Publications by authors named "V D Wheeler"
Huntington's disease (HD) arises from a CAG expansion in the () gene beyond a critical threshold. A major thrust of current HD therapeutic development is lowering levels of mutant mRNA (m) and protein (mHTT) with the aim of reducing the toxicity of these product(s). Human genetic data also support a key role for somatic instability (SI) in 's CAG repeat - whereby it lengthens with age in specific somatic cell types - as a key driver of age of motor dysfunction onset.
View Article and Find Full Text PDFSharing genetic and other study results with the communities who participate in research falls under benefit-sharing and capacity-building initiatives that underpin a more equitable biomedical research relationship. Yet, which results to return and how remain fundamental challenges that persist in the absence of practical guidance and institutional policies. Here, we discuss how the return of results can be implemented across different geographies, study designs, and project budgets.
View Article and Find Full Text PDFco-evolving with the CAG-repeat tract - modulates Huntington's disease phenotypes.
Mol Ther Nucleic Acids
September 2024
Article Synopsis
- Circular RNA (circRNA) is important for brain development and disorders, especially in Huntington's disease (HD).
- Researchers found a specific circRNA from the HD gene, which is most common in the brain and changes with the size of a DNA repeat in people and mice with HD.
- Although this circRNA doesn’t seem to make proteins in adult mouse brains, it might help regulate protein production and improve some problems caused by HD in brain cells.
Article Synopsis
- Huntington's disease (HD) is caused by a CAG repeat expansion and is part of a group of disorders linked to unstable short tandem repeats, highlighting the complexity of genetic influences on the disease.
- Research indicates that both overlapping and unique genetic modifiers affect clinical symptoms and somatic expansion in blood DNA, pointing to specific cell-type interactions in mismatch repair processes.
- The study identifies a 5'-UTR variant that causes somatic expansion without altering clinical HD, and a specific sequence change that accelerates motor symptom onset without increasing expansion, emphasizing potential therapeutic targets for managing HD.
Huntington's disease (HD), one of >50 inherited repeat expansion disorders (Depienne and Mandel, 2021), is a dominantly-inherited neurodegenerative disease caused by a CAG expansion in (The Huntington's Disease Collaborative Research Group, 1993). Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the property driving disease is the CAG length-dependent propensity of the repeat to further expand in brain (Swami ., 2009; GeM-HD, 2015; Hensman Moss .
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