engleski

Runs of homozygosity in European populations

Estimating individual genome-wide autozygosity is important both in the identification of recessive disease variants using homozygosity mapping and in the investigation of the effects of genome-wide homozygosity on traits of biomedical importance. Approaches have tended to involve either single-point estimates or rather complex multipoint methods of inferring individual autozygosity, all on the basis of limited marker data. Now, with the availability of high density genome scans, a new, multipoint, observational method of estimating individual autozygosity is possible. Using data from a 300, 000 SNP panel in 2618 individuals from 2 isolated and 2 more cosmopolitan populations of European origin, we explore the potential of estimating individual autozygosity from data on runs of homozygosity (ROHs). Termed Froh, this is defined as the proportion of the autosomes in ROHs above a specified length. Mean Froh distinguishes clearly between sub-populations classified in terms of grand-parental endogamy and population size. Using good pedigree data for one of the populations (Orkney), Froh was found to correlate strongly with the inbreeding coefficient estimated from pedigrees (r = 0.86). Using pedigrees to identify individuals with no shared maternal and paternal ancestors in at least 5 and probably 10 – 20 generations, we show that ROHs measuring up to 4 Mb in length are common in demonstrably outbred individuals. Given the stochastic variation in ROH number, length and location, and the fact that ROHs are important whether ancient or recent in origin, approaches such as this will provide a more useful description of genomic autozygosity than has hitherto been possible.

individual genome-wide autozygosity; homozygosity mapping

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