Characterisation of a new localisation for susceptibility to inflammatory bowel disease on chromosome 12

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One of the greatest challenges facing contemporary gastroenterology is to understand the causes of the inflammatory bowel diseases in order to develop more effective therapies. Although there have been advances in treatment over the last few years, the causes of IBD are still not known. The existence of a genetic predisposition to IBD is now well established, and there is strong evidence that the disease is the result of the interaction of a number of different genes. To date, two genetic localisations (one on chromosome 16 and a second on chromosome 12) have been confirmed in multicentre studies. We have identified a novel localisation for disease susceptibility on chromosome 12 in the Australian population during the course of a genome scan on 73 multiplex inflammatory bowel disease families. (The importance of this localisation has been confirmed in English and American families.) This localisation is quite separate from that originally described and many genes separate the two localisations. We will refine the new localisation by fine scale mapping in the region of the localisation that we originally identified in pure Crohn's disease families. At this stage, the localisation appears not to be important in families suffering from ulcerative colitis or in families in which both CD and UC occurs (known as mixed families), though this finding will be tested. Using state of the art molecular genetics, we will then identify and characterise the gene involved. The significance of this project lies in the importance of this localisation to the understanding of underlying biochemistry and genetics of a complex disease in which multiple genes are segregating and interacting in, some as yet undefined manner.