Identification of incompletely penetrant variants and interallelic interactions in autosomal recessive disorders by a population-genetic approach
| Autor: | Karolina Schnabel, Dániel Seidl, Ágnes Mikó, Kálmán Tory, Ambrus Kaposi |
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| Rok vydání: | 2021 |
| Předmět: |
Genetics
Male education.field_of_study Population Genetic Diseases Inborn Population genetics Genes Recessive Biology Compound heterozygosity Penetrance Cohort Studies chemistry.chemical_compound Genetics Population chemistry Genotype Humans Female Genes Lethal education Penetrant (biochemical) Gene Allele frequency Genetics (clinical) Alleles |
| Zdroj: | Human mutationREFERENCES. 42(11) |
| ISSN: | 1098-1004 |
| Popis: | We aimed to identify incompletely penetrant (IP) variants and interallelic interactions in autosomal recessive disorders by a population-genetic approach. Genotype and clinical data were collected from 9038 patients of European origin with ASL, ATP7B, CAPN3, CFTR, CTNS, DHCR7, GAA, GALNS, GALT, IDUA, MUT, NPHS1, NPHS2, PAH, PKHD1, PMM2, or SLC26A4-related disorders. We calculated the relative allele frequency of each pathogenic variant (n = 1936) to the loss-of-function (LOF) variants of the corresponding gene in the patient ( A C p t V / A C p t L O F ) and the general population ( AC gnomAD V / AC gnomAD LOF ) and estimated the penetrance of each variant by calculating their ratio: ( A C p t V / A C p t L O F ) ( A C g n o m A D V / A C g n o m A D L O F ) (V/LOF ratio). We classified all variants as null or hypomorphic based on the associated clinical phenotype. We found 25 variants, 29% of the frequent 85 variants, to be underrepresented in the patient population (V/LOF ratio |
| Databáze: | OpenAIRE |
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