Study of haplotypes associated with the F508del mutation in the Tunisian population

Abstract

Since the discovery in 1989 of the gene responsible for cystic fibro-sis, more than 1900 mutations have been reported. The F508del deletion is found on average two thirds of the mutated alleles, the remaining mutations are characterized by their rarity. We are interested in this work to the study of haplotypes associated with the F508del mutation in the Tunisian population. In this study, we analyzed five extra (XV2C and KM19) and intragenic (IVS8CA, IVS17bTA and IVS17bCA) polymorphic markers in 10 CF Tunisians patients carrying the most common mutation F508del. A healthy population of 30 subjects was also included in our study. For this two molecular biology techniques were used : the length polymorphism restriction fragment (PCR-RFLP) and capillary electrophoresis. The results show that F508del mutation is linked to different haplotypes : the B haplotype for the extragenic markers and 23-31-13 (IVS8CA, IVS17bTA and IVS17bCA) for the intragenic markers. These two haplotypes were found associated with the F508del mutation in Europe. These results suggest a common origin for this mutation. The study of haplotype is very interesting because it allows in one hand to determine the ethnicity of the molecular lesions responsible for this disease, and in the other hand to increase the genetic informativity during prenatal diagnosis.