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

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

Scopus

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

摘要

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.

摘要

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