Selection for social genetic effects in purebred pigs improves behaviour and handling of their crossbred progeny.

BACKGROUND: In commercial pig production, reduction of harmful social behavioural traits, such as ear manipulation and tail biting, is of major interest. Moreover, farmers prefer animals that are easy to handle. The aim of this experiment was to determine whether selection on social breeding values (SBV) for growth rate in purebred pigs affects behaviour in a weighing crate, lesions from ear manipulation, and tail biting of their crossbred progeny. Data were collected on crossbred F1 pigs allocated to 274 pens, which were progeny of purebred Landrace sows and Yorkshire boars from a DanBred nucleus herd. RESULTS: Behaviour in the weighing crate scored on a three-level scale showed that groups of pigs with high SBV for growth rate were significantly calmer than groups of pigs with low SBV (P < 0.027). When the mean SBV in the group increased by 1 unit, the proportion of pigs that obtained a calmer score level was increased by 14%. A significant (p = 0.04), favourable effect of SBV was found on both the number of pigs with ear lesions in the group and the mean number of ear lesions per pig. For a 1 unit increase in mean SBV, the mean number of lesions per pig decreased by 0.06 from a mean of 0.98. Individual severity of ear lesions conditional upon the number of ear lesions was also significantly affected (p = 0.05) by the mean SBV in the group. In groups for which the mean SBV increased by 1 unit, the proportion of pigs that were observed with a lower severity score was increased by 20% on a three-level scale. Most pigs received no tail biting injuries and no effect of SBV was observed on the tail injury score. CONCLUSIONS: After 7 weeks in the finisher unit, crossbred progeny with high SBV were calmer in the weighing crate and had fewer ear lesions. These results indicate that selection of purebred parents for SBV for growth rate will increase welfare in their crossbred progeny by decreasing the number of ear lesions and making them easier to handle.

Large-scale association study on daily weight gain in pigs reveals overlap of genetic factors for growth in humans.

BACKGROUND: Imputation from genotyping array to whole-genome sequence variants using resequencing of representative reference populations enhances our ability to map genetic factors affecting complex phenotypes in livestock species. The accumulation of knowledge about gene function in human and laboratory animals can provide substantial advantage for genomic research in livestock species. RESULTS: In this study, 201,388 pigs from three commercial Danish breeds genotyped with low to medium (8.5k to 70k) SNP arrays were imputed to whole genome sequence variants using a two-step approach. Both imputation steps achieved high accuracies, and in total this yielded 26,447,434 markers on 18 autosomes. The average estimated imputation accuracy of markers with minor allele frequency ≥ 0.05 was 0.94. To overcome the memory consumption of running genome-wide association study (GWAS) for each breed, we performed within-breed subpopulation GWAS then within-breed meta-analysis for average daily weight gain (ADG), followed by a multi-breed meta-analysis of GWAS summary statistics. We identified 15 quantitative trait loci (QTL). Our post-GWAS analysis strategy to prioritize of candidate genes including information like gene ontology, mammalian phenotype database, differential expression gene analysis of high and low feed efficiency pig and human GWAS catalog for height, obesity, and body mass index, we proposed MRAP2, LEPROT, PMAIP1, ENSSSCG00000036234, BMP2, ELFN1, LIG4 and FAM155A as the candidate genes with biological support for ADG in pigs. CONCLUSION: Our post-GWAS analysis strategy helped to identify candidate genes not just by distance to the lead SNP but also by multiple sources of biological evidence. Besides, the identified QTL overlap with genes which are known for their association with human growth-related traits. The GWAS with this large data set showed the power to map the genetic factors associated with ADG in pigs and have added to our understanding of the genetics of growth across mammalian species.

Predictive performances of animal models using different multibreed relationship matrices in systems with rotational crossbreeding.

