Our Functional Genomics Approach


Relevance to Type I Diabetes

The purpose of this research consortium is to advance our knowledge of type 1 diabetes and the genetic basis for diabetic complications. This will be achieved by identifying key genes and mutations in people with type 1 diabetes and the complications of renal failure or hypoglycemic unawareness. This will be followed by functional validation of hundreds of these candidate type 1 diabetes complication causing genes and mutations in animal models.

This will be the first study to apply whole genome sequencing to the question of type 1 diabetes complications. It is our objective to make new in-roads into our understanding of the genetic basis for complications in people with type 1 diabetes which we believe will allow identification of novel prognostic markers and new avenues of investigation for novel therapeutic targets.

Why use genomics?

Type 1 diabetes has an enormous impact on the quality of life for the ~140, 000 people in Australia with this disease. In Australia type 1 diabetes is increasing at the rate of ~3% per year, a trend also seen worldwide. Current therapies do not adequately address the root cause of type 1 diabetes or prevent diabetic complications.

The increase in type 1 diabetes has been attributed to interactions between common genetic variants and environment. To date, with the help of genome wide association studies (GWAS), over 40 genetic loci that affect risk of type 1 diabetes have been identified. However these variants do not fully explain the heritability of type 1 diabetes, highlighting the need for alternative strategies and further studies. It is also significant that genes identified by GWAS “hits” may not represent causative alleles.

One alternative strategy is to identify genetic loci that associate with diabetic complications including kidney failure and hypoglycemic unawareness. Further, latest technologies in whole genome sequencing now provide better genome coverage, which when overlayed with GWAS data should allow the discovery of variants in genes near those associated with type 1 diabetes. 


We will utilise whole genome sequencing in combination with state of the art genetic screens to functionally validate, and identify significant disease causing genes and their mutations (see image below). These will provide candidates for further development with respect to diagnostic and therapeutic targets.