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

Goncalo R Abecasis; Adam Auton; Lisa D Brooks; Mark A DePristo; Richard M Durbin; Robert E Handsaker; Hyun Min Kang; Gabor T Marth; Gil A McVean; 1000 Genomes Project Consortium

doi:10.1038/nature11632

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

Journal article

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Peer reviewed

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

Goncalo R Abecasis, Adam Auton, Lisa D Brooks, Mark A DePristo, Richard M Durbin, Robert E Handsaker, Hyun Min Kang, Gabor T Marth, Gil A McVean and 1000 Genomes Project Consortium

Nature (London), Vol.491(7422), pp.56-65

11/01/2012

DOI: 10.1038/nature11632

PMCID: PMC3498066

PMID: 23128226

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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.

Genomics

Genetics, Population

Conserved Sequence - genetics

Genome-Wide Association Study

Humans

Binding Sites - genetics

Continental Population Groups - genetics

Genome, Human - genetics

Transcription Factors - metabolism

Haplotypes - genetics

Genetics, Medical

Nucleotide Motifs

Alleles

Polymorphism, Single Nucleotide - genetics

Genetic Variation - genetics

Evolution, Molecular

Sequence Deletion - genetics

Details

Title: Subtitle: An integrated map of genetic variation from 1,092 human genomes
Creators: Goncalo R Abecasis
Adam Auton
Lisa D Brooks
Mark A DePristo
Richard M Durbin
Robert E Handsaker
Hyun Min Kang
Gabor T Marth
Gil A McVean
1000 Genomes Project Consortium
Contributors: Jacob J Michaelson (Contributor) - University of Iowa, Roy J. Carver Department of Biomedical Engineering
Resource Type: Journal article
Publication Details: Nature (London), Vol.491(7422), pp.56-65
DOI: 10.1038/nature11632
PMID: 23128226
PMCID: PMC3498066
NLM abbreviation: Nature
ISSN: 0028-0836
eISSN: 1476-4687
Publisher: England
Grant note: U01HG6569 / NHGRI NIH HHS U01 HG005211 / NHGRI NIH HHS RC2 HG005581 / NHGRI NIH HHS WT095552/Z/11/Z / Wellcome Trust 090532 / Wellcome Trust R01 HG005701 / NHGRI NIH HHS WT090532/Z/09/Z / Wellcome Trust U01HG5208 / NHGRI NIH HHS P41HG4221 / NHGRI NIH HHS G0900747(91070) / Medical Research Council R01HG3698 / NHGRI NIH HHS U01 HG005725 / NHGRI NIH HHS P20 MD006899 / NIMHD NIH HHS UL1 RR024131 / NCRR NIH HHS WT086084/Z/08/Z / Wellcome Trust U01 HG005728 / NHGRI NIH HHS R01 HL088133 / NHLBI NIH HHS ES015794 / NIEHS NIH HHS R01 ES015794 / NIEHS NIH HHS U54HG3079 / NHGRI NIH HHS U01 HG005214 / NHGRI NIH HHS G0900747 / Medical Research Council RC2HL102925 / NHLBI NIH HHS U01HG5728 / NHGRI NIH HHS R01 HL095045 / NHLBI NIH HHS P01HG4120 / NHGRI NIH HHS R01HG5701 / NHGRI NIH HHS WT085532AIA / Wellcome Trust U01 HG005715 / NHGRI NIH HHS T15LM7033 / NLM NIH HHS U54 HG003079 / NHGRI NIH HHS P30 CA016672 / NCI NIH HHS R01CA166661 / NCI NIH HHS RC2 HL102925 / NHLBI NIH HHS G12 MD007579 / NIMHD NIH HHS U19 AI077439 / NIAID NIH HHS U01HG5214 / NHGRI NIH HHS R01 HG004719 / NHGRI NIH HHS R01HG4719 / NHGRI NIH HHS U41HG4568 / NHGRI NIH HHS AI077439 / NIAID NIH HHS U54HG3273 / NHGRI NIH HHS P41 HG004221 / NHGRI NIH HHS UL1RR024131 / NCRR NIH HHS T32GM7748 / NIGMS NIH HHS R01GM59290 / NIGMS NIH HHS Howard Hughes Medical Institute R01 GM059290 / NIGMS NIH HHS U01HG5715 / NHGRI NIH HHS 085532 / Wellcome Trust U01HG6513 / NHGRI NIH HHS R01 HG007022 / NHGRI NIH HHS AI2009061 / NIAID NIH HHS T32 GM007748 / NIGMS NIH HHS 086084 / Wellcome Trust U54HG3067 / NHGRI NIH HHS WT098051 / Wellcome Trust BB/I021213/1 / Biotechnology and Biological Sciences Research Council HL078885 / NHLBI NIH HHS G0701805 / Medical Research Council R01 CA166661 / NCI NIH HHS G12 RR003050 / NCRR NIH HHS RC2HG5581 / NHGRI NIH HHS T32 GM008283 / NIGMS NIH HHS R01 HG003698 / NHGRI NIH HHS U01HG5209 / NHGRI NIH HHS RC2HG5552 / NHGRI NIH HHS R01 HL078885 / NHLBI NIH HHS T15 LM007033 / NLM NIH HHS DP2OD6514 / NIH HHS BB/I02593X/1 / Biotechnology and Biological Sciences Research Council DP2 OD006514 / NIH HHS R01HG2898 / NHGRI NIH HHS 096599 / Wellcome Trust R01 MH084698 / NIMH NIH HHS R01HL95045 / NHLBI NIH HHS U01 HG005208 / NHGRI NIH HHS R01 HG002898 / NHGRI NIH HHS 095908 / Wellcome Trust R01HG4960 / NHGRI NIH HHS RG/09/012/28096 / British Heart Foundation WT089250/Z/09/Z / Wellcome Trust T15 LM007056 / NLM NIH HHS U01 HG006513 / NHGRI NIH HHS G0801823 / Medical Research Council U01 HG006569 / NHGRI NIH HHS P41 HG002371 / NHGRI NIH HHS HHSN268201100040C / NHLBI NIH HHS T32 HL094284 / NHLBI NIH HHS UL1 TR000124 / NCATS NIH HHS RC2 HG005552 / NHGRI NIH HHS U01HG5211 / NHGRI NIH HHS RG/09/12/28096 / British Heart Foundation U54 HG003067 / NHGRI NIH HHS WT085475/Z/08/Z / Wellcome Trust R01MH84698 / NIMH NIH HHS T32GM8283 / NIGMS NIH HHS P41HG2371 / NHGRI NIH HHS P01 HG004120 / NHGRI NIH HHS U54 HG003273 / NHGRI NIH HHS U01 HG005209 / NHGRI NIH HHS U01HG5725 / NHGRI NIH HHS U41 HG004568 / NHGRI NIH HHS T32HL94284 / NHLBI NIH HHS R01 HG004960 / NHGRI NIH HHS
Language: English
Date published: 11/01/2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984070126602771

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