Oral Presentation International Veterinary Immunology Symposium 2016

Host Response to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection: Evidence for cis-expression Quantitative Trait Loci (cis-eQTL) Markers (#19)

Arun Kommadath 1 , Hua Bao 1 , Igseo Choi 2 , James M Reecy 3 , James E Koltes 3 4 , Eric Fritz-Waters 3 , Chris J Eisley 3 , Raymond R R Rowland 5 , Christopher K Tuggle 3 , Jack C M Dekkers 3 , LeLuo Guan 1 , Paul Stothard 1 , Graham S Plastow 1 , Joan Lunney 2
  1. Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
  2. USDA ARS BARC, Beltsville, MD, United States
  3. Department of Animal Science, Iowa State University, Ames, IA , USA
  4. Department of Animal Science, University of Arkansas, Fayetteville, AR, USA
  5. College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA

Porcine reproductive and respiratory syndrome (PRRS) is economically the most important disease of pigs worldwide. Understanding transcriptional responses to this infection should reveal mechanisms that help control PRRS. The PRRS Host Genetics Consortium (PHGC) was established to combine efforts of scientists from universities, government, commercial pig genetics and animal health companies to assess the role of genetics in determining pig resistance/susceptibility to PRRS virus (PRRSV) infection, pathology and growth effects. The PHGC uses a nursery pig PRRSV infection model with deep sampling for phenotypic analyses, extensive genotyping (60K SNPchip) and a shared database. We integrated genome-wide genotype, gene expression, viremia level (VL) and weight gain (WG) phenotypes to identify differential expression (DE) and genetic variation controlling expression levels and association to phenotypes. RNA was prepared from Tempus tube-preserved blood samples collected prior to challenge (day 0) and at 4, 7, 10 and 14 days post infection from 44 pigs and globin RNA depleted prior to library production. RNA-seq analysis revealed 6,430 genes DE after infection. We mapped genetic variation associated with inter-individual differences in expression levels at each day and found evidence of cis-acting expression quantitative trait loci (cis-eQTL) for 1,201 genes. Associations between cis-eQTL markers and phenotypes using 383 pigs indicated that host genotype-dependent reduced expression of four genes (including GBP5 identified from our earlier study) are associated with higher VL or lower WG following infection and exhibit evidence of allele-specific expression. We also found numerous genetic variants associated with inter-individual variation in the expression of immune related genes that may contribute to the varying immune responses to PRRS. Further studies are needed to define the causal mutations that regulate expression of these candidate susceptibility genes and test how changes in expression of these genes link them to phenotypes. Funding: Genome Canada, Genome Alberta, PigGen Canada and USDA ARS.