The Allele Frequency Spectrum in Genome-Wide Human Variation Data Reveals Signals of Differential Demographic History in Three Large World Populations

We have studied a genome-wide set of single-nucleotide polymorphism (SNP) allele frequency measures for African-American, East Asian, and European-American samples. For this analysis we derived a simple, closed mathematical formulation for the spectrum of expected allele frequencies when the sampled...

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Bibliographic Details
Published in:Genetics (Austin) 2004-01, Vol.166 (1), p.351-372
Main Authors: Marth, Gabor T, Czabarka, Eva, Murvai, Janos, Sherry, Stephen T
Format: Article
Language:English
Subjects:
African Americans - genetics
Alleles
Americas
Asia
Biometry
Data analysis
Demographics
Europe
Gene Frequency
Genetic Variation
Genetics, Population
Genome, Human
Genomics
History
Humans
Linkage Disequilibrium
Models, Genetic
Polymorphism, Single Nucleotide
Population Density
Population genetics
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Summary:We have studied a genome-wide set of single-nucleotide polymorphism (SNP) allele frequency measures for African-American, East Asian, and European-American samples. For this analysis we derived a simple, closed mathematical formulation for the spectrum of expected allele frequencies when the sampled populations have experienced nonstationary demographic histories. The direct calculation generates the spectrum orders of magnitude faster than coalescent simulations do and allows us to generate spectra for a large number of alternative histories on a multidimensional parameter grid. Model-fitting experiments using this grid reveal significant population-specific differences among the demographic histories that best describe the observed allele frequency spectra. European and Asian spectra show a bottleneck-shaped history: a reduction of effective population size in the past followed by a recent phase of size recovery. In contrast, the African-American spectrum shows a history of moderate but uninterrupted population expansion. These differences are expected to have profound consequences for the design of medical association studies. The analytical methods developed for this study, i.e., a closed mathematical formulation for the allele frequency spectrum, correcting the ascertainment bias introduced by shallow SNP sampling, and dealing with variable sample sizes provide a general framework for the analysis of public variation data.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1534/genetics.166.1.351