title: Complete detection of mutations in cystic fibrosis patients of Native American origin.
abstract: An increased incidence of cystic fibrosis (CF) has been reported in some populations of Native Americans of the Southwest such as the Pueblo, which is a genetic isolate. As the most common mutation found in Caucasians (delta F508) was absent and only one chromosome carried the G542X mutation, we decided to analyze the entire coding sequence of the CFTR gene in eight Pueblo CF patients. We have identified four different mutations: G542X, R1162X, 3849+10kbC-->T, and D648V that account for these 16 haplotypes. The R1162X was found on 11 chromosomes. Using intragenic microsatellites, we have compared the haplotypes of those chromosomes to those of Italian origin where the R1162X mutation was initially reported. These haplotypes turned out to be identical, suggesting a common origin and an admixture with Italian or Spanish settlers, followed by typical founder effect. In contrast the 3849+10kbC-->T mutation, which was found on three chromosomes, is associated with different haplotypes than those on chromosomes carrying the same mutation in Caucasians. A novel mutation, D648V, observed on one chromosome has not been found outside the Pueblo population.
authors.affiliation: Centre de Biogénétique, C.D.T.S., Brest, France.
authors.forename: B
authors.initials: B
authors.lastname: Mercier
authors.forename: O
authors.initials: O
authors.lastname: Raguénès
authors.forename: X
authors.initials: X
authors.lastname: Estivill
authors.forename: N
authors.initials: N
authors.lastname: Morral
authors.forename: G C
authors.initials: GC
authors.lastname: Kaplan
authors.forename: M
authors.initials: M
authors.lastname: McClure
authors.forename: T A
authors.initials: TA
authors.lastname: Grebe
authors.forename: D
authors.initials: D
authors.lastname: Kessler
authors.forename: P F
authors.initials: PF
authors.lastname: Pignatti
authors.forename: C
authors.initials: C
authors.lastname: Marigo
mesh_terms: D001483:Base Sequence; D003550:Cystic Fibrosis / Q000208:ethnology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator