Original Paper Hum Hered 1999;49:15–20 Allele Frequencies in a Worldwide Survey of a CA Repeat in the First Intron of the CFTR Gene Eva Mateu a Francesc Calafell a Batsheva Bonné-Tamir c Judith R. Kidd d Teresa Casals b Kenneth K. Kidd d Jaume Bertranpetit a a Unitat d’Antropologia, Facultat de Biologia, Universitat de Barcelona, and Unitat Biologia Evolutiva, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, b Departament Genètica Molecular, Institut de Recerca Oncològica, Barcelona, Catalonia, Spain; c Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; d Department of Genetics, Yale University School of Medicine, New Haven, Conn., USA Jaume Bertranpetit Unitat Biologia Evolutiva, Facultat de Ciències de la Salut i de la Vida Universitat Pompeu Fabra, Doctor Aiguader, 80 E–08003 Barcelona, Catalonia (Spain) Tel. +34 93 542 28 40, Fax +34 93 542 28 02, E-Mail jaume.bertranpetit@cexs.upf.es ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 1999 S. Karger AG, Basel 0001–5652/99/0491–0015$17.50/0 Accessible online at: http://BioMedNet.com/karger Key Words DNA polymorphism W Dinucleotide short tandem repeats W Allele frequency W CFTR gene Abstract A dinucleotide CA repeat within intron 1 of the CFTR gene has recently been identified. We have determined the allele frequencies of this polymorphism in samples from 18 populations covering all major geographical areas, with a total of 1,816 chromosomes. When consid- ering allele distributions, African populations presented a wider range of alleles than other populations and also presented higher expected heterozygosities. Analysis of molecular variance showed that 8.04% of the genetic variance in this locus could be attributed to differences among populations. We concluded that the polymor- phism in the CA repeat in intron 1 of the CFTR gene is highly informative in populations from all geographical regions of the world. Thus, it can be applied to family studies of unknown mutations causing cystic fibrosis (CF) and can provide valuable information for genetic counseling. Moreover, its analysis should be included in the haplotypic analysis of known CF mutations. Introduction Cystic fibrosis (CF) is the most common severe reces- sive disorder in patients of European descent, affecting 1 in 2,000–4,000 individuals. Since the isolation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, more than 700 CF mutations have been identified [1–3; http://www.genet.sickkids.on.ca]. Of all CF mutations, a deletion of 3 bp at codon 508 (the ¢F508 mutation) is the most frequent, accounting for approximately 67% of the global CF chromosomes. Among all other mutations, most are rare and often con- fined to one or a few populations. The internal diversity of CF-causing mutations can vary widely across popula- tions. Some populations (Bretons, Northern French, Bel- gian, Welsh, Hutterite or Ashkenazi Jews) present an apparently high homogeneity, and, in those, the mutation causing the disease has been identified in a large propor- tion of CF chromosomes, although the prevalent muta- tions found are not the same for each group. In contrast, other population groups (Southern French, Spanish) show a high heterogeneity for CF mutations [4], and a larger proportion of CF mutations remains to be identified. Sev- eral highly polymorphic short tandem repeats, also known