Complementing genomic data with other "omics" predictors can increase the probability of success for predicting the best hybrid combinations using complex agronomic traits. Accurate prediction of traits with complex genetic architecture is crucial for selecting superior candidates in animal and plant breeding and for guiding decisions in personalized medicine. Whole-genome prediction has revolutionized these areas but has inherent limitations in incorporating intricate epistatic interactions. Downstream "omics" data are expected to integrate interactions within and between different biological strata and provide the opportunity to improve trait prediction. Yet, predicting traits from parents to progeny has not been addressed by a combination of "omics" data. Here, we evaluate several "omics" predictors-genomic, transcriptomic and metabolic data-measured on parent lines at early developmental stages and demonstrate that the integration of transcriptomic with genomic data leads to higher success rates in the correct prediction of untested hybrid combinations in maize. Despite the high predictive ability of genomic data, transcriptomic data alone outperformed them and other predictors for the most complex heterotic trait, dry matter yield. An eQTL analysis revealed that transcriptomic data integrate genomic information from both, adjacent and distant sites relative to the expressed genes. Together, these findings suggest that downstream predictors capture physiological epistasis that is transmitted from parents to their hybrid offspring. We conclude that the use of downstream "omics" data in prediction can exploit important information beyond structural genomics for leveraging the efficiency of hybrid breeding.
1Complementing genomic data with other "omics" predictors can increase the proba-2 bility of success for predicting the best hybrid combinations using complex agronomic 3 traits. 4Abstract 5 Accurate prediction of traits with complex genetic architecture is crucial for select-6 ing superior candidates in animal and plant breeding and for guiding decisions in 7 personalized medicine. Whole-genome prediction (WGP) has revolutionized these 8 areas but has inherent limitations in incorporating intricate epistatic interactions. Downstream "omics" data are expected to integrate interactions within and between 10 different biological strata and provide the opportunity to improve trait prediction. 11Yet, predicting traits from parents to progeny has not been addressed by a combi-12 nation of "omics" data. Here, we evaluate several "omics" predictors -genomic,
The estimation of dominance effects requires the availability of direct phenotypes, i.e., genotypes and phenotypes in the same individuals. In dairy cattle, classical QTL mapping approaches are, however, relying on genotyped sires and daughter-based phenotypes like breeding values. Thus, dominance effects cannot be estimated. The number of dairy bulls genotyped for dense genome-wide marker panels is steadily increasing in the context of genomic selection schemes. The availability of genotyped cows is, however, limited. Within the current study, the genotypes of male ancestors were applied to the calculation of genotype probabilities in cows. Together with the cows' phenotypes, these probabilities were used to estimate dominance effects on a genome-wide scale. The impact of sample size, the depth of pedigree used in deriving genotype probabilities, the linkage disequilibrium between QTL and marker, the fraction of variance explained by the QTL, and the degree of dominance on the power to detect dominance were analyzed in simulation studies. The effect of relatedness among animals on the specificity of detection was addressed. Furthermore, the approach was applied to a real data set comprising 470,000 Holstein cows. To account for relatedness between animals a mixedmodel two-step approach was used to adjust phenotypes based on an additive genetic relationship matrix. Thereby, considerable dominance effects were identified for important milk production traits. The approach might serve as a powerful tool to dissect the genetic architecture of performance and functional traits in dairy cattle. IN the context of genomic selection in dairy cattle, an abundance of bulls has been genotyped by applying genomewide dense marker panels. In 2010, the European reference population comprised .17,000 bulls representing .20 million daughters (Lund et al. 2010;Liu et al. 2011). In addition to their utilization in genomic prediction, these data are extensively used in genome-wide association studies to unravel the genetic factors affecting performance and functional traits. The expression of these traits is naturally limited to female individuals and thus, the phenotypes used in association studies are usually breeding values of sires based on performance data of many daughters. Such a structure of data allows only the estimation of allele substitution effects. There is no direct possibility to distinguish between additive and dominance effects. For the detection of these allelic interactions, genotypes and phenotypes had to be known in the same individuals. Compared to the bulls, the availability of genotype data for cows is limited. With the increasing number of genotyped bulls, genotypes of male ancestors become available for many cows, enabling the derivation of genotype probabilities. Within the current study, these probabilities were converted to additive and dominance coefficients suitable for regression analysis analogous to the procedures commonly applied to QTL mapping in resource populations (Haley and Knott 199...
Essentially all high-yielding dairy cows experience a negative energy balance during early lactation leading to increased lipomobilization, which is a normal physiological response. However, a severe energy deficit may lead to high levels of ketone bodies and, subsequently, to subclinical or clinical ketosis. It has previously been reported that the ratio of glycerophosphocholine to phosphocholine in milk is a prognostic biomarker for the risk of ketosis in dairy cattle. It was hypothesized that this ratio reflects the ability to break down blood phosphatidylcholine as a fatty acid resource. In the current study, 248 animals from a previous study were genotyped with Illumina BovineSNP50 BeadChip, and genome-wide association studies were carried out for the milk levels of phosphocholine, glycerophosphocholine, and the ratio of both metabolites. It was demonstrated that the latter two traits are heritable with h2 = 0.43 and h2 = 0.34, respectively. A major quantitative trait locus was identified on cattle chromosome 25. The APOBR gene, coding for the apolipoprotein B receptor, is located within this region and was analyzed as a candidate gene. The analysis revealed highly significant associations of polymorphisms within the gene with glycerophosphocholine as well as the metabolite ratio. These findings support the hypothesis that differences in the ability to take up blood phosphatidylcholine from low-density lipoproteins play an important role in early lactation metabolic stability of dairy cows and indicate APOBR to contain a causative variant.
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