Project Number: 3635-31320-008-00
Project Type: Appropriated

Start Date: Aug 02, 2007
End Date: Aug 01, 2012

Objective:
The long-term goal of this project is to develop an improved understanding of genetic resistance and vaccinal responses to Marek¿s disease (MD) in order to increase productivity and safety of poultry products. Over the next 5 years, we will focus on the following specific objectives: Objective 1: Curate and enhance the chicken genetic map and its integration with the genome sequence. Objective 2: Identify and characterize chicken genes and pathways that confer resistance to MD. Sub-objective 2A: Validate, fine-map, and identify positional candidate genes for quantitative trait loci (QTL) that confer resistance to MD. Sub-objective 2B: Evaluate non-major histocompatibility complex (MHC) host genomic effects on MD vaccine efficacy. Objective 3: Functional characterization of the chicken MHC in response to tumor-virus infection or vaccination. Sub-objective 3A: Determine the relationship between in vivo passage of Marek¿s disease virus (MDV) and the emergence of MDV strains with increased virulence. Sub-objective 3B: Determine the relationship between chicken MHC genetics and virus evolution. Sub-objective 3C: Determine the molecular basis for differential levels of cell surface MHC class I glycoprotein expression.

Approach:
We define three interrelated approaches to help achieve our goals. First, we continue to enhance and curate the East Lansing (EL) chicken genetic map, which provides the foundation for molecular genetic studies and the chicken genome assembly. Second, we use an integrative genomics approach to identify QTL and candidate genes that confer genetic resistance or vaccinal immunity to MD. Our efforts are greatly enhanced by the availability of characterized inbred and recombinant congenic strains (RCS), genetic markers from our map, comprehensive DNA microarrays, as well as infectious MDV-BAC clones that we can manipulate to query and characterize specific virus-host protein interactions. And third, we evaluate an in vivo model for MDV virulence evolution and if successful, ask the question whether increased virulence is restricted to specific major histocompatibility (MHC) haplotypes. BSL-2; recertification 8/11/06 valid through 8/10/09.