Vilija Lomeikaite, PhD Candidate

PhD Candidate, Darren Monkton, University of Glasgow, and Caroline Benn, LoQus23 Therapeutics

Improving methods to accurately quantify somatic mosaicism in clinical samples from HD patients

Huntington’s disease (HD) is an inherited genetic disorder caused by an unstable DNA region. The larger this region is inherited by an individual, the earlier the disease symptoms start. This unstable DNA expands over the lifetime of an HD patient in most of the cells of the body. The fastest expansions with the largest expanded DNA regions are found in the brain, which likely explains the pattern of clinical and behavioral signs in HD patients. Research by our and other groups shows that the speed at which this unstable DNA region expands differs between patients, with higher expansion speed in some, and slower speed in others. It appears that when this unstable DNA expands less rapidly, the disease progression in HD patients is also slower. Due to limitations in current methods that we use to measure such expansions, we cannot yet fully understand why or how these DNA regions expand at different speeds. We propose here several novel improvements to the current methods that would enable us to confidently detect the number of expansions and potential contractions in hundreds of HD patients which in turn would facilitate further research towards better understanding of the expansion process. This would not only improve our fundamental understanding of HD, but would also enable new therapeutics development for drugs that aim to reduce the speed or completely stop DNA expansions.