MOLECULAR-GENETIC STUDIES IN MONOGENIC AND POLYGENIC HUMAN-DISEASES

The main goal of this study was to determine and characterise the type s of mutations in two monogenic human disorders: cystic fibrosis (CF) and Duchenne/Becker muscular dystrophy (DMD, BMD) and the susceptibili ty allele frequency in a polygenic disease: type I insulin-dependent d iabetes mellitus (IDDM). After analysing 220 chromosomes somes for mut ations in the CF (Cystic Fibrosis Transmembrane Conductance Regulator = = CFTR) gene, Delta F-508 mutation was most abundant (41%) and out o f the non-Delta F-508 CF mutations 5% was identified as G(542)X, G(551 )D, R553X, N1303K and W1282X. The CF haplotype analysis by using linke d markers to the CFTR gene revealed that the CF ''B'' haplotype occurr ed in 66.7% of patients, and this haplotype was 57.2% in patients carr ying the Delta F-508 mutation. Prenatal genetic diagnosis for CF was p erformed in 10 fetuses: 3 were affected, 6 were carriers, and 1 withou t any CF mutation. Fifty % of 66 patients with DMB/BMD muscular dystro phy had one or more exon deletions in the dystrophin gene. Eighty-five % of the deletions occurred at the 3' and 15% at the 5' end of the ge ne. Out of the three prenatal diagnosis in one case DMD was substantia ted. Thirty-six % of 50 patients with IDDM possessed four, 44% three a nd 20% two susceptibility markers in the HLA-DQA1, -DQB1 region. The o nset of the disease correlated with the number of susceptibility allel es.