Horsthemke B
Institut für Humangenetik, Universitätsklinikum Essen, Germany.
Curr Top Microbiol Immunol. 2006;310:45-59. doi: 10.1007/3-540-31181-5_4.
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.
表观遗传学是对发育过程中基因的研究。基因表达状态由转录激活因子和抑制因子设定，并通过细胞可遗传的染色质状态锁定。基因的不适当表达或抑制会改变发育轨迹并导致疾病。在几种可识别的综合征以及癌症中都检测到了导致异常基因表达模式（表观突变）的异常染色质状态。它们可能继发于顺式或反式作用因子中的DNA突变，或者在没有任何DNA序列变化的情况下作为“真正的”或原发性表观突变出现。原发性表观突变通常在受精后发生，并导致体细胞镶嵌现象。据估计，原发性表观突变的发生率比体细胞DNA突变高一个或两个数量级。因此，表观突变对人类疾病的贡献可能被低估了。
