XV-2c/KM-19 haplotype analysis of cystic fibrosis mutations in Mexican patients

We analyzed 97 unrelated Mexican cystic fibrosis (CF) patients and their fi rst-degree relatives to study the association of XV2C/ TaqI/KM19/PstI haplo types with CF mutations in this population. Haplotype phases could be estab lished in 148 CF and 110 normal chromosomes, and haplotype distributions of normal and CF chromosomes differed significantly (P < 0.001). <Delta>F508 and G542X mutations accounted for 56% of CF chromosomes and were found to b e associated with haplotype B in 97.2% and 72.7% of chromosomes, respective ly. The haplotype distribution of CF chromosomes carrying other rare and un known mutations was similar to that of normal chromosomes (P > 0.05), haplo types A and C being the most frequent. This is in accordance with the exten sive heterogeneity and the spectrum of mutations reported in Mexican CF pat ients. We also report the haplotype distribution of all informative chromos omes bearing rare mutations; some were found to be associated with previous ly reported haplotypes, whereas others were found on different haplotypes. Recombination or recurrence of mutations may explain these different associ ations, although other intragenic markers must be used to better understand the origin and dispersion of CF mutations in our country. XK haplotype ana lysis allowed carrier detection among sibs in 24.3% of families, showing th at this method may be useful for carrier detection in populations with high allelic heterogeneity. (C) 2001 Wiley-Liss, Inc.