H.A. Mulder

Reliability of direct genomic values for animals with different relationships within and to the reference population

Accuracy of genomic selection depends on the accuracy of prediction of single nucleotide polymorphism effects and the proportion of genetic variance explained by markers. Design of the reference population with respect to its family structure may influence the accuracy of genomic selection. The objective of this study was to investigate the effect of various relationship levels within the reference population and different level of relationship of evaluated animals to the reference population on the reliability of direct genomic breeding values (DGV). The DGV reliabilities, expressed as squared correlation between estimated and true breeding value, were calculated for evaluated animals at 3 heritability levels. To emulate a trait that is difficult or expensive to measure, such as methane emission, reference populations were kept small and consisted of females with own performance records. A population reflecting a dairy cattle population structure was simulated. Four chosen reference populations consisted of all females available in the first genotyped generation. They consisted of highly (HR), moderately (MR), or lowly (LR) related animals, by selecting paternal half-sib families of decreasing size, or consisted of randomly chosen animals (RND). Of those 4 reference populations, RND had the lowest average relationship. Three sets of evaluated animals were chosen from 3 consecutive generations of genotyped animals, starting from the same generation as the reference population. Reliabilities of DGV predictions were calculated deterministically using selection index theory. The randomly chosen reference population had the lowest average relationship within the reference population. Average reliabilities increased when average relationship within the reference population decreased and the highest average reliabilities were achieved for RND (e.g., from 0.53 in HR to 0.61 in RND for a heritability of 0.30). A higher relationship to the reference population resulted in higher reliability values. At the average squared relationship of evaluated animals to the reference population of 0.005, reliabilities were, on average, 0.49 (HR) and 0.63 (RND) for a heritability of 0.30; 0.20 (HR) and 0.27 (RND) for a heritability of 0.05; and 0.07 (HR) and 0.09 (RND) for a heritability of 0.01. Substantial decrease in the reliability was observed when the number of generations to the reference population increased [e.g., for heritability of 0.30, the decrease from evaluated set I (chosen from the same generation as the reference population) to II (one generation younger than the reference population) was 0.04 for HR, and 0.07 for RND]. In this study, the importance of the design of a reference population consisting of cows was shown and optimal designs of the reference population for genomic prediction were suggested.

Imputation of genotypes with low-density chips and its effect on reliability of direct genomic values in Dutch Holstein cattle

Genomic selection using 50,000 single nucleotide polymorphism (50k SNP) chips has been implemented in many dairy cattle breeding programs. Cheap, low-density chips make genotyping of a larger number of animals cost effective. A commonly proposed strategy is to impute low-density genotypes up to 50,000 genotypes before predicting direct genomic values (DGV). The objectives of this study were to investigate the accuracy of imputation for animals genotyped with a low-density chip and to investigate the effect of imputation on reliability of DGV. Low-density chips contained 384, 3,000, or 6,000 SNP. The SNP were selected based either on the highest minor allele frequency in a bin or the middle SNP in a bin, and DAGPHASE, CHROMIBD, and multivariate BLUP were used for imputation. Genotypes of 9,378 animals were used, from which approximately 2,350 animals had deregressed proofs. Bayesian stochastic search variable selection was used for estimating SNP effects of the 50k chip. Imputation accuracies and imputation error rates were poor for low-density chips with 384 SNP. Imputation accuracies were higher with 3,000 and 6,000 SNP. Performance of DAGPHASE and CHROMIBD was very similar and much better than that of multivariate BLUP for both imputation accuracy and reliability of DGV. With 3,000 SNP and using CHROMIBD or DAGPHASE for imputation, 84 to 90% of the increase in DGV reliability using the 50k chip, compared with a pedigree index, was obtained. With multivariate BLUP, the increase in reliability was only 40%. With 384 SNP, the reliability of DGV was lower than for a pedigree index, whereas with 6,000 SNP, about 93% of the increase in reliability of DGV based on the 50k chip was obtained when using DAGPHASE for imputation. Using genotype probabilities to predict gene content increased imputation accuracy and the reliability of DGV and is therefore recommended for applications of imputation for genomic prediction. A deterministic equation was derived to predict accuracy of DGV based on imputation accuracy, which fitted closely with the observed relationship. The deterministic equation can be used to evaluate the effect of differences in imputation accuracy on accuracy and reliability of DGV.

Genetic heterogeneity of residual variance - estimation of variance components using double hierarchical generalized linear models

BackgroundThe sensitivity to microenvironmental changes varies among animals and may be under genetic control. It is essential to take this element into account when aiming at breeding robust farm animals. Here, linear mixed models with genetic effects in the residual variance part of the model can be used. Such models have previously been fitted using EM and MCMC algorithms.ResultsWe propose the use of double hierarchical generalized linear models (DHGLM), where the squared residuals are assumed to be gamma distributed and the residual variance is fitted using a generalized linear model. The algorithm iterates between two sets of mixed model equations, one on the level of observations and one on the level of variances. The method was validated using simulations and also by re-analyzing a data set on pig litter size that was previously analyzed using a Bayesian approach. The pig litter size data contained 10,060 records from 4,149 sows. The DHGLM was implemented using the ASReml software and the algorithm converged within three minutes on a Linux server. The estimates were similar to those previously obtained using Bayesian methodology, especially the variance components in the residual variance part of the model.ConclusionsWe have shown that variance components in the residual variance part of a linear mixed model can be estimated using a DHGLM approach. The method enables analyses of animal models with large numbers of observations. An important future development of the DHGLM methodology is to include the genetic correlation between the random effects in the mean and residual variance parts of the model as a parameter of the DHGLM.

