Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Nucleic Acids Res. 2018 Jan 4;46(D1):D92-D99. doi: 10.1093/nar/gkx918.
De novo mutations (DNMs) have been shown to be a major cause of severe early-onset genetic disorders such as autism spectrum disorder and intellectual disability. Over one million DNMs have been identified in developmental disorders by next generation sequencing, but linking these DNMs to the genes that they impact remains a challenge, as the majority of them are embedded in non-coding regions. As most developmental diseases occur in the early stages of development or during childhood, it is crucial to clarify the details of epigenetic regulation in early development in order to interpret the mechanisms underlying developmental disorders. Here, we develop EpiDenovo, a database that is freely available at http://www.epidenovo.biols.ac.cn/, and which provides the associations between embryonic epigenomes and DNMs in developmental disorders, including several neuropsychiatric disorders and congenital heart disease. EpiDenovo provides an easy-to-use web interface allowing users rapidly to find the epigenetic signatures of DNMs and the expression patterns of the genes that they regulate during embryonic development. In summary, EpiDenovo is a useful resource for selecting candidate genes for further functional studies in embryonic development, and for investigating regulatory DNMs as well as other genetic variants causing or underlying developmental disorders.
从头突变（DNMs）已被证明是导致自闭症谱系障碍和智力障碍等严重早发性遗传疾病的主要原因。通过下一代测序，已经在发育障碍中发现了超过 100 万个 DNMs，但将这些 DNMs 与它们影响的基因联系起来仍然是一个挑战，因为它们中的大多数嵌入在非编码区域中。由于大多数发育性疾病发生在发育早期或儿童期，因此阐明早期发育中表观遗传调控的细节对于解释发育障碍的机制至关重要。在这里，我们开发了 EpiDenovo，一个可在 http://www.epidenovo.biols.ac.cn/ 免费获取的数据库，该数据库提供了发育障碍中胚胎表观基因组和 DNMs 之间的关联，包括几种神经精神疾病和先天性心脏病。EpiDenovo 提供了一个易于使用的 Web 界面，允许用户快速找到 DNMs 的表观遗传特征，以及它们在胚胎发育过程中调控的基因的表达模式。总之，EpiDenovo 是一个有用的资源，可用于选择候选基因进行胚胎发育的进一步功能研究，以及研究导致或潜在发育障碍的调节性 DNMs 和其他遗传变异。
