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Selection for disease resilience, which refers to the ability of an animal to maintain performance when exposed to disease, can reduce the impact of infectious diseases. However, direct selection for disease resilience is challenging because nucleus herds must maintain a high health status. A possible solution is indirect selection of indicators of disease resilience. To search for such indicators, we conducted phenotypic and genetic quantitative analyses of the abundances of 377 proteins in plasma samples from 912 young and visually healthy pigs and their relationships with performance and subsequent disease resilience after natural exposure to a polymicrobial disease challenge. Abundances of 100 proteins were significantly heritable (false discovery rate (FDR) <0.10). The abundance of some proteins was or tended to be genetically correlated (rg ) with disease resilience, including complement system proteins (rg = −0.24, FDR = 0.001) and IgG heavy chain proteins (rg = −0.68, FDR = 0.22). Gene set enrichment analyses (FDR < 0.2) based on phenotypic and genetic associations of protein abundances with subsequent disease resilience revealed many pathways related to the immune system that were unfavorably associated with subsequent disease resilience, especially the innate immune system. It was not possible to determine whether the observed levels of these proteins reflected baseline levels in these young and visually healthy pigs or were the result of a response to environmental disturbances that the pigs were exposed to before sample collection. Nevertheless, results show that, under these conditions, the abundance of proteins in some immune-related pathways can be used as phenotypic and genetic predictors of disease resilience and have the potential for use in pig breeding and management. [ABSTRACT FROM AUTHOR]

Angiogenesis and cell proliferation in reproductive tissues are essential events for the maintenance of pregnancy, and alterations can lead to compromised fetal development and survival. Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) induces reproductive disease with negative financial and production impact on the swine industry. PRRSV-2 infection alters placental physiology through inflammatory and apoptotic pathways, yet fetal susceptibility varies. This study aimed to evaluate angiogenesis and cell proliferation in the porcine maternal-fetal interface (MFI) and determine if these physiological processes were altered by PRRSV-2 infection. Thirty-one pregnant gilts were inoculated with PRRSV-2 at gestation day 86 ± 0.4 (mean ± SD). Seven control gilts were sham-inoculated. All gilts were euthanized at 12 days postinoculation. Angiogenesis and cell proliferation were determined through the detection of vascular endothelial growth factor (VEGF) and Ki-67, respectively, using immunofluorescence of the MFI from 4 fetal resilience groups: uninfected (UNIF), high viral load–viable (HVL-VIA), and HVL-meconium-stained (MEC) from PRRSV-infected gilts, as well from sham-inoculated (CON) gilts. VEGF immunolabeling in the uterine submucosa was significantly lower in MEC compared with UNIF and HVL-VIA groups. Significantly greater Ki67 immunolabeling was detected in the trophoblasts of CON fetuses versus all other groups, and in uterine epithelium of CON and UNIF fetuses versus HVL-VIA and MEC. These results suggest that fetal resilience may be related to greater cell proliferation in uterine epithelium, and fetal compromise with reduced uterine submucosal angiogenesis, except fetuses with intrauterine growth restriction, in which inherently lower submucosal angiogenesis may be protective against PRRSV infection. [ABSTRACT FROM AUTHOR]

Background: Disease resilience, which is the ability of an animal to maintain performance under disease, is important for pigs in commercial herds, where they are exposed to various pathogens. Our objective was to investigate population-level gene expression profiles in the blood of 912 healthy F1 barrows at ~ 27 days of age for associations with performance and health before and after their exposure to a natural polymicrobial disease challenge at ~ 43 days of age. Results: Most significant (q < 0.20) associations of the level of expression of individual genes in blood of young healthy pigs were identified for concurrent growth rate and subjective health scores prior to the challenge, and for mortality, a combined mortality-treatment trait, and feed conversion rate after the challenge. Gene set enrichment analyses revealed three groups of gene ontology biological process terms that were related to disease resilience: 1) immune and stress response-related terms were enriched among genes whose increased expression was unfavorably associated with both pre- and post-challenge traits, 2) heme-related terms were enriched among genes that had favorable associations with both pre- and post-challenge traits, and 3) terms related to protein localization and viral gene expression were enriched among genes that were associated with reduced performance and health traits after but not before the challenge. Conclusions: Gene expression profiles in blood from young healthy piglets provide insight into their performance when exposed to disease and other stressors. The expression of genes involved in stress response, heme metabolism, and baseline expression of host genes related to virus propagation were found to be associated with host response to disease. [ABSTRACT FROM AUTHOR]

