Feinberg Andrew P
Department of Medicine and Center for Epigenetics, Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, Maryland 21205, USA.
Nature. 2007 May 24;447(7143):433-40. doi: 10.1038/nature05919.
It is becoming clear that epigenetic changes are involved in human disease as well as during normal development. A unifying theme of disease epigenetics is defects in phenotypic plasticity--cells' ability to change their behaviour in response to internal or external environmental cues. This model proposes that hereditary disorders of the epigenetic apparatus lead to developmental defects, that cancer epigenetics involves disruption of the stem-cell programme, and that common diseases with late-onset phenotypes involve interactions between the epigenome, the genome and the environment. Increased understanding of epigenetic-disease mechanisms could lead to disease-risk stratification for targeted intervention and to targeted therapies.
越来越明显的是,表观遗传变化不仅参与人类疾病,也在正常发育过程中发挥作用。疾病表观遗传学的一个统一主题是表型可塑性的缺陷——即细胞响应内部或外部环境线索改变其行为的能力。该模型提出,表观遗传机制的遗传性疾病会导致发育缺陷,癌症表观遗传学涉及干细胞程序的破坏,而具有迟发表型的常见疾病则涉及表观基因组、基因组与环境之间的相互作用。对表观遗传疾病机制的深入了解可能会实现针对干预的疾病风险分层和靶向治疗。