Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening

Genes (Basel). 2023 Apr 18;14(4):937. doi: 10.3390/genes14040937.

Abstract

Background: Druze individuals, like many genetically homogeneous and isolated populations, harbor recurring pathogenic variants (PV) in autosomal recessive (AR) disorders.

Methods: Variant calling of whole-genome sequencing (WGS) of 40 Druze from the Human Genome Diversity Project (HGDP) was performed (HGDP-cohort). Additionally, we performed whole exome sequencing (WES) of 118 Druze individuals: 38 trios and 2 couples, representing geographically distinct clans (WES-cohort). Rates of validated PV were compared with rates in worldwide and Middle Eastern populations, from the gnomAD and dbSNP datasets.

Results: Overall, 34 PVs were identified: 30 PVs in genes underlying AR disorders, 3 additional PVs were associated with autosomal dominant (AD) disorders, and 1 PV with X-linked-dominant inherited disorder in the WES cohort.

Conclusions: The newly identified PVs associated with AR conditions should be considered for incorporation into prenatal-screening options offered to Druze individuals after an extension and validation of the results in a larger study.

Keywords: druze; founder population; genetic isolate; recurring pathogenic variants; whole exome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exome Sequencing
  • Female
  • Humans
  • Pregnancy
  • Prenatal Diagnosis*
  • Whole Genome Sequencing

Grants and funding

The Shomron Laboratory is supported by Horizon 2020 - Research and Innovation Framework Programme, PSY-PGx-945151; Israel Science Foundation, Israel Precision Medicine Partnership (IPMP) 2923/20; The Edmond J. Safra Center for Bioinformatics at Tel Aviv University; The Koret-UC Berkeley-Tel Aviv University Initiative in Computational Biology and Bioinformatics; The QBI/UCSF-Tel Aviv University joint Initiative in Computational Biology and Drug Discovery; Collaborative clinical Bioinformatics research of the Edmond J. Safra Center for Bioinformatics and Faculty of Medicine at Tel Aviv University; Israeli Ministry of Science and Technology, Israeli–Russia; Kodesz Institute for Technologies in Healthcare; Tel Aviv University Healthy Longevity Research Center; Djerassi-Elias Institute of Oncology; Kirschman Dvora Eleonora Fund for Parkinson’s Disease; Tel Aviv University Innovation Laboratories (TILabs).