Molecular anatomy of CTG expansion in myotonin protein kinase gene among myotonic dystrophy patients from eastern India

Abstract

We have studied the CTG repeat sizes in the DMPK gene and six biallelic markers which are in complete linkage disequlibrium with Caucasian DM patients, to identify any common founder haplotype in 30 clinically diagnosed unrelated DM patients from eastern India. Our results revealed that in 27 patients (90%), CTG expansion took place on a DraIII(‐) ‐ HhaI(‐) ‐ Alu(+) ‐ HinfI(+) ‐ Fnu4H I(‐) ‐ TaqI(+) haplotype (haplotype I), similar to what have been published for Caucasoid and other DM patients. However, in three patients (10%), the expansion of CTG repeat was on DraIII(+) ‐ HhaI(+) ‐ Alu(+) ‐ HinfI(‐) ‐ Fnu4H I(+) ‐ TaqI(‐) background (haplotype II), indicating a new haplotype. The distribution of haplotypes in 52 normal individuals of eastern India revealed that percentage of haplotypes I and II were 23.1% and 7.7% respectively in normal chromosomes. Haplotype II is absent among Caucasian DM patients as well as normal individuals indicating that this particular haplotype may be characteristic of the Indian population. Hum Mutat 16:372, 2000. © 2000 Wiley‐Liss, Inc.

Haplotype analysis of genomic polymorphisms in and around the myotonic dystrophy locus in diverse populations of India

“…This haplotype is in complete linkage disequilibrium with DM chromosomes in Caucasian populations (Neville et al 1994;Goldman et al 1996). Combining the data reported in Basu et al (1999) and Basu et al (2000), we found that in a set of 30 unrelated DM patients the expanded allele was on the (+ + +) background in 27 (90%) individuals. However, in 3 (10%) individuals, the expanded allele was on the (+ --) background.…”

Haplotype analysis of the DM1 locus in the Serbian population

“…Haplotype studies in a large number of populations suggested that (CTG) 18)35 /+++ is the plausible ancestral chromosome, on which lowfrequent mutations gradually lead to full DM1 mutation (5,12). A complete association of (+++) haplotype with the DM1 mutation, as well as a strong association of (+++) haplotype with (CTG) ‡18 alleles in the Serbian population, confirms this hypothesis.…”

“…The most important among those is the model given by Tishkoff et al (5). Conclusions -(CTG) 9)17 /(+++) haplotype is the ancestral haplotype and DM1 mutation occurred on (CTG) 18 found mutated alleles only in association with (+++) haplotype in DM1 individuals of a European origin (12)(13)(14). The relative locations of these polymorphisms are shown in Fig.…”

“…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 found mutated alleles only in association with (+++) haplotype in DM1 individuals of a European origin (12)(13)(14). Accordingly, a founder event established (CTG) 18)35 alleles on a (+++) haplotype, and subsequent expansions produced DM1-causing alleles from one or more of these large-sized alleles (5).…”

“…They investigated two intragenic polymorphisms, Alu(+/)) deletion polymorphism (11) and HinfI(+/)) restriction-site polymorphism (RSP, 11), and one extragenic TaqI(+/)) RSP (D19S463, 12). Accordingly, a founder event established (CTG) 18)35 alleles on a (+++) haplotype, and subsequent expansions produced DM1-causing alleles from one or more of these large-sized alleles (5). 1.…”