August 17, 2012
Runs of homozygosity, short and long
Shorter runs of homozygosity have the potential of informing us about population history. Populations that go through a bottleneck go through a patch of intense inbreeding, that will result in long ROHs as in the previous case. But, as time passes on, and provided that alternative version of genomic regions survived the bottleneck, recombination breaks down these long ROHs and the individual becomes a patchwork of homozygous and heterozygous regions.
Mutation, too, disturbs ROHs by introducing new variants into the population. New mutations appear more often in populations with a larger number of breeding individuals. Finally, admixture may disturb ROHs as well. Admixed individuals are more likely to inherent divergent regions of DNA throughout their genome, and hence be less homozygous.
The data presented in this paper seems to point to the fact that long ROHs are observed in populations where marriages between close kin are common. The authors split -for each population separately- ROHs into different classes based on length, and they observe that the short class of ROHs is shorter in Africans than non-Africans.
The implications of this are not explored, but such a pattern is consistent both with an Out-of-Africa bottleneck, as well as old admixture events within a structured African population. Unlike recent admixture events that result in long heterozygous tracts, old admixture events result in extraneous segments of DNA that become ever-reduced in size due to recombination. At the limit, admixture is equivalent to an excess of mutation, and it is very difficult to distinguish between an excess of apparent mutation that has arisen in a larger breeding population vs. one that has arisen because very divergent populations admixed in the very deep past.
Razib also covers this.
The American Journal of Human Genetics, Volume 91, Issue 2, 275-292, 10 August 2012
Genomic Patterns of Homozygosity in Worldwide Human Populations
Trevor J. Pemberton et al.
Genome-wide patterns of homozygosity runs and their variation across individuals provide a valuable and often untapped resource for studying human genetic diversity and evolutionary history. Using genotype data at 577,489 autosomal SNPs, we employed a likelihood-based approach to identify runs of homozygosity (ROH) in 1,839 individuals representing 64 worldwide populations, classifying them by length into three classes—short, intermediate, and long—with a model-based clustering algorithm. For each class, the number and total length of ROH per individual show considerable variation across individuals and populations. The total lengths of short and intermediate ROH per individual increase with the distance of a population from East Africa, in agreement with similar patterns previously observed for locus-wise homozygosity and linkage disequilibrium. By contrast, total lengths of long ROH show large interindividual variations that probably reflect recent inbreeding patterns, with higher values occurring more often in populations with known high frequencies of consanguineous unions. Across the genome, distributions of ROH are not uniform, and they have distinctive continental patterns. ROH frequencies across the genome are correlated with local genomic variables such as recombination rate, as well as with signals of recent positive selection. In addition, long ROH are more frequent in genomic regions harboring genes associated with autosomal-dominant diseases than in regions not implicated in Mendelian diseases. These results provide insight into the way in which homozygosity patterns are produced, and they generate baseline homozygosity patterns that can be used to aid homozygosity mapping of genes associated with recessive diseases.