来自耶鲁大学的研究人员通过大量患者的DNA样本发现了与炎症性肠病IBD有关的71个新基因区域,揭示了细菌感染与IBD疾病演化之间的关系。

-2012年11月1日《自然》

中文翻译


【题目】宿主-微生物间的互作塑造了炎症性肠病的遗传架构

【译文】 克罗恩病和溃疡性结肠炎是炎症性肠病(IBD)两种最普遍的形式,影响着超过250万欧洲血统的人群,而且在其他人群中发病率也逐年上升。全基因组关联研究和对这两种疾病作为单个表型的后续荟萃分析已经确定在它们发病中以一种先前未知的机制发挥作用,如自体吞噬作用,并且表明一些IBD座位与其他炎症性疾病共享。本研究通过对克罗恩病和溃疡性结肠炎全基因组关联筛选的荟萃分析以及随后对结合超过75000例患者和健康对照显著发现的证实拓展了相关通路的知识。我们为共163个IBD位点鉴定到71个具有基因组范围显著性阈值的相关性。大多数位点有助于两种表型,而且定向(人类历史中一直利于一种等位基因)和平衡(人群中有利于两种等位基因的保存)的选择效应比较明显。许多IBD位点也存在于其他免疫介导的疾病中,大多数是强直性脊柱炎和银屑病。我们也观察到在IBD敏感位点和分支杆菌感染之间的大量的基因重叠。基因共表达网络分析突出了这种关系,即宿主对分支杆菌应答和那些易感IBD之间的共享通路。

英文原稿


[Title]: Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

[Authors]:Luke Jostins,1, 81 Stephan Ripke,2, 3, 81 Rinse K. Weersma,4 Richard H. Duerr,5, 6 Dermot P. McGovern,7, 8 Ken Y. Hui,9 James C. Lee,10 L. Philip Schumm,11 Yashoda Sharma,12 Carl A. Anderson,1 Jonah Essers,13 Mitja Mitrovic,14, 15 Jeffrey C. Barrett1, 81 & Judy H Cho9, 12, 81 et al.

[Abstract]:Crohn’s disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

原文地址

http://www.nature.com/nature/journal/v491/n7422/full/nature11582.html

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