Haplotype distribution of and linkage disequilibrium between four polymorphic markers near the CFTR locus in Brazilian cystic fibrosis patients

To contribute to a better understanding of the origin and distribution of CFTR mutations in the Brazilian population, we have investigated the linkage between four polymorphic markers (XV2c, KM19, GATT, and TUB9) within or near the CFTR locus. The distribution of alleles for each polymorphism for both parental and cystic fibrosis (CF) chromosomes from Rio de Janeiro CF families were ascertained using a maximum-likelihood method. This same method was applied to study the distribution of the haplotypes defined by these markers. There was no significant association between the XV2c and KM19 loci on the parental and CF chromosomes. On the other hand, a strong association between GATT and TUB9 loci was observed on both CF and parental chromosomes, and striking linkage disequilibrium between the GATT-TUB9 pair and deltaF508 was observed (chi2 = 26.48, p < 0.0001). Remarkable linkage disequilibrium between the GATT-TUB9 marker pair and non-deltaF508 was also found (chi2 = 17.05, p < 0.0001). Our finding of a linkage disequilibrium between GATT-TUB9 and the CFTR locus could suggest that gene flow between different ethnic groups, mainly sub-Saharan and Mediterranean populations, with Brazilian populations could have resulted in some CF mutations originating on chromosomes that carried the GATT-TUB9 marker haplotype 7-2 (OR = 1.34 < 2.83 < 6.00; p = 0.0066).