Molecular genetic studies in monogenic and polygenic human diseases

Acta Biol Hung. 1997;48(1):121-8.

Abstract

The main goal of this study was to determine and characterise the types of mutations in two monogenic human disorders: cystic fibrosis (CF) and Duchenne/Becker muscular dystrophy (DMD, BMD) and the susceptibility allele frequency in a polygenic disease: type I insulin-dependent diabetes mellitus (IDDM). After analysing 220 chromosomes for mutations in the CF (Cystic Fibrosis Transmembrane Conductance Regulator = CFTR) gene, delta F508 mutation was most abundant (41%) and out of the non-delta F508 CF mutations 5% was identified as G542X, G551D, R553X, N1303K and W1282X. The CF haplotype analysis by using linked markers to the CFTR gene revealed that the CF "B" haplotype occurred in 66.7% of patients, and this haplotype was 57.2% in patients carrying the delta F508 mutation. Prenatal genetic diagnosis for CF was performed in 10 fetuses: 3 were affected, 6 were carriers, and 1 without any CF mutation. Fifty % of 66 patients with DMB/BMD muscular dystrophy 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 gene. Out of the three prenatal diagnosis in one case DMD was substantiated. Thirty-six % of 50 patients with IDDM possessed four, 44% three and 20% two susceptibility markers in the HLA-DQA1, -DQB1 region. The onset of the disease correlated with the number of susceptibility alleles.

MeSH terms

  • Alleles
  • Child
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Diabetes Mellitus, Type 1 / genetics
  • Dystrophin / genetics
  • Female
  • Gene Frequency
  • Genetic Diseases, Inborn / genetics*
  • Genetic Markers
  • HLA-DQ Antigens / genetics
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Male
  • Molecular Biology
  • Muscular Dystrophies / diagnosis
  • Muscular Dystrophies / genetics
  • Mutation
  • Pregnancy
  • Prenatal Diagnosis

Substances

  • CFTR protein, human
  • Dystrophin
  • Genetic Markers
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Cystic Fibrosis Transmembrane Conductance Regulator