Related Experiment Video
Updated: Jun 23, 2025
Immunostaining for DNA Modifications: Computational Analysis of Confocal Images
Published on: September 7, 2017
Global DNA methylation is not elevated in blood samples from Machado-Joseph disease mutation carriers
Luís Teves1,2,3, Ana Rosa Vieira Melo1, Ana F Ferreira1
1Faculdade de Ciências e Tecnologia, Universidade dos Açores, Ponta Delgada, Portugal.
Abstract:
Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia (SCA) caused by a polyglutamine expansion in the ataxin-3 protein, which initiates a cascade of pathogenic events, including transcriptional dysregulation. Genotype-phenotype correlations in MJD are incomplete, suggesting an influence of additional factors, such as epigenetic modifications, underlying the MJD pathogenesis. DNA methylation is known to impact the pathophysiology of neurodegenerative disorders through gene expression regulation and increased methylation has been reported for other SCAs. In this work we aimed to analyse global methylation in MJD carriers. Global 5-mC levels were quantified in blood samples of 33 MJD mutation carriers (patients and preclinical subjects) and 33 healthy controls, matched by age, sex, and smoking status. For a subset of 16 MJD subjects, a pilot follow-up analysis with two time points was also conducted. No differences were found in median global 5-mC levels between MJD mutation carriers and controls and no correlations between methylation levels and clinical or genetic variables were detected. Also, no alterations in global 5-mC levels were observed over time. Our findings do not support an increase in global blood methylation levels associated with MJD.
Insights
Global DNA methylation levels in blood do not appear to be altered in Machado-Joseph disease (MJD) carriers. This study found no significant differences between MJD patients and healthy individuals, suggesting methylation is not a key factor in MJD.
Area of Science:
- Neurogenetics
- Epigenetics
- Molecular Biology
Background:
- Machado-Joseph disease (MJD), an autosomal dominant spinocerebellar ataxia (SCA), results from polyglutamine expansion in ataxin-3.
- Pathogenesis involves transcriptional dysregulation, with incomplete genotype-phenotype correlations suggesting additional influencing factors like epigenetics.
- DNA methylation impacts neurodegenerative disorders by regulating gene expression; elevated methylation is noted in other SCAs.
Purpose of the Study:
- To investigate global DNA methylation patterns in individuals with Machado-Joseph disease.
- To determine if global 5-methylcytosine (5-mC) levels differ between MJD mutation carriers and healthy controls.
- To explore potential correlations between methylation levels and clinical/genetic variables in MJD.
Main Methods:
- Quantification of global 5-methylcytosine (5-mC) levels in blood samples.
- Comparison between 33 MJD mutation carriers (patients and preclinical) and 33 matched healthy controls.
- Pilot follow-up analysis of methylation levels over time in a subset of 16 MJD subjects.
Main Results:
- No significant differences were observed in median global 5-mC levels between MJD carriers and controls.
- No correlations were found between global methylation levels and clinical or genetic parameters in MJD.
- Global 5-mC levels remained stable over time in the pilot follow-up group.
Conclusions:
- The study's findings do not support an association between increased global blood methylation and Machado-Joseph disease.
- Global DNA methylation in blood does not appear to be a significant biomarker for MJD.
- Further research may be needed to explore specific regional methylation changes or other epigenetic mechanisms in MJD.
Related Concept Videos
01:37Epigenetic Regulation
X-chromosome...
02:30Genomic Imprinting and Inheritance
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
02:59Animal Mitochondrial Genetics