Fine scale mapping and identification of the IBD1 gene on chromsosome 16

现代胃肠病学面临的最大挑战之一是了解炎症性肠病(IBD)的病因。对IBD的患病率、发病率和成本的研究表明，这些疾病在澳大利亚有相当大的影响。患者平均每年失去13天以上的工作时间，在医院，IBD住院患者占总入院人数的7%，占总卧床天数的10%，平均每次入院费用为2600美元。我们估计可能有超过10,000名澳大利亚人患有IBD。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，这种疾病是复杂的，是许多不同基因相互作用的结果。到目前为止，16号染色体上的一个遗传定位已经在几个不同的人群中建立，我们已经确认了这个定位在澳大利亚人群中的重要性。我们将通过鉴定和研究16号染色体着丝粒周围区域新标记的遗传，通过精细的比例作图来进一步完善定位。然后，我们将使用几种互补的方法来识别和描述基因本身，这些方法依赖于疾病组织和正常组织在分子水平上的差异。这项工作是确定所有IBD易感基因的国际努力的一部分。一旦实现了这一点，就可以确定解释基因、其蛋白质产物和环境触发因素之间相互作用的方法。只有了解了这些相互作用的机制，才有可能在理解疾病病因学的基础上进行合理的治疗。

One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases (IBD). Studies on the prevalence, incidence and cost of IBD indicate that these diseases have considerable impact in Australia. On average, patients lose more than 13 days from work each year, and in hospital, IBD in-patients accounted for 7% of total admissions and 10% of total bed days at an average cost of $2600 per admission. We estimate that there may be more than 10,000 Australians who suffer from IBD. The existence of a genetic predisposition to IBD is now well established, and there is strong evidence that the disease is complex, resulting from the interaction of a number of different genes. To date, one genetic localisation on chromosome 16 has been established in several different populations, and we have confirmed the importance of this localisation in the Australian population. We will further refine the localisation by fine scale mapping in the pericentromeric region of chromosome 16 by identifying and studying the inheritance of novel markers in the region. We will then identify and characterise the gene itself using several complementary appoaches that rely on differences at the molecular level between disease and normal tissue. This work is part of the international effort to identify all IBD susceptibility genes. Once that is achieved, approaches to explaining the interactions between the genes, their protein products and environmental triggers can be determined. Only when the mechanisms of these interactions are understood will the expectation of rational therapies based on an understanding of disease aetiology be possible.