Runs of homozygosity are not good for your functioning

A must read review in Nature Reviews Genetics, Runs of homozygosity: windows into population history and trait architecture. Because it’s a paper on runs of homozygosity, James F. Wilson is on the apper.

If you are the product of a first cousin marriage, you have lots of runs of homozygosity. That’s because some of you will have large sections of the genome where both of the homologous chromosomes come from the same individual and are identical. In populations with small populations, this occurs not through recent inbreeding, as much as the reduced genetic diversity cranking up the frequency of some haplotypes over and above others.

The review covers all the bases, from distributions of runs of homozygosity in modern populations to ancient ones, as well as their functional consequences.

To the left, the plot shows that some populations, such as the Makrani of Pakistan, have fewer numbers of runs of homozygosity, but long ones when they have them. The populations on this part of the diagram are part of the “inbreeding belt.” In contrast, there are other populations with lots of runs of homozygosity, but they’re shorter. These are usually part of the “bottleneck belt,” where bottlenecks and small long-term effective populations have produced greater levels of homozygosity even on the genotype scale.

Perhaps the most interesting point though is that runs of homozygosity strongly correlate with changes in the values of a complex trait. In general, inbreeding is not too good, because recessively expressing deleterious alleles get exposed, and runs of homozygosity are a proxy for that.* This is why more exogamy in the Middle East and India may be such a social good.

* There may be confounds here. More educated and smarter people may marry those more distant from them geographically due to mobility.