Variation of CAG repeats and two intragenic polymorphisms at SCA3 locus among Machado-Joseph disease/SCA3 patients and diverse normal populations from eastern India

OBJECTIVES: MJD1/SCA3 is the most common type of spinocerebellar ataxia (SCA) worldwide. To explain the low prevalence of the disease among SCA patients from eastern India, we analysed CAG repeats and two bi-allelic intragenic markers at SCA3 locus among 412 normal individuals and 10 patients. MATERIALS AND METHODS: For CAG repeat analysis, PCR amplified fragments were run on polyacrylamide gel, transferred to a membrane, probed with (CAG)10 and detected on an autoradiograph. Bi-allelic markers were analysed using allele specific PCR amplification. RESULTS: Large normal alleles (>33 CAG repeats) were 0.015 in pooled populations. All the patients had the common haplotype C-A as observed worldwide. Frequency of C-A haplotype among large normal alleles was 0.75. CONCLUSIONS: Observed low prevalence of SCA3 could be because of the low prevalence of large normal alleles that might act as the reservoir for the expanded alleles. SCA3 mutation in Indian populations had the same origin as found worldwide.