BACKGROUND: In livestock breeding, selection for some traits can be improved with direct selection for crossbred performance. However, genetic analyses with phenotypes from crossbred animals require methods for multibreed relationship matrices; especially when some animals are rotationally crossbred. Multiple methods for multibreed relationship matrices exist, but there is a lack of knowledge on how these methods compare for prediction of breeding values with phenotypes from rotationally crossbred animals. Therefore, the objective of this study was to compare models that use different multibreed relationship matrices in terms of ability to predict accurate and unbiased breeding values with phenotypes from two-way rotationally crossbred animals. METHODS: We compared four methods for multibreed relationship matrices: numerator relationship matrices (NRM), García-Cortés and Toro's partial relationship matrices (GT), Strandén and Mäntysaari's approximation to the GT method (SM), and one NRM with metafounders (MF). The methods were compared using simulated data. We simulated two phenotypes; one with and one without dominance effects. Only crossbred animals were phenotyped and only purebred animals were genotyped. RESULTS: The MF and GT methods were the most accurate and least biased methods for prediction of breeding values in rotationally crossbred animals. Without genomic information, all methods were almost equally accurate for prediction of breeding values in purebred animals; however, with genomic information, the MF and GT methods were the most accurate. The GT, MF, and SM methods were the least biased methods for prediction of breeding values in purebred animals. CONCLUSIONS: For prediction of breeding values with phenotypes from rotationally crossbred animals, models using the MF method or the GT method were generally more accurate and less biased than models using the SM method or the NRM method.

Statistical model and testing designs to increase response to selection with constrained inbreeding in genomic breeding programs for pigs affected by social genetic effects.

BACKGROUND: Social genetic effects (SGE) are the effects of the genotype of one animal on the phenotypes of other animals within a social group. Because SGE contribute to variation in economically important traits for pigs, the inclusion of SGE in statistical models could increase responses to selection (RS) in breeding programs. In such models, increasing the relatedness of members within groups further increases RS when using pedigree-based relationships; however, this has not been demonstrated with genomic-based relationships or with a constraint on inbreeding. In this study, we compared the use of statistical models with and without SGE and compared groups composed at random versus groups composed of families in genomic selection breeding programs with a constraint on the rate of inbreeding. RESULTS: When SGE were of a moderate magnitude, inclusion of SGE in the statistical model substantially increased RS when SGE were considered for selection. However, when SGE were included in the model but not considered for selection, the increase in RS and in accuracy of predicted direct genetic effects (DGE) depended on the correlation between SGE and DGE. When SGE were of a low magnitude, inclusion of SGE in the model did not increase RS, probably because of the poor separation of effects and convergence issues of the algorithms. Compared to a random group composition design, groups composed of families led to higher RS. The difference in RS between the two group compositions was slightly reduced when using genomic-based compared to pedigree-based relationships. CONCLUSIONS: The use of a statistical model that includes SGE can substantially improve response to selection at a fixed rate of inbreeding, because it allows the heritable variation from SGE to be accounted for and capitalized on. Compared to having random groups, family groups result in greater response to selection in the presence of SGE but the advantage of using family groups decreases when genomic-based relationships are used.

Selection for social genetic effects in purebreds increases growth in crossbreds.

BACKGROUND: Average daily gain (ADG) in pigs is affected by both direct and social genetic effects (SGE). However, selection for SGE in purebreds has not conclusively been shown to improve ADG in crossbreds, and it is unknown whether SGE in purebreds are equal to those in crossbreds. Moreover, SGE may reflect dominance related behaviour, which is affected by the variation in body weight within a group. Therefore, we hypothesized that (a) there is a positive effect of parent average SGE estimated in purebred pigs on phenotypic ADG in crossbred offspring, and (b) there is an interaction between SGE on ADG and standard deviation in starting weight of pigs within the group. We also hypothesized that (c) social genetic variance for ADG exists in crossbred pigs, and (d) there is a favourable genetic correlation between SGE on ADG in purebred and crossbred pigs. RESULTS: We found a statistically significant interaction between the standard deviation in starting weight and SGE within groups, and conditioning on the mean standard deviation in starting weight, we found a favourable regression coefficient (0.37 ± 0.21) of ADG in crossbreds on SGE in purebreds. Variances for SGE were small in both Landrace (L) and Yorkshire (Y), and higher for SGE in both the dam and sire component of crossbred YL. The genetic correlations between SGE in purebreds and the dam or sire component of SGE in crossbreds were also favourable (0.52 ± 0.48 and 0.34 ± 0.42, respectively), although not significantly different from 0. CONCLUSIONS: We confirmed that there is a positive effect of SGE estimated using purebred information on phenotypic ADG in crossbreds, and that the largest effect is achieved when the within-group variation in starting weight is small. Our results indicate that social genetic variance in crossbreds exists and that there is a favourable genetic correlation between social genetic effects in purebreds and crossbreds. Collectively, our results indicate that selection for SGE on ADG in purebreds in a nucleus farm environment with little competition for resources can improve ADG in crossbreds in a commercial environment.

