Chinese Simmental Beef Cattle Research Articles

Improving Genomic Prediction with Machine Learning Incorporating TPE for Hyperparameters Optimization.

Depending on excellent prediction ability, machine learning has been considered the most powerful implement to analyze high-throughput sequencing genome data. However, the sophisticated process of tuning hyperparameters tremendously impedes the wider application of machine learning in animal and plant breeding programs. Therefore, we integrated an automatic tuning hyperparameters algorithm, tree-structured Parzen estimator (TPE), with machine learning to simplify the process of using machine learning for genomic prediction. In this study, we applied TPE to optimize the hyperparameters of Kernel ridge regression (KRR) and support vector regression (SVR). To evaluate the performance of TPE, we compared the prediction accuracy of KRR-TPE and SVR-TPE with the genomic best linear unbiased prediction (GBLUP) and KRR-RS, KRR-Grid, SVR-RS, and SVR-Grid, which tuned the hyperparameters of KRR and SVR by using random search (RS) and grid search (Gird) in a simulation dataset and the real datasets. The results indicated that KRR-TPE achieved the most powerful prediction ability considering all populations and was the most convenient. Especially for the Chinese Simmental beef cattle and Loblolly pine populations, the prediction accuracy of KRR-TPE had an 8.73% and 6.08% average improvement compared with GBLUP, respectively. Our study will greatly promote the application of machine learning in GP and further accelerate breeding progress.

Incorporating kernelized multi-omics data improves the accuracy of genomic prediction

BackgroundGenomic selection (GS) has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes. Besides genome, transcriptome and metabolome information are increasingly considered new sources for GS. Difficulties in building the model with multi-omics data for GS and the limit of specimen availability have both delayed the progress of investigating multi-omics.ResultsWe utilized the Cosine kernel to map genomic and transcriptomic data as {n}times {n} symmetric matrix (G matrix and T matrix), combined with the best linear unbiased prediction (BLUP) for GS. Here, we defined five kernel-based prediction models: genomic BLUP (GBLUP), transcriptome-BLUP (TBLUP), multi-omics BLUP (MBLUP, boldsymbol M=mathrm{ratio}timesboldsymbol G+(1-mathrm{ratio})timesboldsymbol T), multi-omics single-step BLUP (mssBLUP), and weighted multi-omics single-step BLUP (wmssBLUP) to integrate transcribed individuals and genotyped resource population. The predictive accuracy evaluations in four traits of the Chinese Simmental beef cattle population showed that (1) MBLUP was far preferred to GBLUP (ratio = 1.0), (2) the prediction accuracy of wmssBLUP and mssBLUP had 4.18% and 3.37% average improvement over GBLUP, (3) We also found the accuracy of wmssBLUP increased with the growing proportion of transcribed cattle in the whole resource population.ConclusionsWe concluded that the inclusion of transcriptome data in GS had the potential to improve accuracy. Moreover, wmssBLUP is accepted to be a promising alternative for the present situation in which plenty of individuals are genotyped when fewer are transcribed.

Identification of Candidate Variants Associated With Bone Weight Using Whole Genome Sequence in Beef Cattle.

Bone weight is critical to affect body conformation and stature in cattle. In this study, we conducted a genome-wide association study for bone weight in Chinese Simmental beef cattle based on the imputed sequence variants. We identified 364 variants associated with bone weight, while 350 of them were not included in the Illumina BovineHD SNP array, and several candidate genes and GO terms were captured to be associated with bone weight. Remarkably, we identified four potential variants in a candidate region on BTA6 using Bayesian fine-mapping. Several important candidate genes were captured, including LAP3, MED28, NCAPG, LCORL, SLIT2, and IBSP, which have been previously reported to be associated with carcass traits, body measurements, and growth traits. Notably, we found that the transcription factors related to MED28 and LCORL showed high conservation across multiple species. Our findings provide some valuable information for understanding the genetic basis of body stature in beef cattle.

