Estimation of additive, dominance and epistatic variance components using finite locus models implemented with a single-site Gibbs and a descent graph sampler

In a previous contribution, we implemented a finite locus model (FLM) for estimating additive and dominance genetic variances via a Bayesian method and a single-site Gibbs sampler. We observed a dependency of dominance variance estimates on locus number in the analysis FLM. Here, we extended the FLM to include two-locus epistasis, and implemented the analysis with two genotype samplers (Gibbs and descent graph) and three different priors for genetic effects (uniform and variable across loci, uniform and constant across loci, and normal). Phenotypic data were simulated for two pedigrees with 6300 and 12,300 individuals in closed populations, using several different, non-additive genetic models. Replications of these data were analysed with FLMs differing in the number of loci. Simulation results indicate that the dependency of non-additive genetic variance estimates on locus number persisted in all implementation strategies we investigated. However, this dependency was considerably diminished with normal priors for genetic effects as compared with uniform priors (constant or variable across loci). Descent graph sampling of genotypes modestly improved variance components estimation compared with Gibbs sampling. Moreover, a larger pedigree produced considerably better variance components estimation, suggesting this dependency might originate from data insufficiency. As the FLM represents an appealing alternative to the infinitesimal model for genetic parameter estimation and for inclusion of polygenic background variation in QTL mapping analyses, further improvements are warranted and might be achieved via improvement of the sampler or treatment of the number of loci as an unknown.     

具有亲缘关系矩阵的混合模型的方差组分迭代估计——应用于计算BLUP的方差比值和遗传参数

论述的是来自非均街资料的混合模型中具有亲缘关系矩阵时利用迭代法估计方差组分问题。这篇文章表明计算程序是可行的,只要能够按照混合模型中固定效应的结构矩阵和Henderson方法3的固定效应的假设条件正确地计算二次型约化平方和,就可获得较为精确的方差组分估计值;而且表明方差初始比值k偏高或偏低,不影响迭代求解的最后结果,这是因为在迭代过程中可以通过结构矩阵x'x和x'x的控制而自行调整。这些方差组分不仅可应用于选种种畜用的BLUP计算,还可用来估计遗传参数。     

Principal component and factor analytic models in international sire evaluation

Background

Interbull is a non-profit organization that provides internationally comparable breeding values for globalized dairy cattle breeding programmes. Due to different trait definitions and models for genetic evaluation between countries, each biological trait is treated as a different trait in each of the participating countries. This yields a genetic covariance matrix of dimension equal to the number of countries which typically involves high genetic correlations between countries. This gives rise to several problems such as over-parameterized models and increased sampling variances, if genetic (co)variance matrices are considered to be unstructured.

Methods

Principal component (PC) and factor analytic (FA) models allow highly parsimonious representations of the (co)variance matrix compared to the standard multi-trait model and have, therefore, attracted considerable interest for their potential to ease the burden of the estimation process for multiple-trait across country evaluation (MACE). This study evaluated the utility of PC and FA models to estimate variance components and to predict breeding values for MACE for protein yield. This was tested using a dataset comprising Holstein bull evaluations obtained in 2007 from 25 countries.

Results

In total, 19 principal components or nine factors were needed to explain the genetic variation in the test dataset. Estimates of the genetic parameters under the optimal fit were almost identical for the two approaches. Furthermore, the results were in a good agreement with those obtained from the full rank model and with those provided by Interbull. The estimation time was shortest for models fitting the optimal number of parameters and prolonged when under- or over-parameterized models were applied. Correlations between estimated breeding values (EBV) from the PC19 and PC25 were unity. With few exceptions, correlations between EBV obtained using FA and PC approaches under the optimal fit were ≥ 0.99. For both approaches, EBV correlations decreased when the optimal model and models fitting too few parameters were compared.

Conclusions

Genetic parameters from the PC and FA approaches were very similar when the optimal number of principal components or factors was fitted. Over-fitting increased estimation time and standard errors of the estimates but did not affect the estimates of genetic correlations or the predictions of breeding values, whereas fitting too few parameters affected bull rankings in different countries.     

Breeding Value and Variance Component Estimation from Data Containing Inbred Individuals: Application to Gynogenetic Families in Common Carp (Cyprinus Carpio L.)

