%0 Journal Article
%T Comparative (Computational) Analysis of the DNA Methylation Status of Trinucleotide Repeat Expansion Diseases
%A Mohammadmersad Ghorbani
%A Simon J. E. Taylor
%A Mark A. Pook
%A Annette Payne
%J Journal of Nucleic Acids
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/689798
%X 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. 1. Introduction DNA methylation involving the addition of a methyl group to a CpG sequence is one of the mechanisms of gene regulation commonly associated with transcriptional repression and is necessary for mammalian development, X inactivation, and genomic imprinting [1]. Gene silencing is a major biological consequence of DNA methylation. The phenomenon is widely reported in genes of both healthy cells, where it assists in regulating gene expression during development, for example, and diseased cells, where it is associated with aberrant gene expression most notably in cancerous cells. One group of diseases in which DNA methylation is reported to have an important role is TNR expansion diseases. Here, we investigate the pattern of sequences in variably methylated (VM) and nonvariably methylated (AM always methylated and NM never methylated) CpG sites of three TNR expansion diseases: FRDA, FRAXA, and DM1 [2]. FRDA is an inherited autosomal recessive neurodegenerative disorder characterised by a homozygous GAA repeat expansion within intron 1 sequence of the FXN gene [3]. The consequence of the expanded GAA repeats is to reduce the expression of the mitochondrial protein frataxin. Typically unaffected individuals have 5¨C32 GAA repeats and affected individuals have 66¨C1700
%U http://www.hindawi.com/journals/jna/2013/689798/