Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations.
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.
Pompei
Fiorenza
F
Department of Biology, University of Roma-Tor Vergata, Italy.
Ciminelli
Bianca Maria
BM
Bombieri
Cristina
C
Ciccacci
Cinzia
C
Koudova
Monika
M
Giorgi
Silvia
S
Belpinati
Francesca
F
Begnini
Angela
A
Cerny
Milos
M
Des Georges
Marie
M
Claustres
Mireille
M
Ferec
Claude
C
Macek
Milan
M
Modiano
Guido
G
Pignatti
Pier Franco
PF
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*
D019005:Cystic Fibrosis Transmembrane Conductance Regulator