Under gynogenetic reproduction, offspring receive genes only from their dams and completely homozygous offspring are produced within one generation. When gynogenetic reproduction is applied to fully inbred individuals, homozygous clone lines are produced. A mixed model method was developed for breeding value and variance component estimation in gynogenetic families, which requires the inverse of the numerator relationship matrix. A general method for creating the inverse for a population with unusual relationships between animals is presented, which reduces to simple rules as is illustrated for gynogenetic populations. The presence of clones in gynogenetic populations causes singularity of the numerator relationship matrix. However, clones can be regarded as repeated observations of the same genotype, which can be accommodated by modifying the incidence matrix, and by considering only unique genotypes in the estimation procedure. Optimum gynogenetic sib family sizes for estimating heritabilities and estimates of their accuracy were derived and compared to those for conventional full-sib designs. This was done by means of a deterministic derivation and by stochastic simulation using Gibbs sampling. Optimum family sizes were smallest for gynogenetic families. Only for low heritabilities, there was a small advantage in accuracy under the gynogenetic design.     

Analyzing Variety by Environment Data Using Multiplicative Mixed Models and Adjustments for Spatial Field Trend

The recommendation of new plant varieties for commercial use requires reliable and accurate predictions of the average yield of each variety across a range of target environments and knowledge of important interactions with the environment. This information is obtained from series of plant variety trials, also known as multi-environment trials (MET). Cullis, Gogel, Verbyla, and Thompson (1998) presented a spatial mixed model approach for the analysis of MET data. In this paper we extend the analysis to include multiplicative models for the variety effects in each environment. The multiplicative model corresponds to that used in the multivariate technique of factor analysis. It allows a separate genetic variance for each environment and provides a parsimonious and interpretable model for the genetic covariances between environments. The model can be regarded as a random effects analogue of AMMI (additive main effects and multiplicative interactions). We illustrate the method using a large set of MET data from a South Australian barley breeding program.     

Modeling additive and non-additive effects in a hybrid population using genome-wide genotyping: prediction accuracy implications

Hybrids are broadly used in plant breeding and accurate estimation of variance components is crucial for optimizing genetic gain. Genome-wide information may be used to explore models designed to assess the extent of additive and non-additive variance and test their prediction accuracy for the genomic selection. Ten linear mixed models, involving pedigree- and marker-based relationship matrices among parents, were developed to estimate additive (A), dominance (D) and epistatic (AA, AD and DD) effects. Five complementary models, involving the gametic phase to estimate marker-based relationships among hybrid progenies, were developed to assess the same effects. The models were compared using tree height and 3303 single-nucleotide polymorphism markers from 1130 cloned individuals obtained via controlled crosses of 13 Eucalyptus urophylla females with 9 Eucalyptus grandis males. Akaike information criterion (AIC), variance ratios, asymptotic correlation matrices of estimates, goodness-of-fit, prediction accuracy and mean square error (MSE) were used for the comparisons. The variance components and variance ratios differed according to the model. Models with a parent marker-based relationship matrix performed better than those that were pedigree-based, that is, an absence of singularities, lower AIC, higher goodness-of-fit and accuracy and smaller MSE. However, AD and DD variances were estimated with high s.es. Using the same criteria, progeny gametic phase-based models performed better in fitting the observations and predicting genetic values. However, DD variance could not be separated from the dominance variance and null estimates were obtained for AA and AD effects. This study highlighted the advantages of progeny models using genome-wide information.     

Genetic analysis of agronomic characters in chickpea. II. Estimates of genetic variances from line × tester mating designs

Summary Thirty line x tester experiments involving diverse chickpea (Cicer arietinum L.) germplasm were conducted over 8 years and three locations to determine the nature of the genetic variance for grain yield and related characters, and the effects of generation and environment on these genetic parameters. Days-to-flowering, 100-seed mass, and seeds per pod were predominantly under the control of additive genetic variance, while both additive and non-additive genetic components of variance were important for days-to-maturity, plant height, primary and secondary branches, pods per plant, and seed yield. The F₁ and F₂ generations were found equally useful in estimating the genetic variances for different characters because the generation did not significantly interact with genetic parameters in the majority of cases. Sites or seasons, on the other hand, showed significant interaction with genetic components of variances; additive variance showed a larger interaction with environments than non-additive variance. This indicated the importance of more than one site and/ or season for unbiased estimation of the genetic components of variance. The results were compared with previous findings from diallel analyses.ICRISAT Journal Article No. 1200     