Disease resilience refers to the productivity of an animal under disease. Given the high biosecurity of pig nucleus herds, traits that can be measured on healthy pigs and that are genetically correlated with disease resilience, that is, genetic indicator traits, offer a strategy to select for disease resilience. Our objective was to evaluate mitogen stimulation assays (MSAs) on peripheral blood mononuclear cells (PBMCs) from young healthy pigs as genetic indicators for disease resilience. Data were from a natural disease challenge in which batches of 60 or 75 naïve Yorkshire × Landrace piglets were introduced every 3 wk into a continuous flow barn that was seeded with multiple diseases. In this environment, disease resilience traits, including growth, treatment, and mortality rates, were recorded on 3,136 pigs that were genotyped with a high-density marker panel. PBMCs from 882 of these pigs from 19 batches were isolated from whole blood collected prior to the disease challenge and stimulated with five mitogens: concanavalin A (ConA), phytohemagglutinin (PHA), pokeweed mitogen (PWM), lipopolysaccharide (LPS), and phorbol myristate acetate (PMA). The proliferation of cells was evaluated at 48, 72, and 96 h and compared with unstimulated samples (rest count). Heritabilities of cell proliferation were estimated using a model with batch as a fixed effect and covariates of entry age; rest count; complete blood count proportions of lymphocytes, monocytes, eosinophils, and basophils; and pen, litter, and animal genetics as random effects. Heritability estimates were highest for response to ConA (0.30 ± 0.09, 0.28 ± 0.10, 0.17 ± 0.10, and 0.25 ±0.10 at 48, 72, and 96 h after stimulation and for area under the curve across the three time points, respectively). Estimates were in a similar range for response to PHA and PMA but low for PWM and LPS. Responses to ConA, PHA, and PMA were moderately genetically correlated with several disease resilience traits and in the expected direction, but individual estimates were not significantly different from zero due to large SEs. In conclusion, although validation is needed, MSAss, in particular based on ConA, show promise as genetic indicator traits for disease resilience. [ABSTRACT FROM AUTHOR]

Background: Genetic improvement for disease resilience is anticipated to be a practical method to improve efficiency and profitability of the pig industry, as resilient pigs maintain a relatively undepressed level of performance in the face of infection. However, multiple biological functions are known to be involved in disease resilience and this complexity means that the genetic architecture of disease resilience remains largely unknown. Here, we conducted genome-wide association studies (GWAS) of 465,910 autosomal SNPs for complete blood count (CBC) traits that are important in an animal's disease response. The aim was to identify the genetic control of disease resilience. Results: Univariate and multivariate single-step GWAS were performed on 15 CBC traits measured from the blood samples of 2743 crossbred (Landrace × Yorkshire) barrows drawn at 2-weeks before, and at 2 and 6-weeks after exposure to a polymicrobial infectious challenge. Overall, at a genome-wise false discovery rate of 0.05, five genomic regions located on Sus scrofa chromosome (SSC) 2, SSC4, SSC9, SSC10, and SSC12, were significantly associated with white blood cell traits in response to the polymicrobial challenge, and nine genomic regions on multiple chromosomes (SSC1, SSC4, SSC5, SSC6, SSC8, SSC9, SSC11, SSC12, SSC17) were significantly associated with red blood cell and platelet traits collected before and after exposure to the challenge. By functional enrichment analyses using Ingenuity Pathway Analysis (IPA) and literature review of previous CBC studies, candidate genes located nearby significant single-nucleotide polymorphisms were found to be involved in immune response, hematopoiesis, red blood cell morphology, and platelet aggregation. Conclusions: This study helps to improve our understanding of the genetic basis of CBC traits collected before and after exposure to a polymicrobial infectious challenge and provides a step forward to improve disease resilience. [ABSTRACT FROM AUTHOR]

Disease resilience is a valuable trait to help manage infectious diseases in livestock. It is anticipated that improved disease resilience will sustainably increase production efficiency, as resilient animals maintain their performance in the face of infection. The objective of this study was to identify phenotypes related to disease resilience using complete blood count (CBC) data from a wean-to-finish natural disease challenge model, established to mimic the disease pressure caused by many common pathogens at the commercial level of pig production. In total, 2433 F1 crossbred (Landrace × Yorkshire) barrows that went through the natural disease challenge model were classified into four groups (resilient, average, susceptible, and dead) based on their divergent responses in terms of growth and individual treatment. Three sets of blood samples for CBC analysis were drawn at 2-weeks before, and at 2- and 6-weeks after the challenge: Blood 1, Blood 3, and Blood 4 respectively. CBC of Blood 1 taken from healthy pigs before challenge did not show differences between groups. However, resilient animals were found to be primed to initiate a faster adaptive immune response and recover earlier following infection, with greater increases of lymphocyte concentration from Blood 1 to Blood 3 and for hemoglobin concentration and hematocrit from Blood 3 to Blood 4, but a lower neutrophil concentration from Blood 3 to Blood 4 than in susceptible and dead animals (FDR < 0.05). The CBC traits in response to the challenge were found to be heritable and genetically correlated with growth and treatment, which may indicate the potential for developing CBC under disease or commercial conditions as a phenotype in commercial systems as part of developing predictions for disease resilience. [ABSTRACT FROM AUTHOR]

