Estimating the age of CFTR mutations predominantly found in Brittany (Western France)

Abstract

Background Disparities in the spectrum of mutations within the cystic fibrosis (CF) transmembrane conductance regulator ( CFTR) gene are commonly observed in populations from different ethnical and/or geographical origins. The occurrence of CF in Brittany (western France) is one of the highest in populations from Caucasian origin (< 1/2000 in specific areas). The W846X 2, 1078delT and G551D mutations, as well as the I1027T polymorphism in cis with the ΔF508 mutation (currently referred to as p.F508del) are particularly frequent in this area. We investigated the age of the respective variants in the region of interest. Methods Several polymorphic markers surrounding the CFTR gene were genotyped. Allele frequencies as well as mutation rates and other parameters were used to calculate the respective age of the most recent common ancestors in the region of interest by a previously employed, simple likelihood-based method. Results Following haplotype reconstruction and simulation, the ages were estimated to be approximately 600, 1000, 1200 and 600 years, respectively (with a 95% confidence interval). Conclusions These datings thus provide historical insights in the context of understanding population migrations. They also underline the usefulness of this method for estimating the age of rare mutations with a limited number of carriers.