摘要：SummaryThe cataloging of human genomic variation is a challenging task given the size and diversity of the global human population. Several geographic regions remain under-characterized, such as the Arabian Peninsula (AP), which is unique in being at the cross-roads between Africa, Europe and Asia, and hence is a continuous hot-spot for admixture, counteracted by the worldwide highest levels of consanguinity. We conducted whole exome sequencing enriched for untranslated regions (WES + UTRs) on 90 Arabians, and identified a considerable amount of new variants (∼17,000 out of ∼145,000). By applying pathogenic predicting tools, we demonstrated that AP WES have a high burden in potentially deleterious variants, especially in nonsynonymous and UTR variants, and that these are located in genes associated with neurologic diseases and congenital malformations. This burden was significantly and positively correlated with the consanguinity level. These results testify the importance of surveying consanguineous populations where pathogenic variants are not efficiently eliminated by genetic drift.Graphical abstractDisplay OmittedHighlights•Characterization of 90 Arabian WES enriched for UTRs identified 17,000 new variants•The AP WES have a high burden in potentially pathogenic variants•These variants were in 764 genes associated with neurologic and congenital diseases•This burden was significantly and positively correlated with the consanguinity levelBiological sciences; Genetics; Health sciences; Human genetics.
