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Dual-use models to assess the effect of nutrition on immunity and inflammation; focus on porcine genomics and transcriptomics.

Harry Dawson
Diet Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center
Beltsville, Maryland

Two NIH/USDA sponsored workshops (2004, 2007) were convened with the purpose of promoting domestic species as dual-use biomedical models. Swine were prominantly featured in the summary reports of these conferences because of their known physiological similarities to humans. Summaries from these conferences also stated that enhanced use of domestic species as biomedical models for humans would have the additional benefit of generating important new information directly relevant to many areas of research in animal productivity and health. However, the success of any such efforts would require a sophisticated analysis of specific model suitability and a biological reagent and resource infrastructure that is as highly developed as those available for research on humans and mice. To these ends, we embarked on a series of projects, that will be described in this presentation, to address deficiencies in these areas.

We initially conducted a large-scale comparative assessment of the pig, mouse, and human genomes and conducted a structural and functional analysis of comparable genes involved in immunity and inflammation. This analysis revealed an overwhelming similarity of swine to humans for most parameters evaluated. Because porcine bioinformantics resources are underdeveloped relative to mice and humans, we developed the Porcine Translational Research Database to disseminate information on genes and proteins related to those prominently studied in humans and mice.

This database contains manually-annotated information on over 4,500 genes, including several hundred that have been cloned in our laboratory, and assays we developed to measure over 2,000 genes and proteins. Next, the porcinegenome was recently completed but was annotated using machine-based annotation. Our efforts, as part of an international consortium, resulted in the manualannotation of over 1,400 genes to provide a comprehensive description of the porcine immunome, the portion of the genome devoted to the immune response.

Last, current studies that analyze the transcriptome of pig alveolar macrophages by techniques that are also applied to human studies of whole blood cell responses to changes in diet will be described. These efforts have contributed significantly toward employing swine as dual-use models to promote human and swine health.