Publications by authors named "Jack C M Dekkers"

120 Publications

Investigating the genetic architecture of disease resilience in pigs by genome-wide association studies of complete blood count traits collected from a natural disease challenge model.

BMC Genomics 2021 Jul 13;22(1):535. Epub 2021 Jul 13.

Livestock Gentec, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.

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.
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http://dx.doi.org/10.1186/s12864-021-07835-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278769PMC
July 2021

Predicting the accuracy of genomic predictions.

Genet Sel Evol 2021 Jun 29;53(1):55. Epub 2021 Jun 29.

Department of Animal Science, Iowa State University, Ames, Iowa, USA.

Background: Mathematical models are needed for the design of breeding programs using genomic prediction. While deterministic models for selection on pedigree-based estimates of breeding values (PEBV) are available, these have not been fully developed for genomic selection, with a key missing component being the accuracy of genomic EBV (GEBV) of selection candidates. Here, a deterministic method was developed to predict this accuracy within a closed breeding population based on the accuracy of GEBV and PEBV in the reference population and the distance of selection candidates from their closest ancestors in the reference population.

Methods: The accuracy of GEBV was modeled as a combination of the accuracy of PEBV and of EBV based on genomic relationships deviated from pedigree (DEBV). Loss of the accuracy of DEBV from the reference to the target population was modeled based on the effective number of independent chromosome segments in the reference population (M). Measures of M derived from the inverse of the variance of relationships and from the accuracies of GEBV and PEBV in the reference population, derived using either a Fisher information or a selection index approach, were compared by simulation.

Results: Using simulation, both the Fisher and the selection index approach correctly predicted accuracy in the target population over time, both with and without selection. The index approach, however, resulted in estimates of M that were less affected by heritability, reference size, and selection, and which are, therefore, more appropriate as a population parameter. The variance of relationships underpredicted M and was greatly affected by selection. A leave-one-out cross-validation approach was proposed to estimate required accuracies of EBV in the reference population. Aspects of the methods were validated using real data.

Conclusions: A deterministic method was developed to predict the accuracy of GEBV in selection candidates in a closed breeding population. The population parameter M that is required for these predictions can be derived from an available reference data set, and applied to other reference data sets and traits for that population. This method can be used to evaluate the benefit of genomic prediction and to optimize genomic selection breeding programs.
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http://dx.doi.org/10.1186/s12711-021-00647-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244147PMC
June 2021

Heritability of perching behavior and its genetic relationship with incidence of floor eggs in Rhode Island Red chickens.

Genet Sel Evol 2021 Apr 21;53(1):38. Epub 2021 Apr 21.

Department of Animal Science, Iowa State University, 806 Stange Road, 239E Kildee Hall, Ames, IA, 50010, USA.

Background: As cage-free production systems become increasingly popular, behavioral traits such as nesting behavior and temperament have become more important. The objective of this study was to estimate heritabilities for frequency of perching and proportion of floor eggs and their genetic correlation in two Rhode Island Red lines.

Results: The percent of hens observed perching tended to increase and the proportion of eggs laid on the floor tended to decrease as the test progressed. This suggests the ability of hens to learn to use nests and perches. Under the bivariate repeatability model, estimates of heritability in the two lines were 0.22 ± 0.04 and 0.07 ± 0.05 for the percent of hens perching, and 0.52 ± 0.05 and 0.45 ± 0.05 for the percent of floor eggs. Estimates of the genetic correlation between perching and floor eggs were - 0.26 ± 0.14 and - 0.19 ± 0.27 for the two lines, suggesting that, genetically, there was some tendency for hens that better use perches to also use nests; but the phenotypic correlation was close to zero. Random regression models indicated the presence of a genetic component for learning ability.

Conclusions: In conclusion, perching and tendency to lay floor eggs were shown to be a learned behavior, which stresses the importance of proper management and training of pullets and young hens. A significant genetic component was found, confirming the possibility to improve nesting behavior for cage-free systems through genetic selection.
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http://dx.doi.org/10.1186/s12711-021-00630-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059289PMC
April 2021

Distinct transcriptomic response to Newcastle disease virus infection during heat stress in chicken tracheal epithelial tissue.

Sci Rep 2021 Apr 2;11(1):7450. Epub 2021 Apr 2.

Feed the Future Innovation Lab for Genomics to Improve Poultry, University of California, Davis, CA, 95616, USA.

Newcastle disease (ND) has a great impact on poultry health and welfare with its most virulent (velogenic) strain. In addition, issues exacerbated by the increase in global temperatures necessitates a greater understanding of the host immune response when facing a combination of biotic and abiotic stress factors in poultry production. Previous investigations have revealed that the host immune response is tissue-specific. The goal of this study was to identify genes and/or signaling pathways associated with immune response to NDV (Newcastle disease virus) in the trachea, an essential organ where NDV replicate after the infection, by profiling the tissue specific transcriptome response in two genetically distinct inbred chicken lines when exposed to both abiotic and biotic stressors. Fayoumis appear to be able to respond more effectively (lower viral titer, higher antibody levels, immune gene up-regulation) and earlier than Leghorns. Our results suggest NDV infection in Fayoumis appears to elicit proinflammatory processes, and pathways such as the inhibition of cell viability, cell proliferation of lymphocytes, and transactivation of RNA, more rapidly than in Leghorns. These differences in immune response converge at later timepoints which may indicate that Leghorns eventually regulate its immune response to infection. The profiling of the gene expression response in the trachea adds to our understanding of the chicken host response to NDV infection and heat stress on a whole genome level and provides potential candidate genes and signaling pathways for further investigation into the characterization of the time-specific and pathway specific responses in Fayoumis and Leghorns.
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http://dx.doi.org/10.1038/s41598-021-86795-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018950PMC
April 2021

Genomics of response to porcine reproductive and respiratory syndrome virus in purebred and crossbred sows: antibody response and performance following natural infection vs. vaccination.

J Anim Sci 2021 May;99(5)

Department of Animal Science, Iowa State University, Ames, IA 50011, USA.

