Background Huntington’s disease (HD), an autosomal dominant neurodegenerative syndrome, has a world-wide distribution. An estimated 2.5–10/100,000 people of European ancestry are affected with HD, while the Asian populations have lower prevalence (0.6–3.8/100,000). The epidemiology of HD is not well described in India, and the distribution of the pathogenic CAG expansion, and the associated haplotype, in this population needs to be better understood.
Aim To analyse the distribution of CAG repeats, at the HTT locus and analyse the HD halpotype in Indian sample vis a vis the European HD haplogroup.
Methods The clinical samples (N = 164) were derived from both outpatients and inpatient referrals to Genetic Counselling and Testing Centre (GCAT) at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. The healthy control samples (N = 103) were recruited by purposive sampling of volunteers from different parts of India (Total, N = 267). PCR techniques and fragment analysis has been used to calculate CAG repeat length and for haplotype studies.
Results Control individuals had an average CAG repeat size of 17.6 ± 2 (range: 11–34). Most of the HD subjects (N = 116, 71%) showed CAG repeat expansion (>39) with many having paternal inheritance (45.6%). The results confirmed negative correlation between CAG repeat size and age of onset (AAO) in symptomatic HD cases. Further analysis of the expanded allele revealed a majority of expansions (84.3%) in the range of 40–50 CAG repeats with a late AAO of symptoms (40.2 years). In this sample, based on the three SNPs (rs762855- rs3856973- rs 4690073), haplogroup A was most common which corresponds to the Caucasian HD haplogroup. In addition, individuals from different parts of India shared this haplogroup, indicating that it is not a region specific effect. Sequencing the region further to permit finer mapping of these haplogroups is essential to comment upon the origin and spread of this mutation in India. Region wide analysis showed 62.8% of the southern Indian, 60% of the northern Indian and 46.6% of the eastern Indians tested had the haplogroup A – European haplogroup.
Conclusion This study demonstrates a distribution of CAG repeats, at the HTT locus, comparable to the European population in both normal and HD affected chromosomes. Further, we provide an evidence for similarity of the HD halpotype in Indian sample to the European HD haplogroup.
- CAG repeats
- European Haplogroup.