Identification and characterisation of the genes and pathways in susceptibility to inflammatory bowel disease

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One of the greatest challenges facing contemporary genetics is to understand the genetics of complex diseases such as inflammatory bowel disease, mutiple sclerosis and schizophrenia. This application seeks to unravel the complex interactions between susceptibility genes and environmental triggers that work together to produce the inflammatory bowel diseases (IBD). Current estimates of the prevalence and incidence suggests that there may be 30-40,000 Australians who suffer from these chronic debiltating set of diseases known separately as Crohn's disease and ulcerative colitis. One susceptibility gene for Crohn's disease has been recently been identified and the project outlined will extend our knowledge not only to the susceptibility genes themselves, but also to the genes that interact with them to produce the disease via a cascade of immune and inflammatory events. This work is part of a large international effort to identify all IBD susceptibility genes and builds on the resources of the Australian IBD Familiy Register- an Australia wide register of families in which multiple members are affected by CD or UC. A traditional gene mapping approach is used in concert with mutiple analyses of different gene expression profiles in disease versus normal bowel tissues as well as in cell lines from patients versus controls. Validation studies include identification of the particular tissues and cell types that are involved in the pathological immune response typical of IBD as well as characterisation of specific patient genotypes and- or phenotypes that may correlate with expression profiles. Results obtained will be used to identify genes underlying IBD susceptibility, the mutations that drive the disease and eventually therapeutic targets for modulation and treatment of disease.