Antibody response, measured as sample-to-positive (S/P) ratio, to porcine reproductive and respiratory syndrome virus (PRRSV) following a PRRSV-outbreak (S/POutbreak) in a purebred nucleus and following a PRRSV-vaccination (S/PVx) in commercial crossbred herds have been proposed as genetic indicator traits for improved reproductive performance in PRRSV-infected purebred and PRRSV-vaccinated crossbred sows, respectively. In this study, we investigated the genetic relationships of S/POutbreak and S/PVx with performance at the commercial (vaccinated crossbred sows) and nucleus level (non-infected and PRRSV-infected purebred sows), respectively, and tested the effect of previously identified SNP for these indicator traits. Antibody response was measured on 541 Landrace sows ~54 d after the start of a PRRSV outbreak, and on 906 F1 (Landrace × Large White) gilts ~50 d after vaccination with a commercial PRRSV vaccine. Reproductive performance was recorded for 711 and 428 Landrace sows before and during the PRRSV outbreak, respectively, and for 811 vaccinated F1 animals. The estimate of the genetic correlation (rg) of S/POutbreak with S/PVx was 0.72 ± 0.18. The estimates of rg of S/POutbreak with reproductive performance in vaccinated crossbred sows were low to moderate, ranging from 0.05 ± 0.23 to 0.30 ± 0.20. The estimate of rg of S/PVx with reproductive performance in non-infected purebred sows was moderate and favorable with number born alive (0.50 ± 0.23) but low (0 ± 0.23 to -0.11 ± 0.23) with piglet mortality traits. The estimates of rg of S/PVx were moderate and negative (-0.38 ± 0.21) with number of mummies in PRRSV-infected purebred sows and low with other traits (-0.30 ± 0.18 to 0.05 ± 0.18). Several significant associations (P0 > 0.90) of previously reported SNP for S/P ratio (ASGA0032063 and H3GA0020505) were identified for S/P ratio and performance in non-infected purebred and PRRSV-exposed purebred and crossbred sows. Genomic regions harboring the major histocompatibility complex class II region significantly contributed to the genetic correlation of antibody response to PRRSV with most of the traits analyzed. These results indicate that selection for antibody response in purebred sows following a PRRSV outbreak in the nucleus and for antibody response to PRRSV vaccination measured in commercial crossbred sows are expected to increase litter size in purebred and commercial sows.
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http://dx.doi.org/10.1093/jas/skab097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118356PMC
May 2021

Genetic basis and identification of candidate genes for wooden breast and white striping in commercial broiler chickens.

Sci Rep 2021 Mar 24;11(1):6785. Epub 2021 Mar 24.

Center for Bioinformatics and Computational Biology, University of Delaware, Newark, DE, USA.

Wooden breast (WB) and white striping (WS) are highly prevalent and economically damaging muscle disorders of modern commercial broiler chickens characterized respectively by palpable firmness and fatty white striations running parallel to the muscle fiber. High feed efficiency and rapid growth, especially of the breast muscle, are believed to contribute to development of such muscle defects; however, their etiology remains poorly understood. To gain insight into the genetic basis of these myopathies, a genome-wide association study was conducted using a commercial crossbred broiler population (n = 1193). Heritability was estimated at 0.5 for WB and WS with high genetic correlation between them (0.88). GWAS revealed 28 quantitative trait loci (QTL) on five chromosomes for WB and 6 QTL on one chromosome for WS, with the majority of QTL for both myopathies located in a ~ 8 Mb region of chromosome 5. This region has highly conserved synteny with a portion of human chromosome 11 containing a cluster of imprinted genes associated with growth and metabolic disorders such as type 2 diabetes and Beckwith-Wiedemann syndrome. Candidate genes include potassium voltage-gated channel subfamily Q member 1 (KCNQ1), involved in insulin secretion and cardiac electrical activity, lymphocyte-specific protein 1 (LSP1), involved in inflammation and immune response.
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http://dx.doi.org/10.1038/s41598-021-86176-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990949PMC
March 2021

Cross-validation of best linear unbiased predictions of breeding values using an efficient leave-one-out strategy.

J Anim Breed Genet 2021 Mar 17. Epub 2021 Mar 17.

Department of Animal Science, Iowa State University, Ames, IA, USA.

Empirical estimates of the accuracy of estimates of breeding values (EBV) can be obtained by cross-validation. Leave-one-out cross-validation (LOOCV) is an extreme case of k-fold cross-validation. Efficient strategies for LOOCV of predictions of phenotypes have been developed for a simple model with an overall mean and random marker or animal genetic effects. The objective here was to develop and evaluate an efficient LOOCV method for prediction of breeding values and other random effects under a general mixed linear model with multiple random effects. Conventional LOOCV of EBV requires inverting an (n-1)×(n-1) covariance matrix for each of n (= number of observations) data sets. Our efficient LOOCV obtains the required inverses from the inverse of the covariance matrix for all n observations. The efficient method can be applied to complex models with multiple fixed and random effects, but requires fixed effects to be treated as random, with large variances. An alternative is to precorrect observations using estimates of fixed effects obtained from the complete data, but this can lead to biases. The efficient LOOCV method was compared to conventional LOOCV of predictions of breeding values in terms of computational demands and accuracy. For a data set with 3,205 observations and a model with multiple random and fixed effects, the efficient LOOCV method was 962 times faster than the conventional LOOCV with precorrection for fixed effects based on each training data set but resulted in identical EBV. A computationally efficient LOOCV for prediction of breeding values for single- and multiple-trait mixed models with multiple fixed and random effects was successfully developed. The method enables cross-validation of predictions of breeding values and of any linear combination of random and/or fixed effects, along with leave-one-out precorrection of validation phenotypes.
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http://dx.doi.org/10.1111/jbg.12545DOI Listing
March 2021

Gene expression in tonsils in swine following infection with porcine reproductive and respiratory syndrome virus.

BMC Vet Res 2021 Feb 22;17(1):88. Epub 2021 Feb 22.

Department of Animal Science, Iowa State University, Ames, Iowa, 50011, USA.

Background: Porcine reproductive and respiratory syndrome (PRRS) is a threat to pig production worldwide. Our objective was to understand mechanisms of persistence of PRRS virus (PRRSV) in tonsil. Transcriptome data from tonsil samples collected at 42 days post infection (dpi) were generated by RNA-seq and NanoString on 51 pigs that were selected to contrast the two PRRSV isolates used, NVSL and KS06, high and low tonsil viral level at 42 dpi, and the favorable and unfavorable genotypes at a genetic marker (WUR) for the putative PRRSV resistance gene GBP5.

Results: The number of differentially expressed genes (DEGs) differed markedly between models with and without accounting for cell-type enrichments (CE) in the samples that were predicted from the RNA-seq data. This indicates that differences in cell composition in tissues that consist of multiple cell types, such as tonsil, can have a large impact on observed differences in gene expression. Based on both the NanoString and the RNA-seq data, KS06-infected pigs showed greater activation, or less inhibition, of immune response in tonsils at 42 dpi than NVSL-infected pigs, with and without accounting for CE. This suggests that the NVSL virus may be better than the KS06 virus at evading host immune response and persists in tonsils by weakening, or preventing, host immune responses. Pigs with high viral levels showed larger CE of immune cells than low viral level pigs, potentially to trigger stronger immune responses. Presence of high tonsil virus was associated with a stronger immune response, especially innate immune response through interferon signaling, but these differences were not significant when accounting for CE. Genotype at WUR was associated with different effects on immune response in tonsils of pigs during the persistence stage, depending on viral isolate and tonsil viral level.

