Proceedings, 10th World Congress of Genetics Applied to Livestock Production Genome-wide analysis of the differential response to experimental challenges with Porcine Circovirus 2b T.B. Engle 1 , E.E. Jobman 1 , T.W. Moural 2 , A.M. McKnite 1 , S.Y. Barnes 1 , E.H. Davis 1 , J.K. Qiu 1 , J.W. Bundy 1 , J.K. Tart 1 , T.P. Johnson 1 , M.F. Rothschild 3 , J.A. Galeota 2 , R.K. Johnson 1 , G.S. Plastow 4 , S.D. Kachman 5 , D.C. Ciobanu 1 1 Animal Science Department, University of Nebraska, Lincoln, USA; 2 School of Veterinary Medicine and Biological Sci- ences, University of Nebraska, Lincoln, USA 3 Department of Animal Science, Iowa State University, Ames, Iowa, USA; 4 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton; Canada. 5 Department of Statis- tics, University of Nebraska, Lincoln, USA ABSTRACT: Porcine Circovirus 2 (PCV2) is the causative source of a group of associated diseases (PCVAD) that af- fects production efficiency and can lead to mortality. Using commercial crossbred pigs (n = 974) experimentally infect- ed with PCV2b we analyzed genetic sources of the variation in PCVAD susceptibility. A genome-wide association study including 56,433 SNPs uncovered two major SNPs that ex- plain 11.5% (SSC12) and 2.8% (SSC7) respectively, of the genetic variation for viral load. These SNPs partially ex- plained the negative correlations between viral load and ADG during challenge (r = -0.36, P < 0.0001). The CC gen- otype of the SNP located on SSC12 was associated with lower viral load (P < 0.0001) and higher overall ADG (P < 0.05) compared to CT and TT genotypes. These genetic var- iants influence the ability of the host to react and influence PCV2b replication and immune response and improve gen- eral animal health and welfare while reducing production costs. Key words: PCV2; Genetic Susceptibility; Genome-wide association study Introduction Porcine Circovirus 2 (PCV2) is the essential pathogen of a group of associated diseases (PCVAD) characterized by weight loss, diarrhea, interstitial pneumonia, nephritis, re- productive failure, dermatitis and lymphoid depletion lead- ing to reduced immunity and susceptibility to other patho- gens. PCV2 impairs the immune response, by suppressing the innate immunity role of Natural Interferon Producing Cells (NIPCs) in the maturation of myeloid dendritic cells (McCullough et al. (2009)). Vaccination is effective in con- trolling PCVAD. A common practice is to vaccinate all pigs, increasing production costs, even though many natu- rally infected pigs do not express disease. Variation in susceptibility to PCVAD is influenced by multiple factors including host genetics, exposure to sec- ondary pathogens and management (Madec et al. (2008)). Several reports uncovered breed differences in PCVAD incidence and severity in experimental and natural infec- tions with PCV2 (Zhou et al. (2006); Opriessnig et al. (2006, 2009)). Recent studies quantified the contribution of host genetics in the variation of PCVAD susceptibility in natural (Bates et al. (2009)) and experimental infections (McKnite et al. (2014)) with PCV2. Using an experimental infection approach based on a growing pig model we inves- tigated genetic sources of differences in PCVAD suscepti- bility and showed that host genetics plays a role in the ob- served differences in viremia and specific PCV2 immune responses (McKnite et al. (2014)). Herein, we expanded our study by sampling additional maternal lines from several major North-American swine breeding programs in order to help refine QTL locations. Materials and Methods Experimental design. Animal use and experi- mental procedures were approved by the Institutional Ani- mal Care and Use Committee of the University of Nebraska - Lincoln (UNL). The experimental challenge was carried out in nine batches (B1 to B9) with 81 to 141 pigs per batch. Barrows were used in B1, B4 and B5-B9 and barrows and gilts were used in B2 and B3. We used maternal and termi- nal crossbred pigs produced at University of Nebraska (n = 386) and commercial maternal crossbred pigs (n = 588) provided by members of PigGen Canada. Pigs, 3 per litter, from 320 litters by parity 1 to 9 dams were used. Dams had been vaccinated for PCVAD at 3 weeks of age with a single dose of Ingelvac CircoFLEX vaccine (Boehringer Ingel- heim, St. Joseph, MO). Source farms also included vaccina- tion programs for Porcine parvovirus, Erysipelothrix rhusi- opathiae, Clostridium perfringens, Leptospirosis and Coli- bacillosis and were tested negative for Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). Pigs were co- lostrum fed and raised under similar conditions. Prior to infection all experimental pigs tested negative for presence of PCV2 and had a sample/ positive ratio (S/P) lower than 0.3 for passive IgG and lower than 0.4 for IgM, the specific PCV2 maternal antibodies (McKnite et al.( 2014)). These S/P thresholds differentiate pigs that are actively infected or that were previously exposed to PCV2 (Ingenasa). At an average of 36 d each pig was infected with a titer of 10 4.0 50% tissue culture infection dose (TCID 50 ) intranasally and intramuscularily. Experimental pigs were monitored daily for clini- cal signs of disease, and weights and blood samples were collected at 0, 7, 14, 21 and 28 days post infection (dpi). Detailed experimental conditions were described in McKnite et al. (2014). The PCV2b strain used was isolated from a pig that displayed symptoms characteristic to