Modeling missing pedigree with metafounders and validating single-step genomic predictions in a small dairy cattle population with a great influence of foreign genetics.

Genetic improvement in small countries rely heavily on foreign genetics. In an importing country such as Uruguay, consideration of unknown parent groups (UPG) for foreign sires is essential. However, the use of UPG in genomic model evaluations may lead to bias in genomic estimated breeding values (GEBV). The objective of this study was to study different models including UPG or metafounders (MF) in the Uruguayan Holstein evaluation and to analyze bias, dispersion, and accuracy of GEBV predictions in BLUP and single-step genomic BLUP (ssGBLUP). A gamma matrix (Γ) was estimated either by using base allele population frequencies obtained by bounded linear regression (MFbounded), or by using 2 values to design Γ (i.e., a single value for the diagonal and a different value for the off-diagonal [MFrobust]). Both Γ estimators performed well in terms of GEBV predictions, but MFbounded was the best option. There is, however, some bias whose origin was not completely understood. UPG or MF seem to model correctly genetic progress for unknown parents except for the very first groups (earlier time period). As for validation bulls, bias was observed across all models, whereas for validation cows it was only observed with UPG in BLUP. Overdispersion was found in all models, but it was mostly detected in validation bulls. Ratio of accuracies indicated that ssGBLUP gave better predictions than BLUP.

Application of single-step single nucleotide polymorphism best linear unbiased predictor model with unknown-parent groups for type traits in Japanese Holsteins.

The objectives of this study were to investigate the computational performance and the predictive ability and bias of a single-step SNP BLUP model (ssSNPBLUP) in genotyped young animals with unknown-parent groups (UPG) for type traits, using national genetic evaluation data from the Japanese Holstein population. The phenotype, genotype, and pedigree data were the same as those used in a national genetic evaluation of linear type traits classified between April 1984 and December 2020. In the current study, 2 data sets were prepared: the full data set containing all entries up to December 2020 and a truncated data set ending with December 2016. Genotyped animals were classified into 3 types: sires with classified daughters (S), cows with records (C), and young animals (Y). The computing performance and prediction accuracy of ssSNPBLUP were compared for the following 3 groups of genotyped animals: sires with classified daughters and young animals (SY); cows with records and young animals (CY); and sires with classified daughters, cows with records, and young animals (SCY). In addition, we tested 3 parameters of residual polygenic variance in ssSNPBLUP (0.1, 0.2, or 0.3). Daughter yield deviations (DYD) for the validation bulls and phenotypes adjusted for all fixed effects and random effects other than animal and residual (Yadj) for the validation cows were obtained using the full data set from the pedigree-based BLUP model. The regression coefficients of DYD for bulls (or Yadj for cows) on the genomic estimated breeding value (GEBV) using the truncated data set were used to measure the inflation of the predictions of young animals. The coefficient of determination of DYD on GEBV was used to measure the predictive ability of the predictions for the validation bulls. The reliability of the predictions for the validation cows was calculated as the square of the correlation between Yadj and GEBV divided by heritability. The predictive ability was highest in the SCY group and lowest in the CY group. However, minimal difference was found in predictive abilities with or without UPG models using different parameters of residual polygenic variance. The regression coefficients approached 1.0 as the parameter of residual polygenic variance increased, but regression coefficients were mostly similar regardless of the use of UPG across the groups of genotyped animals. The ssSNPBLUP model, including UPG, was demonstrated as feasible for implementation in the national evaluation of type traits in Japanese Holsteins.

Unknown-parent groups in single-step genomic evaluation.

In single-step genomic evaluation using best linear unbiased prediction (ssGBLUP), genomic predictions are calculated with a relationship matrix that combines pedigree and genomic information. For missing pedigrees, unknown selection processes, or inclusion of several populations, a BLUP model can include unknown-parent groups (UPG) in the animal effect. For ssGBLUP, UPG equations also involve contributions from genomic relationships. When those contributions are ignored, UPG solutions and genetic predictions can be biased. Options to eliminate or reduce such bias are presented. First, mixed model equations can be modified to include contributions to UPG elements from genomic relationships (greater software complexity). Second, UPG can be implemented as separate effects (higher cost of computing and data processing). Third, contributions can be ignored when they are relatively small, but they may be small only after refinements to UPG definitions. Fourth, contributions may approximately cancel out when genomic and pedigree relationships are constructed for compatibility; however, different construction steps are required for unknown parents from the same or different populations. Finally, an additional polygenic effect that also includes UPG can be added to the model.

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.

Modeling genetic differences of combined broiler chicken populations in single-step GBLUP.

