The genetics of inflammatory bowel disease in Ashkenazi Jewish extended multiplex kindreds
Professor Tony Segal - Division of Medicine
Irwin Joffe Memorial Fellowship
Description of Project:
The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are chronic inflammatory diseases predominantly affecting the gastrointestinal tract. They are of unknown aetiology; however, there is a significant genetic component. A multitude of studies have identified common risk variants associated with these diseases; however, they only account for a proportion of the disease heritability. The study of large families with many affected individuals is theoretically a powerful method for identifying rare disease causing variants that might contribute to this ‘missing heritability’. To date, this approach has not been successfully employed in IBD owing, in part, to the moderate size of families identified. This project involves the ascertainment, phenotypic and genomic characterisation of two extended multiplex Ashkenazi Jewish kindreds with over 50 and 25 cases of IBD, respectively, including the utilisation of linkage and exome sequencing with a view to novel variant identification and the development of computational methods for reconstructing haplotype flow information across extended pedigrees and assessing the empirical significance of pedigree exome sequence data.