Estimating Additive and Non-Additive Genetic Variances and Predicting Genetic Merits Using Genome-Wide Dense Single Nucleotide Polymorphism Markers

Non-additive genetic variation is usually ignored when genome-wide markers are used to study the genetic architecture and genomic prediction of complex traits in human, wild life, model organisms or farm animals. However, non-additive genetic effects may have an important contribution to total genetic variation of complex traits. This study presented a genomic BLUP model including additive and non-additive genetic effects, in which additive and non-additive genetic relation matrices were constructed from information of genome-wide dense single nucleotide polymorphism (SNP) markers. In addition, this study for the first time proposed a method to construct dominance relationship matrix using SNP markers and demonstrated it in detail. The proposed model was implemented to investigate the amounts of additive genetic, dominance and epistatic variations, and assessed the accuracy and unbiasedness of genomic predictions for daily gain in pigs. In the analysis of daily gain, four linear models were used: 1) a simple additive genetic model (MA), 2) a model including both additive and additive by additive epistatic genetic effects (MAE), 3) a model including both additive and dominance genetic effects (MAD), and 4) a full model including all three genetic components (MAED). Estimates of narrow-sense heritability were 0.397, 0.373, 0.379 and 0.357 for models MA, MAE, MAD and MAED, respectively. Estimated dominance variance and additive by additive epistatic variance accounted for 5.6% and 9.5% of the total phenotypic variance, respectively. Based on model MAED, the estimate of broad-sense heritability was 0.506. Reliabilities of genomic predicted breeding values for the animals without performance records were 28.5%, 28.8%, 29.2% and 29.5% for models MA, MAE, MAD and MAED, respectively. In addition, models including non-additive genetic effects improved unbiasedness of genomic predictions.     

Data and theory point to mainly additive genetic variance for complex traits

The relative proportion of additive and non-additive variation for complex traits is important in evolutionary biology, medicine, and agriculture. We address a long-standing controversy and paradox about the contribution of non-additive genetic variation, namely that knowledge about biological pathways and gene networks imply that epistasis is important. Yet empirical data across a range of traits and species imply that most genetic variance is additive. We evaluate the evidence from empirical studies of genetic variance components and find that additive variance typically accounts for over half, and often close to 100%, of the total genetic variance. We present new theoretical results, based upon the distribution of allele frequencies under neutral and other population genetic models, that show why this is the case even if there are non-additive effects at the level of gene action. We conclude that interactions at the level of genes are not likely to generate much interaction at the level of variance.     

Multibreed analysis by splitting the breeding values

An equivalent model for multibreed variance covariance estimation is presented. It considers the additive case including or not the segregation variances. The model is based on splitting the additive genetic values in several independent parts depending on their genetic origin. For each part, it expresses the covariance between relatives as a partial numerator relationship matrix times the corresponding variance component. Estimation of fixed effects, random effects or variance components provided by the model are as simple as any model including several random factors. We present a small example describing the mixed model equations for genetic evaluations and two simulated examples to illustrate the Bayesian variance component estimation.     

Simple outlier detection for a multi-environmental field trial

The aim of plant breeding trials is often to identify crop variety that are well adapt to target environments. These varieties are identified through genomic prediction from the analysis of multi-environmental field trial (MET) using linear mixed models. The occurrence of outliers in MET is common and known to adversely impact the accuracy of genomic prediction yet the detection of outliers are often neglected. A number of reasons stand for this—first, complex data such as a MET give rise to distinct levels of residuals (eg, at a trial level or individual observation level). This complexity offers additional challenges for an outlier detection method. Second, many linear mixed model software packages that cater for complex variance structures needed in the analysis of MET are not well streamlined for diagnostics by practitioners. We demonstrate outlier detection methods that are simple to implement in any linear mixed model software packages and computationally fast. Although these methods are not optimal methods in outlier detection, they offer practical value for ease of application in the analysis pipeline of regularly collected data. These are demonstrated using simulation based on two real bread wheat yield METs. In particular, models that consider analysis of yield trials either independently or jointly (thus borrowing strength across trials) are considered. Case studies are presented to highlight benefit of joint analysis for outlier detection.     