Genomic and pedigree-based genetic parameters for scarcely recorded traits when some animals are genotyped

Genetic parameters were estimated using relationships between animals that were based either on pedigree, 43,011 single nucleotide polymorphisms, or a combination of these, considering genotyped and non-genotyped animals. The standard error of the estimates and a parametric bootstrapping procedure was used to investigate sampling properties of the estimated variance components. The data set contained milk yield, dry matter intake and body weight for 517 first-lactation heifers with genotypes and phenotypes, and another 112 heifers with phenotypes only. Multivariate models were fitted using the different relationships in ASReml software. Estimates of genetic variance were lower based on genomic relationships than using pedigree relationships. Genetic variances from genomic and pedigree relationships were, however, not directly comparable because they apply to different base populations. Standard errors indicated that using the genomic relationships gave more accurate estimates of heritability but equally accurate estimates of genetic correlation. However, the estimates of standard errors were affected by the differences in scale between the 2 relationship matrices, causing differences in values of the genetic parameters. The bootstrapping results (with genetic parameters at the same level), confirmed that both heritability and genetic correlations were estimated more accurately with genomic relationships in comparison with using the pedigree relationships. Animals without genotype were included in the analysis by merging genomic and pedigree relationships. This allowed all phenotypes to be used, including those from non-genotyped animals. This combination of genomic and pedigree relationships gave the most accurate estimates of genetic variance. When a small data set is available it might be more advantageous for the estimation of genetic parameters to genotype existing animals, rather than collecting more phenotypes.

Estimation of genetic variation in residual variance in female and male broiler chickens

In breeding programs, robustness of animals and uniformity of end product can be improved by exploiting genetic variation in residual variance. Residual variance can be defined as environmental variance after accounting for all identifiable effects. The aims of this study were to estimate genetic variance in residual variance of body weight, and to estimate genetic correlations between body weight itself and its residual variance and between female and male residual variance for broilers. The data sets comprised 26 972 female and 24 407 male body weight records. Variance components were estimated with ASREML. Estimates of the heritability of residual variance were in the range 0.029 (s.e. = 0.003) to 0.047 (s.e. = 0.004). The genetic coefficients of variation were high, between 0.35 and 0.57. Heritabilities were higher in females than in males. Accounting for heterogeneous residual variance increased the heritabilities for body weight as well. Genetic correlations between body weight and its residual variance were -0.41 (s.e. = 0.032) and -0.45 (s.e. = 0.040), respectively, in females and males. The genetic correlation between female and male residual variance was 0.11 (s.e. = 0.089), indicating that female and male residual variance are different traits. Results indicate good opportunities to simultaneously increase the mean and improve uniformity of body weight of broilers by selection.

Predicting energy balance for dairy cows using high-density single nucleotide polymorphism information.

The objective of this study was to investigate the genetic basis of energy balance (EB) and the potential use of genomic selection to enable EB to be incorporated into selection programs. Energy balance provides an essential link between production and nonproduction traits because both depend on a common source of energy. A small number (527) of Dutch Holstein-Friesian heifers with phenotypes for EB were genotyped. Direct genomic values were predicted for these heifers using a model that included the genotypic information. A polygenic model was also applied to predict estimated breeding values using only pedigree information. A 10-fold cross-validation approach was employed to assess the accuracies of the 2 sets of predicted breeding values by correlating them with phenotypes. Because of the small number of phenotypes, accuracies were relatively low (0.29 for the direct genomic values and 0.21 for the estimated breeding values), where the maximum possible accuracy was the square root of heritability (0.57). Despite this, the genomic model produced breeding values with reliability double that of the breeding values produced by the polygenic model. To increase the accuracy of the genomic breeding values and make it possible to select for EB, measurement and recording of EB would need to improve. The study suggests that it may be possible to select for minimally recorded traits; for instance, those measured on experimental farms, using genomic selection. Overall, the study demonstrated that genomic selection could be used to select for EB, confirming its genetic background.

