Approach to epigenetic analysis in language disorders.

Language and learning disorders such as reading disability and language impairment are recognized to be subject to substantial genetic influences, but few causal mutations have been identified in the coding regions of candidate genes. Association analyses of single nucleotide polymorphisms have suggested the involvement of regulatory regions of these genes, and a few mutations affecting gene expression levels have been identified, indicating that the quantity rather than the quality of the gene product may be most relevant for these disorders. In addition, several of the candidate genes appear to be involved in neuronal migration, confirming the importance of early developmental processes. Accordingly, alterations in epigenetic processes such as DNA methylation and histone modification are likely to be important in the causes of language and learning disorders based on their functions in gene regulation. Epigenetic processes direct the differentiation of cells in early development when neurological pathways are set down, and mutations in genes involved in epigenetic regulation are known to cause cognitive disorders in humans. Epigenetic processes also regulate the changes in gene expression in response to learning, and alterations in histone modification are associated with learning and memory deficits in animals. Genetic defects in histone modification have been reversed in animals through therapeutic interventions resulting in rescue of these deficits, making it particularly important to investigate their potential contribution to learning disorders in humans.