Employing Genomics, Epigenetics, and Immunogenetics to Control Diseases Induced by Avian Tumor Viruses
Project Number: 6040-31320-009-00
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.
Objective 4: Develop alternative methods to preserve genetic diversity of defined chicken lines while maintaining or enhancing fitness, identify host genetic determinants that control disease resistance for poultry viruses; develop sustainable control measures that reduce the evolution of more virulent poultry viruses and elucidate the genetic determinants that modulate poultry gut microbiome interactions with the avian immune system.
Subobjective 4.1: Evaluate husbandry practices that will improve reproductive fitness of defined inbred chicken lines.
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 four 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. 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. And fourth, in an effort to help preserve our unique experimental genetic lines and expand their utility, we address whether alternative husbandry practices will improve reproductive fitness. Our efforts are greatly enhanced by the availability of 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, (4) specific knowledge on how MDV evolves and evades the host, and (5) experimental chicken lines with improved fitness. Ultimately, the poultry industry and US consumers will benefit by the production of safe and economical products.