Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening

Eden Avnat; Guy Shapira; Shelly Shoval; Ifat Israel-Elgali; Anna Alkelai; Alan R. Shuldiner; Claudia Gonzaga-Jauregui; Jamal Zidan; Taiseer Maray; Noam Shomron; Eitan Friedman

doi:10.3390/genes14040937

Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening

Eden Avnat, Guy Shapira, Shelly Shoval, Ifat Israel-Elgali, Anna Alkelai, Alan R. Shuldiner, Claudia Gonzaga-Jauregui, Jamal Zidan, Taiseer Maray, Noam Shomron, Eitan Friedman

Bar-Ilan University - Azrieli Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English
Article number	937
Journal	Genes
Volume	14
Issue number	4
DOIs	https://doi.org/10.3390/genes14040937
State	Published - 18 Apr 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

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).

Funders	Funder number
Israel Precision Medicine Partnership	2923/20
Koret-UC Berkeley-Tel Aviv University
UCSF-Tel Aviv University
Israel Science Foundation
Tel Aviv University
Queensland Brain Institute
Ministry of science and technology, Israel
Horizon 2020	PSY-PGx-945151

Keywords

druze
founder population
genetic isolate
recurring pathogenic variants
whole exome sequencing

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10.3390/genes14040937

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title = "Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening",

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.",

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author = "Eden Avnat and Guy Shapira and Shelly Shoval and Ifat Israel-Elgali and Anna Alkelai and Shuldiner, {Alan R.} and Claudia Gonzaga-Jauregui and Jamal Zidan and Taiseer Maray and Noam Shomron and Eitan Friedman",

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doi = "10.3390/genes14040937",

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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

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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.

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Comprehensive Genetic Analysis of Druze Provides Insights into Carrier Screening

Abstract

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Keywords

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