DNA Methylation and Trinucleotide Repeat Expansion Diseases

DNA methylation of CpG dinucleotides is essential for mammalian development, X inactivation, genomic imprinting, and may also be involved in immobilization of transposons and the control of tissue-specific gene expression (Bird & Wolffe, 1999). The common theme in each of these processes is gene silencing. Therefore, gene silencing is a major biological consequence of DNA methylation. As such, DNA methylation can play a very important role in human disease. For example, DNA methylation-induced silencing of tumour suppressor genes can result in cancer, while gain or loss of DNA methylation can produce loss of genomic imprinting in diseases such as Beckwith-Wiedermann syndrome (BWS), Prader-Willi syndrome (PWS) or Angelman syndrome (AS) (Robertson, 2005). Yet another group of diseases where DNA methylation has a prominent role to play in disease aetiology and pathology is that of the inherited trinucleotide repeat (TNR) expansion diseases.