1. ¹Department of Biology, University of Roma-Tor Vergata, Italy
2. ²Section of Biology and Genetics, Department of Mother and Child and of Biology-Genetics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy
3. ³Department of Molecular Genetics, CF-Centre, Charles University, Prague, Czech Republic
4. ⁴Department of Neonatology, Clinic of Obstetrics and Gynecology, Charles University Prague, Czech Republic
5. ⁵Institute of Biology, University of Montpellier, France
6. ⁶Centre de Biogénétique, CDTS, Brest, France

Correspondence: Professor PF Pignatti, Section of Biology and Genetics, Department of Mother and Child and of Biology-Genetics, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. Tel: +39 045 584602; Fax: +39 045 8027180; E-mail: pierfranco.pignatti@univr.it

Received 3 May 2005; Revised 19 August 2005; Accepted 23 August 2005; Published online 26 October 2005.

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.