The introduction of animals from a different environment or population is a common practice in commercial livestock populations. In this study, we modeled the inclusion of a group of external birds into a local broiler chicken population for the purpose of genomic evaluations. The pedigree was composed of 242,413 birds and genotypes were available for 107,216 birds. A five-trait model that included one growth, two yield, and two efficiency traits was used for the analyses. The strategies to model the introduction of external birds were to include a fixed effect representing the origin of parents and to use unknown parent groups (UPG) or metafounders (MF). Genomic estimated breeding values (GEBV) were obtained with single-step GBLUP using the Algorithm for Proven and Young. Bias, dispersion, and accuracy of GEBV for the validation birds, that is, from the most recent generation, were computed. The bias and dispersion were estimated with the linear regression (LR) method,whereas accuracy was estimated by the LR method and predictive ability. When fixed UPG were fit without estimated inbreeding, the model did not converge. In contrast, models with fixed UPG and estimated inbreeding or random UPG converged and resulted in similar GEBV. The inclusion of an extra fixed effect in the model made the GEBV unbiased and reduced the inflation. Genomic predictions with MF were slightly biased and inflated due to the unbalanced number of observations assigned to each metafounder. When combining local and external populations, the greatest accuracy can be obtained by adding an extra fixed effect to account for the origin of parents plus UPG with estimated inbreeding or random UPG. To estimate the accuracy, the LR method is more consistent among scenarios, whereas the predictive ability greatly depends on the model specification.

Accounting for Genetic Differences Among Unknown Parents in Bubalus bubalis: A Case Study From the Italian Mediterranean Buffalo.

The use of genetic evaluations in the Water Buffalo by means of a Best Linear Unbiased Prediction (BLUP) animal model has been increased over the last two-decades across several countries. However, natural mating is still a common reproductive strategy that can increase the proportion of missing pedigree information. The inclusion of genetic groups in variance component (VC) and breeding value (EBV) estimation is a possible solution. The aim of this study was to evaluate two different genetic grouping strategies and their effects on VC and EBV for composite (n = 5) and linear (n = 10) type traits in the Italian Mediterranean Buffalo (IMB) population. Type traits data from 7,714 buffalo cows plus a pedigree file including 18,831 individuals were provided by the Italian National Association of Buffalo Breeders. VCs and EBVs were estimated for each trait fitting a single-trait animal model and using the official DNA-verified pedigree. Successively, EBVs were re-estimated using modified pedigrees with two different proportion of missing genealogies (30 or 60% of buffalo with records), and two different grouping strategies, year of birth (Y30/Y60) or genetic clustering (GC30, GC60). The different set of VCs, estimated EBVs and their standard errors were compared with the results obtained using the original pedigree. Results were also compared in terms of efficiency of selection. Differences among VCs varied according to the trait and the scenario considered. The largest effect was observed for two traits, udder teat and body depth in the GC60 genetic cluster, whose heritability decreased by -0.07 and increased by +0.04, respectively. Considering buffalo cows with record, the average correlation across traits between official EBVs and EBVs from different scenarios was 0.91, 0.88, 0.84, and 0.79 for Y30, CG30, Y60, and CG60, respectively. In bulls the correlations between EBVs ranged from 0.90 for fore udder attachment and udder depth to 0.96 for stature and body length in the GC30 scenario and from 0.75 for udder depth to 0.90 for stature in the GC60 scenario. When a variable proportion of missing pedigree is present using the appropriate strategy to define genetic groups and including them in VC and EBV is a worth-while and low-demanding solution.

Metafounders May Reduce Bias in Composite Cattle Genomic Predictions.

Metafounders are pseudo-individuals that act as proxies for animals in base populations. When metafounders are used, individuals from different breeds can be related through pedigree, improving the compatibility between genomic and pedigree relationships. The aim of this study was to investigate the use of metafounders and unknown parent groups (UPGs) for the genomic evaluation of a composite beef cattle population. Phenotypes were available for scrotal circumference at 14 months of age (SC14), post weaning gain (PWG), weaning weight (WW), and birth weight (BW). The pedigree included 680,551 animals, of which 1,899 were genotyped for or imputed to around 30,000 single-nucleotide polymorphisms (SNPs). Evaluations were performed based on pedigree (BLUP), pedigree with UPGs (BLUP_UPG), pedigree with metafounders (BLUP_MF), single-step genomic BLUP (ssGBLUP), ssGBLUP with UPGs for genomic and pedigree relationship matrices (ssGBLUP_UPG) or only for the pedigree relationship matrix (ssGBLUP_UPGA), and ssGBLUP with metafounders (ssGBLUP_MF). Each evaluation considered either four or 10 groups that were assigned based on breed of founders and intermediate crosses. To evaluate model performance, we used a validation method based on linear regression statistics to obtain accuracy, stability, dispersion, and bias of (genomic) estimated breeding value [(G)EBV]. Overall, relationships within and among metafounders were stronger in the scenario with 10 metafounders. Accuracy was greater for models with genomic information than for BLUP. Also, the stability of (G)EBVs was greater when genomic information was taken into account. Overall, pedigree-based methods showed lower inflation/deflation (regression coefficients close to 1.0) for SC14, WWM, and BWD traits. The level of inflation/deflation for genomic models was small and trait-dependent. Compared with regular ssGBLUP, ssGBLUP_MF4 displayed regression coefficient closer to one SC14, PWG, WWM, and BWD. Genomic models with metafounders seemed to be slightly more stable than models with UPGs based on higher similarity of results with different numbers of groups. Further, metafounders can help to reduce bias in genomic evaluations of composite beef cattle populations without reducing the stability of GEBVs.