Background: Our recent research showed that antibody response to porcine reproductive and respiratory syndrome (PRRS), measured as sample-to-positive (S/P) ratio, is highly heritable and has a high genetic correlation with reproductive performance during a PRRS outbreak. Two major quantitative trait loci (QTL) on Sus scrofa chromosome 7 (SSC7; QTLMHC and QTL130) accounted for ~40 % of the genetic variance for S/P. Objectives of this study were to estimate genetic parameters for PRRS S/P in gilts during acclimation, identify regions associated with S/P, and evaluate the accuracy of genomic prediction of S/P across populations with different prevalences of PRRS and using different single nucleotide polymorphism (SNP) sets. Methods: Phenotypes and high-density SNP genotypes of female pigs from two datasets were used. The outbreak dataset included 607 animals from one multiplier herd, whereas the gilt acclimation (GA) dataset included data on 2364 replacement gilts from seven breeding companies placed on health-challenged farms. Genomic prediction was evaluated using GA for training and validation, and using GA for training and outbreak for validation. Predictions were based on SNPs across the genome (SNPAll), SNPs in one (SNPMHC and SNP130) or both (SNPSSC7) QTL, or SNPs outside the QTL (SNPRest). Results: Heritability of S/P in the GA dataset increased with the proportion of PRRS-positive animals in the herd (from 0.28 to 0.47). Genomic prediction accuracies ranged from low to moderate. Average accuracies were highest when using only the 269 SNPs in both QTL regions (SNPSSC7, with accuracies of 0.39 and 0.31 for outbreak and GA validation datasets, respectively. Average accuracies for SNPALL, SNPMHC, SNP130, and SNPRest were, respectively, 0.26, 0.39, 0.21, and 0.05 for the outbreak, and 0.28, 0.25, 0.22, and 0.12, for the GA validation datasets. Conclusions: Moderate genomic prediction accuracies can be obtained for PRRS antibody response using SNPs located within two major QTL on SSC7, while the rest of the genome showed limited predictive ability. Results were obtained using data from multiple genetic sources and farms, which further strengthens these findings. Further research is needed to validate the use of S/P ratio as an indicator trait for reproductive performance during PRRS outbreaks. [ABSTRACT FROM AUTHOR]

Disease resilience is the ability of an animal to maintain performance under pathogen exposure but is difficult to select for because breeding populations are raised in biosecure, high-health facilities. Selection for resilience requires an indicator trait that is easy to measure on healthy young animals, heritable, and genetically correlated with resilience. Our objective was to investigate circulating Natural Antibody (NAb) levels as potential indicators for disease resilience in pigs. Data were from a natural polymicrobial disease challenge, in which batches of 60–75 weaned LWxLR barrows were sourced every three weeks (28 batches, 1799 pigs) from healthy multipliers. NAb and total IgG were evaluated by indirect ELISA in blood samples collected around 35 d of age. Disease resilience data were collected until pigs reached market age. All pigs were genotyped on a 650k panel. Genetic parameters were estimated by univariate and bivariate analyses in ASReml4. Single-marker and Bayesian variable selection methods were used for GWAS. Heritability estimates were lower for IgG NAb (0.03–0.22) than for IgM NAb (0.24–0.42) but maternal effects were larger for IgG (0.49–0.58) than for IgM (0.04–0.12). Phenotypically, IgM titers correlated with each other (0.26–0.71), as did IgG titers (0.40–0.81), but correlations between IgM and IgG were low (0.00–0.13). Genetic correlations showed similar patterns, ranging from 0.44–0.99, 0.45–0.84, and -0.30–0.25 for IgG, IgM, and IgG/IgM, respectively. Genetically, higher levels of NAb tended to be associated with fewer treatments, lower mortality, higher finishing ADG, and lower day-to-day fluctuations in feed intake but SE were large. Phenotypically, pigs that reached market age had significantly higher levels of IgG NAb than pigs that died. GWAS identified several genomic regions for NAb levels. In conclusion, levels of circulating NAb in healthy young piglets are potential indicators of polymicrobial disease resilience. Funded by Genome Canada and Alberta, and by USDA-NIFA. [ABSTRACT FROM AUTHOR]

