Cenetic dissection ofHLA associated diseases

The HLA complex are a gene complex of huge medical importance. The most polymorphic genes in the human genome are located here and no gene complex has been found associated to as many diseases as HLA. Fine mapping the genes involved in HLA associated diseases has proven difficult. In this project we will type a dense map of SNPs (average inter-marker distance of 3 kb) in healthy individuals to define recombination hot spots (globally and haplotype spec ific) and conserved ancestral haplotypes within HLA. SNPs will be evaluated for their ability to identify ancestral haplotype fragments and so-called "SNP haplotype tags" will be identified. Finally we will type these "SNP haplotype tags" in large materia ls of patients, their family members and healthy controls for two different HLA associated diseases in order to fine map disease susceptibility genes. The diseases that will be studied are type 1 diabetes and Addison's disease. The haplotypic patterns and SNP haplotype tags identified in this projects should be important for gene mapping of the HLA complex in general and help identifying disease involved genes in HLA associated diseases.