title: Discrimination between recurrent mutation and identity by descent: application to point mutations in exon 11 of the cystic fibrosis (CFTR) gene.
abstract: A total of 75 non-delta F508 chromosomes from 59 German cystic fibrosis patients was screened for mutations in exon 11 of the cystic fibrosis (CFTR) gene. These Caucasian patients were found to possess an identical haplotype background for two common mutations (G551D, R553X) consistent with their being identical by descent. However, a different R553X associated haplotype found in American black patients was suggestive of recurrent mutation, a postulate supported by the location of the R553X alteration in a hypermutable CpG dinucleotide. Likelihood estimates for recurrent mutation and identity by descent were compared and strongly supported the hypothesis of recurrent R553X mutation. The ability to distinguish between these two alternatives provides an indication of whether or not the search for mutations should be restricted to chromosomes with similar haplotypes.
authors.affiliation: Institut für Humangenetik, Göttingen, Federal Republic of Germany.
authors.forename: J
authors.initials: J
authors.lastname: Reiss
authors.forename: D N
authors.initials: DN
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Bal
authors.forename: R
authors.initials: R
authors.lastname: Slomski
authors.forename: G R
authors.initials: GR
authors.lastname: Cutting
authors.forename: M
authors.initials: M
authors.lastname: Krawczak
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D015226:Dinucleoside Phosphates / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015183:Restriction Mapping
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D015226:Dinucleoside Phosphates; D008565:Membrane Proteins; C505032:CFTR protein, human; C015772:CpG dinucleotide