title: Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations.
abstract: An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed.
authors.affiliation: Department of Biology, University of Roma-Tor Vergata, Italy.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Pompei
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Ciminelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Bombieri
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ciccacci
authors.forename: Monika
authors.initials: M
authors.lastname: Koudova
authors.forename: Silvia
authors.initials: S
authors.lastname: Giorgi
authors.forename: Francesca
authors.initials: F
authors.lastname: Belpinati
authors.forename: Angela
authors.initials: A
authors.lastname: Begnini
authors.forename: Milos
authors.initials: M
authors.lastname: Cerny
authors.forename: Marie
authors.initials: M
authors.lastname: Des Georges
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Claude
authors.initials: C
authors.lastname: Ferec
authors.forename: Milan
authors.initials: M
authors.lastname: Macek
authors.forename: Guido
authors.initials: G
authors.lastname: Modiano
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
mesh_terms: D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D044465:White People / Q000235:genetics*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator