An integrative genomics approach to uncover genetic mechanisms underlying susceptibility to important infectious diseases in pigs

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In animal production systems infectious diseases are of great concern due to their effects on animal health and welfare, animal productivity, and in some cases human health. Variation in the ability of individuals to overcome infection has long been observed, and this variation has a genetic component, although the particular genes and genetic variants (polymorphisms) are largely unknown. Recent work has identified one of the mechanisms underlying variation in host response to infection, at least in the case of pigs and the porcine respiratory and reproductive syndrome virus (PRRSV). A polymorphism in a host gene called GBP5 affects the ability of the gene to function. Pigs with two copies of the less active version of the gene show reduced growth and higher levels of the virus. Although GBP5 has a known role in immune response in other species, its contribution to variation in viral response in pigs was previously not known. Our more recent work has revealed several additional genes that appear to differ in activity among individuals because of polymorphisms, such that certain versions of the gene (alleles) lead to greater host resistance to PRRSV. We will study the expression of these genes to learn more about what they do, and to verify the effects of polymorphisms on their activity. Next we will leverage a large existing collection of samples and phenotypic (trait) data from previous and current projects investigating Salmonella infection in pigs, to determine if these genes and polymorphisms can also provide some protection against Salmonella. Previous studies in other species suggest that this is a reasonable expectation for some genes. Indeed, in mice a link between GBP5 activity and Salmonella growth has been previously identified. The approaches we are using have the potential to identify mechanisms of pathogen resistance not previously described in pigs or other species. Moreover, the genes and polymorphisms we confirm to influence PRRSV resistance or Salmonella resistance can be used to guide the development of new non-drug based strategies for dealing with these pathogens. For example, when pigs are selected for breeding, efforts can be made to avoid individuals that carry an abundance of susceptible alleles.**