CYSTIC-FIBROSIS MUTATIONS AND ASSOCIATED HAPLOTYPES IN BULGARIA - A COMPARATIVE POPULATION GENETIC-STUDY

We present data on the population genetics of cystic fibrosis (CF) in Bulgaria, obtained by comprehensive mutation analysis and the construc tion of intragenic microsatellite haplotypes. The sample of 262 CF all eles analysed is representative of the patients diagnosed during the p eriod of referral and of the three main ethnic groups in the country. Delta F508 accounted for 100% of Gypsy CF alleles, which thus differed significantly from both Bulgarians and ethnic Turks. Ln Bulgarian and Turkish CF patients, 92% of the mutant alleles were identified, yield ing a total of 25 different mutations, of which only 7 occurred at fre quencies higher than 1%. The findings were compared to other European populations and to the distribution of phenylketonuria mutations. Gene tic distances and population trees demonstrated that in the south-east ern tip of Europe, the overall distribution of CF mutations and polymo rphic haplotypes is very close to that of Mediterranean populations, w ith a high frequency of N1303K and G542X, a large number of rare mutat ions and a prevalence of the 23 31 13 haplotype in association with De lta F508. These findings are consistent with a main role for the Neoli thic expansion in the shaping of the CF mutation spectrum in Bulgaria and southern Europe.