Identification and characterisation of the genes and pathways in susceptibility to inflammatory bowel disease

当代遗传学面临的最大挑战之一是了解炎症性肠病、多发性硬化症和精神分裂症等复杂疾病的遗传学。该应用程序旨在揭示易感基因和环境触发因素之间复杂的相互作用，共同产生炎症性肠病（IBD）。目前对患病率和发病率的估计表明，可能有3 -4万澳大利亚人患有这些慢性衰弱性疾病，分别被称为克罗恩病和溃疡性结肠炎。克罗恩病的一个易感基因最近已被确定，该项目概述将扩展我们的知识不仅到易感基因本身，而且到与它们相互作用的基因通过级联免疫和炎症事件产生疾病。这项工作是一项大型国际努力的一部分，旨在确定所有IBD易感基因，并建立在澳大利亚IBD家庭登记处的资源基础上。澳大利亚IBD家庭登记处是澳大利亚广泛的家庭登记册，其中有多名成员受到CD或UC的影响。传统的基因定位方法与疾病与正常肠组织以及患者与对照组细胞系中不同基因表达谱的多种分析相结合。验证性研究包括鉴定IBD典型病理性免疫反应中涉及的特定组织和细胞类型，以及可能与表达谱相关的特定患者基因型和-或表型的特征。获得的结果将用于确定IBD易感性的潜在基因，驱动疾病的突变以及最终调节和治疗疾病的治疗靶点。

One of the greatest challenges facing contemporary genetics is to understand the genetics of complex diseases such as inflammatory bowel disease, mutiple sclerosis and schizophrenia. This application seeks to unravel the complex interactions between susceptibility genes and environmental triggers that work together to produce the inflammatory bowel diseases (IBD). Current estimates of the prevalence and incidence suggests that there may be 30-40,000 Australians who suffer from these chronic debiltating set of diseases known separately as Crohn's disease and ulcerative colitis. One susceptibility gene for Crohn's disease has been recently been identified and the project outlined will extend our knowledge not only to the susceptibility genes themselves, but also to the genes that interact with them to produce the disease via a cascade of immune and inflammatory events. This work is part of a large international effort to identify all IBD susceptibility genes and builds on the resources of the Australian IBD Familiy Register- an Australia wide register of families in which multiple members are affected by CD or UC. A traditional gene mapping approach is used in concert with mutiple analyses of different gene expression profiles in disease versus normal bowel tissues as well as in cell lines from patients versus controls. Validation studies include identification of the particular tissues and cell types that are involved in the pathological immune response typical of IBD as well as characterisation of specific patient genotypes and- or phenotypes that may correlate with expression profiles. Results obtained will be used to identify genes underlying IBD susceptibility, the mutations that drive the disease and eventually therapeutic targets for modulation and treatment of disease.