Analysis of yield and oil from a series of canola breeding trials. Part I. Fitting factor analytic mixed models with pedigree information

In this paper multiplicative mixed models have been used for the analysis of multi-environment trial (MET) data for canola oil and grain yield. Information on pedigrees has been included to allow for the modelling of additive and nonadditive genetic effects. The MET data set included a total of 19 trials (synonymous with sites or environments), which were sown across southern Australia in 2007 and 2008. Each trial was designed as a p-rep design using DiGGeR with the default prespecified spatial model. Lines in their first year of testing were unreplicated, whereas there were two or three replications of advanced lines or varieties. Pedigree information on a total of 578 entries was available, and there were 69 entries that had unknown pedigrees. The degree of inbreeding varied from 0 (55 entries) to nearly fully inbred (337 entries). Subsamples of 2 g harvested grain were taken from each plot for determination of seed oil percentage by near infrared reflectance spectroscopy. The MET analysis for both yield and oil modelled genetic effects in different trials using factor analytic models and the residual plot effects for each trial were modelled using spatial techniques. Models in which pedigree information was included provided significantly better fits to both yield and oil data.     

Factor analysis models for structuring covariance matrices of additive genetic effects: a Bayesian implementation

Multivariate linear models are increasingly important in quantitative genetics. In high dimensional specifications, factor analysis (FA) may provide an avenue for structuring (co)variance matrices, thus reducing the number of parameters needed for describing (co)dispersion. We describe how FA can be used to model genetic effects in the context of a multivariate linear mixed model. An orthogonal common factor structure is used to model genetic effects under Gaussian assumption, so that the marginal likelihood is multivariate normal with a structured genetic (co)variance matrix. Under standard prior assumptions, all fully conditional distributions have closed form, and samples from the joint posterior distribution can be obtained via Gibbs sampling. The model and the algorithm developed for its Bayesian implementation were used to describe five repeated records of milk yield in dairy cattle, and a one common FA model was compared with a standard multiple trait model. The Bayesian Information Criterion favored the FA model.     

Estimates of genetic parameters and breeding values from western larch open-pollinated families using marker-based relationship

The availability and affordability of genetic markers made it possible to estimate quantitative genetic parameters without mating designs' structured pedigree. Here, we compared 4-year height's heritability and individuals' breeding values for a western larch common-garden population of 1,418 offspring representing 15 open-pollinated families from a 41-clone seed orchard using (a) classical pedigree models such as half- and full-sib families and (b) a molecular marker-based pedigree-free model using four pair-wise relationship estimation methods using eight informative SSR markers. The results highlighted the commonly observed inflated estimates of genetic parameters often obtained from half-sib analyses, as well as demonstrating some of the full-sib analyses' caveats. The pedigree reconstruction permitted the identification of selfed individuals, thus allowing evaluating the impact of selfing on marker-based genetic parameter estimation. The results demonstrated the utility of marker-based methods as an alternative to the classical pedigree-based approaches. Unlike the pedigree-based methods, the marker-based approach allowed better partitioning the variance components as well as separating the non-additive and additive genetic variance. The theoretical underpinning of the marker-based approach was discussed.     

Integrating Crop Growth Models with Whole Genome Prediction through Approximate Bayesian Computation

Genomic selection, enabled by whole genome prediction (WGP) methods, is revolutionizing plant breeding. Existing WGP methods have been shown to deliver accurate predictions in the most common settings, such as prediction of across environment performance for traits with additive gene effects. However, prediction of traits with non-additive gene effects and prediction of genotype by environment interaction (G×E), continues to be challenging. Previous attempts to increase prediction accuracy for these particularly difficult tasks employed prediction methods that are purely statistical in nature. Augmenting the statistical methods with biological knowledge has been largely overlooked thus far. Crop growth models (CGMs) attempt to represent the impact of functional relationships between plant physiology and the environment in the formation of yield and similar output traits of interest. Thus, they can explain the impact of G×E and certain types of non-additive gene effects on the expressed phenotype. Approximate Bayesian computation (ABC), a novel and powerful computational procedure, allows the incorporation of CGMs directly into the estimation of whole genome marker effects in WGP. Here we provide a proof of concept study for this novel approach and demonstrate its use with synthetic data sets. We show that this novel approach can be considerably more accurate than the benchmark WGP method GBLUP in predicting performance in environments represented in the estimation set as well as in previously unobserved environments for traits determined by non-additive gene effects. We conclude that this proof of concept demonstrates that using ABC for incorporating biological knowledge in the form of CGMs into WGP is a very promising and novel approach to improving prediction accuracy for some of the most challenging scenarios in plant breeding and applied genetics.     

