C10 Haplotype structure analysis of Indian Huntington’s disease patients at HTT gene locus

Abstract

Background
Huntington’s disease (HD), caused by a pathogenic expansion of CAG triplet repeats in exon 1 of the Huntingtin (HTT) gene, has also been linked to three major haplogroups (A, B, and C), which may impact the prevalence of HD. The distribution of these haplotypes in diverse populations is thus important.

Aim
To study the haplotype structure in Indian HD patients.

Methodology
Thirty-three SNPs at the HTT locus were genotyped using Fluidigm in individuals with HD (N= 84). The SNP genotypes were run on PHASE 2.0 to obtain the haplotype structure.

Result
We were able to describe A, B, and C haplogroups for 85% of HD patients, and the A4 was the major (46%) haplotype. We also identified three novel variants in our sample. These included, an A2 variant (19%), and two new C variants C-Var1 (5%) and C-Var2 (3%). The novel haplotype classification were able to cover only 48% of the HD patients, who belong to seven different haplotypes, HT-1 to HT-7. Haplotypes HT-1(10%), HT-1.1(11%), and HT-3(10%) were the major haplotypes.

Discussion
The prevalence of the A, B, and C haplogroup structure in Indian HD patients suggest admixture from both European and East Asian populations. As, half of the HD patients did not belong to any of the novel haplotype structure, its shows the diverse nature of the selected SNPs at the HTT locus. The variation observed might be due to the heterogeneity in the population, or multiple founders.