Porcine Reproductive and Respiratory Syndrome (PRRS) is caused by a virus that poses a threat to the global swine industry, costing the U.S. industry over 664 million dollars annually. Vaccination has limited effectiveness due to the virus' antigenic and genetic shifts. Leveraging genetics to develop more resilient swine can, however, mitigate the effects of PRRS. Previous studies identified a Single Nucleotide Polymorphism (SNP) near the GBP5 gene (WUR) that was associated with resistance and resilience to PRRS, with the G allele being favorable over A. The objective of this study was to determine whether the WUR SNP is also associated with resilience to a polymicrobial natural disease challenge. Using a continuous flow system, a new batch of 60-75 naïve Yorkshire x Landrace nursery piglets was introduced every three weeks into a natural challenge facility that was initially seeded with multiple diseases, including PRRS. Traits recorded were growth rate, feed intake, backfat, loin depth, veterinary treatments, and mortality. Pigs were genotyped using a 600K SNP chip. Data from 2133 pigs were analyzed using a univariate linear mixed model that included, pen, litter, and animal genetics as random effects and WUR genotype as a fixed effect. Frequencies were 0.85, 0.14, and 0.01 for AA, AG, and GG. The G allele was favorable for most traits, with the contrast of AA vs AG significant for average daily gain in the nursery (0.339 vs 0.365 kg/d, p = 0.013) and number of treatments (2.48 vs 2.16 over 180 days, p = 0.072). Mortality rate was 26.0% for AA and 23.8% for AG (not significantly different). In conclusion, the G allele at the WUR SNP is potentially also associated with resilience to multi-factorial disease. Funded by Genome Canada, Genome Alberta, Genome Prairie, PigGen Canada, and USDA-NIFA. [ABSTRACT FROM AUTHOR]

Infectious diseases cause tremendous financial losses in the pork industry, emphasizing the importance of disease resilience, which is the ability of an animal to maintain performance under disease. Previously, a natural polymicrobial disease challenge model was established, in which pigs were challenged in the late nursery phase by multiple pathogens to maximize expression of genetic differences in disease resilience. Genetic analysis found that performance traits in this model, including growth rate, feed and water intake, and carcass traits, as well as clinical disease phenotypes, were heritable and could be selected for to increase disease resilience of pigs. The objectives of the current study were to identify genomic regions that are associated with disease resilience in this model, using genome-wide association studies and fine-mapping methods, and to use gene set enrichment analyses to determine whether genomic regions associated with disease resilience are enriched for previously published quantitative trait loci, functional pathways, and differentially expressed genes subject to physiological states. Multiple quantitative trait loci were detected for all recorded performance and clinical disease traits. The major histocompatibility complex region was found to explain substantial genetic variance for multiple traits, including for growth rate in the late nursery (12.8%) and finisher (2.7%), for several clinical disease traits (up to 2.7%), and for several feeding and drinking traits (up to 4%). Further fine mapping identified 4 quantitative trait loci in the major histocompatibility complex region for growth rate in the late nursery that spanned the subregions for class I, II, and III, with 1 single-nucleotide polymorphism in the major histocompatibility complex class I subregion capturing the largest effects, explaining 0.8-27.1% of genetic variance for growth rate and for multiple clinical disease traits. This single-nucleotide polymorphism was located in the enhancer of TRIM39 gene, which is involved in innate immune response. The major histocompatibility complex region was pleiotropic for growth rate in the late nursery and finisher, and for treatment and mortality rates. Growth rate in the late nursery showed strong negative genetic correlations in the major histocompatibility complex region with treatment or mortality rates (-0.62 to -0.85) and a strong positive genetic correlation with growth rate in the finisher (0.79). Gene set enrichment analyses found genomic regions associated with resilience phenotypes to be enriched for previously identified disease susceptibility and immune capacity quantitative trait loci, for genes that were differentially expressed following bacterial or virus infection and immune response, and for gene ontology terms related to immune and inflammatory response. In conclusion, the major histocompatibility complex and other quantitative trait loci that harbor immune-related genes were identified to be associated with disease resilience traits in a large-scale natural polymicrobial disease challenge. The major histocompatibility complex region was pleiotropic for growth rate under challenge and for clinical disease traits. Four quantitative trait loci were identified across the class I, II, and III subregions of the major histocompatibility complex for nursery growth rate under challenge, with 1 single-nucleotide polymorphism in the major histocompatibility complex class I subregion capturing the largest effects. The major histocompatibility complex and other quantitative trait loci identified play an important role in host response to infectious diseases and can be incorporated in selection to improve disease resilience, in particular the identified single-nucleotide polymorphism in the major histocompatibility complex class I subregion. [ABSTRACT FROM AUTHOR]