Huntington's disease LIG1 modifier variant increases ligase fidelity and suppresses somatic CAG repeat expansion.

ABSTRACT: Huntington's disease (HD) is a fatal neurodegenerative disorder caused by inheriting an expanded CAG repeat tract in the huntingtin gene (HTT) that further expands in somatic cells over an individual's lifetime. Genome-wide association studies have provided critical insight into factors that modify the course of disease. These include DNA repair genes that alter the rate of somatic expansion and other genes that do not appear to directly influence this process. One modifier gene is DNA ligase 1 (LIG1), in which a variant specifying a lysine to asparagine substitution (K845N) is associated with a profound (7-8 year) delay in the onset of motor signs. Here, we have taken a multifaceted approach to gain insight into the protective nature of this variant in HD. We demonstrate usi

SUBMITTER: Lee E 

PROVIDER: S-EPMC12338604 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature