Dimensionality of genomic information and its impact on genome-wide associations and variant selection for genomic prediction: a simulation study.

BACKGROUND: Identifying true positive variants in genome-wide associations (GWA) depends on several factors, including the number of genotyped individuals. The limited dimensionality of genomic information may give insights into the optimal number of individuals to be used in GWA. This study investigated different discovery set sizes based on the number of largest eigenvalues explaining a certain proportion of variance in the genomic relationship matrix (G). In addition, we investigated the impact on the prediction accuracy by adding variants, which were selected based on different set sizes, to the regular single nucleotide polymorphism (SNP) chips used for genomic prediction. METHODS: We simulated sequence data that included 500k SNPs with 200 or 2000 quantitative trait nucleotides (QTN). A regular 50k panel included one in every ten simulated SNPs. Effective population size (Ne) was set to 20 or 200. GWA were performed using a number of genotyped animals equivalent to the number of largest eigenvalues of G (EIG) explaining 50, 60, 70, 80, 90, 95, 98, and 99% of the variance. In addition, the largest discovery set consisted of 30k genotyped animals. Limited or extensive phenotypic information was mimicked by changing the trait heritability. Significant and large-effect size SNPs were added to the 50k panel and used for single-step genomic best linear unbiased prediction (ssGBLUP). RESULTS: Using a number of genotyped animals corresponding to at least EIG98 allowed the identification of QTN with the largest effect sizes when Ne was large. Populations with smaller Ne required more than EIG98. Furthermore, including genotyped animals with a higher reliability (i.e., a higher trait heritability) improved the identification of the most informative QTN. Prediction accuracy was highest when the significant or the large-effect SNPs representing twice the number of simulated QTN were added to the 50k panel. CONCLUSIONS: Accurately identifying causative variants from sequence data depends on the effective population size and, therefore, on the dimensionality of genomic information. This dimensionality can help identify the most suitable sample size for GWA and could be considered for variant selection, especially when resources are restricted. Even when variants are accurately identified, their inclusion in prediction models has limited benefits.

Using pre-selected variants from large-scale whole-genome sequence data for single-step genomic predictions in pigs.

BACKGROUND: Whole-genome sequence (WGS) data harbor causative variants that may not be present in standard single nucleotide polymorphism (SNP) chip data. The objective of this study was to investigate the impact of using preselected variants from WGS for single-step genomic predictions in maternal and terminal pig lines with up to 1.8k sequenced and 104k sequence imputed animals per line. METHODS: Two maternal and four terminal lines were investigated for eight and seven traits, respectively. The number of sequenced animals ranged from 1365 to 1491 for the maternal lines and 381 to 1865 for the terminal lines. Imputation to sequence occurred within each line for 66k to 76k animals for the maternal lines and 29k to 104k animals for the terminal lines. Two preselected SNP sets were generated based on a genome-wide association study (GWAS). Top40k included the SNPs with the lowest p-value in each of the 40k genomic windows, and ChipPlusSign included significant variants integrated into the porcine SNP chip used for routine genotyping. We compared the performance of single-step genomic predictions between using preselected SNP sets assuming equal or different variances and the standard porcine SNP chip. RESULTS: In the maternal lines, ChipPlusSign and Top40k showed an average increase in accuracy of 0.6 and 4.9%, respectively, compared to the regular porcine SNP chip. The greatest increase was obtained with Top40k, particularly for fertility traits, for which the initial accuracy based on the standard SNP chip was low. However, in the terminal lines, Top40k resulted in an average loss of accuracy of 1%. ChipPlusSign provided a positive, although small, gain in accuracy (0.9%). Assigning different variances for the SNPs slightly improved accuracies when using variances obtained from BayesR. However, increases were inconsistent across the lines and traits. CONCLUSIONS: The benefit of using sequence data depends on the line, the size of the genotyped population, and how the WGS variants are preselected. When WGS data are available on hundreds of thousands of animals, using sequence data presents an advantage but this remains limited in pigs.

Reducing lesion incidence in pork carcasses by heating foot-and-mouth disease vaccine before injection.

OBJECTIVE: This study was conducted to investigate the effect of heating of foot-and-mouth disease (FMD) vaccine before injection, on the incidence of lesions at the injection site (pork butt), amount of discarded meat, and economical benefit. METHODS: In total, 101,086 piglets raised in 30 farms, were vaccinated in the neck with 2 mL of FMD vaccine at 56 d and 84 d of age using a commercial syringe. The heat treatment group (48,511 pigs) was injected with the FMD vaccine after it had been heated in a water bath at 40°C for 20 min. After slaughter, the incidence of lesions on the pork butt was inspected, and the subsequent amount of discarded meat was recorded. RESULTS: Heat treatment of FMD vaccine reduced the incident rate of lesions on the pork butt (p<0.01). Overall, 17.81% of the pigs in the heat treatment group had lesions, while the incident rate in the control group was 21.70%. The amount of discarded meat per head of total pigs and per head of pigs with lesions were significantly lower in the heat treatment group than the control group (p<0.01). Thus, the proportion of discarded meat to dressed carcass was lower in the heat treatment group (0.249%) compared with the control group (0.338%) (p<0.01). Farms that rear 1,000 sows can gain 1,863,289 KRW (1,600 USD) in one year when they adopt heat treatment of FMD vaccine before injection. CONCLUSION: Heat treatment of FMD vaccine using simple heat equipment (water bath) can be effective in reducing lesions caused by FMD vaccination and increase the economic benefits in pig farms.

Multi-line ssGBLUP evaluation using preselected markers from whole-genome sequence data in pigs.

