The landscape of autosomal recessive variants in an isolated community: Implications for population screening for reproductive purposes

As a result of the preference for consanguineous/endogamous marriages, the Israeli Arab population is composed of isolated communities with relatively frequent autosomal recessive (AR) conditions in each community. Clinical diagnosis of affected individuals has uncovered the pathogenic variants throughout the years. We investigated the diversity of pathogenic AR variants in a single village in northern Israel by exome analysis of 50 random, healthy adults descendants of the founders. Only likely pathogenic and pathogenic variants in known AR genes were selected. In this study 48 AR variants were found, of which 12 had been previously diagnosed in patients from this village, and for 11 with a frequency compatible with the frequency already known. Among the other 36 variants, 12 had been previously diagnosed in affected individuals in other Arab communities in Israel and 24 variants had not been previously characterized in this population. Of the 35 variants associated with conditions of moderate-severe medical consequences, only eight were known previously in this village. These findings emphasize the importance to better delineate the conditions at risk in a defined community, in particular for the development of preventive measures such as screening tests for reproductive couples, and for genetic counseling.

Automated summary

Due to the prevalence of consanguineous/endogamous marriages in the Israeli Arab population, isolated communities with relatively frequent autosomal recessive conditions have emerged. A study in a village in northern Israel found a diverse range of pathogenic autosomal recessive variants among descendants of the founders, highlighting the importance of delineating risk conditions in specific communities for preventive measures and genetic counseling.