Haplotype analysis of the CFTR gene on normal and mutant CFTR genes.

ABSTRACT

BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for Cystic Fibrosis (CF) disease. Since the distribution of polymorphisms varies among populations, a comparison between the frequency of CFTR polymorphisms in patients and healthy population may further identify their role in CF disease. The results obtained from this research may facilitate the prediction of disease phenotype in prenatal diagnosis or newborn screening program as well as determine the possible associations between haplotypes and specific mutations. METHODS: Blood samples collected from 27 unrelated West Iranian families contain at least one CF patient and 55 control families with no history of CF. Samples were analyzed for c.1210-12 T [5-9], c.1242-35-1242-12GT [8-10], c.744-33GATT [6-8] and c.869 + 11C > T polymorphisms by automated direct DNA sequencing following DNA extraction. RESULTS: Our results showed that the T7 allele is the most common allele in normal and non-ΔF508 CF chromosomes with the frequencies of 93.6% and 100%, respectively. Conversely, T9 was the only allele detected in ΔF508 chromosomes. Moreover, the c.1242-35-1242-12GT analysis showed that (TG)11 repeat was the most common dinucleotide repeat in both, non-ΔF508 and normal chromosomes with the frequencies of 91% and 71%, respectively. The c.744-33GATT and c.869 + 11C > T polymorphism analyses indicated that (GATT)6 and T allele are only found in ΔF508 CF chromosomes. Besides, the [T7-TG11-GATT7-C] haplotype was the most common haplotype in both, normal and non-ΔF508 CF subjects while the [T9-TG10- GATT6-T] haplotype was only detected in CF patients carrying ΔF508 mutation. CONCLUSIONS: Our findings identified an informative haplotype that could be used in genetic counseling, prenatal diagnosis and future screening of CF in Iran.