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

当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，以开发更有效的治疗方法。虽然在过去的几年里，IBD的治疗取得了进展，但IBD的病因仍然不清楚。IBD的遗传易感性的存在现在已经得到了很好的证实，并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。迄今为止，两个遗传定位（一个在16号染色体上，第二个在12号染色体上）已在多中心研究中得到证实。在对73个多发性炎症性肠病家族进行基因组扫描的过程中，我们在澳大利亚人群中确定了12号染色体上疾病易感性的新定位。(The这种本土化的重要性在英国和美国的家庭中得到了证实。这种定位与最初描述的定位完全不同，许多基因将这两种定位分开。我们将完善新的本地化的精细规模映射在该地区的本地化，我们最初确定在纯克罗恩病的家庭。在这个阶段，局部化在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）中似乎并不重要，尽管这一发现将被检验。使用最先进的分子遗传学，我们将识别和鉴定相关基因。该项目的意义在于，这种定位对于理解复杂疾病的基础生物化学和遗传学的重要性，在这种复杂疾病中，多个基因以某种尚未定义的方式分离和相互作用。

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.