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  • Carrier frequency of autoso...
    Schmitz, Matthew J.; Aarabi, Mahmoud; Bashar, Ali; Rajkovic, Aleksandar; Gregg, Anthony R.; Yatsenko, Svetlana A.

    Clinical genetics, August 2022, Letnik: 102, Številka: 2
    Journal Article

    An equitable approach by the American College of Medical Genetics and Genomics (ACMG) has recently recommended carrier screening for genes associated with moderate to severe autosomal recessive conditions with a carrier frequency of ≥1/200 in the Genome Aggregation Database exomes (gnomADv2.0.2). We analyzed carrier frequencies in gnomADv3.1.1 genomes representing diverse populations. ClinVar data on 35 996 pathogenic/likely pathogenic variants in 419 genes were used to estimate the gnomAD frequency of heterozygous carriers. We found that ninety‐two genes had a carrier frequency of ≥1/200, of which 63 were shared between v3.1.1 and v2.0.2 and 29 were new in v3.1.1. Addition of new populations (Amish, Finnish and Middle Eastern) increased the number of new genes with a carrier frequency of ≥1/200 to 71. Changes in carrier frequencies were attributed to new gnomAD populations, different sample sizes, new ClinVar data, and technical differences between exomes and genomes. This study highlights the dynamic changes in carrier frequencies due to new datasets from diverse populations and provides updated carrier frequencies based on the combined data from 184 352 genomes and exomes in gnomAD. We recommend a periodic review for inclusion of new population data to update carrier screening panels in the future. Updated carrier frequencies of autosomal recessive conditions are provided using the combined data from 184 352 genomes and exomes in gnomAD. We highlight the dynamic changes in carrier frequencies as genome data from new diverse populations become available and provide a bioinformatic framework for future comparative analyses of population databases.