Conclusions: Results of this study provide insights into the effects of PRRSV isolate, tonsil viral level, and WUR genotype on host immune response and into potential mechanisms of PRRSV persistence in tonsils that could be targeted to improve strategies to reduce viral rebreaks. Finally, to understand transcriptome responses in tissues that consist of multiple cell types, it is important to consider differences in cell composition.
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http://dx.doi.org/10.1186/s12917-021-02785-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901068PMC
February 2021

Vector space algebra for scaling and centering relationship matrices under non-Hardy-Weinberg equilibrium conditions.

Genet Sel Evol 2021 Jan 18;53(1). Epub 2021 Jan 18.

Department of Animal Science, Iowa State University, Ames, IA, USA.

Background: Scales are linear combinations of variables with coefficients that add up to zero and have a similar meaning to "contrast" in the analysis of variance. Scales are necessary in order to incorporate genomic information into relationship matrices for genomic selection. Statistical and biological parameterizations using scales under different assumptions have been proposed to construct alternative genomic relationship matrices. Except for the natural and orthogonal interactions approach (NOIA) method, current methods to construct relationship matrices assume Hardy-Weinberg equilibrium (HWE). The objective of this paper is to apply vector algebra to center and scale relationship matrices under non-HWE conditions, including orthogonalization by the Gram-Schmidt process.

Theory And Methods: Vector space algebra provides an evaluation of current orthogonality between additive and dominance vectors of additive and dominance scales for each marker. Three alternative methods to center and scale additive and dominance relationship matrices based on the Gram-Schmidt process (GSP-A, GSP-D, and GSP-N) are proposed. GSP-A removes additive-dominance co-variation by first fitting the additive and then the dominance scales. GSP-D fits scales in the opposite order. We show that GSP-A is algebraically the same as the NOIA model. GSP-N orthonormalizes the additive and dominance scales that result from GSP-A. An example with genotype information on 32,645 single nucleotide polymorphisms from 903 Large-White × Landrace crossbred pigs is used to construct existing and newly proposed additive and dominance relationship matrices.

Results: An exact test for departures from HWE showed that a majority of loci were not in HWE in crossbred pigs. All methods, except the one that assumes HWE, performed well to attain an average of diagonal elements equal to one and an average of off diagonal elements equal to zero. Variance component estimation for a recorded quantitative phenotype showed that orthogonal methods (NOIA, GSP-A, GSP-N) can adjust for the additive-dominance co-variation when estimating the additive genetic variance, whereas GSP-D does it when estimating dominance components. However, different methods to orthogonalize relationship matrices resulted in different proportions of additive and dominance components of variance.

Conclusions: Vector space methodology can be applied to measure orthogonality between vectors of additive and dominance scales and to construct alternative orthogonal models such as GSP-A, GSP-D and an orthonormal model such as GSP-N. Under non-HWE conditions, GSP-A is algebraically the same as the previously developed NOIA model.
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http://dx.doi.org/10.1186/s12711-020-00589-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812663PMC
January 2021

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

Front Genet 2020 23;11:593804. Epub 2020 Oct 23.

Department of Animal Science, Iowa State University, Ames, IA, United States.

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), (MH), porcine circovirus (PCV2), and (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 (r ) of Ab response to IAV with MH, PCV2, PRRSV, and APP (average Ab responses for all serotypes of APP) were positive (>0.29) at entry. APP was negatively correlated with PCV2 and MH at entry and parity 2 but positively correlated with MH at post-acclimation 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.
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http://dx.doi.org/10.3389/fgene.2020.593804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646516PMC
October 2020

Genetic Analysis of Antibody Response to Porcine Reproductive and Respiratory Syndrome Vaccination as an Indicator Trait for Reproductive Performance in Commercial Sows.

Front Genet 2020 11;11:1011. Epub 2020 Sep 11.

Department of Animal Science, Iowa State University, Ames, IA, United States.

We proposed to investigate the genomic basis of antibody response to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) vaccination and its relationship to reproductive performance in non-PRRSV-infected commercial sows. Nine hundred and six F1 replacement gilts (139 ± 17 days old) from two commercial farms were vaccinated with a commercial modified live PRRSV vaccine. Blood samples were collected about 52 days after vaccination to measure antibody response to PRRSV as sample-to-positive (S/P) ratio and for single-nucleotide polymorphism (SNP) genotyping. Reproductive performance was recorded for up to 807 sows for number born alive (NBA), number of piglets weaned, number born mummified (MUM), number of stillborn (NSB), and number of pre-weaning mortality (PWM) at parities (P) 1-3 and per sow per year (PSY). Fertility traits such as farrowing rate and age at first service were also analyzed. BayesC0 was used to estimate heritability and genetic correlations of S/P ratio with reproductive performance. Genome-wide association study (GWAS) and genomic prediction were performed using BayesB. The heritability estimate of S/P ratio was 0.34 ± 0.05. High genetic correlations ( ) of S/P ratio with farrowing performance were identified for NBA P1 (0.61), PWM P2 (-0.70), NSB P3 (-0.83), MUM P3 (-0.84), and NSB PSY (-0.90), indicating that genetic selection for increased S/P ratio would result in improved performance of these traits. A quantitative trait locus was identified on chromosome 7 (∼25 Mb), at the major histocompatibility complex (MHC) region, explaining ∼30% of the genetic variance for S/P ratio, mainly by SNPs ASGA0032113, H3GA0020505, and M1GA0009777. This same region was identified in the bivariate GWAS of S/P ratio and reproductive traits, with SNP H3GA0020505 explaining up to 10% (for NBA P1) of the genetic variance of reproductive performance. The heterozygote genotype at H3GA0020505 was associated with greater S/P ratio and NBA P1 ( = 0.06), and lower MUM P3 and NSB P3 ( = 0.07). Genomic prediction accuracy for S/P ratio was high when using all SNPs (0.67) and when using only those in the MHC region (0.59) and moderate to low when using all SNPs excluding those in the MHC region (0.39). These results suggest that there is great potential to use antibody response to PRRSV vaccination as an indicator trait to improve reproductive performance in commercial pigs.
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http://dx.doi.org/10.3389/fgene.2020.01011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516203PMC
September 2020

The genetic basis of natural antibody titers of young healthy pigs and relationships with disease resilience.

BMC Genomics 2020 Sep 22;21(1):648. Epub 2020 Sep 22.

Department of Large Animal Clinical Sciences, University of Saskatchewan, Saskatoon, SK, Canada.

Background: 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.

Results: 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.

