Australian scientists have discovered that a tiny genetic irregularity, which boosts the expression of a key gene, may lead to the development of Type 1 diabetes.

Type 1 diabetes is an autoimmune disease, where the body attacks and destroys its own insulin-producing cells. A serious illness, leading to many complications, it often starts in childhood or teenage years.

While there is no cure yet, prevention therapies are on the horizon, making the development of reliable screening tools critical. And that's where the current finding has promise.

PhD student Helen McGuire and Dr Cecile King from Sydney's Garvan Institute of Medical Research isolated the irregular DNA from mice that spontaneously develop Type 1 diabetes. They also demonstrated that it increases production of very high levels of the immune stimulating molecule interleukin 21 (IL-21). Their findings are published in the Proceedings of the National Academy of Sciences (PNAS), now online.

The genetic irregularity occurs in the 'promoter region' of the IL-21 gene. In the world of genetics, the promoter region operates like the fuse on a bomb. In the same way as you need to light the fuse to set off a bomb, you need to activate the promoter region to transcribe a gene.

"Our study demonstrates that a small defect in the IL-21 promoter region is associated with the development of Type 1 diabetes in this model," said project leader Dr King.

"The small genetic mutation boosts production of IL-21, a molecule that plays a role in many autoimmune diseases including Type 1 diabetes, rheumatoid arthritis, lupus and celiac disease."

By a meticulous process of elimination, Helen McGuire isolated the defect, spanning only two 'base pairs' of DNA. First, she chopped up the promoter region into smaller and smaller parts, finally locating what she believed to be the anomaly.

To check, she spliced the suspected fragment into a healthy IL-21 gene and IL-21 was produced in abundance. Conversely, its removal from a diabetes-prone IL-21 gene led to IL-21 production slowing down.

"Our next step will be to analyse the IL-21 promoter region in humans with Type 1 diabetes to see if there's an analogous defect," said King. "If there is, then it becomes a predictive marker."

"It's important to remember that everyone has a similar genetic makeup. Our health depends on how our genes are regulated - and that can vary enormously."

ABOUT GARVAN
The Garvan Institute of Medical Research was founded in 1963.  Initially a research department of St Vincent's Hospital in Sydney, it is now one of Australia's largest medical research institutions with nearly 500 scientists, students and support staff. Garvan's main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan's mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan's discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.

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