[CTG expansion and haplotype analysis of DM1 gene in healthy Iranian population]

ABSTRACT

Myotonic dystrophy type 1 [DM1] is due to an unstable expansion of CTG repeat in the DMPK gene [19q13.3]. The CTG repeat is highly polymorphic [5 to 37] in healthy individuals. According to the hypothesis that expanded [CTG]n alleles originated from larger normal alleles, there may exist a correlation between the prevalence of DM1 and the frequency of large size normal alleles. Strong linkage disequilibrium between different length alleles and the three biallelic markers, Alu, Hinf1 and Taq1, has been reported. Therefore, we decided to determine the distribution of normal alleles, the frequency of larger normal alleles and analysis of the three biallelic markers, in healthy Iranian controls. Polymerase chain reaction was conducted on two hundred unrelated healthy individuals from different ethnic groups living in Iran to determine the size of the alleles. Markers were analyzed by PCR/RFLP on 174 chromosomes from other control healthy individuals. Our data reveals that 23.7% of alleles had 5 CTG repeats and 7.2% of alleles had >18 CTG repeats. The analysis of haplotypes revealed that 75% of CTG5 and 80% of CTG>18 had the [+++] haplotype. In this study, we find that the frequency of alleles with CTG>18 is similar to that of Western Europe and Japan