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Vol. 12, Issue 12, 1805-1814, December 2002

LETTER
Interrogating a High-Density SNP Map for Signatures of Natural Selection

Joshua M. Akey,1 Ge Zhang,1 Kun Zhang,1,2 Li Jin,1 and Mark D. Shriver3,4

1 Center for Genome Information, University of Cincinnati, Cincinnati, Ohio, USA; 2 Human Genetics Center, University of Texas-Houston, Houston, Texas 77225, USA; 3 Department of Anthropology, Penn State University, University Park, Pennsylvania 16802, USA

Identifying genomic regions that have been targets of natural selection remains one of the most important and challenging areas of research in genetics. To this end, we report an analysis of 26,530 single nucleotide polymorphisms (SNPs) with allele frequencies that were determined in three populations. Specifically, we calculated a measure of genetic differentiation, FST, for each locus and examined its distribution at the level of the genome, the chromosome, and individual genes. Through a variety of analyses, we have found statistically significant evidence supporting the hypothesis that selection has influenced extant patterns of human genetic variation. Importantly, by contrasting the FST of individual SNPs to the empirical genome-wide distribution of FST, our results are not confounded by tenuous assumptions of population demographic history. Furthermore, we have identified 174 candidate genes with distribution of genetic variation that indicates that they have been targets of selection. Our work provides a first generation natural selection map of the human genome and provides compelling evidence that selection has shaped extant patterns of human genomic variation.

[Supplemental material is available online at www.genome.org.]


4 Corresponding author.


12:1805-1814 ©2002 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/02 $5.00

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