A haplotype sharing method for determining the relative age of SNP alleles

Abstract

There are two aspects regarding the age of alleles that are relevant as indicators of the timing of mutational events. The first is to know which alleles are species-specific; the second is about the time of origin of species-specific alleles. Both aspects can be analyzed using haplotype-sharing methods, by using the length of shared haplotypes as a measure of the speed of coalescence to common ancestors. The availability of sequence data for closely related species makes it possible to infer the original SNP allele. The allele present in more than one species is the original allele. In general, original alleles are expected to be more frequent, because the cumulative effects of genetic drift determine the maximum frequency a new mutant can reach. The human species is relatively young, and founder effects are still observable as extended linkage disequilibrium. Coalescence to a single founder takes place in human populations over a time frame that is so small that original haplotypes spanning several markers are still observable in current high-density SNP genotyping arrays. We show here that the length of shared haplotypes surrounding alleles is an indicator of the relative ages of alleles, and it is applicable to original and species-specific alleles. Copyright © 2009 S. Karger AG, Basel.