Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries.

Autor:	Hotakainen R; Laboratory of Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Järvinen T; Laboratory of Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Kettunen K; Laboratory of Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Anttonen AK; Laboratory of Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland., Jakkula E; Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland. Electronic address: eveliina.salminen@helsinki.fi.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Oct 25, pp. 101304. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1016/j.gim.2024.101304
Abstrakt:	Purpose: Monogenic rare diseases contribute significantly to infant deaths and pediatric hospitalizations and cause burden to the patients and their families. The American College of Medical Genetics and Genomics recommended in 2021 that carrier screening of autosomal recessive and X-linked conditions with a carrier frequency of ≥ 1/200 and a severe or moderate phenotype should be offered when planning or during pregnancy. In November 2023 gnomAD v4.0 was released. It contains in total 807,162 individuals, being nearly 5x larger than previous versions, that have been used to estimate gene carrier frequencies (GCF). Methods: We utilized gnomAD v4.0 (GRCh38) to calculate the GCFs for available genetic ancestry groups for variants having pathogenic or likely pathogenic classification (>80% of submissions) in ClinVar. We calculated GCF separately for exomes and genomes, and combined data, and at-risk couple frequencies (ACF) per genetic ancestry group RESULTS: In total, 324 genes had a GCF ≥ 1/200 in at least one ancestry subgroup. The number of genes with GCF ≥ 1/200 varied greatly between subgroups. ACFs were more similar, Ashkenazi Jewish having the highest ACF of 6.11%. Conclusion: Improved understanding of carrier risks and updated carrier screening content would allow patients to make more informed reproductive decisions. (Copyright © 2024. Published by Elsevier Inc.)
Databáze:	MEDLINE
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