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Haplotype analysis of 94 cystic fibrosis mutations with seven polymorphic CFTR DNA markers
Author(s) -
Morral Núria,
Dörk Thilo,
Llevadot Roser,
Dziadek Violetta,
Mercier Bernard,
Férec Claude,
Costes Bruno,
Girodon Emmanuelle,
Zielenski Julian,
Tsui LapChee,
Tümmler Burkhard,
Estivill Xavier
Publication year - 1996
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1996)8:2<149::aid-humu7>3.0.co;2-6
Subject(s) - biology , haplotype , genetics , cystic fibrosis , genetic marker , dna , gene , genotype
Abstract We have analyzed 416 normal and 467 chromosomes carrying 94 different cystic fibrosis (CF) mutations with polymorphic genetic markers J44, IVS6aGATT, IVS8CA, T854, IVS17BTA, IVS17BCA, and TUB20. The number of mutations found with each haplotype is proportional to its frequency among normal chromosomes, suggesting that there is no preferential haplotype in which mutations arise and thus excluding possible selection for specific haplotypes. While many common mutations in the worldwide CF population showed absence of haplotype variation, indicating their recent origins, some mutations were associated with more than one haplotype. The most common CF mutations, ΔF508, G542X, and N1303K, showed the highest number of slippage events at microsatellites, suggesting that they are the most ancient CF mutations. Recurrence was probably the case for 9 CF mutations (R117H, H199Y, R347YH, R347P, L558S, 2184insA, 3272‐26A → G, R1162X, and 3849 + 10kbC → T). This analysis of 94 CF mutations should facilitate mutation screening and provides useful data for studies on population genetics of CF. © 1996 Wiley‐Liss, Inc.