title: Identical intragenic microsatellite haplotype found in cystic fibrosis chromosomes bearing mutation G551D in Irish, English, Scottish, Breton and Czech patients.
abstract: Mutation G551D of exon 11 of the cystic fibrosis transmembrane conductance regulator gene is one of the most common mutations in patients of European origin. In order to test the hypothesis that the mutation is identical by descent in these patients, we have studied haplotypes for the three intragenic microsatellite markers IVS8CA, IVS17bTA and IVS17bCA from 92 patients bearing this mutation, who had been referred to laboratories in Ireland, Scotland, England, France (Brittany) and the Czech Republic. In all cases we found that only haplotype 16-7-17 is associated with mutation G551D. Our results support the hypothesis of identity by descent of all cystic fibrosis chromosomes bearing mutation G551D in these patient populations, and suggest that given the combined mutation rate of the microsatellite markers, there is a low probability (p < 0.05) that the haplotype where mutation G551D first occurred remained unaltered for more than 170 generations.
authors.affiliation: Department of Genetics, Trinity College, Dublin, Ireland.
authors.forename: S M
authors.initials: SM
authors.lastname: Cashman
authors.forename: A
authors.initials: A
authors.lastname: Patino
authors.forename: A
authors.initials: A
authors.lastname: Martinez
authors.forename: M
authors.initials: M
authors.lastname: Garcia-Delgado
authors.forename: Z
authors.initials: Z
authors.lastname: Miedzybrodzka
authors.forename: M
authors.initials: M
authors.lastname: Schwarz
authors.forename: A
authors.initials: A
authors.lastname: Shrimpton
authors.forename: C
authors.initials: C
authors.lastname: Ferec
authors.forename: O
authors.initials: O
authors.lastname: Raguenes
authors.forename: M
authors.initials: M
authors.lastname: Macek
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics*; D018153:Czech Republic; D004252:DNA Mutational Analysis; D004276:DNA, Satellite / Q000032:analysis*; D004739:England; D005602:France; D006239:Haplotypes; D006801:Humans; D007494:Ireland; D009154:Mutation; D012606:Scotland
chemical_list: D004276:DNA, Satellite