Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, ICTEM 5th floor, Du Cane Road, London, W12 0NN, UK.
Curr Diab Rep. 2019 Nov 21;19(12):145. doi: 10.1007/s11892-019-1230-6.
Common genetic variants that associate with type 2 diabetes risk are markedly enriched in pancreatic islet transcriptional enhancers. This review discusses current advances in the annotation of islet enhancer variants and their target genes.
Recent methodological advances now allow genetic and functional mapping of diabetes causal variants at unprecedented resolution. Mapping of enhancer-promoter interactions in human islets has provided a unique appreciation of the complexity of islet gene regulatory processes and enabled direct association of noncoding diabetes risk variants to their target genes. The recently improved human islet enhancer annotations constitute a framework for the interpretation of diabetes genetic signals in the context of pancreatic islet gene regulation. In the future, integration of existing and yet to come regulatory maps with genetic fine-mapping efforts and in-depth functional characterization will foster the discovery of novel diabetes molecular risk mechanisms.
与 2 型糖尿病风险相关的常见遗传变异在胰腺胰岛转录增强子中明显富集。这篇综述讨论了胰岛增强子变异及其靶基因注释的最新进展。
最近的方法学进展现在允许以空前的分辨率对糖尿病因果变异进行遗传和功能作图。在人类胰岛中对增强子-启动子相互作用的作图提供了对胰岛基因调控过程复杂性的独特认识，并能够将非编码糖尿病风险变异直接与其靶基因相关联。最近改进的人类胰岛增强子注释构成了在胰腺胰岛基因调控背景下解释糖尿病遗传信号的框架。在未来，将现有和即将出现的调控图谱与遗传精细映射工作和深入的功能特征相结合，将促进新的糖尿病分子风险机制的发现。
