2008 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 Genetic variation that has been identified within the prion gene (25.2-kb) of British classical BSE cases and controls is currently under analysis. Previously, variation within the prion gene (PRNP) of U.S. cattle was defined through two independent median-joining networks that cover PRNP areas of high and low linkage disequilibrium. These networks provide a backbone of PRNP variants within cattle. PRNP variation identified in BSE cases and controls will first be analyzed within a framework of the median-joining networks. If particular PRNP variants within the networks show an association with classical BSE susceptibility, full-length PRNP sequence from the cases and controls will be used to fine-map PRNP variation along the reference backbone sequence. This may lead to the identification of PRNP alleles that are strongly correlated with classical BSE susceptibility. Assays that target informative SNPs within two PRNP paralogs, PRND (doppel) and PRNT are being designed. These assays will be applied to the classical BSE case and control animals. This will facilitate testing of genetic variation throughout the prion gene complex for an association with classical BSE. National Program 103 - Animal Health, Program Component - Problem Statement 8: Countermeasures to Prevent and Control Transmissible Spongiform Encephalopathies - Bovine Spongiform Encephalopathy (BSE). The ADODR is in continuous contact with our collaborators in Italy and in the United States by email and phone. Additionally, a meeting with collaborators from Italy and Canada was held earlier this year in San Diego to discuss progress to date and future plans.