Pedigree analysis for quantitative traits: variance components without matrix inversion

Recent developments in the animal breeding literature facilitate estimation of the variance components in quantitative genetic models. However, computation remains intensive, and many of the procedures are restricted to specialized designs and models, unsuited to data arising from studies of natural populations. We develop algorithms that allow maximum likelihood estimation of variance components for data on arbitrary pedigree structures. The proposed methods can be implemented on microcomputers, since no intensive matrix computations or manipulations are involved. Although parts of our procedures have been previously presented, we unify these into an overall scheme whose intuitive justification clarifies the approach. Two examples are analyzed: one of data on a natural population of Salivia lyrata and the other of simulated data on an extended pedigree.     

Parameter estimation techniques for interaction and redistribution models: a predator-prey example

Summary The use of parameter estimation techniques for partial differential equations is illustrated using a predatorprey model. Whereas ecologists have often estimated parameters in models, they have not previously been able to do so for models that describe interactions in heterogeneous environments. The techniques we describe for partial differential equations will be generally useful for models of interacting species in spatially complex environments and for models that include the movement of organisms. We demonstrate our methods using field data from a ladybird beetle (Coccinella septempunctata) and aphid (Uroleucon nigrotuberculatum) interaction. Our parameter estimation algorithms can be employed to identify models that explain better than 80% of the observed variance in aphid and ladybird densities. Such parameter estimation techniques can bridge the gap between detail-rich experimental studies and abstract mathematical models. By relating the particular bestfit models identified from our experimental data to other information on Coccinella behavior, we conclude that a term describing local taxis of ladybirds towards prey (aphids in this case) is needed in the model.     

Genetic parameter estimates in a clonally replicated progeny test of teak (Tectona grandis Linn. f.)

Teak (Tectona grandis Linn. f.) has been planted extensively in the tropics for its highly valued timber. We analysed data from a 3.5-year-old teak progeny test with clonal replication located in northern Australia. Additive and non-additive genetic variances were estimated for commercially important traits. Trees originating from seedlings were on average 2% taller and 4% straighter than those of the same genotype originating from cuttings. Non-additive genetic variance represented 35–50% of total genetic variance for growth traits and 63% of total genetic variance for incidence of flowering. Narrow-sense heritability was 0.22 for diameter, 0.18 for height and volume, 0.07 for stem straightness, 0.05 for insect defoliation, 0.03 for epicormic sprouts and 0.30 for incidence of flowering (estimated on an assumed underlying continuous scale). Broad-sense heritability was 0.37 for diameter, 0.28 for height, 0.35 for volume, 0.12 for stem straightness, 0.06 for insect defoliation, 0.12 for epicormic sprouts and 0.71 for incidence of flowering. Positive correlations were found between tree volume and flowering and between tree volume and stem straightness. The presence of sizeable non-additive variance supports the selection and deployment of clones to capture the full extent of genetic variation in commercially important traits.     

The importance and type of non-additive genetic effects for growth in Eucalyptus globulus

The paper investigates the importance of additive and non-additive genetic variances for growth in Eucalyptus globulus (Tasmanian Blue Gum), based on a large collection of diameter growth data covering 40 sites and more than 4,200 genotypes, most of them cloned, and spanning three generations of breeding. The variance estimates were based on a model accounting for additive, full-sib family and clone within full-sib family terms. The results indicated a small amount of additive genetic variance for diameter ( [^(h)]² = 0.10 ) \left( {{{\widehat{h}}^2} = 0.10} \right) and although non-additive genetic variance was also small, it accounted for a significant proportion of the total genetic variance present, corresponding to 80% of the additive variance. The interpretation of these non-additive effects is difficult. The results suggest, however, a possible role of epistasis. The evidence for this came from a strong observed bias in additive variance when clone effects were removed from the model and a larger than expected variance due to full-sib families relative to the variance due to clones within family. The relatively large proportion of genetic variance for growth that seems to be due to non-additive genetic effects has obvious implications in the breeding and deployment options in eucalypts, and these are briefly discussed.