An integrated map of genetic variation from 1,092 human genomes

Authors：Altshuler D M; Durbin R M; Abecasis G R; Bentley D R; Chakravarti A; Clark A G; Donnelly P; Eichler E E; Flicek P; Gabriel S B; Gibbs R A; Green E D; Hurles M E; Knoppers B M; Korbel J O; Lander E S; Lee C; Lehrach H; Mardis E R; Marth G T; McVean G A; Nickerson D A; Schmidt J P; Sherry S T; Wang J; Wilson R K; Dinh H; Kovar C; Lee S; Lewis L; Muzny D; Reid J; Wang M; Fang X; Guo X; Jian M; Jiang H; Jin X; Li G; Li J; Li Y; Li Z; Liu X; Lu Y; Ma X

Source：Nature, 2012, 491(7422): 56-65.

DOI：10.1038/nature11632

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.

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  The University of Texas, MD Anderson Cancer Center; University of Texas MD Anderson Cancer Center; harvard university; harvard medical school; University of Texas M. D. Anderson Cancer Center; DUKE University; johns hopkins university school of medicine; MIT; The University of Chicago; 中国医学科学院; The university of Texas,M.D.Anderson Cancer Center; Baylor college of Medicine; Johns Hopkins University,School of Medicine; University of Medicine and Dentistry of New Jersey; Washington University ,School of Medicine; Johns Hopkins University School of Medicine; University of Barcelona; Washington University School of Medicine; Cardiff University; University of Texas, M.D. Anderson Cancer Center; 5; university of chicago; university of michigan; University of Maryland School of Medicine; University of Medicine & Dentistry of New Jersey; The University of North carolina at Chapel Hill; The University of Michigan; Johns Hopkins University School of Medicine; 6; University of California; The University of Texas M.D anderson Cancer Center; BAYLOR COLLEGE OF MEDICINE; University of North Carolina at Chapel Hill; The University of Texas Health Science Center; Penn State University; Albert Einstein College of Medicine; new; the university of Texas MD Anderson Cancer Center; Rutgers University; Sanger Institute; University of Pennsylvania School of Medicine; University of Texas M.D.Anderson Cancer Center; university of maryland school of medicine; Oxford University; Harvard medical school; The University of Texas M.D Anderson Cancer Center; The Johns Hopkins University School of Medicine; Baylor college of medicine; University of Texas M.D.Anderson cancer center; University of Texas,M.D.Anderson Cancer Center; university college london; STANFORD UNIVERSITY; university of california; University of medicine and dentistry of New Jersey; United States; UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER; The University of North Carolina at Chapel Hill; The University of Texas M.D.Anderson Cancer Center; Leiden University Medical Center; The university of Texas Health Science Center; National Institutes of Health; University of Washington, Seattle; University Of Texas MD Anderson Cancer Center; Stanford University.; Harvard Medical School; University of Utah School of Medicine; State University of New Jersey; University of Washington School of Medicine; 1; louisiana state university; Johns hopkins university school of medicine; Mount Sinai School of Medicine; Brigham and Women's Hospital; University of Wisconsin; DUKE UNIVERSITY; yale university; 14; The University of Texas MD Anderson Cancer Center; cardiff university; The State University of New Jersey