The relationship between microsatellite polymorphism and recombination hot spots in the human genome

Abstract

Although previous studies have failed to detect an association between microsatellite polymorphism and broadscale recombination rates in the human genome, there are several possible reasons why such a relationship could exist. For instance, there might be a direct link if recombination is mutagenic to microsatellite sequences or if polymorphic microsatellites act as recombination signals. Alternatively, recombination could exert an indirect effect by uncoupling of natural selection at linked loci, promoting polymorphism. As recombination is concentrated in narrow hotspot regions in the human genome, we investigated the relationship between microsatellite polymorphism and recombination hot spots. By using data from a common allele frequency database, we found several polymorphism estimates to be similar for hot spots and the genomic average. However, this is likely explained by an ascertainment bias because markers with high polymorphism information content are usually selected for genotyping in human populations and pedigrees. In contrast, by using an unbiased set of shotgun sequence data, we found an excess of microsatellite polymorphism in recombination hot spots of 14%. However, when other genomic variables are taken into account in a generalized model and using wavelet analysis, the effect is no longer detectable and the only firm predictor of microsatellite polymorphism is the incidence of SNPs and indels. One possible neutral explanation to these observations is that there is a common denominator affecting the local rate of mutation in unique as well as in repetitive DNA, for example, base composition. © The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.