Runs of homozygosity analysis reveals consensus homozygous regions affecting production traits in Chinese Simmental beef cattle

BackgroundGenomic regions with a high frequency of runs of homozygosity (ROH) are related to important traits in farm animals. We carried out a comprehensive analysis of ROH and evaluated their association with production traits using the BovineHD (770 K) SNP array in Chinese Simmental beef cattle.ResultsWe detected a total of 116,953 homozygous segments with 2.47Gb across the genome in the studied population. The average number of ROH per individual was 99.03 and the average length was 117.29 Mb. Notably, we detected 42 regions with a frequency of more than 0.2. We obtained 17 candidate genes related to body size, meat quality, and reproductive traits. Furthermore, using Fisher’s exact test, we found 101 regions were associated with production traits by comparing high groups with low groups in terms of production traits. Of those, we identified several significant regions for production traits (P < 0.05) by association analysis, within which candidate genes including ECT2, GABRA4, and GABRB1 have been previously reported for those traits in beef cattle.ConclusionsOur study explored ROH patterns and their potential associations with production traits in beef cattle. These results may help to better understand the association between production traits and genome homozygosity and offer valuable insights into managing inbreeding by designing reasonable breeding programs in farm animals.

Genome-Wide Association Study Based on Random Regression Model Reveals Candidate Genes Associated with Longitudinal Data in Chinese Simmental Beef Cattle.

Simple SummaryGenome-wide association study (GWAS) has become the main approach for detecting functional genes that affects complex traits. For growth traits, the conventional GWAS method can only deal with the single-record traits observed at specific time points, rather than the longitudinal traits measured at multiple time points. Previous studies have reported the random regression model (RRM) for longitudinal data could overcome the limitation of the traditional GWAS model. Here, we present an association analysis based on RRM (GWAS-RRM) for 808 Chinese Simmental beef cattle at four stages of age. Ultimately, 37 significant single-nucleotide polymorphisms (SNPs) and several important candidate genes were screened to be associated with the body weight. Enrichment analysis showed these genes were significantly enriched in the signaling transduction pathway and lipid metabolism. This study not only offers a further understanding of the genetic basis for growth traits in beef cattle, but also provides a robust analytics tool for longitudinal traits in various species.Body weight (BW) is an important longitudinal trait that directly described the growth gain of bovine in production. However, previous genome-wide association study (GWAS) mainly focused on the single-record traits, with less attention paid to longitudinal traits. Compared with traditional GWAS models, the association studies based on the random regression model (GWAS-RRM) have better performance in the control of the false positive rate through considering time-stage effects. In this study, the BW trait data were collected from 808 Chinese Simmental beef cattle aged 0, 6, 12, and 18 months, then we performed a GWAS-RRM to fit the time-varied SNP effect. The results showed a total of 37 significant SNPs were associated with BW. Gene functional annotation and enrichment analysis indicated FGF4, ANGPT4, PLA2G4A, and ITGA5 were promising candidate genes for BW. Moreover, these genes were significantly enriched in the signaling transduction pathway and lipid metabolism. These findings will provide prior molecular information for bovine gene-based selection, as well as facilitate the extensive application of GWAS-RRM in domestic animals.

Genomic Prediction Using LD-Based Haplotypes Inferred From High-Density Chip and Imputed Sequence Variants in Chinese Simmental Beef Cattle.

A haplotype is defined as a combination of alleles at adjacent loci belonging to the same chromosome that can be transmitted as a unit. In this study, we used both the Illumina BovineHD chip (HD chip) and imputed whole-genome sequence (WGS) data to explore haploblocks and assess haplotype effects, and the haploblocks were defined based on the different LD thresholds. The accuracies of genomic prediction (GP) for dressing percentage (DP), meat percentage (MP), and rib eye roll weight (RERW) based on haplotype were investigated and compared for both data sets in Chinese Simmental beef cattle. The accuracies of GP using the entire imputed WGS data were lower than those using the HD chip data in all cases. For DP and MP, the accuracy of GP using haploblock approaches outperformed the individual single nucleotide polymorphism (SNP) approach (GBLUP_In_Block) at specific LD levels. Hotelling’s test confirmed that GP using LD-based haplotypes from WGS data can significantly increase the accuracies of GP for RERW, compared with the individual SNP approach (∼1.4 and 1.9% for GHBLUP and GHBLUP+GBLUP, respectively). We found that the accuracies using haploblock approach varied with different LD thresholds. The LD thresholds (r2 ≥ 0.5) were optimal for most scenarios. Our results suggested that LD-based haploblock approach can improve accuracy of genomic prediction for carcass traits using both HD chip and imputed WGS data under the optimal LD thresholds in Chinese Simmental beef cattle.

