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Positional cloning of a susceptibility gene for type 1 diabetes and otherautoimmune diseases on chromosome 3q

Objectif



Research objectives and content
The aim of the proposed project is to continue the cloning and physical mapping of the diabetes susceptibility gene (IDDM9) on chromosome 3q22. This region is of special interest because it has also been linked to rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. So it may be an important overall autoirnmuoity locus. The IDDM9 locus has been localised to a 2 or 3 cM region. A physical map of at least I Mb of the central region containing polymorphic microsatellite markers associated with type I diabetes will be constructed in order to find the region of strongest allelic association and also to define haplotypes which allow fine mapping of the disease gene. Furthermore, genes will be characterised from the most associated region to define a subset of gene associated polymorphisms that can be considered as candidate polymorphisms for the aetiological variant responsible for the association and linkage of the region. Polymorphic microsatellites characterised from the region and also gene associated polymorphisms will be analysed in more than 2,000 families available in the Todd laboratory, providing a high power of statistical analysis. Ultimately these results will lead directly to functional analyses of higly associated polymorphisms in or near genes to ascertain the mechanism of IDDM9 in type 1 diabetes.
Training content (objective, benefit and expected impact)
The objective is to become competent in all techoiques and approaches in statistical and molecular genetics as applied to the positional cloning of a susceptibility gene in a common disease. Insight into the genes and their variants that controlsusceptibility and protection from autoimmune disease will provide key information on disease mechanisms and help the development of future strategies for disease prevention. The project will extend and improve methods and approaches to the positional cloning and identification of susceptibility genes not only for type 1 diabetes but for other common multifactorial diseases.
Links with industry / industrial relevance (22)
Currently Oxford University have signed a Research and Licence Agreement with Merck Research Laboratories (a US company) and The Wellcome Trust which covers the terms and conditions covering the research programme in connection with which this TRM fellowship is being submitted, and under which all results are joint owned by Merck and by The Wellcome Trust (but can be used for further research by the University). This collaboration enables high through-put DNA sequencing and computer analysis of chromosome regions associated with type I diabetes, and will facilitate a better and direct exploitation of disease genes towards the ultimate goal of prevention of the disease. The Agreement will be transferred to Cambridge University in the next three months.

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Coordinateur

University of Cambridge
Contribution de l’UE
Aucune donnée
Adresse
Hills Road
CB2 Cambridge
Royaume-Uni

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