The relationship between haplotype-based FST and haplotype length

Abstract

The population-genetic statistic FST is used widely to describe allele frequency distributions in subdivided populations. The increasing availability of DNA sequence data has recently enabled computations of FST from sequence-based “haplotype loci.” At the same time, theoretical work has revealed that FST has a strong dependence on the underlying genetic diversity of a locus from which it is computed, with high diversity constraining values of FST to be low. In the case of haplotype loci, for which two haplotypes that are distinct over a specified length along a chromosome are treated as distinct alleles, genetic diversity is influenced by haplotype length: longer haplotype loci have the potential for greater genetic diversity. Here, we study the dependence of FST on haplotype length. Using a model in which a haplotype locus is sequentially incremented by one biallelic locus at a time, we show that increasing the length of the haplotype locus can either increase or decrease the value of FST , and usually decreases it. We compute FST on haplotype loci in human populations, finding a close correspondence between the observed values and our theoretical predictions. We conclude that effects of haplotype length are valuable to consider when interpreting FST calculated on haplotypic data.