Extended tracts of homozygosity in outbred human populations

Abstract

Long tracts of consecutive homozygous single nucleotide polymorphisms (SNPs) can arise in the genome through a number of mechanisms. These include inbreeding in which an individual inherits chromosomal segments that are identical by descent from each parent. However, recombination and other processes break up chromosomal segments over generations. The longest tracts are therefore to be expected in populations with an appreciable degree of inbreeding. We examined the length, number and distribution of long tracts of homozygosity in the apparently outbred HapMap populations. We observed 1393 tracts exceeding 1 Mb in length among the 209 unrelated HapMap individuals. The longest was an uninterrupted run of 3922 homozygous SNPs spanning 17.9 Mb in a Japanese individual. We find that homozygous tracts are significantly more common in regions with high linkage disequilibrium and low recombination, and the location of tracts is similar across all populations. The Yoruba sample has the fewest long tracts per individual, consistent with a larger number of generations (and hence amount of recombination) since the founding of that population. Our results suggest that multiple-megabase-scale ancestral haplotypes persist in outbred human populations in broad genomic regions which have lower than average recombination rates. We observed three outlying individuals who have exceptionally long and numerous homozygous tracts that are not associated with recombination suppressed areas of the genome. We consider that this reflects a high level of relatedness in their ancestry which is too recent to have been influenced by the local recombination intensity. Possible alternative mechanisms and the implications of long homozygous tracts in the genome are discussed.