Haplotype analysis of the DM1 locus in the Serbian population

Abstract

Objectives - Analysis of the CTG-repeat number and three biallelic markers, Alu(+/-), HinfI(+/-), and TaqI(+/-), in the DMPK gene in healthy and myotonic dystrophy type 1 (DM1) Serbian individuals. Also, the consideration of haplotypes in the light of the proposed models of CTG-repeat evolution and origin of the DM1 mutation. Materials and methods - Markers were analyzed by PCR and haplotypes were obtained on 203 unrelated normal chromosomes and 24 unrelated DM1 chromosomes. Results - A strong linkage disequilibrium was detected between the three biallelic markers alone (P < 0.0001) and between distinct CTG-repeat size classes and reconstructed haplotypes. Greater than 98% of normal chromosomes contain (+ + +) and (- - -) haplotypes. The (+ + +) haplotype is the most common, while the (CTG) 9-17 are the most frequent alleles. We found a complete association of (+ + +) haplotype with (CTG) ≥18 and mutated alleles. Conclusions - (CTG) 9-17 /(+ + +) haplotype is the ancestral haplotype and DM1 mutation occurred on (CTG) 18-35 / + + + chromosome. Copyright © Blackwell Munksgaard 2005.