Evaluation of measures of correctness of genotype imputation in the context of genomic prediction: a review of livestock applications

In livestock, many studies have reported the results of imputation to 50k single nucleotide polymorphism (SNP) genotypes for animals that are genotyped with low-density SNP panels. The objective of this paper is to review different measures of correctness of imputation, and to evaluate their utility depending on the purpose of the imputed genotypes. Across studies, imputation accuracy, computed as the correlation between true and imputed genotypes, and imputation error rates, that counts the number of incorrectly imputed alleles, are commonly used measures of imputation correctness. Based on the nature of both measures and results reported in the literature, imputation accuracy appears to be a more useful measure of the correctness of imputation than imputation error rates, because imputation accuracy does not depend on minor allele frequency (MAF), whereas imputation error rate depends on MAF. Therefore imputation accuracy can be better compared across loci with different MAF. Imputation accuracy depends on the ability of identifying the correct haplotype of a SNP, but many other factors have been identified as well, including the number of genotyped immediate ancestors, the number of animals with genotypes at the high-density panel, the SNP density on the low- and high-density panel, the MAF of the imputed SNP and whether imputed SNP are located at the end of a chromosome or not. Some of these factors directly contribute to the linkage disequilibrium between imputed SNP and SNP on the low-density panel. When imputation accuracy is assessed as a predictor for the accuracy of subsequent genomic prediction, we recommend that: (1) individual-specific imputation accuracies should be used that are computed after centring and scaling both true and imputed genotypes; and (2) imputation of gene dosage is preferred over imputation of the most likely genotype, as this increases accuracy and reduces bias of the imputed genotypes and the subsequent genomic predictions.

Genotype-by-environment interaction of growth traits in rainbow trout (Oncorhynchus mykiss): a continental scale study.

Rainbow trout is a globally important fish species for aquaculture. However, fish for most farms worldwide are produced by only a few breeding companies. Selection based solely on fish performance recorded at a nucleus may lead to lower-than-expected genetic gains in other production environments when genotype-by-environment (G × E) interaction exists. The aim was to quantify the magnitude of G × E interaction of growth traits (tagging weight; BWT, harvest weight; BWH, and growth rate; TGC) measured across 4 environments, located in 3 different continents, by estimating genetic correlations between environments. A total of 100 families, of at least 25 in size, were produced from the mating 58 sires and 100 dams. In total, 13,806 offspring were reared at the nucleus (selection environment) in Washington State (NUC) and in 3 other environments: a recirculating aquaculture system in Freshwater Institute (FI), West Virginia; a high-altitude farm in Peru (PE), and a cold-water farm in Germany (GER). To account for selection bias due to selective mortality, a multitrait multienvironment animal mixed model was applied to analyze the performance data in different environments as different traits. Genetic correlation (rg) of a trait measured in different environments and rg of different traits measured in different environments were estimated. The results show that heterogeneity of additive genetic variances was mainly found for BWH measured in FI and PE. Additive genetic coefficient of variation for BWH in NUC, FI, PE, and GER were 7.63, 8.36, 8.64, and 9.75, respectively. Genetic correlations between the same trait in different environments were low, indicating strong reranking (BWT: rg = 0.15 to 0.37, BWH: rg = 0.19 to 0.48, TGC: rg = 0.31 to 0.36) across environments. The rg between BWT in NUC and BWH in both FI (0.31) and GER (0.36) were positive, which was also found between BWT in NUC and TGC in both FI (0.10) and GER (0.20). However, rg were negative between BWT in NUC and both BWH (-0.06) and TGC (-0.20) in PE. Correction for selection bias resulted in higher additive genetic variances. In conclusion, strong G × E interaction was found for BWT, BWH, and TGC. Accounting for G × E interaction in the breeding program, either by using sib information from testing stations or environment-specific breeding programs, would increase genetic gains for environments that differ significantly from NUC.

Variance component and breeding value estimation for genetic heterogeneity of residual variance in Swedish Holstein dairy cattle

Trait uniformity, or micro-environmental sensitivity, may be studied through individual differences in residual variance. These differences appear to be heritable, and the need exists, therefore, to fit models to predict breeding values explaining differences in residual variance. The aim of this paper is to estimate breeding values for micro-environmental sensitivity (vEBV) in milk yield and somatic cell score, and their associated variance components, on a large dairy cattle data set having more than 1.6 million records. Estimation of variance components, ordinary breeding values, and vEBV was performed using standard variance component estimation software (ASReml), applying the methodology for double hierarchical generalized linear models. Estimation using ASReml took less than 7 d on a Linux server. The genetic standard deviations for residual variance were 0.21 and 0.22 for somatic cell score and milk yield, respectively, which indicate moderate genetic variance for residual variance and imply that a standard deviation change in vEBV for one of these traits would alter the residual variance by 20%. This study shows that estimation of variance components, estimated breeding values and vEBV, is feasible for large dairy cattle data sets using standard variance component estimation software. The possibility to select for uniformity in Holstein dairy cattle based on these estimates is discussed.

Identification of proteomic biomarkers in M. Longissimus dorsi as potential predictors of pork quality

Meat quality traits have low heritability and large environmental influences. To predict, improve and manage meat quality, proteomic biomarkers are superior to genetic markers. The objectives of this research were (1) to find associations between proteome profiles of longissimus muscle at slaughter and meat quality accuracies of prediction of traits ranged from 20 up to 80%. Differentially expressed proteins related to drip loss and ultimate pH were identified by NanoLC-FTMSMS. The proteins highlight biological mechanisms that may explain how these traits develop biologically and how they are related to each other.