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Constitutive Variation in Hepatic Expression of Porcine Innate Immune Genes Associated with Novel Promoter Polymorphisms

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Title: Constitutive Variation in Hepatic Expression of Porcine Innate Immune Genes Associated with Novel Promoter Polymorphisms
Author: Snyman, Heindrich
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Lillie, Brandon
Abstract: Infectious diseases are an important factor limiting production, growth performance, economics and animal welfare in the global swine industry. Numerous pathogenic, environmental and host genetic factors contribute to infectious disease susceptibility, including defects in the innate immune system. The secreted, membrane-bound and intracellular proteins of the innate immune system are critical components in the defense against infectious pathogens, especially in young pigs. Previous studies have identified a number of single nucleotide polymorphisms (SNPs) in the innate immune genes of pigs, some of which are more frequent in pigs with economically important infectious diseases such as enteritis, serositis and pneumonia. Additional novel genetic differences (SNPs, insertions, deletions or other genetic variations) that alter the expression and/or function of important resistance-conferring innate immune proteins could, together with previously identified markers, form the basis for future development of genetic selection strategies aimed at increasing innate disease resistance in pigs. In this thesis, genome-wide expression analysis and DNA sequencing were used to screen for polymorphisms that were associated with decreased or increased expression of selected innate immune genes in the liver of healthy market weight pigs. Using expression microarrays, innate immune genes were identified that exhibited widely variable hepatic gene expression. The promoter regions of these variably expressed genes were characterized and novel promoter SNPs, insertions and deletions were identified in genes coding for proteins such as secretoglobin, family 1A, member 1; porcine surfactant protein D; retinoic acid-inducible gene 1 and porcine hepcidin antimicrobial peptide. Some of these SNPs were found to be more prevalent in animals with either impaired or enhanced hepatic gene expression. Genotyping healthy and diseased pigs using MassArray MALDI-TOF mass spectrometry revealed that genetic defects were widely variable in their frequency in different breeds of pigs and some were more or less frequent in pigs with certain common infectious diseases and/or pathogens. Information from these studies will be used to develop a comprehensive panel of genetic markers that can be used to breed for pigs with increased disease resistance. Such a panel could help improve pig production, promote animal health and welfare, and decrease the need for antimicrobial drugs.
Date: 2013-11
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