DNA Methylation and Trinucleotide Repeat Expansion Diseases

Pook, Mark A.

doi:10.5772/34169

Cited by 3 publications

(2 citation statements)

References 95 publications

(112 reference statements)

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“…This heterogeneity might produce a high variability in the results. Our results agree with different studies in which different authors show that global DNA methylation changes with aging and that these changes are linked to certain neurodegenerative diseases [24,[26][27][28]. Different authors have described a decrease of 5mC or 5hmC levels in brains and blood samples in different animal models and human samples of these disorders [28][29][30][31][32][33][34][35].…”

Section: Discussionsupporting

confidence: 92%

DNA Methylation in Neurodegenerative and Cerebrovascular Disorders

Martínez-Iglesias

Carrera

Carril

et al. 2020

IJMS

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DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer’s, Parkinson’s or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer’s disease mouse model (3xTg-AD). Our results show that both global methylation (n = 141) and hydroxymethylation (n = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia (n = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD (n = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.

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Section: Discussionsupporting

confidence: 92%

DNA Methylation in Neurodegenerative and Cerebrovascular Disorders

Martínez-Iglesias

Carrera

Carril

et al. 2020

IJMS

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“…Methylation of repeat units adds another dimension of variability to these elements; locally it may regulate the function of individual units, and globally it can change the effective number of units in an array, altering its activity. In this context, methylation levels of repetitive DNA have been shown to be correlated with repeat-related genetic diseases (Balog et al 2012;Pook 2012), as well as various types of cancer and their severity (Hansen et al 2011). One example of a repeat-related disease, addressed in this work, is facioscapulohumeral muscular dystrophy (FSHD), one of the most common forms of muscular dystrophy, affecting approximately one in 7000-20,000 individuals (INSERM and French Ministry of Health 2008;Sacconi et al 2013;Gaillard et al 2014;Huichalaf et al 2014).…”

mentioning

confidence: 98%

Long-read single-molecule maps of the functional methylome

et al. 2019

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We report on the development of a methylation analysis workflow for optical detection of fluorescent methylation profiles along chromosomal DNA molecules. In combination with Bionano Genomics genome mapping technology, these profiles provide a hybrid genetic/epigenetic genome-wide map composed of DNA molecules spanning hundreds of kilobase pairs. The method provides kilobase pair-scale genomic methylation patterns comparable to whole-genome bisulfite sequencing (WGBS) along genes and regulatory elements. These long single-molecule reads allow for methylation variation calling and analysis of large structural aberrations such as pathogenic macrosatellite arrays not accessible to single-cell second-generation sequencing. The method is applied here to study facioscapulohumeral muscular dystrophy (FSHD), simultaneously recording the haplotype, copy number, and methylation status of the disease-associated, highly repetitive locus on Chromosome 4q.

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The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases

2014

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DNA methylation primarily occurs within human cells as a 5-methylcytosine (5mC) modification of the cytosine bases in CpG dinucleotides. 5mC has proven to be an important epigenetic mark that is involved in the control of gene transcription for processes such as development and differentiation. However, recent studies have identified an alternative modification, 5-hydroxymethylcytosine (5hmC), which is formed by oxidation of 5mC by ten-eleven translocation (TET) enzymes. The overall levels of 5hmC in the mammalian genome are approximately 10% of 5mC levels, although higher levels have been detected in tissues of the central nervous system (CNS). The functions of 5hmC are not yet fully known, but evidence suggests that 5hmC may be both an intermediate product during the removal of 5mC by passive or active demethylation processes and also an epigenetic modification in its own right, regulating chromatin or transcriptional factors involved in processes such as neurodevelopment or environmental stress response. This review highlights our current understanding of the role that 5hmC plays in neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), fragile X-associated tremor/ataxia syndrome (FXTAS), Friedreich ataxia (FRDA), Huntington's disease (HD), and Parkinson's disease (PD).

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DNA Methylation and Trinucleotide Repeat Expansion Diseases

Cited by 3 publications

References 95 publications

DNA Methylation in Neurodegenerative and Cerebrovascular Disorders

DNA Methylation in Neurodegenerative and Cerebrovascular Disorders

Long-read single-molecule maps of the functional methylome

The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases

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