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% 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 alleles, 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 deltaF508 (ΔF508) CFTR mutations and their haplotypes were compared to affected family-based controls. ΔF508 showed marked linkage disequilibrium with XV-2c/KM.19 haplotype B, with 90% of alleles on that haplotype. There was no difference in haplotype distribution between unknown mutations and normal controls. These results support a European origin for ΔF508 alleles in Chilean patients, and make unlikely the presence of a predominant founder mutation in the so-far unknown alleles.

Preliminary study of haplotypes linked to the rare cystic fibrosis E1104X mutation

“…The pJ3.11 marker is located at 750 Kb of the 3' end of the CFTR gene (6), the XV2C and KM19 markers are located 175 and 125 Kb up stream of the 5' end of the CFTR gene (22).…”

“…To analyze XV2C marker, the products were digested by TaqI restriction enzyme (22). For pJ3.11 and KM19 markers, amplified products were analyzed by PstI restriction enzyme (14,22). PCR and restriction products were separated by electrophoresis on 2% agarose gel.…”

“…(Table I) (6,22). To analyze XV2C marker, the products were digested by TaqI restriction enzyme (22).…”

“…(Table I) (6,22). To analyze XV2C marker, the products were digested by TaqI restriction enzyme (22). For pJ3.11 and KM19 markers, amplified products were analyzed by PstI restriction enzyme (14,22).…”