Genetic Resistance to Disease in Chickens Utilizing Novel Biological Resources and Contemporary Genetic Approaches to Further the Understanding of Host Resistance Mechanisms

NON-TECHNICAL SUMMARY: There are many compelling reasons to improve the health status of poultry: improved poultry health will improve animal welfare, production efficiency, and profitability of poultry agriculture; and protect the human food supply from possible contamination with harmful microbes and residues of antimicrobial drugs. Scientific approaches that enhance the innate, genetic capabilities of poultry populations to ward off disease are especially desirable, because they are environmentally friendly, permanent, reduce use of antibiotics, and are generally synergistic with the protective effects of vaccination. Iowa State University has developed and maintained unique genetic lines of chickens that are well-suited for in-depth study to discover the genetic mechanisms that contribute to successful resistance to disease in poultry. This project will reproduce and maintain the chicken genetic lines so that they remain available for study, and will produce special populations to characterize resistance to Salmonella, Eimeria and avian influenza. The collaborative studies on pathogen resistance will determine the associations of naturally existing variation of genomic structure and gene expression with resistance traits. These discoveries can be applied in the poultry breeding industry to enhance the genetic resistance to disease of future commercial populations.
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APPROACH: We will maintain breeding colonies of chickens of unique genetic structure and phenotypes. Chicks will be wingbanded and raised with contemporary groups in floor pens with ad libitum access to water and a nutritionally complete diet. Light cycle will be controlled to manage onset of lay. At sexual maturity, birds will be transferred to individual laying cages. Lines will be maintained with fully pedigreed, artificial insemination matings. Eggs will be marked with parental information, stored to accumulate large full-sib families, and incubated to hatch. As needed for specific trials, additional numbers of eggs or chicks will be produced. Chickens will have a minimal program of vaccinations to protect them from environmentally ubiquitous pathogens. Birds will be blood-typed for line-specific red cell antigens, to help ensure pedigree integrity. Biological resources (semen, ovaries, fertile eggs) will be provided to the USDA National Germplasm Preservation Center for cryopreservation efforts. To obtain a systems-level assessment of changes in gene expression that are associated with infection, we will analyze the transcriptomes of birds from Iowa State University chicken genetic lines that either were or were not infected with pathogens. Number of birds challenged will be sufficient to generate a wide range of phenotypic responses to the infection, which will allow the analysis of the phenotypic extremes (resistant/susceptible) for the microarray, along with samples from non-infected birds. Individual samples of cDNA isolated from various tissues of infected birds and non-infected birds will be analyzed in a pair-wise infected/non-infected design on 44K element Agilent microarrays, with dye-swap incorporated into the design. Statistical analysis will contrast the infected/non-infected response, and account for dye label, slide and batch. Statistically significant differentially expressed genes will be bioinformatically interrogated for pathway and functional group membership and over-represented categories of gene ontology. The output of these studies will be novel information about the gene pathways that are altered in a various tissues or cells upon whole-bird infection with pathogens. This information will highlight targets for genetic selection, vaccine development and additional research topics. Information generated in this project will be promptly and widely disseminated to target audiences of fellow scientist, poultry breeders and poultry producers through presentation at scientific meetings, industry meetings, direct contact with poultry geneticists, and publication of results in peer-reviewed journals. Trainees at various levels (undergrad, graduate and post-doctoral) will be mentored and trained in the conduct of this project. Indicators of success will include presentations and publications based upon the project, and numbers of trainees educated in the project. Long-term success (outside the period of this project) will be use of the new knowledge by the poultry breeding industry to improve genetic resistance traits of commercial populations.