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United States Department of Agriculture

Agricultural Research Service

Research Project: USING THE GENOME TO UNDERSTAND IMMUNOGENETICS OF POULTRY
2010 Annual Report


1a.Objectives (from AD-416)
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.


1b.Approach (from AD-416)
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.


3.Progress Report
Substantial progress was made on all three objectives and their subobjectives. Under Objectives 1 and 2, we made significant progress in identifying genomic regions and candidates genes that confer either genetic resistant to Marek’s disease or enhance vaccine response. Furthermore, specific genes were characterized that reveal the underlying biological pathways for host-pathogen interactions. And additional tools and resources such as advanced intercross lines and resource populations have been generated that set the foundation for future efforts. Finally, efforts to evaluate genomic selection in five different commercial poultry lines have suggested that this is a very promising method to accelerate genetic improvement though we still need to be cognizant about the economics of implementation. Substantial progress on Objective 3 was also made that advances our understanding of the chicken immune response when it encounters the virus. Of particularly note is the role of genetic resistance and MHC haplotypes on viral evolution to higher virulence.


4.Accomplishments
1. Using genetic markers to accelerate, enhance, and improve precision in poultry breeding. Genomic selection, which involves the use of a very dense genetic marker panel to predict breeding values, is an exciting method that has great potential for accelerating the breeding of commercial chickens to meet growing consumer demands worldwide. Prior to commercial implementation, genomic selection has to be experimentally tested in the field and the limitations fully understood. Using two elite broiler (meat-type) and three layer (egg-type) commercial lines, an ARS scientist in East Lansing, MI leads an international consortium to select birds over multiple generations based on predictions from 60K genetic markers. Thus far, compared to birds selected in parallel using current state-of-the-art breeding methods, genomic selection was superior for the vast majority of the traits selected including body weight and breast yield. This research strongly suggests that genomic selection is an improved breeding method. If costs for genetic testing continue to go down, then poultry breeders should be able to economically breed chickens faster using genomic selection and adapt more readily to changing consumer demands. The economic impact could be great since 1 million meat-type birds are processed per hour in the U.S. alone, the net effect of even small improvements are large and worth millions of dollars.

2. Comprehensive identification of targets in the chicken genome for a viral oncogene. Marek’s disease, a T cell lymphoma of chickens caused by a pathogenic virus, costs the poultry industry approximately $1 billion worldwide annually in losses and control measures. Thus, understanding how the Marek’s disease virus leads to disease is of both scientific and commercial interest. Meq is the putative cancer-causing viral protein and leads to aberrant expression of chicken proteins. Using molecular biology techniques and high-throughput sequencing, an ARS scientist in East Lansing, MI identified all the targets candidate genes in the chicken genome that Meq might alter. This information can help efforts to develop more effective vaccines or improve genetic resistance, both of which would reduce costs and improve animal welfare.

3. DNA fingerprinting of unique chicken lines developed and maintained at the USDA-ARS, Avian Disease and Oncology Laboratory (ADOL). For over seventy years, ADOL has developed and maintained about forty unique genetic lines of chickens, which serve scientists at ADOL as well as other non-USDA institutes and universities for their critical research needs. Many of these important chicken lines have been DNA fingerprinted with 3K and 60K genetic marker panels. Continuous efforts have been put forward in exploring and analyzing this unique data to improve and enhance the general understanding of the genetic variability between and within the chicken lines with respect to the underlying mechanisms that confer disease resistance. The findings from such efforts will enhance the power of scientists to solve problems facing the poultry industry, especially with respect to infectious diseases and animal welfare issues. Ultimately, U.S. consumers will benefit with safe and affordable poultry products.

4. Fine-mapping of genes conferring genetic resistance to Marek’s disease (MD). MD is an avian herpesvirus-induced disease, which continues to pose a real threat to the prosperity of the poultry industry. Although MD has been controlled by vaccines since the 1970s, the importance of host genetic resistance to MD in fighting against MD is widely recognized. A special chicken population was generated from highly inbred chicken lines, which differ in genetic resistance to MD. Chickens from the special population were challenged with the causative virus and examined for MD incidence. DNA samples from 254 chickens have been comprehensively analyzed for sequence variations throughout the entire chicken genome. Preliminary analyses of the data identified 172 genetic markers located on four chromosomes, some of which agreed with previous reports while others are new. The identified genetic markers will be very useful in two ways: to search for causal genes responsible for disease resistance and to accelerate genetic improvement of chickens in selection and breeding programs.

5. Evaluation of host (chicken) genetics effect on vaccine efficacy. Since their invention, vaccines have proven to be the most effective and economical method to combat infectious diseases in humans as well as in livestock. Efforts to improve vaccine protective efficiency have continued and expanded. Host genetics differences were investigated for the influence on Marek’s disease (MD) vaccine efficacy using unique genetic lines of chickens. Our data suggests that host genetics play an important role influencing MD vaccine protection efficiency. Continuous analyses of our research data further suggested that different genetic lines of chickens respond to the same one vaccine with different protective efficiency.

6. Marek’s disease virus evolves to higher virulence in birds with limited genetic variation. Marek’s disease (MD), a serious problem for the poultry industry caused by the pathogenic Marek’s disease virus (MDV), is primarily controlled by vaccines. However, MD is still a major concern as MDV continues to evolve to higher virulence. Most studies addressing the evolution of MDV virulence have concentrated on the virus while largely ignoring the hosts’ influence. The host system called the major histocompatibility complex (MHC) represents a highly polymorphic system designed to defend the species from extinction by the fast paced evolution of a parasite. In natural chicken populations, there are hundreds of different MHC haplotypes that oscillate in response to pathogen evolution, but commercial poultry breeding has limited the number of MHC haplotypes to six or less. Our current work has shown that MDV can evolve to higher virulence in birds with a single MHC haplotype. Thus, we predict the best way to reduce the chronic problem of MD incidence in commercial chickens is to rotate the placement of MHC haplotypes similar to the simple method of crop rotation used to control pests in the field. Incorporation of this method into modern poultry production may greatly reduce future virus evolution resulting in substantial savings to the poultry industry.


Review Publications
Hunt, H.D., Jadhao, S., Swayne, D.E. 2010. Major Histocompatibility Complex and Background Genes in Chickens Influence Susceptibility to High Pathogenicity Avian Influenza Virus. Avian Diseases. 54(Supplement 1):572-575.

Mao,W., Hunt, H.D., Cheng, H.H. 2010. Cloning and Functional Characterization of Chicken Stem Cell Antigen 2. Developmental and Comparative Immunology. 34(3):360-368.

Kim, T., Hunt, H.D., Cheng, H.H. 2010. Marek's Disease Viruses Lacking Either R-LORF10 or LORF4 Have Altered Virulence in Chickens. Virus Genes. 40(3):410-420.

Tai, S.H., Niikura, M., Cheng, H.H., Kruger, J.M., Wise, A.G., Maes, R.K. 2010. Complete Genomic Sequence and an Infectious BAC Clone of Feline Herpesvirus-1 (FHV-1). Virology. 401(2):215-227.

Last Modified: 11/28/2014
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