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Genomic prediction for crossbred performance using metafounders.

ABSTRACT: Future genomic evaluation models to be used routinely in breeding programs for pigs and poultry need to be able to optimally use information of crossbred (CB) animals to predict breeding values for CB performance of purebred (PB) selection candidates. Important challenges in the commonly used single-step genomic best linear unbiased prediction (ssGBLUP) model are the definition of relationships between the different line compositions and the definition of the base generation per line. The use of metafounders (MFs) in ssGBLUP has been proposed to overcome these issues. When relationships between lines are known to be different from 0, the use of MFs generalizes the concept of genetic groups relying on the genotype data. Our objective was to investigate the effect of using MFs in genomic prediction for CB performance on estimated variance components, and accuracy and bias of GEBV. This was studied using stochastic simulation to generate data representing a three-way crossbreeding scheme in pigs, with the parental lines being either closely related or unrelated. Results show that using MFs, the variance components should be scaled appropriately, especially when basing them on estimates obtained with, for example a pedigree-based model. The accuracies of GEBV that were obtained using MFs were similar to accuracies without using MFs, regardless whether the lines involved in the CB were closely related or unrelated. The use of MFs resulted in a model that had similar or somewhat better convergence properties compared to other models. We recommend the use of MFs in ssGBLUP for genomic evaluations in crossbreeding schemes.

SUBMITTER: van Grevenhof EM

PROVIDER: S-EPMC6358227 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Genomic prediction for crossbred performance using metafounders.

van Grevenhof Elizabeth M EM Vandenplas Jérémie J Calus Mario P L MPL

Journal of animal science 20190201 2

Future genomic evaluation models to be used routinely in breeding programs for pigs and poultry need to be able to optimally use information of crossbred (CB) animals to predict breeding values for CB performance of purebred (PB) selection candidates. Important challenges in the commonly used single-step genomic best linear unbiased prediction (ssGBLUP) model are the definition of relationships between the different line compositions and the definition of the base generation per line. The use of ...[more]

PMID: 30423111

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Project description:In crossbreeding programs, various genomic prediction models have been proposed for using phenotypic records of crossbred animals to increase the selection response for crossbred performance in purebred animals. A possible model is a model that assumes identical single nucleotide polymorphism (SNP) effects for the crossbred performance trait across breeds (ASGM). Another model is a genomic model that assumes breed-specific effects of SNP alleles (BSAM) for crossbred performance. The aim of this study was to derive and validate equations for predicting the reliability of estimated genomic breeding values for crossbred performance in both these models. Prediction equations were derived for situations when all (phenotyping and) genotyping data have already been collected, i.e. based on the genetic evaluation model, and for situations when all genotyping data are not yet available, i.e. when designing breeding programs.When all genotyping data are available, prediction equations are based on selection index theory. Without availability of all genotyping data, prediction equations are based on population parameters (e.g., heritability of the traits involved, genetic correlation between purebred and crossbred performance, effective number of chromosome segments). Validation of the equations for predicting the reliability of genomic breeding values without all genotyping data was performed based on simulated data of a two-way crossbreeding program, using either two closely-related breeds, or two unrelated breeds, to produce crossbred animals. The proposed equations can be used for an easy comparison of the reliability of genomic estimated breeding values across many scenarios, especially if all genotyping data are available. We show that BSAM outperforms ASGM for a specific breed, if the effective number of chromosome segments that originate from this breed and are shared by selection candidates of this breed and crossbred reference animals is less than half the effective number of all chromosome segments that are independently segregating in the same animals.The derived equations can be used to predict the reliability of genomic estimated breeding values for crossbred performance using ASGM or BSAM in many scenarios, and are thus useful to optimize the design of breeding programs. Scenarios can vary in terms of the genetic correlation between purebred and crossbred performances, heritabilities, number of reference animals, or distance between breeds.

Project description:BackgroundIn pig and poultry breeding, the objective is to improve the performance of crossbred production animals, while selection takes place in the purebred parent lines. One way to achieve this is to use genomic prediction with a crossbred reference population. A crossbred reference population benefits from expressing the breeding goal trait but suffers from a lower genetic relatedness with the purebred selection candidates than a purebred reference population. Our aim was to investigate the benefit of using a crossbred reference population for genomic prediction of crossbred performance for: (1) different levels of relatedness between the crossbred reference population and purebred selection candidates, (2) different levels of the purebred-crossbred correlation, and (3) different reference population sizes. We simulated a crossbred breeding program with 0, 1 or 2 multiplication steps to generate the crossbreds, and compared the accuracy of genomic prediction of crossbred performance in one generation using either a purebred or a crossbred reference population. For each scenario, we investigated the empirical accuracy based on simulation and the predicted accuracy based on the estimated effective number of independent chromosome segments between the reference animals and selection candidates.ResultsWhen the purebred-crossbred correlation was 0.75, the accuracy was highest for a two-way crossbred reference population but similar for purebred and four-way crossbred reference populations, for all reference population sizes. When the purebred-crossbred correlation was 0.5, a purebred reference population always resulted in the lowest accuracy. Among the different crossbred reference populations, the accuracy was slightly lower when more multiplication steps were used to create the crossbreds. In general, the benefit of crossbred reference populations increased when the size of the reference population increased. All predicted accuracies overestimated their corresponding empirical accuracies, but the different scenarios were ranked accurately when the reference population was large.ConclusionsThe benefit of a crossbred reference population becomes larger when the crossbred population is more related to the purebred selection candidates, when the purebred-crossbred correlation is lower, and when the reference population is larger. The purebred-crossbred correlation and reference population size interact with each other with respect to their impact on the accuracy of genomic estimated breeding values.

Project description:This study assessed the accuracy and bias of genomic prediction (GP) in purebred Holstein (H) and Jersey (J) as well as crossbred (H and J) validation cows using different reference sets and prediction strategies. The reference sets were made up of different combinations of 36,695 H and J purebreds and crossbreds. Additionally, the effect of using different sets of marker genotypes on GP was studied (conventional panel: 50k, custom panel enriched with, or close to, causal mutations: XT_50k, and conventional high-density with a limited custom set: pruned HDnGBS). We also compared the use of genomic best linear unbiased prediction (GBLUP) and Bayesian (emBayesR) models, and the traits tested were milk, fat, and protein yields. On average, by including crossbred cows in the reference population, the prediction accuracies increased by 0.01-0.08 and were less biased (regression coefficient closer to 1 by 0.02-0.16), and the benefit was greater for crossbreds compared to purebreds. The accuracy of prediction increased by 0.02 using XT_50k compared to 50k genotypes without affecting the bias. Although using pruned HDnGBS instead of 50k also increased the prediction accuracy by about 0.02, it increased the bias for purebred predictions in emBayesR models. Generally, emBayesR outperformed GBLUP for prediction accuracy when using 50k or pruned HDnGBS genotypes, but the benefits diminished with XT_50k genotypes. Crossbred predictions derived from a joint pure H and J reference were similar in accuracy to crossbred predictions derived from the two separate purebred reference sets and combined proportional to breed composition. However, the latter approach was less biased by 0.13. Most interestingly, using an equalized breed reference instead of an H-dominated reference, on average, reduced the bias of prediction by 0.16-0.19 and increased the accuracy by 0.04 for crossbred and J cows, with a little change in the H accuracy. In conclusion, we observed improved genomic predictions for both crossbreds and purebreds by equalizing breed contributions in a mixed breed reference that included crossbred cows. Furthermore, we demonstrate, that compared to the conventional 50k or high-density panels, our customized set of 50k sequence markers improved or matched the prediction accuracy and reduced bias with both GBLUP and Bayesian models.

Project description:Breeding programs aiming to improve the performance of crossbreds may benefit from genomic prediction of crossbred (CB) performance for purebred (PB) selection candidates. In this review, we compared genomic prediction strategies that differed in 1) the genomic prediction model used or 2) the data used in the reference population. We found 27 unique studies, two of which used deterministic simulation, 11 used stochastic simulation, and 14 real data. Differences in accuracy and response to selection between strategies depended on i) the value of the purebred crossbred genetic correlation (rpc), ii) the genetic distance between the parental lines, iii) the size of PB and CB reference populations, and iv) the relatedness of these reference populations to the selection candidates. In studies where a PB reference population was used, the use of a dominance model yielded accuracies that were equal to or higher than those of additive models. When rpc was lower than ~0.8, and was caused mainly by G × E, it was beneficial to create a reference population of PB animals that are tested in a CB environment. In general, the benefit of collecting CB information increased with decreasing rpc. For a given rpc, the benefit of collecting CB information increased with increasing size of the reference populations. Collecting CB information was not beneficial when rpc was higher than ~0.9, especially when the reference populations were small. Collecting only phenotypes of CB animals may slightly improve accuracy and response to selection, but requires that the pedigree is known. It is, therefore, advisable to genotype these CB animals as well. Finally, considering the breed-origin of alleles allows for modeling breed-specific effects in the CB, but this did not always lead to higher accuracies. Our review shows that the differences in accuracy and response to selection between strategies depend on several factors. One of the most important factors is rpc, and we, therefore, recommend to obtain accurate estimates of rpc of all breeding goal traits. Furthermore, knowledge about the importance of components of rpc (i.e., dominance, epistasis, and G × E) can help breeders to decide which model to use, and whether to collect data on animals in a CB environment. Future research should focus on the development of a tool that predicts accuracy and response to selection from scenario specific parameters.

Project description:BackgroundThis study investigated if the allele effect of a given single nucleotide polymorphism (SNP) for crossbred performance in pigs estimated in a genomic prediction model differs depending on its breed-of-origin, and how these are related to estimated effects for purebred performance.ResultsSNP-allele substitution effects were estimated for a commonly used SNP panel using a genomic best linear unbiased prediction model with breed-specific partial relationship matrices. Estimated breeding values for purebred and crossbred performance were converted to SNP-allele effects by breed-of-origin. Differences between purebred and crossbred, and between breeds-of-origin were evaluated by comparing percentage of variance explained by genomic regions for back fat thickness (BF), average daily gain (ADG), and residual feed intake (RFI). From ten regions explaining most additive genetic variance for crossbred performance, 1 to 5 regions also appeared in the top ten for purebred performance. The proportion of genetic variance explained by a genomic region and the estimated effect of a haplotype in such a region were different depending upon the breed-of-origin. To illustrate underlying mechanisms, we evaluated the estimated effects across breeds-of-origin for haplotypes associated to the melanocortin 4 receptor (MC4R) gene, and for the MC4Rsnp itself which is a missense mutation with a known effect on BF and ADG. Although estimated allele substitution effects of the MC4Rsnp mutation were very similar across breeds, explained genetic variance of haplotypes associated to the MC4R gene using a SNP panel that does not include the mutation, was considerably lower in one of the breeds where the allele frequency of the mutation was the lowest.ConclusionsSimilar regions explaining similar additive genetic variance were observed across purebred and crossbred performance. Moreover, there was some overlap across breeds-of-origin between regions that explained relatively large proportions of genetic variance for crossbred performance; albeit that the actual proportion of variance deviated across breeds-of-origin. Results based on a missense mutation in MC4R confirmed that even if a causal locus has similar effects across breeds-of-origin, estimated effects and explained variance in its region using a commonly used SNP panel can strongly depend on the allele frequency of the underlying causal mutation.

Project description:Background In genomic prediction including data of 3- or 4-way crossbred animals, line composition is usually fitted as a regression on expected line proportions, which are 0.5, 0.25 and 0.25, respectively, for 3-way crossbred animals. However, actual line proportions for the dam lines can vary between ~ 0.1 and 0.4, and ignoring this variation may affect the genomic estimated breeding values of purebred selection candidates. Our aim was to validate a proposed gold standard to evaluate different approaches for estimating line proportions using simulated data, and to subsequently use this in actual 3-way crossbred broiler data to evaluate several other methods. Results Analysis of simulated data confirmed that line proportions computed from assigned breed-origin-of-alleles (BOA) provide a very accurate gold standard, even if the parental lines are closely related. Alternative investigated methods were linear regression of genotypes on line-specific allele frequencies, maximum likelihood estimation using the program ADMIXTURE, and the genomic relationship of crossbred animals with their maternal grandparents. The results from the simulated data showed that the genomic relationship with the maternal grandparent was most accurate, and least affected by closer relationships between the dam lines. Linear regression and ADMIXTURE performed similarly for unrelated lines, but their accuracy dropped considerably when the dam lines were more closely related. In almost all cases, estimates improved after adjusting them to ensure that the sum of dam line contributions within animals was equal to 0.5, and within dam line and across animals the average was equal to 0.25. Results from the broiler data were much more similar between methods. In both cases, stringent linkage disequilibrium pruning of genotype data led to a relatively low accuracy of predicted line proportions, due to the loss of too many single nucleotide polymorphisms. Conclusions With relatively unrelated parental lines as typical in crosses in pigs and poultry, linear regression of crossbred genotypes on line-specific allele frequencies and ADMIXTURE are very competitive methods. Thus, linear regression may be the method of choice, as it does not require genotypes of grandparents, is computationally very efficient, and easily implemented and adapted for considering the specific nature of the crossbred animals analysed. Supplementary Information The online version contains supplementary material available at 10.1186/s12711-022-00728-4.