Genome-wide association analyses using a Bayesian approach for litter size and piglet mortality in Danish Landrace and Yorkshire pigs.

BACKGROUND: Litter size and piglet mortality are important traits in pig production. The study aimed to identify quantitative trait loci (QTL) for litter size and mortality traits, including total number of piglets born (TNB), litter size at day 5 (LS5) and mortality rate before day 5 (MORT) in Danish Landrace and Yorkshire pigs by genome-wide association studies (GWAS). METHODS: The phenotypic records and genotypes were available in 5,977 Landrace pigs and 6,000 Yorkshire pigs born from 1998 to 2014. A linear mixed model (LM) with a single SNP regression and a Bayesian mixture model (BM) including effects of all SNPs simultaneously were used for GWAS to detect significant QTL association. The response variable used in the GWAS was corrected phenotypic value which was obtained by adjusting original observations for non-genetic effects. For BM, the QTL region was determined by using a novel post-Gibbs analysis based on the posterior mixture probability. RESULTS: The detected association patterns from LM and BM models were generally similar. However, BM gave more distinct detection signals than LM. The clearer peaks from BM indicated that the BM model has an advantage in respect of identifying and distinguishing regions of putative QTL. Using BM and QTL region analysis, for the three traits and two breeds a total of 15 QTL regions were identified on SSC1, 2, 3, 6, 7, 9, 13 and 14. Among these QTL regions, 6 regions located on SSC2, 3, 6, 7 and 13 were associated with more than one trait. CONCLUSION: This study detected QTL regions associated with litter size and piglet mortality traits in Danish pigs using a novel approach of post-Gibbs analysis based on posterior mixture probability. All of the detected QTL regions overlapped with regions previously reported for reproduction traits. The regions commonly detected in different traits and breeds could be resources for multi-trait and across-bred selection. The proposed novel QTL region analysis method would be a good alternative to detect and define QTL regions.

Genomic evaluation by including dominance effects and inbreeding depression for purebred and crossbred performance with an application in pigs.

BACKGROUND: Improved performance of crossbred animals is partly due to heterosis. One of the major genetic bases of heterosis is dominance, but it is seldom used in pedigree-based genetic evaluation of livestock. Recently, a trivariate genomic best linear unbiased prediction (GBLUP) model including dominance was developed, which can distinguish purebreds from crossbred animals explicitly. The objectives of this study were: (1) methodological, to show that inclusion of marker-based inbreeding accounts for directional dominance and inbreeding depression in purebred and crossbred animals, to revisit variance components of additive and dominance genetic effects using this model, and to develop marker-based estimators of genetic correlations between purebred and crossbred animals and of correlations of allele substitution effects between breeds; (2) to evaluate the impact of accounting for dominance effects and inbreeding depression on predictive ability for total number of piglets born (TNB) in a pig dataset composed of two purebred populations and their crossbreds. We also developed an equivalent model that makes the estimation of variance components tractable. RESULTS: For TNB in Danish Landrace and Yorkshire populations and their reciprocal crosses, the estimated proportions of dominance genetic variance to additive genetic variance ranged from 5 to 11%. Genetic correlations between breeding values for purebred and crossbred performances for TNB ranged from 0.79 to 0.95 for Landrace and from 0.43 to 0.54 for Yorkshire across models. The estimated correlation of allele substitution effects between Landrace and Yorkshire was low for purebred performances, but high for crossbred performances. Predictive ability for crossbred animals was similar with or without dominance. The inbreeding depression effect increased predictive ability and the estimated inbreeding depression parameter was more negative for Landrace than for Yorkshire animals and was in between for crossbred animals. CONCLUSIONS: Methodological developments led to closed-form estimators of inbreeding depression, variance components and correlations that can be easily interpreted in a quantitative genetics context. Our results confirm that genetic correlations of breeding values between purebred and crossbred performances within breed are positive and moderate. Inclusion of dominance in the GBLUP model does not improve predictive ability for crossbred animals, whereas inclusion of inbreeding depression does.

