XV-2c and KM: 19 haplotype analysis in Chilean patients with cystic fibrosis and unknown CFTR gene mutations

ABSTRACT

Cystic fibrosis (CF) is caused by mutations in the CFTR gene. More than 1600 mutations have been described, with frequencies that differ worldwide according to the ethnic origin of patients. A small group of mutations are recurrent on several populations. It has been shown that they each tend occur on specific chromosome 7 haplotypes, supporting the notion of a single origin for them. Less than 50 percent of mutations in Chilean patients have been identified to date. To indirectly assess the possible presence of a predominant founder mutation in the remaining unknown al¡eles, we evaluated 2 polymorphic markers, XV-2c and KM.19, tightly linked to the CFTR locus. The study was done in Chilean CF patients with unknown or delt F508 ( F508) CFTR mutations and their haplotypes were compared to affected family-based controls. F508 showed marked linkage disequilibrium with XV-2c/KM.19 haplotype B, with 90 percent of al¡eles on that haplotype. There was no difference in haplotype distribution between unknown mutations and normal controls. These results support a European origin for F508 al¡eles in Chilean patients, and make unlikely the presence of a predominant founder mutation in the so-far unknown alíeles.