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

TitleAn integrated map of genetic variation from 1,092 human genomes.
Publication TypeJournal Article
Year of Publication2012
AuthorsAbecasis, GR, Auton, A, Brooks, LD, DePristo, MA, Durbin, RM, Handsaker, RE, Kang, HMin, Marth, GT, McVean, GA
Corporate Authors1000 Genomes Project Consortium
JournalNature
Volume491
Issue7422
Pagination56-65
Date Published2012 Nov 1
ISSN1476-4687
KeywordsAlleles, Binding Sites, Conserved Sequence, Continental Population Groups, Evolution, Molecular, Genetic Variation, Genetics, Medical, Genetics, Population, Genome, Human, Genome-Wide Association Study, Genomics, Haplotypes, Humans, Nucleotide Motifs, Polymorphism, Single Nucleotide, Sequence Deletion, Transcription Factors
Abstract

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.

DOI10.1038/nature11632
Alternate JournalNature
PubMed ID23128226
PubMed Central IDPMC3498066
Grant List085532 / / Wellcome Trust / United Kingdom
086084 / / Wellcome Trust / United Kingdom
090532 / / Wellcome Trust / United Kingdom
095908 / / Wellcome Trust / United Kingdom
096599 / / Wellcome Trust / United Kingdom
AI077439 / AI / NIAID NIH HHS / United States
AI2009061 / AI / NIAID NIH HHS / United States
BB/I021213/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/I02593X/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
DP2OD6514 / OD / NIH HHS / United States
ES015794 / ES / NIEHS NIH HHS / United States
G0701805 / / Medical Research Council / United Kingdom
G0801823 / / Medical Research Council / United Kingdom
G0900747 / / Medical Research Council / United Kingdom
G0900747(91070) / / Medical Research Council / United Kingdom
G12 MD007579 / MD / NIMHD NIH HHS / United States
G12 RR003050 / RR / NCRR NIH HHS / United States
HHSN268201100040C / / PHS HHS / United States
HL078885 / HL / NHLBI NIH HHS / United States
P01 HG004120 / HG / NHGRI NIH HHS / United States
P01HG4120 / HG / NHGRI NIH HHS / United States
P20 MD006899 / MD / NIMHD NIH HHS / United States
P41HG2371 / HG / NHGRI NIH HHS / United States
P41HG4221 / HG / NHGRI NIH HHS / United States
R01 CA166661 / CA / NCI NIH HHS / United States
R01 HG002898 / HG / NHGRI NIH HHS / United States
R01 HG004960 / HG / NHGRI NIH HHS / United States
R01 HG007022 / HG / NHGRI NIH HHS / United States
R01CA166661 / CA / NCI NIH HHS / United States
R01GM59290 / GM / NIGMS NIH HHS / United States
R01HG2898 / HG / NHGRI NIH HHS / United States
R01HG3698 / HG / NHGRI NIH HHS / United States
R01HG4719 / HG / NHGRI NIH HHS / United States
R01HG4960 / HG / NHGRI NIH HHS / United States
R01HG5701 / HG / NHGRI NIH HHS / United States
R01HL95045 / HL / NHLBI NIH HHS / United States
R01MH84698 / MH / NIMH NIH HHS / United States
RC2HG5552 / HG / NHGRI NIH HHS / United States
RC2HG5581 / HG / NHGRI NIH HHS / United States
RC2HL102925 / HL / NHLBI NIH HHS / United States
RG/09/012/28096 / / British Heart Foundation / United Kingdom
RG/09/12/28096 / / British Heart Foundation / United Kingdom
T15 LM007056 / LM / NLM NIH HHS / United States
T15LM7033 / LM / NLM NIH HHS / United States
T32GM7748 / GM / NIGMS NIH HHS / United States
T32GM8283 / GM / NIGMS NIH HHS / United States
T32HL94284 / HL / NHLBI NIH HHS / United States
U01 HG005728 / HG / NHGRI NIH HHS / United States
U01 HG006513 / HG / NHGRI NIH HHS / United States
U01HG5208 / HG / NHGRI NIH HHS / United States
U01HG5209 / HG / NHGRI NIH HHS / United States
U01HG5211 / HG / NHGRI NIH HHS / United States
U01HG5214 / HG / NHGRI NIH HHS / United States
U01HG5715 / HG / NHGRI NIH HHS / United States
U01HG5725 / HG / NHGRI NIH HHS / United States
U01HG5728 / HG / NHGRI NIH HHS / United States
U01HG6513 / HG / NHGRI NIH HHS / United States
U01HG6569 / HG / NHGRI NIH HHS / United States
U41HG4568 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U54HG3067 / HG / NHGRI NIH HHS / United States
U54HG3079 / HG / NHGRI NIH HHS / United States
U54HG3273 / HG / NHGRI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1RR024131 / RR / NCRR NIH HHS / United States
WT085475/Z/08/Z / / Wellcome Trust / United Kingdom
WT085532AIA / / Wellcome Trust / United Kingdom
WT086084/Z/08/Z / / Wellcome Trust / United Kingdom
WT089250/Z/09/Z / / Wellcome Trust / United Kingdom
WT090532/Z/09/Z / / Wellcome Trust / United Kingdom
WT095552/Z/11/Z / / Wellcome Trust / United Kingdom
WT098051 / / Wellcome Trust / United Kingdom
/ / Howard Hughes Medical Institute / United States