Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308656 | PMC |
| http://dx.doi.org/10.1002/mds.29035 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.
Brain Commun
November 2024
Department of Neurodegenerative Disease, Huntington's Disease Centre, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression.
View Article and Find Full Text PDFWhen repetita no-longer iuvant: somatic instability of the CAG triplet in Huntington's disease.
Nucleic Acids Res
December 2024
Department of Biosciences, University of Milan, street Giovanni Celoria, 26, 20133, Milan, Italy.
Trinucleotide repeats in DNA exhibit a dual nature due to their inherent instability. While their rapid expansion can diversify gene expression during evolution, exceeding a certain threshold can lead to diseases such as Huntington's disease (HD), a neurodegenerative condition, triggered by >36 C-A-G repeats in exon 1 of the Huntingtin gene. Notably, the discovery of somatic instability (SI) of the tract allows these mutations, inherited from an affected parent, to further expand throughout the patient's lifetime, resulting in a mosaic brain with specific neurons exhibiting variable and often extreme CAG lengths, ultimately leading to their death.
View Article and Find Full Text PDFExpansions and contractions of tandem DNA repeats are a source of genetic variation in human populations and in human tissues: some expanded repeats cause inherited disorders, and some are also somatically unstable. We analyzed DNA sequence data, derived from the blood cells of >700,000 participants in UK Biobank and the Research Program, and developed new computational approaches to recognize, measure and learn from DNA-repeat instability at 15 highly polymorphic CAG-repeat loci. We found that expansion and contraction rates varied widely across these 15 loci, even for alleles of the same length; repeats at different loci also exhibited widely variable relative propensities to mutate in the germline versus the blood.
View Article and Find Full Text PDFSuppression of Huntington's Disease Somatic Instability by Transcriptional Repression and Direct CAG Repeat Binding.
bioRxiv
November 2024
Department of Neurology, University of Washington, Seattle WA 98104, USA.
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 PDFBlastocyst complementation generates exogenous donor-derived liver in ahepatic pigs.
FASEB J
November 2024
RenOVAte Biosciences Inc, Reisterstown, Maryland, USA.
Liver diseases are one of the leading causes of morbidity and mortality worldwide. Globally, liver diseases are responsible for approximately 2 million deaths annually (1 of every 25 deaths). Many of the patients with chronic liver diseases can benefit from organ transplantation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!