Year: 2024
Type: conference-paper
Abstract: Background Huntington’s disease (HD) arises from abnormal expansion of CAG repeats in the HTT gene, with individuals carrying 36–39 repeats at risk due to incomplete penetrance, while those with 40 or more repeats are certain to develop HD. Those with fewer than 26 repeats typically remain unaffected, while 27–35 repeats constitute an intermediate allele. The reasons for entering the intermediate range and the intergenerational changes in HTT CAG length remain unclear. HD exhibits a paternal anticipation bias, with expansions inherited from fathers resulting in earlier onset and more severe symptoms. Enroll-HD, an ongoing observational study, collects clinical, family and biological data to aid in biomarker and therapeutic development. Aims We aim to explore ENROLL-HD family results and GWA variant data to identify the genetic variants that drive intergenerational CAG length changes and paternal anticipation. Methods We used the family history results of the Enroll-HD study to evaluate anticipation effects in this cohort. We further explored these results in the context of available genetic variant data from GWAS 3, 4 and 5 results to understand the effect of known modifiers of HD onset on the intergenerational CAG length changes. Results and Conclusions Analyzing family history data from Enroll-HD revealed strong paternal CAG length intergenerational expansion and stable maternal inheritance patterns. We integrated available GWA variant data and performed quality control, confirming genetic relationships. Explorative analysis of the impact of known HD onset modifiers on intergenerational CAG length changes, revealed a weak interaction of certain variants with male expansion bias.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402374370