,MESH: Genome-Wide Association Study ,marqueur de sélection ,Population Genetics ,030217 neurology & neurosurgery ,Evolutionary Genetics ,Cancer Research ,cartographie génomique ,LINKAGE DISEQUILIBRIUM ,MESH: Selection, Genetic ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Natural Selection ,Body Size ,WIDE ASSOCIATION ,Genetics (clinical) ,DOMESTIC DOG ,MESH: Heterozygote ,Gene Ontologies ,Homozygote ,race canine ,402 Animal and Dairy Science ,Ear ,Gene Pool ,Phenotype ,Research Article ,MESH: Homozygote ,Heterozygote ,403 Veterinary Science ,lcsh:QH426-470 ,Population ,Polymorphism, Single Nucleotide ,Dogs ,Genetic drift ,Genome Analysis Tools ,DNA-SEQUENCE ,Evolutionary Modeling ,Genetic variation ,Animals ,Selection, Genetic ,Selection (genetic algorithm) ,030304 developmental biology ,Evolutionary Biology ,MESH: Body Size ,Genetic Maps ,Comparative Genomics ,GENE ,lcsh:Genetics ,Haplotypes ,Neutral Theory ,Genetic Polymorphism ,Animal Genetics ,Genome-Wide Association Study - Abstract
The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of .170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.
- Published
- 2011
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