Haplotype analysis of the myotonic dystrophy type 1 (DM1) locus in the Korean population

Myotonic dystrophy type 1 (DM1) is caused by unstable expansion of the CTG repeat in the DMPK gene. According to the hypothesis that expanded CTG repeat alleles originated from larger normal alleles, a correlation exists between prevalence of DM1 and frequency of large normal alleles. We examined the number of CTG repeats in a group of 481 non-DM1 individuals and 116 DM1 patients. Among these subjects, we analyzed the haplotype in 76 unrelated non-DM1 individuals and 14 unrelated DM1 patients using 8 bialleleic markers on the DM1 locus. Different CTG repeats from 5 to 36 and variable allele frequencies were observed. The most common allele was 12 CTG repeats (27.3%), and the frequency of larger normal alleles (>19 CTG repeats) was 3.7%. Haplotype analysis revealed that 100% of alleles with 5 and >19 CTG repeats were haplotype A. In this study, we provide the first haplotypic molecular evidence for a founder effect of DM1 mutations in Korea, and reinforce the hypothesis that out-of-Africa DM1 alleles were derived by expansion from a pool of non-DM1 alleles with haplotype A.