Over 0,5% of the Western (Eurasia and America) population suffers from coeliac disease (gluten hypersensitivity), which presents itself by decreased food intake, chronic diarrhoea, osteoporosis, lymphoma and several other clinical symptoms. Until today is complete and life long elimination of gluten from the daily diet the only sensible option. This places a burden upon the patient. Wheat, barley and rye are the most important gluten containing food constituents. Gluten are a cheap, but also a high grade protein, which is part of an increasing number of food products. The availability of less allergic (toxic) glutenproteins would be of importance in the prevention of coeliac disease. Several allergenic epitopes have already been identified, but the gluten protein is still incompletely covered. Central hypothesis of this project is aimed at the total elimination of allergenic sequences from the wheat genome while retaining the industrial quality of the gluten proteins. The project will focus on the genomics of the gluten genes in wheat (Tricicum). The genus Tricium contains several diploid, tetraploid and hexaploid species; the polyploid species are considered alloploids. T.aestivum, for example, the bred wheat is an alloploid containing and A, B and D genome. Based on this property is the variability in gluten proteins very large. Depending on the wheat species, particular cultivar and ploidy status up to 150 gluten genes have been identified. In this project gluten genes from a representative sample of wheat species and cultivars will be isolated and sequenced. This will enable reconstruction of possible evolution of gluten genes from the genome (A,B or D) from which they have originated. Wheat cultivars will be screened for their toxicity in collaboration with the Leiden University Medical Centre. This will lead to the identification of low toxic cultivars from which individual recombinant gene products will be screened for their toxicity. This will enable the identification of the toxic amino acid residues (epitopes) from gluten proteins and how these are represented in the several species and cultivars. Also the presence of micro satelites in these genes will be analysed. We still address these sequences are determining the toxicity of gluten, whether the industrial quality of the gluten is determined by them, what was the path of their evolution after the initiation of polyploidy, and whether selection and upgrading of baking quality (bread, food, and pasta wheat) has resulted in variability in repeat length of these microsatelite sequences. This research will result in the identification of genetic markers enabling the improvement of non-toxic cultivars. The results can also be used to study gluten gene expression under various selection conditions and to design assays for the detection of potentially toxic gluten sequences in food. These application will result in improvement in the quality of life of patitents suffering from coeliac disease by the development of non-toxic food constituents.