Conclusions: Levels of NAb in blood of healthy young piglets are heritable and potential genetic indicators of resilience to polymicrobial disease.
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http://dx.doi.org/10.1186/s12864-020-06994-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510148PMC
September 2020

Transcriptome Analysis Reveals Inhibitory Effects of Lentogenic Newcastle Disease Virus on Cell Survival and Immune Function in Spleen of Commercial Layer Chicks.

Genes (Basel) 2020 08 26;11(9). Epub 2020 Aug 26.

Department of Animal Science, Iowa State University, Ames, IA 50011, USA.

As a major infectious disease in chickens, Newcastle disease virus (NDV) causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 days post inoculation (dpi) at day 21 with a lentogenic NDV in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV-challenged and non-challenged groups, 526 differentially expressed genes (DEGs) (false discovery rate (FDR) < 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, Ingenuity Pathway Analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis, and angiogenesis. Up-regulation of interferon induced protein with tetratricopeptide repeats 5 () in response to NDV was consistent between the current and most previous studies. Sprouty RTK signaling antagonist 1 (), a DEG in the current study, is in a significant quantitative trait locus associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.
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http://dx.doi.org/10.3390/genes11091003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565929PMC
August 2020

Genetic Basis of Response of Ghanaian Local Chickens to Infection With a Lentogenic Newcastle Disease Virus.

Front Genet 2020 28;11:739. Epub 2020 Jul 28.

Department of Animal Science, Iowa State University, Ames, IA, United States.

Newcastle disease (ND) is a global threat to domestic poultry, especially in rural areas of Africa and Asia, where the loss of entire backyard local chicken flocks often threatens household food security and income. To investigate the genetics of Ghanaian local chicken ecotypes to Newcastle disease virus (NDV), in this study, three popular Ghanaian chicken ecotypes (regional populations) were challenged with a lentogenic NDV strain at 28 days of age. This study was conducted in parallel with a similar study that used three popular Tanzanian local chicken ecotypes and after two companion studies in the United States, using Hy-line Brown commercial laying birds. In addition to growth rate, NDV response traits were measured following infection, including anti-NDV antibody levels [pre-infection and 10 days post-infection (dpi)], and viral load (2 and 6 dpi). Genetic parameters were estimated, and two genome-wide association study analysis methods were used on data from 1,440 Ghanaian chickens that were genotyped on a chicken 600K Single Nucleotide Polymorphism (SNP) chip. Both Ghana and Tanzania NDV challenge studies revealed moderate to high (0.18 - 0.55) estimates of heritability for all traits, except viral clearance where the heritability estimate was not different from zero for the Tanzanian ecotypes. For the Ghana study, 12 quantitative trait loci (QTL) for growth and/or response to NDV from single-SNP analyses and 20 genomic regions that explained more than 1% of genetic variance using the Bayes B method were identified. Seven of these windows were also identified as having at least one significant SNP in the single SNP analyses for growth rate, anti-NDV antibody levels, and viral load at 2 and 6 dpi. An important gene for growth during stress, CHORDC1 associated with post-infection growth rate was identified as a positional candidate gene, as well as other immune related genes, including VAV2, IL12B, DUSP1, and IL17B. The QTL identified in the Ghana study did not overlap with those identified in the Tanzania study. However, both studies revealed QTL with genes vital for growth and immune response during NDV challenge. The Tanzania parallel study revealed an overlapping QTL on chromosome 24 for viral load at 6 dpi with the US NDV study in which birds were challenged with NDV under heat stress. This QTL region includes genes related to immune response, including TIRAP, ETS1, and KIRREL3. The moderate to high estimates of heritability and the identified QTL suggest that host response to NDV of local African chicken ecotypes can be improved through selective breeding to enhance increased NDV resistance and vaccine efficacy.
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http://dx.doi.org/10.3389/fgene.2020.00739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402339PMC
July 2020

Genetic analysis of disease resilience in wean-to-finish pigs from a natural disease challenge model.

J Anim Sci 2020 Aug;98(8)

Department of Animal Science, Iowa State University, Ames, IA.

The objective was to estimate the genetic parameters of performance and resilience of growing pigs under disease. Data were from 3,139 Yorkshire × Landrace wean-to-finish pigs that were exposed to a natural polymicrobial disease challenge that was established by entering naturally infected animals into a nursery barn, targeting various viral and bacterial diseases. The challenge was maintained by entering batches of 60 or 75 healthy nursery pigs every 3 wk in a continuous flow system. Traits analyzed included average daily gain (ADG), feed intake (ADFI) and duration (ADFD); feed conversion ratio (FCR); residual feed intake (RFI); mortality (MOR); number of health treatments (TRT); health scores (HScore); carcass weight (CWT), back fat (CBF) and loin depth (CLD); dressing percentage (DRS); lean yield (LYLD); day-to-day variation in feed intake and duration (VARFI and VARDUR); and the proportion of off-feed days (OFFFI and OFFDUR). Analyses were performed by mixed linear models with genomic relationships. The resilience traits, such as TRT, MOR, and HScore, were lowly heritable (up to 0.15) but had high genetic correlations with each other. Performance traits, such as ADG, ADFI, ADFD, FCR, RFI, and carcass traits, were moderate to highly heritable (0.17 to 0.49). Heritabilities of resilience indicator traits such as OFF and VAR had low to moderate heritabilities (0.08 to 0.23) but were higher when based on duration vs. amount. ADFI had a low genetic correlation with ADFD (0.13). ADG in the challenge nursery had stronger negative genetic correlations with both TRT and MOR than ADG in the finisher (-0.37 to -0.74 vs. -0.15 to -0.56). ADFI and FCR had moderate negative (-0.21 to -0.39) and positive (0.34 to 0.49) genetic correlations, respectively, with TRT and MOR. ADFD and RFI had very low genetic correlations with TRT and MOR. CWT and DRS were moderately negatively correlated with TRT and MOR (-0.33 to -0.59). Resilience indicator traits based on feed intake or duration had moderate to high positive genetic correlations with TRT (0.18 to 0.81) and MOR (0.33 to 0.87). In conclusion, performance and resilience traits under a polymicrobial disease challenge are heritable and can be changed by selection. Phenotypes extracted from feed intake patterns can be used as genetic indicator traits for disease resilience. Most promising is day-to-day variation in intake duration, which had a sizeable heritability (0.23) and favorable genetic correlations with MOR (0.79) and treatment rate (0.20).
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http://dx.doi.org/10.1093/jas/skaa244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531181PMC
August 2020

Effects of divergent selection for residual feed intake on nitrogen metabolism and lysine utilization in growing pigs.

J Anim Sci 2020 May;98(5)

Department of Animal and Food Sciences, Texas Tech University, Lubbock, TX.

