Including Indirect Genetic Effects (IGE) in breeding programs to reduce aggression in group housed animals has been proposed. However, the effect of selection for IGE for growth on animal metabolism ...and physiology is unknown. The purpose of this study was twofold: (1) To investigate the effects of this new breeding method along with two housing (barren and straw), coping style (high and low resisters) and sex (female and castrated males) options on the metabolome profile of pigs. (2) To identify and map biological processes associated with a regrouping test at 9 weeks of age. We used Nuclear Magnetic Resonance to quantify 49 serum metabolites at week 8, 9 and 22. Also, we quantified 3 catecholamines (tyramine, epinephrine, phenylethylamine) and serotonin and three water soluble vitamins (B2, B5 and B7). Overall, no significant differences were observed between negative and positive IGE animals. The magnitude of change (delta) of many metabolites as a response to the regrouping test was significantly affected by IGE, especially that of the amino acids (P < 0.05), being greater in positive IGE pigs. The regrouping test was associated with alteration in glycine, serine and threonine metabolism. In conclusion positive and negative IGE animals respond differently to the regrouping test.
Abstract Background Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) infection during late gestation substantially lowers fetal viability and survival. In a previous genome-wide ...association study, a single nucleotide polymorphism on chromosome 7 was significantly associated with probability of fetuses being viable in response to maternal PRRSV-2 infection at 21 days post maternal inoculation. The iodothyronine deiodinase 2 ( DIO2 ) gene, located ~ 14 Kilobase downstream of this SNP, was selected as a priority candidate related to fetal susceptibility following maternal PRRSV-2 infection. Our objectives were to identify mutation(s) within the porcine DIO2 gene and to determine if they were associated with fetal outcomes after PRRSV-2 challenge. Sequencing of the DIO2 , genotyping identified variants, and association of DIO2 genotypes with fetal phenotypes including DIO2 mRNA levels, viability, survival, viral loads, cortisol and thyroid hormone levels, and growth measurements were conducted. Results A missense variant (p.Asn91Ser) was identified in the parental populations from two independent PRRSV-2 challenge trials. This variant was further genotyped to determine association with fetal PRRS outcomes. DIO2 mRNA levels in fetal heart and kidney differed by the genotypes of Asn91Ser substitution with significantly greater DIO2 mRNA expression in heterozygotes compared with wild-type homozygotes ( P < 0.001 for heart, P = 0.002 for kidney). While Asn91Ser did not significantly alter fetal viability and growth measurements, interaction effects of the variant with fetal sex or trial were identified for fetal viability or crown rump length, respectively. However, this mutation was not related to dysregulation of the hypothalamic-pituitary-adrenal and thyroid axis, indicated by no differences in circulating cortisol, T4, and T3 levels in fetuses of the opposing genotypes following PRRSV-2 infection. Conclusions The present study suggests that a complex relationship among DIO2 genotype, DIO2 expression, fetal sex, and fetal viability may exist during the course of fetal PRRSV infection. Our study also proposes the increase in cortisol levels, indicative of fetal stress response, may lead to fetal complications, such as fetal compromise, fetal death, or premature farrowing, during PRRSV infection.
Disease resilience is the ability to maintain performance under pathogen exposure but is difficult to select for because breeding populations are raised under high health. Selection for resilience ...requires a trait that is heritable, easy to measure on healthy animals, and genetically correlated with resilience. Natural antibodies (NAb) are important parts of the innate immune system and are found to be heritable and associated with disease susceptibility in dairy cattle and poultry. Our objective was to investigate NAb and total IgG in blood of healthy, young pigs as potential indicator traits for disease resilience.
