ArticleHuman molecular genetics2013
Dominant effects of the Huntington's disease HTT CAG repeat length are captured in gene-expression data sets by a continuous analysis mathematical modeling strategy.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Effect of Trinucleotide Repeats in the Huntington's Gene on Intelligence.EBioMedicine · 2018Trial
- Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington's Disease.Genes · 2022Review
- Identification of Novel Therapeutic Targets for Polyglutamine Diseases That Target Mitochondrial Fragmentation.International journal of molecular sciences · 2021Article
- Targeting Mitochondrial Network Disorganization is Protective inAging and disease · 2021Article
- Article
- Shared Molecular Signatures Across Neurodegenerative Diseases and Herpes Virus Infections Highlights Potential Mechanisms for Maladaptive Innate Immune Responses.Scientific reports · 2019Article
- Trinucleotide Repeat Expansion Diseases, RNAi, and Cancer.Trends in cancer · 2018Review
- Population-specific genetic modification of Huntington's disease in Venezuela.PLoS genetics · 2018Article
- Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells.EMBO reports · 2018Article
- Novel allele-specific quantification methods reveal no effects of adult onset CAG repeats on HTT mRNA and protein levels.Human molecular genetics · 2017Article
- Sex-specific effects of the Huntington gene on normal neurodevelopment.Journal of neuroscience research · 2017Article
- Optical Coherence Tomography in Alzheimer's Disease and Other Neurodegenerative Diseases.Frontiers in neurology · 2017Review
- Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Making (anti-) sense out of huntingtin levels in Huntington disease.Molecular neurodegeneration · 2015Article
- Transcription, epigenetics and ameliorative strategies in Huntington's Disease: a genome-wide perspective.Molecular neurobiology · 2015Review
- Invited review: decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: a review of the current state of the art.Neuropathology and applied neurobiology · 2015Review
- Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
In Huntington's disease (HD), the size of the expanded HTT CAG repeat mutation is the primary driver of the processes that determine age at onset of motor symptoms. However, correlation of cellular biochemical parameters also extends across the normal repeat range, supporting the view that the CAG repeat represents a functional polymorphism with dominant effects determined by the longer allele. A central challenge to defining the functional consequences of this single polymorphism is the difficulty of distinguishing its subtle effects from the multitude of other sources of biological variation. We demonstrate that an analytical approach based upon continuous correlation with CAG size was able to capture the modest (∼21%) contribution of the repeat to the variation in genome-wide gene expression in 107 lymphoblastoid cell lines, with alleles ranging from 15 to 92 CAGs. Furthermore, a mathematical model from an iterative strategy yielded predicted CAG repeat lengths that were significantly positively correlated with true CAG allele size and negatively correlated with age at onset of motor symptoms. Genes negatively correlated with repeat size were also enriched in a set of genes whose expression were CAG-correlated in human HD cerebellum. These findings both reveal the relatively small, but detectable impact of variation in the CAG allele in global data in these peripheral cells and provide a strategy for building multi-dimensional data-driven models of the biological network that drives the HD disease process by continuous analysis across allelic panels of neuronal cells vulnerable to the dominant effects of the HTT CAG repeat.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.