Comparative (Computational) Analysis of the DNA Methylation Status of Trinucleotide Repeat Expansion Diseases

Previous studies have examined DNA methylation in different trinucleotide repeat diseases. We have combined this data and used a pattern searching algorithm to identify motifs in the DNA surrounding aberrantly methylated CpGs found in the DNA of patients with one of the three trinucleotide repeat (TNR) expansion diseases: fragile X syndrome (FRAXA), myotonic dystrophy type I (DM1), or Friedreich's ataxia (FRDA). We examined sequences surrounding both the variably methylated (VM) CpGs, which are hypermethylated in patients compared with unaffected controls, and the nonvariably methylated CpGs which remain either always methylated (AM) or never methylated (NM) in both patients and controls. Using the J48 algorithm of WEKA analysis, we identified that two patterns are all that is necessary to classify our three regions CCGG∗ which is found in VM and not in AM regions and AATT∗ which distinguished between NM and VM + AM using proportional frequency. Furthermore, comparing our software with MEME software, we have demonstrated that our software identifies more patterns than MEME in these short DNA sequences. Thus, we present evidence that the DNA sequence surrounding CpG can influence its susceptibility to be de novo methylated in a disease state associated with a trinucleotide repeat.

• Publication year

  2013

• Venue

  Journal of Nucleic Acids

• Publication date

  2013-12-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1155/2013/689798PMID 24455203PMCID 3884633
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Supplementary Table 1

  2015cited by this paper
• Data Mining Practical Machine Learning Tools and Techniques

  2014cited by this paper
• Genome-wide DNA methylation profiles in hematopoietic stem and progenitor cells reveal overrepresentation of ETS transcription factor binding sites

  2012cited by this paper
• DNA Methylation and Trinucleotide Repeat Expansion Diseases

  2012influential reference
• Prediction of Epigenetic Target Sites by Using Genomic DNA Sequence

  2011cited by this paper
• A natural antisense transcript at the Huntington's disease repeat locus regulates HTT expression.

  2011influential reference
• Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production.

  2011cited by this paper
• Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues.

  2011influential reference
• Interplay between microRNAs and the epigenetic machinery: an intricate network.

  2010cited by this paper
• A comparative study for characterisation and prediction of tissue-specific DNA methylation of CpG islands in chromosomes 6, 20 and 22

  2010influential reference
• Repeat instability as the basis for human diseases and as a potential target for therapy

  2010cited by this paper
• Predicting DNA methylation status using word composition

  2010influential reference
• A multifactorial signature of DNA sequence and polycomb binding predicts aberrant CpG island methylation.

  2009cited by this paper
• Epigenetic Silencing in Friedreich Ataxia Is Associated with Depletion of CTCF (CCCTC-Binding Factor) and Antisense Transcription

  2009influential reference
• Dnmt3/transcription factor interactions as crucial players in targeted DNA methylation

  2009cited by this paper
• The FMR1 gene and fragile X‐associated tremor/ataxia syndrome

  2009cited by this paper
• Methylation-sensitive Regulation of TMS1/ASC by the Ets Factor, GA-binding Protein-α*

  2009cited by this paper
• A distinct DNA-methylation boundary in the 5'- upstream sequence of the FMR1 promoter binds nuclear proteins and is lost in fragile X syndrome.

  2009influential reference
• Computational epigenetics

  2008influential reference
• Prediction of Genomic Methylation Status on CpG Islands Using DNA Sequence Features

  2008cited by this paper
• Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex

  2008cited by this paper
• Bidirectional Transcription Directs Both Transcriptional Gene Activation and Suppression in Human Cells

  2008cited by this paper
• The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues.

  2007cited by this paper
• An antisense transcript spanning the CGG repeat region of FMR1 is upregulated in premutation carriers but silenced in full mutation individuals.

  2007cited by this paper
• Serum response factor binding sites differ in three human cell types.

  2007cited by this paper
• Heterochromatin revisited

  2007cited by this paper
• Myotonic dystrophies type 1 and 2: a summary on current aspects.

  2006cited by this paper
• DNA motifs associated with aberrant CpG island methylation.

  2006influential reference
• Genomic DNA methylation: the mark and its mediators.

  2006influential reference
• Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8

  2006influential reference
• Antisense transcription and heterochromatin at the DM1 CTG repeats are constrained by CTCF.

  2005influential reference
• Isolation and Characterization of Biochemical Properties of DNA Methyltransferase FauIA Modifying the Second Cytosine in the Nonpalindromic Sequence 5′-CCCGC-3′

  2005cited by this paper
• Fragile X syndrome and Friedreich's ataxia: two different paradigms for repeat induced transcript insufficiency.

  2001cited by this paper
• CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus

  2001cited by this paper
• Data mining

  1997cited by this paper
• Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion

  1996cited by this paper
• Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member.

  1992influential reference
• Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox.

  1991influential reference
• Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome.

  1991cited by this paper
• Digital Commons@Becker

  year unknowncited by this paper

• Distrofia miotónica tipo 1 y embarazo. Asesoramiento genético. Presentación de caso

  2025cites this paper
• Using gut microbiota as a diagnostic tool for colorectal cancer: machine learning techniques reveal promising results.

  2023cites this paper
• Comparative analysis of weka-based classification algorithms on medical diagnosis datasets

  2023cites this paper
• Cardiovascular Research in Friedreich Ataxia

  2022cites this paper
• Using CatBoost algorithm to identify middle-aged and elderly depression, national health and nutrition examination survey 2011-2018.

  2021cites this paper
• Detection of Colorectal Carcinoma Based on Microbiota Analysis Using Generalized Regression Neural Networks and Nonlinear Feature Selection

  2020cites this paper
• Final Report Summary-EFACTS ( European Friedreich ' s Ataxia Consortium for Translational Studies )

  2020cites this paper
• Beyond Borders: Myotonic Dystrophies – A European Perception

  2019cites this paper
• Myotonic Dystrophy—A Progeroid Disease?

  2018cites this paper
• Expanded [CCTG]n repetitions are not associated with abnormal methylation at the CNBP locus in myotonic dystrophy type 2 (DM2) patients.

  2018cites this paper
• Systematic evaluation of supervised classifiers for fecal microbiota-based prediction of colorectal cancer

  2017cites this paper
• Genome wide classification and characterisation of CpG sites in cancer and normal cells

  2016cites this paper
• Repeat DNA in genome organization and stability.

  2015cites this paper
• Muscle wasting in myotonic dystrophies: a model of premature aging

  2015cites this paper
• Genomics and Machine Learning for Taxonomy Consensus: The Mycobacterium tuberculosis Complex Paradigm

  2015cites this paper
• Identifying biological associations from high-throughput datasets

  2015cites this paper