Community data-driven approach to identify pathogenic founder variants for pan-ethnic carrier screening panels.

Autor: Einhorn Y; Genoox, Tel Aviv, Israel., Einhorn M; Genoox, Tel Aviv, Israel., Kurolap A; The Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, Israel., Steinberg D; Genoox, Tel Aviv, Israel., Mory A; The Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, Israel., Bazak L; Beilinson Hospital, Rabin Medical Center, Recanati Genetics Institute, Petah Tikva, Israel., Paperna T; Rambam Health Care Campus, The Genetics Institute, Haifa, Israel., Grinshpun-Cohen J; Community Genetic Services, Ministry of Health, Tel Aviv, Israel., Basel-Salmon L; Beilinson Hospital, Rabin Medical Center, Recanati Genetics Institute, Petah Tikva, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Weiss K; Rambam Health Care Campus, The Genetics Institute, Haifa, Israel.; The Ruth and Bruce Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel., Singer A; Community Genetic Services, Ministry of Health, Tel Aviv, Israel., Yaron Y; The Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Baris Feldman H; The Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, Israel. hagitbf@tlvmc.gov.il.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. hagitbf@tlvmc.gov.il.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2023 Mar 28; Vol. 17 (1), pp. 30. Date of Electronic Publication: 2023 Mar 28.
DOI: 10.1186/s40246-023-00472-w
Abstrakt: Background: The American College of Medical Genetics and Genomics (ACMG) recently published new tier-based carrier screening recommendations. While many pan-ethnic genetic disorders are well established, some genes carry pathogenic founder variants (PFVs) that are unique to specific ethnic groups. We aimed to demonstrate a community data-driven approach to creating a pan-ethnic carrier screening panel that meets the ACMG recommendations.
Methods: Exome sequencing data from 3061 Israeli individuals were analyzed. Machine learning determined ancestries. Frequencies of candidate pathogenic/likely pathogenic (P/LP) variants based on ClinVar and Franklin were calculated for each subpopulation based on the Franklin community platform and compared with existing screening panels. Candidate PFVs were manually curated through community members and the literature.
Results: The samples were automatically assigned to 13 ancestries. The largest number of samples was classified as Ashkenazi Jewish (n = 1011), followed by Muslim Arabs (n = 613). We detected one tier-2 and seven tier-3 variants that were not included in existing carrier screening panels for Ashkenazi Jewish or Muslim Arab ancestries. Five of these P/LP variants were supported by evidence from the Franklin community. Twenty additional variants were detected that are potentially pathogenic tier-2 or tier-3.
Conclusions: The community data-driven and sharing approaches facilitate generating inclusive and equitable ethnically based carrier screening panels. This approach identified new PFVs missing from currently available panels and highlighted variants that may require reclassification.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: