Szpiech et al are reporting in the latest issue of AJHG their findings about the prevalence of deleterious mutations in ROH. Starting from two contradicting hypotheses, one predicting that ROH should be depleted of deleterious variants compared to the rest of the genome and a second predicting the opposite result, they studied 27 individuals representing all the spectrum of ROH coverage in the human populations (from 4 to 46%). Based on previous work from the same group the divided ROH in different classes representing different times in human history, from those predating continental migration (short) to the ones resulting from parental relatedness (long) and compared the number of damaging variants (as predicted by either PolyPhen2 or SIFT) inside and outside the ROH. Their results show that ROH are enriched for damaging versus non damaging homozygotes an effect that becomes stronger with the increase of the size of ROH indicating a role of inbreeding and founder events in increasing the occurrence of recessive deleterious events. Based in their results they are also suggesting that apart the of the increased occurrence of variants of significant fitness effect, the burden of mildly deleterious homozygote variants may also be amplified.
Periklis Makrythanasis, MD, PhD