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Epigenetic changes and non-coding expanded repeats Nakamori M; Thornton CNeurobiol Dis 2010[Jul]; 39 (1): 21-7Many neurogenetic disorders are caused by unstable expansions of tandem repeats. Some of the causal mutations are located in non-protein-coding regions of genes. When pathologically expanded, these repeats can trigger focal epigenetic changes that repress the expression of the mutant allele. When the mutant gene is not repressed, the transcripts containing the expanded repeat can give rise to a toxic gain-of-function by the mutant RNA. These two mechanisms, heterochromatin-mediated gene repression and RNA dominance, produce a wide range of neurodevelopmental and neurodegenerative abnormalities. Here we review the mechanisms of gene dysregulation induced by non-coding repeat expansions, and early indications that some of these disorders may prove to be responsive to therapeutic intervention.|*Repetitive Sequences, Nucleic Acid[MESH]|Animals[MESH]|Chromosome Disorders/genetics/metabolism/physiopathology[MESH]|Epigenesis, Genetic/*genetics[MESH]|Heredodegenerative Disorders, Nervous System/*genetics/metabolism/physiopathology[MESH]|Humans[MESH]|Mutation/genetics[MESH] |
