Characterisation of a new localisation for susceptibility to inflammatory bowel disease on chromosome 12

现代胃肠病学面临的最大挑战之一是了解炎症性肠病的原因，以便开发更有效的治疗方法。尽管过去几年在治疗方面取得了进展，但IBD的病因仍不清楚。现在，IBD的遗传易感性已经得到了很好的证实，而且有强有力的证据表明，这种疾病是许多不同基因相互作用的结果。到目前为止，多中心研究已经证实了两个遗传定位(一个在16号染色体上，另一个在12号染色体上)。在对73个多发性炎症性肠病家系进行基因组扫描的过程中，我们在澳大利亚人群的12号染色体上发现了一个新的疾病易感性定位。(这种本地化的重要性在英国和美国家庭中得到了证实。)这一定位与最初描述的完全不同，许多基因将这两个定位分开。我们将通过在我们最初在纯克罗恩病家系中发现的局部化区域的精细比例尺绘图来完善新的局部化。在这个阶段，本地化似乎对患有溃疡性结肠炎的家庭或同时发生CD和UC的家庭(称为混合家庭)并不重要，尽管这一发现将得到检验。利用最先进的分子遗传学，我们将识别和描述涉及的基因。这个项目的意义在于这种定位对理解一种复杂疾病的潜在生化和遗传学的重要性，在这种疾病中，多个基因相互分离和相互作用，其中一些尚未确定。

One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases in order to develop more effective therapies. Although there have been advances in treatment over the last few years, the causes of IBD are still not known. The existence of a genetic predisposition to IBD is now well established, and there is strong evidence that the disease is the result of the interaction of a number of different genes. To date, two genetic localisations (one on chromosome 16 and a second on chromosome 12) have been confirmed in multicentre studies. We have identified a novel localisation for disease susceptibility on chromosome 12 in the Australian population during the course of a genome scan on 73 multiplex inflammatory bowel disease families. (The importance of this localisation has been confirmed in English and American families.) This localisation is quite separate from that originally described and many genes separate the two localisations. We will refine the new localisation by fine scale mapping in the region of the localisation that we originally identified in pure Crohn's disease families. At this stage, the localisation appears not to be important in families suffering from ulcerative colitis or in families in which both CD and UC occurs (known as mixed families), though this finding will be tested. Using state of the art molecular genetics, we will then identify and characterise the gene involved. The significance of this project lies in the importance of this localisation to the understanding of underlying biochemistry and genetics of a complex disease in which multiple genes are segregating and interacting in, some as yet undefined manner.