基于gnomAD v4.0数据对不同血统中常染色体和X连锁隐性遗传疾病的携带者频率进行估计。

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

作者信息

Hotakainen Ronja, Järvinen Timo, Kettunen Kaisa, Anttonen Anna-Kaisa, Jakkula Eveliina

机构信息

Laboratory of Genetics, HUS Diagnostic Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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.

出版信息

Genet Med. 2025 Jan;27(1):101304. doi: 10.1016/j.gim.2024.101304. Epub 2024 Nov 1.

DOI:10.1016/j.gim.2024.101304

PMID:39492094

Abstract

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 5× larger than previous versions, which 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, 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 1 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.

摘要

目的

单基因罕见病是婴儿死亡和儿科住院的重要原因，给患者及其家庭带来负担。美国医学遗传学与基因组学学会在2021年建议，在计划怀孕或怀孕期间，应对携带频率≥1/200且具有严重或中度表型的常染色体隐性和X连锁疾病进行携带者筛查。2023年11月发布了gnomAD v4.0。它总共包含807,162个个体，几乎是以前版本的5倍，以前的版本已用于估计基因携带者频率（GCF）。