An integrated map of genetic variation from 1,092 human genomes
Zamin IqbalWellcome Trust Centre for Human Genetics, Oxford University, Oxford, OX3 7BN, UKZamin IqbalWellcome Trust Centre for Human Genetics, Oxford University, Oxford, OX3 7BN, UKAndy RimmerWellcome Trust Centre for Human Genetics, Oxford University, Oxford, OX3 7BN, UKAnjali Gupta-HinchWellcome Trust Centre for Human Genetics, Oxford University, Oxford, OX3 7BN, UKGil A. McVeanDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKPeter DonnellyHarvard UniversityAngeliki KerasidouWellcome Trust Centre for Human Genetics, Oxford University, Oxford, OX3 7BN, UKDionysia K. XifaraDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKIain MathiesonWellcome Trust Centre for Human Genetics, Oxford University, Oxford, OX3 7BN, UKGil A. McVeanDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKOlivier DelaneauDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKGil McVeanDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKPeter DonnellyDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKDionysia K. XifaraDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKGil A. McVeanDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKClaire ChurchhouseDepartment of Statistics, Oxford University, Oxford, OX1 3TG, UKGaurav BhatiaThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAJames C. NemeshThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USANamrata GuptaThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAEric BanksThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USARobert E. HandsakerDepartment of Genetics, Harvard Medical School, Cambridge, 02142, Massachusetts, USAKhalid ShakirThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USASharon R. GrossmanCenter for Systems Biology and Department Organismic and Evolutionary Biology, Harvard University, Cambridge, 02138, Massachusetts, USAHeng LiThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAStacey B. GabrielThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAEric S. LanderThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAChris HartlThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAMark A. DePristoThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAMauricio O. CarneiroThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAGuillermo del AngelThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAStephen F. SchaffnerThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USASteven A. McCarrollThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USARyan E. PoplinThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAShervin TabriziCenter for Systems Biology and Department Organismic and Evolutionary Biology, Harvard University, Cambridge, 02138, Massachusetts, USARidhi TariyalCenter for Systems Biology and Department Organismic and Evolutionary Biology, Harvard University, Cambridge, 02138, Massachusetts, USAGiulio GenoveseThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USADavid M. AltshulerCenter for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, Massachusetts, USAMark A. DePristoThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USADavid M. AltshulerCenter for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, Massachusetts, USADavid M. AltshulerCenter for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, Massachusetts, USADavid ReichDepartment of Genetics, Harvard Medical School, Cambridge, 02142, Massachusetts, USADavid M. AltshulerCenter for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, Massachusetts, USAMatthew E. HurlesWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKNi HuangWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKYali XueWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKThomas M. KeaneWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKYuan ChenWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKJennifer HarrowWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKAylwyn ScallyWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKPetr DanecekWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKHeng LiThe Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USAKlaudia WalterWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKVincenza ColonnaInstitute of Genetics and Biophysics, National Research Council (CNR), Naples, 80125, ItalyJames StalkerWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKZemin NingWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKSenduran BalasubramaniamWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKShane McCarthyWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKBen BlackburneWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKRichard DurbinWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKJohn BurtonWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKAlison J. CoffeyWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKSarah J. LindsayWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKLuke JostinsWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKChris Tyler-SmithWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKQasim AyubWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKYujun ZhangWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKAdam FrankishWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKMichael QuailWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKAnja Kolb-KokocinskiWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UKFabio BusoneroCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAAdrian TanCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAGonçalo R. AbecasisCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAJin YuCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAGoo JunCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAPaul AndersonCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USACarlo SidoreCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAChristian FuchsbergerCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USATom BlackwellCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAMary Kate TrostCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAEleonora PorcuCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAAndrea MaschioCenter for Statistical Genetics, Biostatistics, University of Michigan, Ann Arbor, 48109, Michigan, USAZoya KingsburyIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Lisa MurrayIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,R. Keira CheethamIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Russell GrocockIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Tony CoxIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Richard ShawIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Tony CoxIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Terena JamesIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Michael EberleIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Markus BauerIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,David R. BentleyIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Sean HumphrayIllumina United Kingdom, Chesterford Research Park, Little Chesterford, Near Saffron Walden, Essex CB10 1XL, UK.,Aravinda ChakravartiMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USAJuan L. Rodriguez-FloresCenter for Comparative and Population Genomics, Cornell University, Ithaca, 14850, New York, USAJeremiah DegenhardtCenter for Comparative and Population Genomics, Cornell University, Ithaca, 14850, New York, USAAndrew G. ClarkCenter for Comparative and Population Genomics, Cornell University, Ithaca, 14850, New York, USAFrancisco M. De La VegaCenter for Comparative and Population Genomics, Cornell University, Ithaca, 14850, New York, USA
2012en
ABI
Аннотация
By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations. This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual. This report by the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations. Integrative analyses reveal profiles of rare and common variants in different populations. The frequencies of rare variants vary across biological pathways, and hundreds of rare, non-coding variants at conserved sites — such as changes disrupting transcription-factor motifs — can be established for each individual.
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