Marc Pybus | bioRxiv Science

bioRxiv2015

Purging of deleterious variants due to drift and founder effect in Italian populations with extended autozygosity

Purging through inbreeding occurs when consanguineous marriages increases the rate at which deleterious alleles are present in a homozygous state. In this study we carried out low-read depth (4-10x) whole-genome sequencing in 568 individuals from three Italian founder populations, and compared it to data from other Italian and European populations from the 1000 Genomes Project. We show extended consanguinity and depletion of homozygous genotypes at potentially detrimental sites in the founder populations compared to outbred populations. However these patterns are not compatible with the hypothesis of consanguinity driving the purging of highly deleterious mutations according to simulations. Therefore we conclude that genetic drift and the founder effect should be responsible for the observed purging of deleterious variants.

Evolutionary Biology↗

bioRxiv2014

Human genomic regions with exceptionally high or low levels of population differentiation identified from 911 whole-genome sequences

BackgroundPopulation differentiation has proved to be effective for identifying loci under geographically-localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes.\n\nResultsWe demonstrate that while sites of low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively.\n\nConclusionsWe have identified known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.

Genomics↗