Genomic prediction of crossbred performance based on purebred Landrace and Yorkshire data using a dominance model.

BACKGROUND: In pig breeding, selection is usually carried out in purebred populations, although the final goal is to improve crossbred performance. Genomic selection can be used to select purebred parental lines for crossbred performance. Dominance is the likely genetic basis of heterosis and explicitly including dominance in the genomic selection model may be an advantage when selecting purebreds for crossbred performance. Our objectives were two-fold: (1) to compare the predictive ability of genomic prediction models with additive or additive plus dominance effects, when the validation criterion is crossbred performance; and (2) to compare the use of two pure line reference populations to a single combined reference population. METHODS: We used data on litter size in the first parity from two pure pig lines (Landrace and Yorkshire) and their reciprocal crosses. Training was performed (1) separately on pure Landrace (2085) and Yorkshire (2145) sows and (2) the two combined pure lines (4230), which were genotyped for 38 k single nucleotide polymorphisms (SNPs). Prediction accuracy was measured as the correlation between genomic estimated breeding values (GEBV) of pure line boars and mean corrected crossbred-progeny performance, divided by the average accuracy of mean-progeny performance. We evaluated a model with additive effects only (MA) and a model with both additive and dominance effects (MAD). Two types of GEBV were computed: GEBV for purebred performance (GEBV) based on either the MA or MAD models, and GEBV for crossbred performance (GEBV-C) based on the MAD. GEBV-C were calculated based on SNP allele frequencies of genotyped animals in the opposite line. RESULTS: Compared to MA, MAD improved prediction accuracy for both lines. For MAD, GEBV-C improved prediction accuracy compared to GEBV. For Landrace (Yorkshire) boars, prediction accuracies were equal to 0.11 (0.32) for GEBV based on MA, and 0.13 (0.34) and 0.14 (0.36) for GEBV and GEBV-C based on MAD, respectively. Combining animals from both lines into a single reference population yielded higher accuracies than training on each pure line separately. In conclusion, the use of a dominance model increased the accuracy of genomic predictions of crossbred performance based on purebred data.

Genomic prediction using models with dominance and imprinting effects for backfat thickness and average daily gain in Danish Duroc pigs.

