Haplotype analysis at HTT locus in Huntington’s disease patients from India

Abstract Huntington's disease (HD) is caused by an increase in the number of CAG triplet repeats in exon 1 of the Huntingtin ( HTT ) gene. Expansions that contain more than 39 repeats predispose to disease. Some specific genetic elements (SNPs), and the haplotypes they create (haplogroups A, B, and C), located at the HTT locus seem to impact CAG repeat instability, and thus the prevalence of disease across different ethnic groups. We describe the haplotype structure in HD patients from India, using previously described informative SNPs at the HTT locus. We found that 27.8% of the HD patients are associated with high-risk haplotype variants (A1 and A2) and identified new variants within haplogroup A2 and C in HD patients. However, the representative control populations (1000 Genome South Asian and Genome Asia India) showed a complete absence of haplogroup A1. The major haplogroup in both HD and control populations was A4. The distribution of haplogroups A, B, and C among Indian HD patients suggested a mixture of genetic influences from European, East Asian and African populations. Also, a new variant of Hap.15 was identified in the Hap.01-Hap.16 haplotype classification. Additionally, we propose a new haplotype classification specifically for HD patients in India. The novel HTT haplotypes (HT-1 to HT-7) classification exhibited significant heterogeneity in HD patients. The observed variation may be attributed to population heterogeneity or multiple ancestral origins.