Validation of the Prediction Accuracy for 13 Traits in Chinese Simmental Beef Cattle Using a Preselected Low-Density SNP Panel.

Simple SummaryTo reduce the breeding costs and promote the application of genomic selection (GS) in Chinese Simmental beef cattle, we developed a customized low-density single-nucleotide polymorphism (SNP) panel consisting of 30,684 SNPs. When comparing the predictive performance of the low-density SNP panel to that of the BovineHD Beadchip for 13 traits, we found that this ~30 K panel achieved moderate to high prediction accuracies for most traits, while reducing the prediction accuracies of six traits by 0.04–0.09 and decreasing the prediction accuracy of one trait by 0.2. For the remaining six traits, the usage of the low-density SNP panel was associated with a slight increase in prediction accuracy. Our studies suggested that the low-density SNP panel (~30 K) is a feasible and promising tool for cost-effective genomic prediction in Chinese Simmental beef cattle, which may provide breeding organizations with a cheaper option and greater returns on investment.Chinese Simmental beef cattle play a key role in the Chinese beef industry due to their great adaptability and marketability. To achieve efficient genetic gain at a low breeding cost, it is crucial to develop a customized cost-effective low-density SNP panel for this cattle population. Thirteen growth, carcass, and meat quality traits and a BovineHD Beadchip genotyping of 1346 individuals were used to select trait-associated variants and variants contributing to great genetic variance. In addition, highly informative SNPs with high MAF in each 500 kb sliding window and in each genic region were also included separately. A low-density SNP panel consisting of 30,684 SNPs was developed, with an imputation accuracy of 97.4% when imputed to the 770 K level. Among 13 traits, the average prediction accuracy levels evaluated by genomic best linear unbiased prediction (GBLUP) and BayesA/B/Cπ were 0.22–0.47 and 0.18–0.60 for the ~30 K array and BovineHD Beadchip, respectively. Generally, the predictive performance of the ~30 K array was trait-dependent, with reduced prediction accuracies for seven traits. While differences in terms of prediction accuracy were observed among the 13 traits, the low-density SNP panel achieved moderate to high accuracies for most of the traits and even improved the accuracies for some traits.

Transcriptome profiling analysis of muscle tissue reveals potential candidate genes affecting water holding capacity in Chinese Simmental beef cattle

Water holding capacity (WHC) is an important sensory attribute that greatly influences meat quality. However, the molecular mechanism that regulates the beef WHC remains to be elucidated. In this study, the longissimus dorsi (LD) muscles of 49 Chinese Simmental beef cattle were measured for meat quality traits and subjected to RNA sequencing. WHC had significant correlation with 35 kg water loss (r = − 0.99, p < 0.01) and IMF content (r = 0.31, p < 0.05), but not with SF (r = − 0.20, p = 0.18) and pH (r = 0.11, p = 0.44). Eight individuals with the highest WHC (H-WHC) and the lowest WHC (L-WHC) were selected for transcriptome analysis. A total of 865 genes were identified as differentially expressed genes (DEGs) between two groups, of which 633 genes were up-regulated and 232 genes were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that DEGs were significantly enriched in 15 GO terms and 96 pathways. Additionally, based on protein–protein interaction (PPI) network, animal QTL database (QTLdb), and relevant literature, the study not only confirmed seven genes (HSPA12A, HSPA13, PPARγ, MYL2, MYPN, TPI, and ATP2A1) influenced WHC in accordance with previous studies, but also identified ATP2B4, ACTN1, ITGAV, TGFBR1, THBS1, and TEK as the most promising novel candidate genes affecting the WHC. These findings could offer important insight for exploring the molecular mechanism underlying the WHC trait and facilitate the improvement of beef quality.

Genome-Wide Association Analysis of Growth Curve Parameters in Chinese Simmental Beef Cattle.