A study was conducted to evaluate the effects of divergent genetic selection for residual feed intake (RFI) on nitrogen (N) metabolism and lysine utilization in growing pigs. Twenty-four gilts (body weight [BW] 66 ± 5 kg) were selected from generation nine of the low RFI (LRFI; n = 12) and high RFI (HRFI; n = 12) Iowa State University Yorkshire RFI selection lines. Six pigs from each genetic line were assigned to each of two levels of lysine intake: 70% and 100% of estimated requirements based on the potential of each genetic line for protein deposition (PD) and feed intake. For all diets, lysine was first limiting among amino acids. Using isotope tracer, N-balance, and nutrient digestibility evaluation approaches, whole-body N metabolism and the efficiency of lysine utilization were determined for each treatment group. No significant interaction effects of line and diet on dietary N or gross energy digestibility, PD, and the efficiency of lysine utilization for PD were observed. The line did not have a significant effect on PD and digestibility of dietary N and GE. An increase in lysine intake improved N retention in both lines (from 15.0 to 19.6 g/d, SE 1.44, in LRFI pigs; and from 16.9 to 19.8 g/d, SE 1.67, in HRFI pigs; P < 0.01). At the low lysine intakes and when lysine clearly limited PD, the efficiency of using available lysine intake (above maintenance requirements) for PD was 80% and 91% (SE 4.6) for the LRFI and HRFI pigs, respectively (P = 0.006). There were no significant effects of line or of the line by diet interaction on N flux, protein synthesis, and protein degradation. Lysine intake significantly increased (P < 0.05) N flux (from 119 to 150, SE 8.7 g/d), protein synthesis (from 99 to 117, SE 10.6 g of N/d), and protein degradation (from 85 to 100, SE 6.6 g of N/d). The protein synthesis-to-retention ratio tended to be higher in the LRFI line compared with the HRFI line (6.5 vs. 5.8 SE 0.62; P = 0.06), indicating a tendency for the lower efficiency of PD in this group. Collectively, these results indicate that genetic selection for low RFI is not associated with improvements in lysine utilization efficiency, protein turnover, and nutrient digestibility.
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http://dx.doi.org/10.1093/jas/skaa152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247536PMC
May 2020

CD3ε Cells in Pigs With Severe Combined Immunodeficiency Due to Defects in .

Front Immunol 2020 31;11:510. Epub 2020 Mar 31.

Department of Animal Science, Iowa State University, Ames, IA, United States.

Severe combined immunodeficiency (SCID) is described as the lack of functional T and B cells. In some cases, mutant genes encoding proteins involved in the process of VDJ recombination retain partial activity and are classified as hypomorphs. Hypomorphic activity in the products from these genes can function in the development of T and B cells and is referred to as a leaky phenotype in patients and animals diagnosed with SCID. We previously described two natural, single nucleotide variants in () in a line of Yorkshire pigs that resulted in SCID. One allele contains a splice site mutation within intron 8 of the gene (), while the other mutation is within exon 10 that results in a premature stop codon (). While initially characterized as SCID and lacking normal levels of circulating lymphoid cells, low levels of CD3ε cells can be detected in most SCID animals. Upon further assessment, we found that , and SCID pigs had abnormally small populations of CD3ε cells, but not CD79α cells, in circulation and lymph nodes. Newborn pigs (0 days of age) had CD3ε cells within lymph nodes prior to any environmental exposure. CD3ε cells in SCID pigs appeared to have a skewed CD4αCD8αCD8β T helper memory phenotype. Additionally, in some pigs, rearranged VDJ joints were detected in lymph node cells as probed by PCR amplification of TCRδ V5 and J1 genomic loci, as well as TCRβ V20 and J1.1, providing molecular evidence of residual Artemis activity. We additionally confirmed that TCRα and TCRδ constant region transcripts were expressed in the thymic and lymph node tissues of SCID pigs; although the expression pattern was abnormal compared to carrier animals. The leaky phenotype is important to characterize, as SCID pigs are an important tool for biomedical research and this additional phenotype may need to be considered. The pig model also provides a relevant model for hypomorphic human SCID patients.
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http://dx.doi.org/10.3389/fimmu.2020.00510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136459PMC
March 2021

A biphasic curve for modeling, classifying, and predicting egg production in single cycle and molted flocks.

Poult Sci 2020 Apr 7;99(4):2007-2010. Epub 2020 Feb 7.

Department of Animal Science, Iowa State University, Ames, IA 50011.

Egg production on a flock level can be summarized into several phases determined by biology of individual birds: rapid increase in production reflecting achieving sexual maturity, peak production related to maximum laying potential, followed by gradual decrease in the rate of lay as the birds age. In 1989 Yang et al. proposed a mathematical model (modified compartmental model) to describe this process. In this study a biphasic modified compartmental model was proposed for modeling, classifying, and predicting egg production in single cycle and molted flocks. Goodness-of-fit was high for both single cycle (average R = 0.99) and molted flocks (average R = 0.97), suggesting that the model could be used for benchmarking molted flocks. The difference in R between the biphasic model and the model used by Yang et al in 1989 can be used to differentiate between single cycle and molted flocks. The biphasic model was shown to predict future records well up to 8 wk in advance, but as with any regression model, caution is recommended when predicting records outside of the observed age range.
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http://dx.doi.org/10.1016/j.psj.2019.11.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587815PMC
April 2020

Exploring Phenotypes for Disease Resilience in Pigs Using Complete Blood Count Data From a Natural Disease Challenge Model.

Front Genet 2020 13;11:216. Epub 2020 Mar 13.

Livestock Gentec, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.

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 ( < 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.
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http://dx.doi.org/10.3389/fgene.2020.00216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083204PMC
March 2020

Novel Combined Tissue Transcriptome Analysis After Lentogenic Newcastle Disease Virus Challenge in Inbred Chicken Lines of Differential Resistance.

Front Genet 2020 4;11:11. Epub 2020 Feb 4.

Department of Animal Science, Iowa State University, Ames, IA, United States.

Disease has large negative impacts on poultry production. A more comprehensive understanding of host-pathogen interaction can lead to new and improved strategies to maintain health. In particular, host genetic factors can lead to a more effective response to pathogens, hereafter termed resistance. Fayoumi and Leghorn chicken lines have demonstrated relative resistance and susceptibility, respectively, to the Newcastle disease virus (NDV) vaccine strain and many other pathogens. This biological model was used to better understand the host response to a vaccine strain of NDV across three tissues and time points, using RNA-seq. Analyzing the Harderian gland, trachea, and lung tissues together using weighted gene co-expression network analysis (WGCNA) identified important genes that were co-expressed and associated with parameters including: genetic line, days post-infection (dpi), challenge status, sex, and tissue. Pathways and driver genes, such as , , and , associated with challenge status, dpi, and genetic line were of particular interest as candidates for disease resistance. Overall, by jointly analyzing the three tissues, this study identified genes and gene networks that led to a more comprehensive understanding of the whole animal response to lentogenic NDV than that obtained by analyzing the tissues individually.
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http://dx.doi.org/10.3389/fgene.2020.00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013128PMC
February 2020

Novel Engraftment and T Cell Differentiation of Human Hematopoietic Cells in SCID Pigs.

