Genetic Dissection of a QTL Influencing the Development of Type 2 Diabetes and the Metabolic Syndrome.

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Diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individuals metabolism. These other factors include high blood pressure and the control of fats (eg cholesterol), and sugars (glucose) in the blood stream. Physicians have noted that these abnormalities often cluster together in individuals and have called it the metabolic syndrome, the main long term implication of which is to increase a persons risk of developing heart disease and disorders in blood circulation. The number of affected people with one the major components of the metabolic syndrome, 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 appear 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 3 is likely to carry one or more of these disease genes. But there are over 100 genes in the region, so to help choose the most likely candidates first for testing, we have developed an automated computer database searching program that narrowed the list to the six most likely genes. This project will determine which if any of these genes are involved. 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.