To identify functional elements in the cis-region of the huntingtin (HTT) gene that modulate age of onset in a Huntington's disease patients carrying the B-haplotype previously shown to be associated with late AO. This will be achieved using Cas9-targeted Nanopore sequencing which will provide targeted DNA methylation profiling of the HTT promoter and the sequence downstream of the CAG repeat in the HTT gene.
Even in HD cases that carry the B-haplotype, we observe variation in the age of onset. The aim in this project is to identify the differences in methylation profiles or sequence in the HTT promoter and the downstream CAG repeat sequence that might modulate age of onset. We will compare the methylation profiles and the sequences of HD cases carrying the B-haplotype (n=20-30)