Supplementary Material for: Increased Rate of Deleterious Variants in Long Runs of Homozygosity of an Inbred Population from Qatar

Objective: The aim of this study is to evaluate the
fraction of putatively deleterious variants within genomic runs of
homozygosity (ROH) regions in an inbred and selected cohort of Qatari
individuals. Methods: High-density SNP array analysis was
performed in 36 individuals, and for 14 of them whole-exome sequencing
(WES) was also carried out. Results: In all individuals,
regions characterized by a high (hotspot) or low (coldspot) degree of
homozygosity in all the analysed individuals were mapped, and the most
frequent hotspot regions were selected. WES data were exploited to
identify the single nucleotide variations (SNVs) harboured by genes
located within both regions in each individual. Evolutionary
conservation-based algorithms were employed to predict the potential
deleteriousness of SNVs. The amount of in silico predicted deleterious
SNVs was significantly different (p < 0.05) between homozygosity
hotspot and coldspot regions. Conclusion: Genes located
within ROH hotspot regions contain a significant burden of predicted
putatively deleterious variants compared to genes located outside these
regions, suggesting inbreeding as a possible mechanism allowing an
enrichment of putatively deleterious variants at the homozygous state.