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University of Toronto Scarborough
Larry Sawchuk

EpigeneticsThe term epigenetics defines all meiotically and mitotically heritable changes in gene expression that are not coded in the DNA sequence itself Three systems including DNA methylation RNAassociated silencing and histone modification are used to initiate and sustain epigenetic silencing Unravelling the relationships between these component has led to surprising and rapidly evolving new concepts showing how they interact and stabilize each other Fig 1 Disruption of one or other of these interacting systems can lead to inappropriate expression or silencing of genes resulting in epigenetic diseasesMulticellular organisms require mutually reinforcing mechanisms permitting heritable patterns of gene silencing Mutations in genes that affect global epigenetic profiles can give rise to human diseases which can be inherited or somatically acquired Table 1 Interestingly many of these epigenetic abnormalities result in chromosomal alterations and learning disabilitiesSeveral inherited syndromes are due to faulty genomic imprintingdefined as parentspecific monoallelic expression of a genesuch as Angelmans syndrome PraderWilli syndrome and Beckwith Wiedemann syndrome BWS In these conditions an abnormal phenotype is established as a result of the absence of the paternal or maternal copy of an imprinted gene or because of deregulation of an imprinted geneParticular interest has recently been generated by the finding that one of the most common forms of intellectual disability in young girls namely Rett syndrome is due to germline mutations of MeCP2The fact that many human diseases including cancer have an epigenetic aetiology has encouraged the development of a new therapeutic option that might be termed epigenetic therapyEpigenetic disorders give rise to several significant human diseases and the race is on to find therapies that can reverse silencing Sometimes it might be possible to reuse a wildtype embryonic gene in place of a mutated adult gene such as in thalassaemia or sicklecell anaemiaIn addition because multiple genes become methylated in individual cancers80 there is the possibility of hitting many targets with one drug Finally because methylation of CpG islands increases with age39 and could therefore contribute to the development of chronic diseases in addition to cancer there might be benefits in drugs and lifestyle changes that could bring about reversion or slow gradual epigenetic silencingContagion
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