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Understanding Animal-to-Animal Variation in Disease Management
A long-term goal of animal health research is to understand causes of animal-to animal variation in innate immune function such that this knowledge can be applied to breeding, selection, management or other strategies to generate animals with enhanced disease resistance. Key to this research is an accurate determination of phenotype. However, variation in expression of the phenotype due to differing environmental conditions, including differing physiological states of the animal, confound the ability to accurately compare animal-to animal responses except under well-defined experimental conditions. The range of infection responsive phenotypes is quite likely dependent on underlying genetic variation that gives much promise to finding genetic markers for use in breeding programs. However, the evolving field of epigenetics suggests that in utero and early life environments can have significant effects on gene expression. Model systems to evaluate variation in the innate immune response may assist in more accurate determination of phenotype to enable detection of genetic or epigenetic biomarkers. These model systems may also be of use in testing immature animals for a prediction of adult performance. An example of a model system is the in vivo endotoxin (LPS) challenge that has been used to identify hyper responder animals. Another approach is the dermal fibroblast model in which substantial animal-to-animal variation has been revealed by how their fibroblasts respond to an in vitro LPS challenge. In this model the cells are cultured under controlled conditions for a number of passages to limit environmental effects in an attempt to reveal underlying genetic or epigenetic causes for animal variation. Future studies employing these and other model systems, combined with well-controlled disease challenges of extreme phenotypes will lead to a greater understanding of factors contributing to variation in disease resistance.
Keywords:
innate immunity, epigenetics, LPS