TY - JOUR
T1 - Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening
AU - Avnat, Eden
AU - Shapira, Guy
AU - Shoval, Shelly
AU - Israel-Elgali, Ifat
AU - Alkelai, Anna
AU - Shuldiner, Alan R.
AU - Gonzaga-Jauregui, Claudia
AU - Zidan, Jamal
AU - Maray, Taiseer
AU - Shomron, Noam
AU - Friedman, Eitan
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - druze
KW - founder population
KW - genetic isolate
KW - recurring pathogenic variants
KW - whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85158934565&partnerID=8YFLogxK
U2 - 10.3390/genes14040937
DO - 10.3390/genes14040937
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C2 - 37107695
AN - SCOPUS:85158934565
SN - 2073-4425
VL - 14
JO - Genes
JF - Genes
IS - 4
M1 - 937
ER -