title: Mutation analysis of the cystic fibrosis transmembrane regulator gene in Native American populations of the southwest.
abstract: We report DNA and clinical analyses of cystic fibrosis (CF) in two previously unstudied, genetically isolated populations: Pueblo and Navajo Native Americans. Direct mutation analysis of six mutations of the CFTR gene--namely, delta F508, G542X, G551D, R553X, N1303K, and W1282X--was performed on PCR-amplified genomic DNA extracted from blood samples. Haplotype analyses with marker/enzyme pairs XV2c/TaqI and KM19/PstI were performed as well. Of the 12 affected individuals studied, no delta F508 mutation was detected; only one G542X mutation was found. None of the other mutations was detected. All affected individuals have either an AA, AC, or CC haplotype, except for the one carrying the G542X mutation, who has the haplotype AB. Clinically, six of the affected individuals examined exhibit growth deficiency, and five (all from the Zuni Pueblo) have a severe CF phenotype. Four of the six Zunis with CF are also microcephalic, a finding not previously noted in CF patients. Our DNA data have serious implications for risk assessment of CF carrier status for these people.
authors.affiliation: Department of Zoology, Arizona State University, Tempe 85287-1501.
authors.forename: T A
authors.initials: TA
authors.lastname: Grebe
authors.forename: W W
authors.initials: WW
authors.lastname: Doane
authors.forename: S F
authors.initials: SF
authors.lastname: Richter
authors.forename: C
authors.initials: C
authors.lastname: Clericuzio
authors.forename: R A
authors.initials: RA
authors.lastname: Norman
authors.forename: W K
authors.initials: WK
authors.lastname: Seltzer
authors.forename: S N
authors.initials: SN
authors.lastname: Rhodes
authors.forename: B E
authors.initials: BE
authors.lastname: Goldberg
authors.forename: L S
authors.initials: LS
authors.lastname: Hernried
authors.forename: M
authors.initials: M
authors.lastname: McClure
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005809:Genes, Regulator; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D015183:Restriction Mapping; D015206:Southwestern United States
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator