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Characterization of Arabian Peninsula whole exomes: exploring high inbreeding features

Ferreira, J. C.; Alshamali, F.; Pereira, L.; Fernandes, V.

2022-02-22 genetics
10.1101/2022.02.22.481461 bioRxiv
Show abstract

The exome (WES) capture enriched for UTRs on 90 Arabian Peninsula (AP) populations contributed nearly 20,000 new variants from a total over 145,000 total variants. Almost half of these variants were in UTR3, reflecting the low effort we have dedicated to cataloguing these regions, which can bear an important proportion of functional variants, as being discovered in genome-wide association studies. By applying several pathogenic predicting tools, we have demonstrated the high burden in potentially deleterious variants (especially in nonsynonymous and UTR variants located in genes that have been associated mainly with neurologic disease and congenital malformations) contained in AP WES, and the burden was as high as the consanguinity level (inferred as sum of runs of homozygosity, SROH) increased. Arabians had twice SROH values in relation to Europeans and East Asians, and within AP, Saudi Arabia had the highest values and Oman the lowest. We must pursuit cataloguing diversity in populations with high consanguinity, as the potentially pathogenic variants are not eliminated by genetic drift as much as in less consanguineous populations.

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