Mackay Deborah J G, Temple I Karen
Faculty of Medicine, University of Southampton, Duthie Building (MP808), Southampton University Hospital, Tremona Road, Southampton SO16 6YD, UK.
Faculty of Medicine, University of Southampton, Duthie Building (MP808), Southampton University Hospital, Tremona Road, Southampton SO16 6YD, UK.
Eur J Med Genet. 2017 Nov;60(11):618-626. doi: 10.1016/j.ejmg.2017.08.014. Epub 2017 Aug 14.
Epigenetic regulation orchestrates gene expression with exquisite precision, over a huge dynamic range and across developmental space and time, permitting genomically-homogeneous humans to develop and adapt to their surroundings. Every generation, these epigenetic marks are re-set twice: in the germline, to enable differentiation of sperm and eggs, and at fertilisation, to create the totipotent zygote that then begins growth and differentiation into a new human. A small group of genes evades the second, zygotic wave of epigenetic reprogramming, and these genes retain an epigenetic 'imprint' of the parent from whom they were inherited. Imprinted genes are (as a general rule) expressed from one parental allele only. Some imprinted genes are critical regulators of growth and development, and thus disruption of their normal monoallelic expression causes congenital imprinting disorders, with clinical features impacting growth, development, behaviour and metabolism. Imprinting disorders as a group have characteristics that challenge diagnosis and management, including clinical and molecular heterogeneity, overlapping clinical features, somatic mosaicism, and multi-locus involvement. New insights into the biology and epigenomics of the early embryo offers new clues about the origin and importance of imprinting disorders.
表观遗传调控以极高的精度协调基因表达，其作用范围广泛、跨越发育时空，使基因组相同的人类得以发育并适应周围环境。每一代中，这些表观遗传标记会重新设定两次：一次在生殖细胞系中，以使精子和卵子分化；另一次在受精时，形成全能受精卵，随后该受精卵开始生长并分化成一个新个体。一小部分基因逃避了第二次即合子阶段的表观遗传重编程，这些基因保留了它们所继承的亲本的表观遗传“印记”。印记基因（一般来说）仅从一个亲本等位基因表达。一些印记基因是生长和发育的关键调节因子，因此其正常单等位基因表达的破坏会导致先天性印记障碍，其临床特征会影响生长、发育、行为和代谢。作为一个群体，印记障碍具有一些挑战诊断和管理的特征，包括临床和分子异质性、重叠的临床特征、体细胞镶嵌现象以及多位点受累。对早期胚胎生物学和表观基因组学的新见解为印记障碍的起源和重要性提供了新线索。
