Novel Resilience Phenotypes from a Natural Disease Challenge Model for Wean-to-Finish Pigs

Novel phenotypes from a commercial testing system could add value to selection for resilience to disease and other stressors beyond simply collecting mortality. Day-to-day variability in feed intake (FI) and in duration at the feeder (DUR), quantified by root mean squared errors (RMSE), were investigated as novel measures of resilience using data from grow-finish pigs in a natural disease challenge facility. • RMSE of FI and DUR were moderately heritable • RMSE of FI and DUR showed moderate to strong genetic correlations with mortality and treatments These results show that day-to-day variation in FI and DUR in a challenge environment can be used as indicator traits to select for disease resilience

Genome-wide association study of disease resilience traits from a natural polymicrobial disease challenge model in pigs identifies the importance of the major histocompatibility complex region

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 singlenucleotide 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 singlenucleotide polymorphism in the major histocompatibility complex class I subregion

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo

Development of a 3D printed device to support long term intestinal culture as an alternative to hyperoxic chamber methods

Abstract Background Most interactions between pathogenic microorganisms and their target host occur on mucosal surfaces of internal organs such as the intestine. In vitro organ culture (IVOC) provides an unique tool for studying host-pathogen interactions in a controlled environment. However, this technique requires a complex laboratory setup and specialized apparatus. In addition, issues arise when anaerobic pathogens are exposed to the hyperoxic environment required for intestinal culture. The objective of this study was to develop an accessible 3D–printed device that would allow manipulation of the gas mixture used to supply the tissue culture media separately from the gas mixture exposed to the mucosal side of explants. Results Porcine colon explants from 2 pigs were prepared (n = 20) and cultured for 0h, 8h, 18h and 24h using the device. After the culture period, explants were fixed in formalin and H&E stained sections were evaluated for histological defects of the mucosa. At 8h, 66% of samples displayed no histological abnormalities, whereas samples collected at 18h and 24h displayed progressively increasing rates of superficial epithelial erosion and epithelial metaplasia. Conclusions The 3D–design reported here allows investigators to setup intestinal culture explants while manipulating the gas media explants are exposed to, to support tissue viability for a minimal of 8h. The amount of media necessary and tissue contamination are potential issues associated with this apparatus

Understanding fetal immune responses to congenital porcine reproductive and respiratory syndrome virus infection

Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most economically significant diseases in the global swine industry, causing approximately $600 million annually in productivity losses in the United States alone. While this virus can cause a respiratory infection, it can also cross through the maternal endometrium and fetal placenta during late gestation and cause congenital infections and fetal death. Studying the extent to which the disease affects growing fetuses has been difficult because it is variable between gilts (a young female pig who has not had a litter) and between fetuses in her litter. Few studies have previously explored the immune pathways that alter fetal PRRS resistance/ susceptibility. We used a model where 3rd trimester pregnant gilts were euthanized at 2, 5, 8, 12, or 14 days post infection (DPI) with PRRS virus (PRRSV). Samples from the fetal thymus and placenta, and maternal endometrium were collected and viral loads measured (U Saskatchewan) to determine when the virus crosses the placental barrier and the level of PRRSV infection in each tissue. Fetal RNA was extracted with a Qiagen RNA Isolation kit, and gene expression was determined using a 230-gene swine immune NanoString array to evaluate differential expression (DE) of genes and biomarkers previously predicted to alter PRRS resistance and susceptibility. Biomarkers included measures of innate immunity, interferon signaling, B and T cell receptors, cell division, apoptosis, tissue remodeling and epithelial integrity, based on pathways identified using Ingenuity Pathway Analysis. Neighboring fetuses from PRRSV infected gilts from the same DPI but with different infection statuses and viral levels will be compared to determine DE genes between fetuses, litters and across DPI. Data should reveal immunological pathways that contribute to fetal susceptibility or resistance. Understanding these mechanisms will benefit future research dedicated to exploring targeted approaches to halt the congenital spread of this disease

Quantitative polymerase chain reaction for Porcine circovirus-2 in swine feces in a Porcine circovirus disease-affected commercial herd and a nonaffected commercial herd

This study examined if pigs in a Porcine circovirus disease (PCVD)-affected herd (n = 100) had shed more Porcine circovirus-2 (PCV-2) in their feces than pigs in a PCVD-nonaffected herd (n = 101), and if differences in shedding among production stages within and between the herds existed. The PCV-2 shedding was quantified by real-time polymerase chain reaction. The highest median PCV-2 shedding was found in the nursery of the PCVD-affected herd and in the grower of the PCVD-nonaffected herd. The PCV-2 shedding was significantly higher in earlier stages (newly weaned, nursery, and pregrower) in the PCVD-affected herd (Wilcoxon rank sum; P < 0.001) compared with the PCVD-nonaffected herd. Porcine circovirus-2 DNA was not detected in a significant proportion of lactating sows (parity ≥ 3) in the PCVD-nonaffected herd (Fisher’s exact test; P = 0.001). The results of this study suggest there may be an association between the presence of PCV-2 in the feces of lactating sows and increased PCV-2 shedding in younger pigs

Genomic Analysis of IgG Antibody Response to Common Pathogens in Commercial Sows in Health-Challenged Herds

Losses due to infectious diseases are one of the main factors affecting productivity in the swine industry, motivating the investigation of disease resilience-related traits for genetic selection. However, these traits are not expected to be expressed in the nucleus herds, where selection is performed. One alternative is to use information from the commercial level to identify and select nucleus animals genetically superior for coping with pathogen challenges. In this study, we analyzed the genetic basis of antibody (Ab) response to common infectious pathogens in health-challenged commercial swine herds as potential indicator traits for disease resilience, including Ab response to influenza A virus of swine (IAV), Mycoplasma hyopneumoniae (MH), porcine circovirus (PCV2), and Actinobacillus pleuropneumoniae (APP; different serotypes). Ab response was measured in blood at entry into gilt rearing, post-acclimation (~40 days after entering the commercial herd), and parities 1 and 2. Heritability estimates for Ab response to IAV, MH, and PCV2 ranged from 0 to 0.76. Ab response to APP ranged from 0 to 0.40. The genetic correlation (rG) of Ab response to IAV with MH, PCV2, PRRSV, and APPmean (average Ab responses for all serotypes of APP) were positive (\u3e0.29) at entry. APPmean was negatively correlated with PCV2 and MH at entry and parity 2 but positively correlated with MH at postacclimation and parity 1. Genomic regions associated with Ab response to different APP serotypes were identified on 13 chromosomes. The region on chromosome 14 (2 Mb) was associated with several serotypes of APP, explaining up to 4.3% of the genetic variance of Ab to APP7 at entry. In general, genomic prediction accuracies for Ab response were low to moderate, except average Ab response to all infectious pathogens evaluated. These results suggest that genetic selection of Ab response in commercial sows is possible, but with variable success depending on the trait and the time-point of collection. Future work is needed to determine genetic correlations of Ab response with disease resilience, reproductive performance, and other production traits