BACKGROUND: Dominance and imprinting genetic effects have been shown to contribute to genetic variance for certain traits but are usually ignored in genomic prediction of complex traits in livestock. The objectives of this study were to estimate variances of additive, dominance and imprinting genetic effects and to evaluate predictions of genetic merit based on genomic data for average daily gain (DG) and backfat thickness (BF) in Danish Duroc pigs. METHODS: Corrected phenotypes of 8113 genotyped pigs from breeding and multiplier herds were used. Four Bayesian mixture models that differed in the type of genetic effects included: (A) additive genetic effects, (AD) additive and dominance genetic effects, (AI) additive and imprinting genetic effects, and (ADI) additive, dominance and imprinting genetic effects were compared using Bayes factors. The ability of the models to predict genetic merit was compared with regard to prediction reliability and bias. RESULTS: Based on model ADI, narrow-sense heritabilities of 0.18 and 0.31 were estimated for DG and BF, respectively. Dominance and imprinting genetic effects accounted for 4.0 to 4.6 and 1.3 to 1.4 % of phenotypic variance, respectively, which were statistically significant. Across the four models, reliabilities of the predicted total genetic values (GTV, sum of all genetic effects) ranged from 16.1 (AI) to 18.4 % (AD) for DG and from 30.1 (AI) to 31.4 % (ADI) for BF. The least biased predictions of GTV were obtained with model AD, with regression coefficients of corrected phenotypes on GTV equal to 0.824 (DG) and 0.738 (BF). Reliabilities of genomic estimated breeding values (GBV, additive genetic effects) did not differ significantly among models for DG (between 16.5 and 16.7 %); however, for BF, model AD provided a significantly higher reliability (31.3 %) than model A (30.7 %). The least biased predictions of GBV were obtained with model AD with regression coefficients of 0.872 for DG and 0.764 for BF. CONCLUSIONS: Dominance and genomic imprinting effects contribute significantly to the genetic variation of BF and DG in Danish Duroc pigs. Genomic prediction models that include dominance genetic effects can improve accuracy and reduce bias of genomic predictions of genetic merit.

Genomic diversity revealed by whole-genome sequencing in three Danish commercial pig breeds.

Whole-genome sequencing of 217 animals from three Danish commercial pig breeds (Duroc, Landrace [LL], and Yorkshire [YY]) was performed. Twenty-six million single-nucleotide polymorphisms (SNPs) and 8 million insertions or deletions (indels) were uncovered. Among the SNPs, 493,099 variants were located in coding sequences, and 29,430 were predicted to have a high functional impact such as gain or loss of stop codon. Using the whole-genome sequence dataset as the reference, the imputation accuracy for pigs genotyped with high-density SNP chips was examined. The overall average imputation accuracy for all biallelic variants (SNP and indel) was 0.69, while it was 0.83 for variants with minor allele frequency > 0.1. This study provides whole-genome reference data to impute SNP chip-genotyped animals for further studies to fine map quantitative trait loci as well as improving the prediction accuracy in genomic selection. Signatures of selection were identified both through analyses of fixation and differentiation to reveal selective sweeps that may have had prominent roles during breed development or subsequent divergent selection. However, the fixation indices did not indicate a strong divergence among these three breeds. In LL and YY, the integrated haplotype score identified genomic regions under recent selection. These regions contained genes for olfactory receptors and oxidoreductases. Olfactory receptor genes that might have played a major role in the domestication were previously reported to have been under selection in several species including cattle and swine.

Genomic Model with Correlation Between Additive and Dominance Effects.

Dominance genetic effects are rarely included in pedigree-based genetic evaluation. With the availability of single nucleotide polymorphism markers and the development of genomic evaluation, estimates of dominance genetic effects have become feasible using genomic best linear unbiased prediction (GBLUP). Usually, studies involving additive and dominance genetic effects ignore possible relationships between them. It has been often suggested that the magnitude of functional additive and dominance effects at the quantitative trait loci are related, but there is no existing GBLUP-like approach accounting for such correlation. Wellmann and Bennewitz (2012) showed two ways of considering directional relationships between additive and dominance effects, which they estimated in a Bayesian framework. However, these relationships cannot be fitted at the level of individuals instead of loci in a mixed model, and are not compatible with standard animal or plant breeding software. This comes from a fundamental ambiguity in assigning the reference allele at a given locus. We show that, if there has been selection, assigning the most frequent as the reference allele orients the correlation between functional additive and dominance effects. As a consequence, the most frequent reference allele is expected to have a positive value. We also demonstrate that selection creates negative covariance between genotypic additive and dominance genetic values. For parameter estimation, it is possible to use a combined additive and dominance relationship matrix computed from marker genotypes, and to use standard restricted maximum likelihood algorithms based on an equivalent model. Through a simulation study, we show that such correlations can easily be estimated by mixed model software and that the accuracy of prediction for genetic values is slightly improved if such correlations are used in GBLUP. However, a model assuming uncorrelated effects and fitting orthogonal breeding values and dominant deviations performed similarly for prediction.