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------来源：生物谷
全基因组关联研究(GWASs)表明，若干基因与1-型糖尿病(T1D)和其他常见疾病相关，但在多数情况下，DNA变化影响疾病风险的机制还远不清楚。现在，在大鼠基因组研究方面的最新进展使得系统性遗传研究方法成为可能，它应可帮助揭示疾病与基因功能之间的联系。
利用跨越七种不同类型大鼠组织的基因表达研究结果，结合GWASs和人类遗传学方法，Heinig等人现在识别出，由“干扰素调控因子-7” (IRF7)驱动的炎症网络是1-型糖尿病的一个贡献因子。
他们还将先天病毒响应通道和巨噬细胞牵涉进了疾病的病因学中。这项研究表明了一个问题，即跨越不同物种的共同表达网络何以能提供基因的功能注解，这些注解可被用来揭示GWASs没有检测到的、影响较小的常见遗传变异的信号。（生物谷Bioon.com）
延伸阅读：
Circulation Res.：可提前10年预测糖尿病的新血检
据国外媒体9月19日报道，美国《循环研究》杂志刊登一项最新研究宣称，一种新型血检可以比目前诊断措施提前10年预测出糖尿病风险。
英国科学家在伯明翰英国科学节上宣称，这种血液测试预测10年后2型糖尿病风险的准确率可达50%以上。其原理是，识别血液中的遗传分子“微RNA”（MiR，又译“小分子RNA”）。该分子有助于确定患者心脏病和血管疾病的风险。
研究者表示，在英国，目前现有的约200万糖尿病患者中，这项测试还可以识别出哪些人已经或将会出现糖尿病并发症，比如，血管损伤导致的心脏病、中风及血液循环系统问题等。
新研究主持人伦敦国王学院曼纽尔·梅耶博士表示，希望这种新型MiR血检能与传统诊疗方法相结合，以提高糖尿病及其并发症的确诊准确率。新型MiR血检费用估计为2英镑（约合21元人民币）。这一血检的最大优势是，可以直接测试出糖尿病对血管造成的损伤情况。>>阅读全文
原文摘要：
Nature doi:10.1038/nature09386
A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
Matthias Heinig, Enrico Petretto, Chris Wallace, Leonardo Bottolo, Maxime Rotival, Han Lu, Yoyo Li, Rizwan Sarwar, Sarah R. Langley, Anja Bauerfeind, Oliver Hummel, Young-Ae Lee, Svetlana Paskas, Carola Rintisch, Kathrin Saar, Jason Cooper, Rachel Buchan, Elizabeth E. Gray, Jason G. Cyster, Cardiogenics Consortium, Jeanette Erdmann, Christian Hengstenberg, Seraya Maouche, Willem H. Ouwehand, Catherine M. Rice, Nilesh J. Samani, Heribert Schunkert, Alison H. Goodall, Herbert Schulz, Helge G. Roider, Martin Vingron, Stefan Blankenberg, Thomas Münzel, Tanja Zeller, Silke Szymczak, Andreas Ziegler, Laurence Tiret, Deborah J. Smyth, Michal Pravenec, Timothy J. Aitman, Francois Cambien, David Clayton, John A. Todd, Norbert Hubner & Stuart A. Cook
Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches1, 2. Here we report the use of integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF73)-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein–Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration4, 5, is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)—a macrophage-associated autoimmune disease—than randomly selected immune response genes (P = 8.85?×?10?6). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0?×?10?10; odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D. |