Front Immunol 2020 6;11:100. Epub 2020 Feb 6.

Department of Animal Science, Iowa State University, Ames, IA, United States.

Pigs with severe combined immunodeficiency (SCID) are an emerging biomedical animal model. Swine are anatomically and physiologically more similar to humans than mice, making them an invaluable tool for preclinical regenerative medicine and cancer research. One essential step in further developing this model is the immunological humanization of SCID pigs. In this work we have generated T B NK SCID pigs through site directed CRISPR/Cas9 mutagenesis of within a naturally occurring genetic background. We confirmed pigs lacked T, B, and NK cells in both peripheral blood and lymphoid tissues. Additionally, we successfully performed a bone marrow transplant on one male SCID pig with bone marrow from a complete swine leukocyte antigen (SLA) matched donor without conditioning to reconstitute porcine T and NK cells. Next, we performed injections of cultured human CD34 selected cord blood cells into the fetal SCID pigs. At birth, human CD45 CD3ε cells were detected in cord and peripheral blood of injected SCID piglets. Human leukocytes were also detected within the bone marrow, spleen, liver, thymus, and mesenteric lymph nodes of these animals. Taken together, we describe critical steps forwards the development of an immunologically humanized SCID pig model.
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http://dx.doi.org/10.3389/fimmu.2020.00100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017803PMC
March 2021

Investigating the relationship between vaginal microbiota and host genetics and their impact on immune response and farrowing traits in commercial gilts.

J Anim Breed Genet 2020 Jan 25;137(1):84-102. Epub 2019 Nov 25.

Department of Animal Science, Iowa State University, Ames, Iowa.

Our objectives were to evaluate the interaction between host genetics and vaginal microbiota and their relationships with antibody (Ab) response to porcine reproductive and respiratory syndrome virus (PRRSV) vaccination and farrowing performance in commercial gilts. The farrowing performance traits were number born alive, number weaning (NW), total number born, number born dead, stillborn, mummies and preweaning mortality (PWM). The vaginal microbiota was collected on days 4 (D4) and 52 (D52) after vaccination for PRRSV. Blood samples were collected on D52 for Ab measurement. Actinobacteria, Bacterioidetes, Firmicutes, Proteobacteria and Tenericutes were the most abundant Phyla identified in the vaginal microbiota. Heritability ranged from ~0 to 0.60 (Fusobacterium) on D4 and from ~0 to 0.63 (Terrisporobacter) on D52, with 43 operational taxonomic units (OTUs) presenting moderate to high heritability. One major QTL on chromosome 12 was identified for 5 OTUs (Clostridiales, Acinetobacter, Ruminococcaceae, Campylobacter and Anaerococcus), among other 19 QTL. The microbiability for Ab response to PRRSV vaccination was low for both days (<0.07). For farrowing performance, microbiability varied from <0.001 to 0.15 (NW on D4). For NW and PWM, the microbiability was greater than the heritability estimates. Actinobacillus, Streptococcus, Campylobacter, Anaerococcus, Mollicutes, Peptostreptococcus, Treponema and Fusobacterium showed different abundance between low and high Ab responders. Finally, canonical discriminant analyses revealed that vaginal microbiota was able to classify gilts in high and low Ab responders to PRRSV vaccination with a misclassification rate of <0.02. Although the microbiota explained limited variation in Ab response and farrowing performance traits, there is still potential to explore the use of vaginal microbiota to explain variation in traits such as NW and PWM. In addition, these results revealed that there is a partial control of host genetic over vaginal microbiota, suggesting a possibility for genetic selection on the vaginal microbiota.
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http://dx.doi.org/10.1111/jbg.12456DOI Listing
January 2020

Effect of a dual enteric and respiratory pathogen challenge on swine growth, efficiency, carcass composition, and pork quality1.

J Anim Sci 2019 Dec;97(12):4710-4720

Department of Animal Science, Iowa State University, Ames, IA.

The objective of this study was to determine the influence of a dual respiratory and enteric pathogen challenge on growth performance, carcass composition, and pork quality of high and low feed efficient pigs. Pigs divergently selected for low and high residual feed intake (RFI, ~68 kg) from the 11th generation of Iowa State University RFI project were used to represent high and low feed efficiency. To elicit a dual pathogen challenge, half of the pigs (n = 12/line) were inoculated with Mycoplasma hyopneumoniae (Mh) and Lawsonia intracellularis (MhLI) on days post-inoculation (dpi) 0. Pigs in a separate room of the barn were not inoculated and used as controls (n = 12/RFI line). Pigs were weighed and feed intake was recorded to calculate ADG, ADFI, and G:F for the acclimation period (period 1: dpi -21 to 0), during peak infection (period 2: dpi 0 to 42), and during the remaining growth period to reach market weight (period 3: dpi 42 to harvest). At ~125 kg, pigs were harvested using standard commercial procedures. Carcasses were evaluated for composition (weight, fat free lean, loin eye area, 10th rib fat depth) and meat quality (pH decline, temperature decline, Hunter L, a, and b, subjective color and marbling, star probe, drip loss, cook loss, proximate composition, and desmin degradation). Challenged pigs had lesser ADFI than controls during period 2 (P < 0.05), but had greater ADG and G:F during period 3 (P < 0.05). Selection for feed efficiency did not result in a differential response to MhLI (P > 0.05). Loin chops from the less feed efficient, high RFI pigs, had greater drip loss, greater cook loss, lesser moisture content, greater Hunter L values, and greater Hunter b values (P < 0.05) than loin chops from low RFI pigs. Infection status did not significantly affect carcass composition or pork quality traits (P > 0.05). These results indicate that a MhLI challenge early in growth did not significantly affect ultimate carcass composition or meat quality traits. Selection for greater feed efficiency in pigs did not affect their response to pathogenic challenge.
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http://dx.doi.org/10.1093/jas/skz332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915223PMC
December 2019

The effects of a globin blocker on the resolution of 3'mRNA sequencing data in porcine blood.

BMC Genomics 2019 Oct 15;20(1):741. Epub 2019 Oct 15.

Department of Animal Science, Iowa State University, Ames, 50011, Iowa, USA.

Background: Gene expression profiling in blood is a potential source of biomarkers to evaluate or predict phenotypic differences between pigs but is expensive and inefficient because of the high abundance of globin mRNA in porcine blood. These limitations can be overcome by the use of QuantSeq 3'mRNA sequencing (QuantSeq) combined with a method to deplete or block the processing of globin mRNA prior to or during library construction. Here, we validated the effectiveness of QuantSeq using a novel specific globin blocker (GB) that is included in the library preparation step of QuantSeq.

