Demographic history and rare allele sharing among human populations.

TitleDemographic history and rare allele sharing among human populations.
Publication TypeJournal Article
Year of Publication2011
AuthorsGravel, S, Henn, BM, Gutenkunst, RN, Indap, AR, Marth, GT, Clark, AG, Yu, F, Gibbs, RA, Bustamante, CD
Corporate Authors1000 Genomes Project
JournalProc Natl Acad Sci U S A
Volume108
Issue29
Pagination11983-8
Date Published2011 Jul 19
ISSN1091-6490
KeywordsDemography, Evolution, Molecular, Gene Frequency, Genes, Genetic Drift, Genetic Variation, Genetics, Population, Genomics, Humans, Models, Genetic, Racial Groups, Sequence Analysis, DNA
Abstract

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2-4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.

DOI10.1073/pnas.1019276108
Alternate JournalProc Natl Acad Sci U S A
PubMed ID21730125
PubMed Central IDPMC3142009
Grant ListR01 HL072904 / HL / NHLBI NIH HHS / United States
R01 HL072810-06 / HL / NHLBI NIH HHS / United States
R01 HL072810-05A1 / HL / NHLBI NIH HHS / United States
R01 HL072810-03 / HL / NHLBI NIH HHS / United States
R01 HL072810-07 / HL / NHLBI NIH HHS / United States
R01 HG003229 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R01 HL072904-08 / HL / NHLBI NIH HHS / United States
R01 HL072810-09 / HL / NHLBI NIH HHS / United States
R01 HL072810-01 / HL / NHLBI NIH HHS / United States
085532 / WT_ / Wellcome Trust / United Kingdom
R01 HL072810-08 / HL / NHLBI NIH HHS / United States
R01 HL072810-02 / HL / NHLBI NIH HHS / United States
R01 HL072810-04 / HL / NHLBI NIH HHS / United States
R01 HL072810 / HL / NHLBI NIH HHS / United States
G1000758 / MRC_ / Medical Research Council / United Kingdom
090532 / WT_ / Wellcome Trust / United Kingdom

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