Measures of human population structure show heterogeneity among genomic regions

Abstract

Estimates of genetic population structure (F ST ) were constructed from all autosomes in two large SNP data sets. The Perlegen data set contains genotypes on ∼1 million SNPs segregating in all three samples of Americans of African, Asian, and European descent; and the Phase I HapMap data set contains genotypes on ∼0.6 million SNPs segregating in all four samples from specific Caucasian, Chinese, Japanese, and Yoruba populations. Substantial heterogeneity of F ST values was found between segments within chromosomes, although there was similarity between the two data sets. There was also substantial heterogeneity among population-specific F ST values, with the relative sizes of these values often changing along each chromosome. Population-structure estimates are often used as indicators of natural selection, but the analyses presented here show that individual-marker estimates are too variable to be useful. There is inherent variation in these statistics because of variation in genealogy even among neutral loci, and values at pairs of loci are correlated to an extent that reflects the linkage disequilibrium between them. Furthermore, it may be that the best indications of selection will come from population-specific F ST values rather than the usually reported population-average values.Publication of the Perlegen SNP data set (Hinds et al. 2005) and completion of Phase I of the International HapMap Project (The International HapMap Consortium 2005) have allowed a new perspective on the genetic structure of human populations. These two whole-genome data sets allow population genetic analyses at an unprecedented scale: Previous estimates of genetic population structure (for review, see Garte 2003) have been based on a limited number of loci and provided only average figures of quantities such as F ST (Wright 1951) across the whole genome. The precision of previous estimates is not high, and they relate only to specific genes rather than to the region in which the markers are located. We can expect there to be some diversity in the magnitude of population structure between regions of the genome because the precise genealogy is not the same for each chromosome or part thereof, with values becoming increasingly similar the more closely linked are the regions. The genealogy can differ both by random events and by non-random events such as selection. Strong selection at a locus will induce hitchhiking of nearby regions (Maynard Smith and Haigh 1974), leading to both a reduction in heterozygosity within populations and an increase in diversity between populations as measured by F ST . Examination of the differences in diversity between regions therefore provides an opportunity to identify those that cannot be explained solely in terms of random sampling of the genealogy due to Mendelian segregation, variation in family size, migration, and recombination between genetic sites.Methods for estimating F ST from samples of a group of populations are well established (e.g., Weir and Cockerham 1984).More recently they have been ...

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