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

Date
2012
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.
Advisor
Instructor
Source Title
Nature
Print ISSN
0028-0836
Electronic ISSN
Publisher
Nature Publishing Group
Volume
491
Issue
7422
Pages
56 - 65
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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. © 2012 Macmillan Publishers Limited. All rights reserved.

Course
Other identifiers
Book Title
Keywords
transcription factor, untranslated RNA, 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
Citation
Published Version (Please cite this version)