Keywords: Remote consanguinity; Homozygous by descent; Inbreeding coefficient
Authors: N. Jalkh1,2, M. Sahbatou3, E. Chouery1, A. Megarbane1, A. Leutennegger4,5, J. Serre2; 1Unité de Génétique Médicale et Laboratoire associé INSERM à l’Unité UMR_S910, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon, 2EA 2493 « pathologie cellulaire & génétique, de la conception à la naissance », Université de Versailles-Saint Quentin en Yvelines, Paris, France, 3Fondation Jean Dausset-CEPH, Paris, France, 4Université Paris Diderot, Institut Universitaire d’Hématologie, UMR-S946, Paris, France, 5Inserm, U946, F-75010, Paris, France.
Abstract: Consanguineous marriages have been widely practiced, with variable rates, in several global communities depending on religion, culture, and geography. The populations of the Middle East are among those with the highest inbreeding level and frequency of inbred individuals. A genome wide analyses of 165 unrelated Lebanese has been performed either through the estimation of LOH (Loss of Heterozygosity) or through the FEstim algorithm depending on SNP frequencies. Relying on these genome-wide data that identify regions of homozygosity by descent (HBD), this study was able to estimate total inbreeding levels, remote consanguinity, and population admixture and structure. The inbreeding coefficient value was estimated to be 1.6% in offspring of unrelated parents (over 3 generations) and 8% in offspring of first cousins. In either case, the remote consanguinity (RC) value was approximately equal to 0.6% resulting from genetic drift or recurrent consanguineous unions. This RC value suggests that for any unrelated marriages in Lebanon, the mates could be related as third cousins or as second cousins once removed. Under the hypothesis that 25% of marriages occur between first cousins, the mean inbreeding (F) value of 2.2% found may explain the increased incidence of recessive disease within offspring. The LOH and FEstim genome wide approaches were applied to investigate the genomic similarity of Lebanese communities. Both approaches revealed a unique ancestral population of the four studied communities (Greek Orthodox, Maronite, Shiite and Sunni).