title: Analysis of four diverse population groups indicates that a subset of cystic fibrosis mutations occur in common among Caucasians.
abstract: To determine the nature and frequency of non-delta F508 cystic fibrosis (CF) mutations among diverse populations, we have sequenced exons 9-12 and 19-23 of the CF transmembrane conductance regulator (CFTR) gene from 128 CF chromosomes (39 U.S. Caucasian, 27 African-American, 42 Northern Irish, and 20 Israeli chromosomes). These regions were chosen because they encode the two putative ATP-binding folds of CFTR, domains which appear to have functional significance. In addition, CFTR exons 1 and 2 were analyzed in the American patients. Mutations were found on 49 of the 128 CF chromosomes. Nineteen different mutations were observed; six were novel, while the remaining 13 had been reported previously by our group or by other investigators. Six of nine different mutations found in African-American patients were unique to that population. However, the vast majority of the mutations found in U.S. Caucasians (eight of nine), Northern Irish (four of five), and Israelis (three of three) also occurred in other Caucasian groups. The preponderance of previously reported mutations in these three groups suggested that a subset of the non-delta F508 mutations occur in common among Caucasians. A survey of mutation frequencies in other Caucasian groups confirmed this observation. Unfortunately, this subset accounts for less than half of non-delta F508 CF mutations in most groups. These data suggest that screening for delta F508 and this select group of mutations will efficiently and economically maximize the number of CF mutations identified in Caucasian groups. However, it will be difficult to detect more than 90% of mutant CFTR alleles except in ethnically and geographically discrete populations where CF is the result of founder effect.
authors.affiliation: Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: G R
authors.initials: GR
authors.lastname: Cutting
authors.forename: S M
authors.initials: SM
authors.lastname: Curristin
authors.forename: E
authors.initials: E
authors.lastname: Nash
authors.forename: B J
authors.initials: BJ
authors.lastname: Rosenstein
authors.forename: I
authors.initials: I
authors.lastname: Lerer
authors.forename: D
authors.initials: D
authors.lastname: Abeliovich
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.forename: C
authors.initials: C
authors.lastname: Graham
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D002872:Chromosome Deletion; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D005006:Ethnicity / Q000235:genetics; D005091:Exons; D016368:Frameshift Mutation; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012326:RNA Splicing; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA