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)(> or =18) and mutated alleles.
Conclusions: (CTG)(9-17)/(+++) haplotype is the ancestral haplotype and DM1 mutation occurred on (CTG)(18-35)/+++ chromosome.