Genomic evaluations in pigs could benefit from using multi-line data along with whole-genome sequencing (WGS) if the data are large enough to represent the variability across populations. The objective of this study was to investigate strategies to combine large-scale data from different terminal pig lines in a multi-line genomic evaluation (MLE) through single-step GBLUP (ssGBLUP) models while including variants preselected from whole-genome sequence (WGS) data. We investigated single-line and multi-line evaluations for five traits recorded in three terminal lines. The number of sequenced animals in each line ranged from 731 to 1,865, with 60k to 104k imputed to WGS. Unknown parent groups (UPG) and metafounders (MF) were explored to account for genetic differences among the lines and improve the compatibility between pedigree and genomic relationships in the MLE. Sequence variants were preselected based on multi-line genome-wide association studies (GWAS) or linkage disequilibrium (LD) pruning. These preselected variant sets were used for ssGBLUP predictions without and with weights from BayesR, and the performances were compared to that of a commercial porcine single-nucleotide polymorphisms (SNP) chip. Using UPG and MF in MLE showed small to no gain in prediction accuracy (up to 0.02), depending on the lines and traits, compared to the single-line genomic evaluation (SLE). Likewise, adding selected variants from the GWAS to the commercial SNP chip resulted in a maximum increase of 0.02 in the prediction accuracy, only for average daily feed intake in the most numerous lines. In addition, no benefits were observed when using preselected sequence variants in multi-line genomic predictions. Weights from BayesR did not help improve the performance of ssGBLUP. This study revealed limited benefits of using preselected whole-genome sequence variants for multi-line genomic predictions, even when tens of thousands of animals had imputed sequence data. Correctly accounting for line differences with UPG or MF in MLE is essential to obtain predictions similar to SLE; however, the only observed benefit of an MLE is to have comparable predictions across lines. Further investigation into the amount of data and novel methods to preselect whole-genome causative variants in combined populations would be of significant interest.

Inclusion of sire by herd interaction effect in the genomic evaluation for weaning weight of American Angus.

A spurious negative genetic correlation between direct and maternal effects of weaning weight (WW) in beef cattle has historically been problematic for researchers and industry. Previous research has suggested the covariance between sires and herds may be contributing to this relationship. The objective of this study was to estimate the variance components (VC) for WW in American Angus with and without sire by herd (S×H) interaction effect when genomic information is used or not. Five subsets of ~100k animals for each subset were used. When genomic information was included, genotypes were added for 15,637 animals. Five replicates were performed. Four different models were tested, namely, M1: without S×H interaction effect and with covariance between direct and maternal effect (σam) ≠ 0; M2: with S×H interaction effect and σam ≠ 0; M3: without S×H interaction effect and with σam = 0; M4: with S×H interaction effect and σam = 0. VC were estimated using the restricted maximum likelihood (REML) and single-step genomic REML (ssGREML) with the average information algorithm. Breeding values were computed using single-step genomic BLUP for the models above and one additional model, which had the covariance zeroed after the estimation of VC (M5). The ability of each model to predict future breeding values was investigated with the linear regression method. Under REML, when the S×H interaction effect was added to the model, both direct and maternal genetic variances were greatly reduced, and the negative covariance became positive (i.e., when moving from M1 to M2). Similar patterns were observed under ssGREML, but with less reduction in the direct and maternal genetic variances and still a negative covariance. Models with the S×H interaction effect (M2 and M4) had a better fit according to the Akaike information criteria. Breeding values from those models were more accurate and had less bias than the other three models. The rankings and breeding values of artificial insemination sires (N = 1,977) greatly changed when the S×H interaction effect was fit in the model. Although the S×H interaction effect accounted for 3% to 5% of the total phenotypic variance and improved the model fit, this change in the evaluation model will cause severe reranking among animals.

A spurious negative genetic correlation between direct and maternal effects of weaning weight (WW) in beef cattle has been problematic for researchers and industry. Previous research suggested the covariance between sires and herds may contribute to this relationship. The objective of this study was to estimate the variance components (VC) for WW in American Angus with and without sire by herd (S×H) interaction effect when genomic information is used or not. Four models were designed to investigate the S×H effect. The restricted maximum likelihood (REML) and single-step genomic REML (ssGREML) were used to estimate VC. Breeding values were computed using single-step genomic BLUP and the validation was done through the linear regression method. Under REML, when the S×H was added to the model, both direct and maternal genetic variances were greatly reduced, and the negative covariance became positive. Similar patterns were observed under ssGREML, but with less reduction in the direct and maternal genetic variances and still a negative covariance. Breeding values from models with S×H were more accurate and had less bias than the other models. Although the S×H improved the model, this change in the evaluation model will cause severe reranking among key animals.

Genome-wide identification of major genes and genomic prediction using high-density and text-mined gene-based SNP panels in Hanwoo (Korean cattle).

It was hypothesized that single-nucleotide polymorphisms (SNPs) extracted from text-mined genes could be more tightly related to causal variant for each trait and that differentially weighting of this SNP panel in the GBLUP model could improve the performance of genomic prediction in cattle. Fitting two GRMs constructed by text-mined SNPs and SNPs except text-mined SNPs from 777k SNPs set (exp_777K) as different random effects showed better accuracy than fitting one GRM (Im_777K) for six traits (e.g. backfat thickness: + 0.002, eye muscle area: + 0.014, Warner-Bratzler Shear Force of semimembranosus and longissimus dorsi: + 0.024 and + 0.068, intramuscular fat content of semimembranosus and longissimus dorsi: + 0.008 and + 0.018). These results can suggest that attempts to incorporate text mining into genomic predictions seem valuable, and further study using text mining can be expected to present the significant results.