Data were from Yorkshire x Landrace pigs, with IgG and IgM NAb (four antigens) and total IgG measured by ELISA in blood plasma collected ~ 1 week after weaning, prior to their exposure to a natural polymicrobial challenge. Heritability estimates were lower for IgG NAb (0.12 to 0.24, + 0.05) and for total IgG (0.19 + 0.05) than for IgM NAb (0.33 to 0.53, + 0.07) but maternal effects were larger for IgG NAb (0.41 to 0.52, + 0.03) and for total IgG (0.19 + 0.05) than for IgM NAb (0.00 to 0.10, + 0.04). Phenotypically, IgM NAb titers were moderately correlated with each other (average 0.60), as were IgG NAb titers (average 0.42), but correlations between IgM and IgG NAb titers were weak (average 0.09). Phenotypic correlations of total IgG were moderate with NAb IgG (average 0.46) but weak with NAb IgM (average 0.01). Estimates of genetic correlations among NAb showed similar patterns but with small SE, with estimates averaging 0.76 among IgG NAb, 0.63 among IgM NAb, 0.17 between IgG and IgM NAb, 0.64 between total IgG and IgG NAb, and 0.13 between total IgG and IgM NAb. Phenotypically, pigs that survived had slightly higher levels of NAb and total IgG than pigs that died. Genetically, higher levels of NAb tended to be associated with greater disease resilience based on lower mortality and fewer parenteral antibiotic treatments. Genome-wide association analyses for NAb titers identified several genomic regions, with several candidate genes for immune response.
Levels of NAb in blood of healthy young piglets are heritable and potential genetic indicators of resilience to polymicrobial disease.
We describe the organization of a nascent international effort, the Functional Annotation of Animal Genomes (FAANG) project, whose aim is to produce comprehensive maps of functional elements in the ...genomes of domesticated animal species.
Heterosis has been suggested to be caused by dominance effects. We performed a joint genome-wide association analysis (GWAS) using data from multi-breed and crossbred beef cattle to identify single ...nucleotide polymorphisms (SNPs) with significant dominance effects associated with variation in growth and carcass traits and to understand the mode of action of these associations.
Illumina BovineSNP50 genotypes and phenotypes for 11 growth and carcass traits were available for 6796 multi-breed and crossbred beef cattle. After performing quality control, 42,610 SNPs and 6794 animals were used for further analyses. A single-SNP GWAS for the joint association of additive and dominance effects was conducted in purebred, crossbred, and combined datasets using the ASReml software. Genomic breed composition predicted from admixture analyses was included in the mixed effect model to account for possible population stratification and breed effects. A threshold of 10% genome-wide false discovery rate was applied to declare associations as significant. The significant SNPs with dominance association were mapped to their corresponding genes at 100 kb.
Seven SNPs with significant dominance associations were detected for birth weight, weaning weight, pre-weaning daily gain, yearling weight and marbling score across the three datasets at a false discovery rate of 10%. These SNPs were located on bovine chromosomes 1, 3, 4, 6 and 21 and mapped to six putative candidate genes: U6atac, AGBL4, bta-mir-2888-1, REPIN1, ICA1 and NXPH1. These genes have interesting biological functions related to the regulation of gene expression, glucose and lipid metabolism and body fat mass. For most of the identified loci, we observed over-dominance association with the studied traits, such that the heterozygous individuals at any of these loci had greater genotypic values for the trait than either of the homozygous individuals.
Our results revealed very few regions with significant dominance genetic effects across all the traits studied in the three datasets used. Regarding the SNPs that were detected with dominance associations, further investigation is needed to determine their relevance in crossbreeding programs assuming that dominance effects are the main cause of (or contribute usefully to) heterosis.
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. 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. 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.
