2007 Annual Report 1a.Objectives (from AD-416) Associate prion gene complex haplotypes with susceptibility to BSE. 1b.Approach (from AD-416) The project will take a population-based approach employing principles of genetic epidemiology. We will utilize comprehensive knowledge of genetic variation in the prion gene region to analyze BSE case-control sets for association with specific alleles. We hypothesize that alleles of the bovine prion gene complex are associated with increased susceptibility to BSE. 3.Progress Report This report documents research conducted under a Specific Cooperative Agreement between ARS and Parco Tecnologico Padano, Lodi, Italy. Additional details of research can be found in the report for the in-house associated project 5438-32000-029-00D, Genetic and Biological Determinants of Respiratory Disease Susceptibility. Identification of polymorphisms in the bovine prion gene. A 25.2-kb genomic region encompassing the bovine prion gene (PRNP) was sequenced in panels representing British BSE cases and controls (n=192 individuals). Each amplicon spanning this region had greater than 95% coverage of cattle with high quality sequence (Phred score > 20). In addition to the previously described 388 total polymorphisms, 350 single nucleotide polymorphisms (SNP) and 38 insertion/deletions, this sequencing has identified an additional 24 candidate polymorphisms. A collaborative project has tentatively identified an association between BSE and one of these SNPs. Sequencing of the rest of the prion gene complex, including the PRNP paralogs PRND (doppel) and PRNT through this case-control panel has been initiated. ADODR monitoring: We are in continuous contact with our collaborators in Italy by email and phone. Data is either emailed or sent on CD by international carrier. In addition, we held a meeting in Denver with our colleagues on this project from PTP and from the University of Alberta to present progress to date and discuss future plans. It is intended that a similar meeting be held next year.