Publications by authors named "J Gusella"
Article Synopsis
- Researchers tackled the challenge of studying structural variants (SVs) in repetitive genomic regions using advanced technologies like long-read sequencing and the gapless T2T assembly.
- They successfully analyzed 13 complex cases, resolving 10 by identifying specific genomic breakpoints and structures that were previously difficult to sequence, including Robertsonian translocations and ring chromosomes.
- The study highlighted new mechanisms for SV formation and provided insights into how these genome variations affect gene expression and potential implications for disease diagnosis and genome biology.
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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- * Researchers developed a transgenic sheep model (OVT73) to study HD, which shows early signs of the disease without motor symptoms or cell loss at a young age, aiding in understanding disease onset.
- * A study of the sheep's brain revealed increased expression of certain receptors and transporters, suggesting that excitotoxicity from glutamate may trigger early neurodegeneration, but protective mechanisms could help buffer against cell damage.
Huntington's disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin's polyglutamine tract. Lowering mutant huntingtin has been proposed for treating HD, but genetic modifiers implicate somatic CAG repeat expansion as the driver of onset. We find that branaplam and risdiplam, small molecule splice modulators that lower huntingtin by promoting HTT pseudoexon inclusion, also decrease expansion of an unstable HTT exon 1 CAG repeat in an engineered cell model.
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