Results: In data set 1, four concentrations of the GB were applied to RNA samples from two pigs. The GB significantly reduced the proportion of globin reads compared to non-GB (NGB) samples (P = 0.005) and increased the number of detectable non-globin genes. The highest evaluated concentration (C1) of the GB resulted in the largest reduction of globin reads compared to the NGB (from 56.4 to 10.1%). The second highest concentration C2, which showed very similar globin depletion rates (12%) as C1 but a better correlation of the expression of non-globin genes between NGB and GB (r = 0.98), allowed the expression of an additional 1295 non-globin genes to be detected, although 40 genes that were detected in the NGB sample (at a low level) were not present in the GB library. Concentration C2 was applied in the rest of the study. In data set 2, the distribution of the percentage of globin reads for NGB (n = 184) and GB (n = 189) samples clearly showed the effects of the GB on reducing globin reads, in particular for HBB, similar to results from data set 1. Data set 3 (n = 84) revealed that the proportion of globin reads that remained in GB samples was significantly and positively correlated with the reticulocyte count in the original blood sample (P < 0.001).

Conclusions: The effect of the GB on reducing the proportion of globin reads in porcine blood QuantSeq was demonstrated in three data sets. In addition to increasing the efficiency of sequencing non-globin mRNA, the GB for QuantSeq has an advantage that it does not require an additional step prior to or during library creation. Therefore, the GB is a useful tool in the quantification of whole gene expression profiles in porcine blood.
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http://dx.doi.org/10.1186/s12864-019-6122-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794815PMC
October 2019

Acute systemic inflammatory response to lipopolysaccharide stimulation in pigs divergently selected for residual feed intake.

BMC Genomics 2019 Oct 11;20(1):728. Epub 2019 Oct 11.

Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA, 50011, USA.

Background: It is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs' immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells.

Results: LPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p = 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count or levels of several plasma cytokines were detected between the two lines. Profiling blood transcriptomes at 0, 2, 6, and 24 hpi by RNA-sequencing revealed that LPS induced dramatic transcriptional changes, with 6296 genes differentially expressed at at least one time point post injection relative to baseline in at least one line (n = 4 per line) (|log(fold change)| ≥ log(1.2); q < 0.05). Furthermore, applying the same cutoffs, we detected 334 genes differentially expressed between the two lines at at least one time point, including 33 genes differentially expressed between the two lines at baseline. But no significant line-by-time interaction effects were detected. Genes involved in protein translation, defense response, immune response, and signaling were enriched in different co-expression clusters of genes responsive to LPS stimulation. The two lines were largely similar in their peripheral blood transcriptomic responses to LPS stimulation at the pathway level, although the low-RFI line had a slightly lower level of inflammatory response than the high-RFI line from 2 to 6 hpi and a slightly higher level of inflammatory response than the high-RFI line at 24 hpi.

Conclusions: The pig lines divergently selected for RFI had a largely similar response to LPS stimulation. However, the low-RFI line had a relatively lower-level, but longer-lasting, inflammatory response compared to the high-RFI line. Our results suggest selection for feed efficient pigs does not significantly compromise a pig's acute systemic inflammatory response to LPS, although slight differences in intensity and duration may occur.
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http://dx.doi.org/10.1186/s12864-019-6127-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792331PMC
October 2019

Autozygosity and Genetic Differentiation of Landrace and Large White Pigs as Revealed by the Genetic Analyses of Crossbreds.

Front Genet 2019 5;10:739. Epub 2019 Sep 5.

Department of Animal Science, Iowa State University, Ames, IA, United States.

Genomic information from crossbreds is routinely generated for genomic evaluations. The objective of this study is to investigate autozygosity and genetic differentiation in Landrace by Large-White breeds by using the genotypic information of SNP arrays in 1,173 crossbreds. A maximum likelihood approach was developed to estimate the probability of autozygosity ( ). Regions of differentiation between breeds were investigated using and the difference in allele frequencies between the two parental breeds (릌Δ) at each single-nucleotide polymorphism (SNP) position. A maximum likelihood approach was proposed to estimate allele frequencies in the parental populations. The average length of runs of homozygosity (ROH) across the genome was 3.91, 2.3, and 0.7 Mb for segments with at least 25, 15, and 5 SNPs, respectively. Average age to coalesce was 46, 414, and 388 years for segments with at least 25, 15, and 5 SNPs, respectively. The probability of autozygosity was not uniform along the crossbred genome, being higher at the center for most chromosomes. The correlation between autozygosity and distance to the closest telomere was positive and significant in most chromosomes, which could be attributed to the higher recombination rate near telomeres. We also report a relatively high negative correlation between probability of recombination (from a published map) and probability of autozygosity. It supports that structural characteristics of the chromosomes related to recombination rate determine autozygosity at each chromosomal position of the pig genome. The average is Δ across the genome was 0.17 (SD = 0.16). After testing for differences in allele frequencies between the parental breeds, there were 4,184 SNPs with a likelihood ratio test, LRT ≥ 32.02. The average across the genome was 0.038 (SD = 0.059). There were 2,949 SNPs with > 0.125. The correlation between estimates of and estimates of across the genome was -0.10 (SE = 0.006). Analysis of the gene content of the genomic regions with the 2000 SNPs with highest LRT for and high showed overrepresentation of genes with a regulatory function. Genes with biological functions associated with production, such as tissue development, anatomical structure, and animal organ development, were also overrepresented in regions with a high .
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http://dx.doi.org/10.3389/fgene.2019.00739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739446PMC
September 2019

Genetic Analyses of Tanzanian Local Chicken Ecotypes Challenged with Newcastle Disease Virus.

Genes (Basel) 2019 07 17;10(7). Epub 2019 Jul 17.

Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011, USA.

Newcastle Disease (ND) is a continuing global threat to domestic poultry, especially in developing countries, where severe outbreaks of velogenic ND virus (NDV) often cause major economic losses to households. Local chickens are of great importance to rural family livelihoods through provision of high-quality protein. To investigate the genetic basis of host response to NDV, three popular Tanzanian chicken ecotypes (regional populations) were challenged with a lentogenic (vaccine) strain of NDV at 28 days of age. Various host response phenotypes, including anti-NDV antibody levels (pre-infection and 10 days post-infection, dpi), and viral load (2 and 6 dpi) were measured, in addition to growth rate. We estimated genetic parameters and conducted genome-wide association study analyses by genotyping 1399 chickens using the Affymetrix 600K chicken SNP chip. Estimates of heritability of the evaluated traits were moderate (0.18-0.35). Five quantitative trait loci (QTL) associated with growth and/or response to NDV were identified by single-SNP analyses, with some regions explaining ≥1% of genetic variance based on the Bayes-B method. Immune related genes, such as ETS1, TIRAP, and KIRREL3, were located in regions associated with viral load at 6 dpi. The moderate estimates of heritability and identified QTL indicate that NDV response traits may be improved through selective breeding of chickens to enhance increased NDV resistance and vaccine efficacy in Tanzanian local ecotypes.
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http://dx.doi.org/10.3390/genes10070546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678660PMC
July 2019

Infectivity of GII.4 human norovirus does not differ between T-B-NK severe combined immunodeficiency (SCID) and non-SCID gnotobiotic pigs, implicating the role of NK cells in mediation of human norovirus infection.

