Haplotype analysis and LD detection at DM1 locus.

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy affecting adults and is due to trinucleotide sequence (CTG) in the 3' UTR region of DMPK gene located at 19q13.3 chromosome. Several neighboring genes (markers) located on the same chromosomes that are statistically associated and transmitted together (haplotype), influence the disease pathogenesis as caused by mutated DMPK. The intention of the study was to investigate the population genetic characteristics and to identify founder haplotypes from Northern India. Clinically diagnosed and molecularly confirmed DM1 patients (=27) and their family members (=76) were included in the study. PCR-RFLP analysis was performed for intron 5 (C/T)/HhaI, DMPK (G/T) intron 9/HinfI, Bpm1 and CKMM genetic polymorphism. The SNP Stat Online Software was used to construct haplotype group and for linkage-disequilibrium analysis. In all DM chromosomes: allele 2 had higher frequency in HhaI and HinfI while allele 1 had higher frequency in BpmI and CKMM. Total 11, 7, 10 and 11 haplotype groups had been formed in proband (patients), proband's father, proband's mother and in combined group respectively. Haplotype combination 2 (HhaI)/2 (HinfI)/1 (BpmI)/1 (CKMM TaqI)/1 (CKMM Nco1) had higher frequency, 0.4096 and 0.2867 in patients and combined group respectively. The haplotype combination 1/1/1/1/1 and 2/1/1/1/1 was most common for patient's father and mother respectively. The polymorphic markers HhaI & HinfI; HinfI & BpmI; and HinfI & CKMM TaqI showed significant LD. In comparison to other population, HhaI and HinfI have common origin of mutation.