EMPLOYING GENOMICS, EPIGENETICS, AND IMMUNOGENETICS TO CONTROL DISEASES INDUCED BY AVIAN TUMOR VIRUSES
Location: Avian Disease and Oncology Laboratory
Project Number: 3635-31320-009-00
Start Date: Aug 02, 2012
End Date: Aug 01, 2017
Objective 1: Enhance the chicken genetic map and integration with the genome sequence specifically chromosomes 16, 25, 29-38, and W to enhance genetic/genomic opportunity for control of MD.
Objective 2: Identify and characterize chicken genes and pathways that confer resistance to Marek’s disease or vaccinal response including determination of the relationship between gut microbes and MHC haplotype of the chicken or immune response to MDV infection.
Subobjective 2.1: Genomic selection for MD resistance in chickens.
Subobjective 2.2: Genetic resistance and Meq regulated pathways.
Subobjective 2.3: Determine if host MHC haplotype, MD genetic resistance, or MDV infection alters gut microbial composition.
Subobjective 2.4: Identify genes conferring MD vaccinal protective efficacy.
Subobjective 2.5: Identify differentially expressed host genes and DNA methylation patterns induced by MD vaccination.
Objective 3: Development of a laboratory model for MDV evolution to higher virulence to develop effective industry tools for the control of Marek’s disease.
Subobjective 3.1: Identify the genomic changes in MDV selected through resistant and susceptible host genotypes.
Subobjective 3.2: Compare in vivo virus replication of the Md5B40BAC with the Md5B40BAC viruses passed in through the MHC-B21 and MHC-B13 hosts.
Subobjective 3.3: Determine if in vivo back passage will increase the pathotype of the Md4B40BAC.
Control of Marek’s disease (MD), a T-cell lymphoma induced by the Marek’s disease virus (MDV), is of particular concern to the poultry industry. Since the 1960s, MDV has evolved to higher virulence probably due to the selective pressure of MD vaccines that do not prevent viral replication or spread. Consequently, there is a need to (1) understand how MDV evolves and evades the immune system, and (2) develop alternative strategies to augment current MD control methods. In this project, we define three interrelated objectives to help achieve these goals. First, we continue to enhance and curate the East Lansing (EL) chicken genetic map, which provides the foundation for the chicken genome assembly and many of our molecular genetic studies. Second, we use genomic approaches to identify quantitative trait loci (QTL) and candidate genes that confer genetic resistance or vaccinal immunity to MD. In addition, we explore the potential role of the gut microbial community on the chicken immune response. 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. Our efforts are greatly enhanced by the availability of characterized inbred chicken lines and genomic tools especially next generation sequencing (NGS). If successful, this project will provide a number of products including (1) more genetic markers and an enhanced genetic map, (2) candidate genes conferring MD resistance or vaccinal response for evaluation in commercial breeding lines, (3) a laboratory model for MDV evolution, and (4) specific knowledge on how MDV evolves and evades the host. Ultimately, the poultry industry and US consumers will benefit by the production of safe and economical products.