Virus Res 2019 07 2;267:21-25. Epub 2019 May 2.

Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio, USA. Electronic address:

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. It is unclear which arm of the immune system regulates resistance to HuNoV infection. Thus, we studied the pathogenesis of human norovirus (HuNoV) in TBNK Severe Combined Immunodeficiency (SCID) gnotobiotic pigs to investigate the role of innate (especially, natural killer (NK) cells) immunity in HuNoV infection. Forty SCID and non-SCID pigs were randomly grouped: 1) SCID+HuNoV (n = 12); 2) non-SCID+HuNoV (n = 14); 3) SCID mock-inoculated (n = 6); and 4) non-SCID mock-inoculated (n = 8). Pigs (8-14-day-old) were inoculated orally with GII.4 HuNoV strain HS292 (mean 9.1 log genomic equivalents/pig) or mock. Daily fecal consistency and fecal viral RNA shedding, and histopathology (at euthanasia) were evaluated. Frequencies of blood and ileal T, B, and NK cells were analyzed by flow cytometry, and a NK cell cytotoxicity assay was performed at post-inoculation day (PID) 8. Unlike the increased infectivity of HuNoV observed previously in TBNK SCID pigs (Lei et al., 2016. Sci. Rep. 6, 25,222), there was no significant difference in frequency of pigs with diarrhea and diarrhea days between TBNK SCID+HuNoV and non-SCID+HuNoV groups. Cumulative fecal HuNoV RNA shedding at PIDs 1-8, PIDs 9-27, and PIDs 1-27 also did not differ statistically. These observations coincided with the presence of NK cells and NK cell cytotoxicity in the ileum and blood of the SCID pigs. Based on our observations, innate immunity, including NK cell activity, may be critical to mediate or reduce HuNoV infection in TBNK SCID pigs, and potentially in immunocompetent patients.
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http://dx.doi.org/10.1016/j.virusres.2019.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534450PMC
July 2019

Identification of recombination hotspots and quantitative trait loci for recombination rate in layer chickens.

J Anim Sci Biotechnol 2019 26;10:20. Epub 2019 Feb 26.

1Department of Animal Science, Iowa State University, Ames, IA 50010 USA.

Background: The frequency of recombination events varies across the genome and between individuals, which may be related to some genomic features. The objective of this study was to assess the frequency of recombination events and to identify QTL (quantitative trait loci) for recombination rate in two purebred layer chicken lines.

Methods: A total of 1200 white-egg layers (WL) were genotyped with 580 K SNPs and 5108 brown-egg layers (BL) were genotyped with 42 K SNPs (single nucleotide polymorphisms). Recombination events were identified within half-sib families and both the number of recombination events and the recombination rate was calculated within each 0.5 Mb window of the genome. The 10% of windows with the highest recombination rate on each chromosome were considered to be recombination hotspots. A BayesB model was used separately for each line to identify genomic regions associated with the genome-wide number of recombination event per meiosis. Regions that explained more than 0.8% of genetic variance of recombination rate were considered to harbor QTL.

Results: Heritability of recombination rate was estimated at 0.17 in WL and 0.16 in BL. On average, 11.3 and 23.2 recombination events were detected per individual across the genome in 1301 and 9292 meioses in the WL and BL, respectively. The estimated recombination rates differed significantly between the lines, which could be due to differences in inbreeding levels, and haplotype structures. Dams had about 5% to 20% higher recombination rates per meiosis than sires in both lines. Recombination rate per 0.5 Mb window had a strong negative correlation with chromosome size and a strong positive correlation with GC content and with CpG island density across the genome in both lines. Different QTL for recombination rate were identified in the two lines. There were 190 and 199 non-overlapping recombination hotspots detected in WL and BL respectively, 28 of which were common to both lines.

Conclusions: Differences in the recombination rates, hotspot locations, and QTL regions associated with genome-wide recombination were observed between lines, indicating the breed-specific feature of detected recombination events and the control of recombination events is a complex polygenic trait.
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http://dx.doi.org/10.1186/s40104-019-0332-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390344PMC
February 2019

Genetics of male reproductive performance in White Leghorns.

Poult Sci 2019 Jul;98(7):2729-2733

Department of Animal Science, Iowa State University, Ames, IA 50011-3150.

The ability to produce viable progeny is a complex trait, involving both male and female components. In poultry, mating ratios are usually 1 male to 6 to 12 females. Consequently, the impact of male reproductive failure is much greater than that for a female. In this study, the genetic determination of male reproductive performance, by natural mating and artificial insemination (AI), was evaluated. Semen quality was studied in 1,575 pre-selected (using a selection index of multiple egg production and quality traits) White Leghorn males of a single pure line from multiple generations. A subset of individuals with satisfactory semen quality (based on sperm count and motility) were further tested for subsequent fertility and hatchability. Genetic parameters for fertility (FER), hatch of fertile (HOF), hatch of set (HOS), sperm motility (SM), sperm count (SC), and fertility using AI (FER-AI) were estimated using single- and multi-trait animal models, with generation as fixed effect. Selected birds were genotyped using the 600K Affymetrix SNP chip. Genomic data were analyzed with the BayesB method. FER, HOS, and HOF were highly correlated, both genetically (0.82 to 0.99) and phenotypically (0.28 to 0.99), but genetic correlations with semen quality traits were not strong (0.05 to 0.43) and phenotypic correlations varied between generations (-0.13 to 0.14). Birds used for fertility and hatchability tests were pre-selected based on SM and SC, which could contribute to the lack of strong correlations between these traits (due to truncation of the distribution). Based on pedigree information, low to moderate heritabilities were estimated for reproductive traits (0.08 to 0.21). Markers explained a low proportion of phenotypic variance (0.04 to 0.15), probably due to stringent selection of genotyped individuals and the limited training set size. No genes with large effects were identified. Genomic estimated breeding values were more accurate than pedigree-based estimates but only for HOF and FERT-AI. Despite low estimates of accuracy in validation, genetic trends were positive for all analyzed traits. In conclusion, continued long-term selection can result in genetic improvement of reproductive performance of roosters.
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http://dx.doi.org/10.3382/ps/pez077DOI Listing
July 2019
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