Imputed whole-genome sequence (WGS) has been proposed to improve genome-wide association studies (GWAS), since all causative mutations responsible for phenotypic variation are expected to be present ...in the data. This approach was applied on a large number of purebred (PB) and crossbred (CB) pigs for 18 pork color traits to evaluate the impact of using imputed WGS relative to medium-density marker panels. The traits included Minolta A*, B*, and L* for fat (FCOL), quadriceps femoris muscle (QFCOL), thawed loin muscle (TMCOL), fresh ham gluteus medius (GMCOL), ham iliopsoas muscle (ICOL), and longissimus dorsi muscle on the fresh loin (FMCOL). Sequence variants were imputed from a medium-density marker panel (61K for CBs and 50K for PBs) in all genotyped pigs using BeagleV5.0. We obtained high imputation accuracy (average of 0.97 for PBs and 0.91 for CBs). GWAS were conducted for three datasets: 954 CBs and 891 PBs, and the combined CBs and PBs. For most traits, no significant associations were detected, regardless of panel density or population type. However, quantitative trait loci (QTL) regions were only found for a few traits including TMCOL Minolta A* and GMCOL Minolta B* (CBs), FMCOL Minolta B*, FMCOL Minolta L*, and ICOL Minolta B* (PBs) and FMCOL Minolta A*, FMCOL Minolta B*, GMCOL Minolta B*, and ICOL Minolta B* (Combined dataset). More QTL regions were identified with WGS (
n
= 58) relative to medium-density marker panels (
n
= 22). Most of the QTL were linked to previously reported QTLs or candidate genes that have been previously reported to be associated with meat quality, pH and pork color; e.g.,
VIL1, PRKAG3, TTLL4,
and
SLC11A1, USP37
.
CTDSP1
gene on SSC15 has not been previously associated with meat color traits in pigs. The findings suggest any added value of WGS was only for detecting novel QTL regions when the sample size is sufficiently large as with the Combined dataset in this study. The percentage of phenotypic variance explained by the most significant SNPs also increased with WGS compared with medium-density panels. The results provide additional insights into identification of a number of candidate regions and genes for pork color traits in different pig populations.
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection of pregnant females causes fetal death and increased piglet mortality, but there is substantial variation in the extent of ...reproductive pathology between individual dams. This study used RNA-sequencing to characterize the whole blood transcriptional response to type 2 PRRSV in pregnant gilts during the first week of infection (at 0, 2, and 6 days post-inoculation), and attempted to identify gene expression signatures associated with a low or high level of fetal mortality rates (LFM and HFM; n = 8/group) at necropsy, 21 days post-inoculation. The initial response to infection measured at 2 days post-inoculation saw an upregulation of genes involved in innate immunity, such as interferon-stimulated antiviral genes and inflammatory markers, and apoptosis. A concomitant decrease in expression of protein synthesis and T lymphocyte markers was observed. By day 6 the pattern had reversed, with a drop in innate immune signaling and an increase in the expression of genes involved in cell division and T cell signaling. Differentially expressed genes (DEGs) associated with extremes of litter mortality rate were identified at all three time-points. Among the 15 DEGs upregulated in LFM gilts on all three days were several genes involved in platelet function, including integrins ITGA2B and ITGB3, and the chemokine PF4 (CXCL4). LFM gilts exhibited a higher baseline expression of interferon-stimulated and pro-inflammatory genes prior to infection, and of T cell markers two days post-infection, indicative of a more rapid progression of the immune response to PRRSV. This study has increased our knowledge of the early response to PRRSV in the blood of pregnant gilts, and could ultimately lead to the development of a biomarker panel that can be used to predict PRRSV-associated reproductive pathology.
One potential role of miRNAs is to buffer variation in gene expression, although conflicting results have been reported. To investigate the buffering role of miRNAs in response to Salmonella ...infection in pigs, we sequenced miRNA and mRNA in whole blood from 15 pig samples before and after Salmonella challenge. By analyzing inter-individual variation in gene expression patterns, we found that for moderately and lowly expressed genes, putative miRNA targets showed significantly lower expression variance compared with non-miRNA-targets. Expression variance between highly expressed miRNA targets and non-miRNA-targets was not significantly different. Further, miRNA targets demonstrated significantly reduced variance after challenge whereas non-miRNA-targets did not. RNA binding proteins (RBPs) are significantly enriched among the miRNA targets with dramatically reduced variance of expression after Salmonella challenge. Moreover, we found evidence that targets of young (less-conserved) miRNAs showed lower expression variance compared with targets of old (evolutionarily conserved) miRNAs. These findings point to the importance of a buffering effect of miRNAs for relatively lowly expressed genes, and suggest that the reduced expression variation of RBPs may play an important role in response to Salmonella infection.
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. Univariate and multivariate single-step GWAS were performed on 15 CBC traits measured from the blood samples of 2743 crossbred (Landrace x 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. 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.
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