Epimutations in Human Disease

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Abstract
Epigenetics is the study of genes during development. Gene expression states are set by transcriptional activators and repressors and locked in by cell-heritable chromatin states. Inappropriate expression or repression of genes can change developmental trajectories and result in disease. Aberrant chromatin states leading to aberrant gene expression patterns (epimutations) have been detected in several recognizable syndromes as well as in cancer. They can occur secondary to a DNA mutation in a cis- or trans-acting factor, or as a “true” or primary epimutation in the absence of any DNA sequence change. Primary epimutations often occur after fertilization and lead to somatic mosaicism. It has been estimated that the rate of primary epimutations is one or two orders of magnitude greater than somatic DNA mutation. Therefore, the contribution of epimutations to human disease is probably underestimated.