Identification of Novel Genes Influencing Development of Type 2 Diabetes

2型糖尿病通常与肥胖有关，通常是影响个人能量代谢的更广泛障碍的一部分。自1981年以来，澳大利亚受影响的2型糖尿病患者人数增加了两倍，而且还在增加。除了个人痛苦之外，这还给该国带来了重大的公共卫生负担(每年约30亿美元)。目前可用的基于生活方式的治疗和药物治疗不足以控制日益增加的受影响个人数量。不幸的是，人们对疾病的原因知之甚少，尽管众所周知遗传因素很重要，换句话说，它是在家族中遗传的。该项目建议确定其中的一些因素(基因)以及它们如何导致疾病。使用DNA上的分子标记(如DNA指纹)，我们先前已经发现，12号染色体上的一个小区域可能携带一个或多个这些疾病基因。但该地区有100多个基因。为了帮助选择最有可能的候选基因首先进行测试，我们开发了一个自动计算机数据库搜索程序，根据已知的基因对基因进行排序。我们还在一大群人中采取了大量的生理措施。其中一些指标由相同的12号染色体区域控制--因此，为了提高我们快速找到基因的机会，我们将研究那些在糖尿病患者和非糖尿病患者之间变化最大的基因。在这个项目中，我们将根据生理指标的变化和已知的情况，研究最有可能影响糖尿病的20个基因。成功的发现意味着我们将更多地了解疾病发展的机制，并能够更好地开发新的治疗和预防方法。如果这些基因都不是罪魁祸首，我们将继续检查下一组可能涉及的基因，以此类推，直到我们成功。

Type 2 diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individual's energy metabolism. The number of affected people with type 2 diabetes has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies are inadequate to control the increasing numbers of affected individuals. Unfortunately the cause of disease is poorly understood, although genetic factors are known to be important, in other words it runs in the family. This project proposes to identify some of these factors (genes) and how they contribute to the disease. Using molecular flags on the DNA (like DNA fingerprinting) we have previously found that a small region on chromosome 12 is likely to carry one or more of these disease genes. But there are over 100 genes in the region. To help choose the most likely candidates first for testing, we have developed an automated computer database searching program ranked the genes based on what is already known about them. We have also taken a large number of physiological measures in a large group of people. Some of these measures are controlled by the same chromosome 12 region - thus to improve our chances of finding the genes quickly we will look at those that change the most between people with diabetes and people without diabetes. In this project we shall investigate the 20 genes most likely affect diabetes based on changes in physiological measures and what is already known about them. A successful finding means we will know more about the mechanism of disease development and be able to better develop new therapies for treatment and prevention. If none of these genes are the culprit, we would continue examination of the next set of genes likely to be involved and so on until we are successful.