ANALYSIS OF THE CFTR GENE CONFIRMS THE HIGH HETEROGENEITY OF THE SPANISH POPULATION - 43 MUTATIONS ACCOUNT FOR ONLY 78-PERCENT OF CF CHROMOSOMES

We have analysed 972 unrelated Spanish cystic fibrosis patients for 70 known mutations. Analysis was performed on exons 1, 2, 3, 4, 5, 6a, 6 b, 7, 10, 11, 12, 13, 14a, 14b, 15, 16, 17b, 18, 19, 20 and 21 of the cystic fibrosis transmembrane regulator gene using single strand confo rmation polymorphism analysis and denaturing gradient gel electrophore sis. The major mutation DELTAF508 accounts for 50.6% of CF chromosomes , whereas another 42 mutations account for 27.6% of CF chromosomes, wi th 21.8% of Spanish CF chromosomes remaining uncharacterised. At prese nt, we have identified 36 mutations that have frequency of less than 1 % and that are spread over 15 different exons. This indicates that, in the Spanish population, with the exception of DELTAF508 (50.6%) and G 542X (8%), the mutations are not concentrated in a few exons of the ge ne nor are there any predominating mutations. This high degree of gene tic heterogeneity is mainly a result of the different ethnic groups th at have populated Spain and of the maintenance of separated population sets (Basques, Arab-Andalusian, Mediterranean, Canarian and Gallician ). The high proportion of CF chromosomes still unidentified (21.8%) to gether with association analysis with intragenic markers suggest that at least 100 different mutations causing CF are present in our populat ion.