1a.Objectives (from AD-416)
1) Characterize variation in the bovine prion gene complex in U.S. cattle populations. 2) 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. First, we will characterize polymorphisms and haplotype structure in the prion gene complex in U.S. and U.K. cattle populations. Then we will utilize this comprehensive knowledge of genetic variation 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

The entire prion gene (25.2 kb) has been sequenced from 192 European, classical-BSE case and control samples (94 cases, 98 controls). The sequencing was completed prior to 2009; however, the endeavor generated 33,567 trace files that are currently under analysis. In the last year, 335 polymorphisms within the prion gene (PRNP) and two closely related paralog genes (PRND and PRNT) were targeted for Illumina assay design. Most of these polymorphisms were discovered through earlier work from this project. Once reliable assays have been designed, they will be applied to a large European, classical-BSE case and control sample set for testing of PRNP, PRND and PRNT variation for an association with classical BSE susceptibility.

This research was conducted through the U.S. Meat Animal Research Center with significant contributions from collaborators in Canada and Italy. The ADODR has been in constant contact with collaborators through emails, phone conference calls and meetings.