Project description:A variety of statistical methods, such as admixture models, have been used to estimate genomic breed composition (GBC). These methods, however, tend to produce non-zero components to reference breeds that shared some genomic similarity with a test animal. These non-essential GBC components, in turn, offset the estimated GBC for the breed to which it belongs. As a result, not all purebred animals have 100% GBC of their respective breeds, which statistically indicates an elevated false-negative rate in the identification of purebred animals with 100% GBC as the cutoff. Otherwise, a lower cutoff of estimated GBC will have to be used, which is arbitrary, and the results are less interpretable. In the present study, three admixture models with regularization were proposed, which produced sparse solutions through suppressing the noise in the estimated GBC due to genomic similarities. The regularization or penalty forms included the L1 norm penalty, minimax concave penalty (MCP), and smooth clipped absolute deviation (SCAD). The performances of these regularized admixture models on the estimation of GBC were examined in purebred and composite animals, respectively, and compared to that of the non-regularized admixture model as the baseline model. The results showed that, given optimal values for ?, the three sparsely regularized admixture models had higher power and thus reduced the false-negative rate for the breed identification of purebred animals than the non-regularized admixture model. Of the three regularized admixture models, the two with a non-convex penalty outperformed the one with L1 norm penalty. In the Brangus, a composite cattle breed, estimated GBC were roughly comparable among the four admixture models, but all the four models underestimated the GBC for these composite animals when non-ancestral breeds were included as the reference. In conclusion, the admixture models with sparse regularization gave more parsimonious, consistent and interpretable results of estimated GBC for purebred animals than the non-regularized admixture model. Nevertheless, the utility of regularized admixture models for estimating GBC in crossbred or composite animals needs to be taken with caution.

Project description:Genomic selection increases the rate of genetic gain in breeding programs, which results in significant cumulative improvements in commercially important traits such as disease resistance. Genomic selection currently relies on collecting genome-wide genotype data accross a large number of individuals, which requires substantial economic investment. However, global aquaculture production predominantly occurs in small and medium sized enterprises for whom this technology can be prohibitively expensive. For genomic selection to benefit these aquaculture sectors, more cost-efficient genotyping is necessary. In this study the utility of low and medium density SNP panels (ranging from 100 to 9,000 SNPs) to accurately predict breeding values was tested and compared in four aquaculture datasets with different characteristics (species, genome size, genotyping platform, family number and size, total population size, and target trait). The traits show heritabilities between 0.19-0.49, and genomic prediction accuracies using the full density panel of 0.55-0.87. A consistent pattern of genomic prediction accuracy was observed across species with little or no accuracy reduction until SNP density was reduced below 1,000 SNPs (prediction accuracies of 0.44-0.75). Below this SNP density, heritability estimates and genomic prediction accuracies tended to be lower and more variable (93% of maximum accuracy achieved with 1,000 SNPs, 89% with 500 SNPs, and 70% with 100 SNPs). A notable drop in accuracy was observed between 200 SNP panels (0.44-0.75) and 100 SNP panels (0.39-0.66). Now that a multitude of studies have highlighted the benefits of genomic over pedigree-based prediction of breeding values in aquaculture species, the results of the current study highlight that these benefits can be achieved at lower SNP densities and at lower cost, raising the possibility of a broader application of genetic improvement in smaller and more fragmented aquaculture settings.

Dataset Information

Genomic prediction for crossbred performance using metafounders.

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Genomic prediction for crossbred performance using metafounders.

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