Simple SummaryComplex traits that require observations over multiple time points for the same individual are called longitudinal traits. Understanding the genetic architecture of beef cattle growth cannot be limited simply to a genome-wide association study (GWAS) for body weight at any specific ages, but should be extended to a more general purpose by considering the longitudinal weight–age using a growth curve approach. We compared three nonlinear models that described the body weight data of Chinese Simmental beef cattle. The parameters of the suitable model were treated as phenotypes of single-trait GWAS and multi-trait GWAS. We identified 87 significant single nucleotide polymorphisms (SNPs) associated with body weight. Many candidate genes associated with body weight were identified which may be useful for exploring the full genetic architecture underlying growth and development traits in livestock.The objective of the present study was to perform a genome-wide association study (GWAS) for growth curve parameters using nonlinear models that fit original weight–age records. In this study, data from 808 Chinese Simmental beef cattle that were weighed at 0, 6, 12, and 18 months of age were used to fit the growth curve. The Gompertz model showed the highest coefficient of determination (R2 = 0.954). The parameters’ mature body weight (A), time-scale parameter (b), and maturity rate (K) were treated as phenotypes for single-trait GWAS and multi-trait GWAS. In total, 9, 49, and 7 significant SNPs associated with A, b, and K were identified by single-trait GWAS; 22 significant single nucleotide polymorphisms (SNPs) were identified by multi-trait GWAS. Among them, we observed several candidate genes, including PLIN3, KCNS3, TMCO1, PRKAG3, ANGPTL2, IGF-1, SHISA9, and STK3, which were previously reported to associate with growth and development. Further research for these candidate genes may be useful for exploring the full genetic architecture underlying growth and development traits in livestock.

Application of ensemble learning to genomic selection in chinese simmental beef cattle.

Genomic selection (GS) using the whole-genome molecular makers to predict genomic estimated breeding values (GEBVs) is revolutionizing the livestock and plant breeding. Seeking out novel strategies with higher prediction accuracy for GS has been the ultimate goal of breeders. With the rapid development of artificial intelligence, machine learning algorithms were applied to estimate the GEBVs increasingly. Although some machine learning methods have better performance in phenotype prediction, there is still considerable room for improvement. In this study, we applied an ensemble-learning algorithm, Adaboost.RT, which integrated support vector regression (SVR), kernel ridge regression (KRR) and random forest (RF), to predict genomic breeding values of three economic traits (carcass weight, live weight, and eye muscle area) in Chinese Simmental beef cattle. Predictive accuracy measured as the Pearson correlation between the corrected phenotypes and predicted GEBVs. Moreover, we compared the reliability of SVR, KRR, RF, Adaboost.RT and GBLUP methods. The result showed that machine learning methods outperformed GBLUP, and the average improvement of four machine learning methods over the GBLUP was 12.8%, 14.9%, 5.4% and 14.4%, respectively. Among the four machine learning methods, the reliability of Adaboost.RT was comparable to KRR with higher stability. We therefore believe that the Adaboost.RT algorithm is a reliable and efficient method for GS.

Genomic sequencing analysis reveals copy number variations and their associations with economically important traits in beef cattle

Copy number variation (CNV) represents a major source of genetic variation, which may have potentially large effects, including alternating gene regulation and dosage, as well as contributing to gene expression and risk for normal phenotypic variability. We carried out a comprehensive analysis of CNV based on whole genome sequencing in Chinese Simmental beef cattle. Totally, we found 9313 deletion and 234 duplication events, covering 147.5 Mb autosomal regions. Within them, 257 deletion events of high frequency overlapped with 193 known RefGenes. Among these genes, we observed several genes were related to economically important traits, like residual feed intake, immune responding, pregnancy rate and muscle differentiation. Using a locus-based analysis, we identified 11 deletions and 1 duplication, which were significantly associated with three traits including carcass weight, tenderloin and longissimus muscle area. Our sequencing-based study provided important insights into investigating the association of CNVs with important traits in beef cattle.

Incorporating Genome Annotation Into Genomic Prediction for Carcass Traits in Chinese Simmental Beef Cattle.

Various methods have been proposed for genomic prediction (GP) in livestock. These methods have mainly focused on statistical considerations and did not include genome annotation information. In this study, to improve the predictive performance of carcass traits in Chinese Simmental beef cattle, we incorporated the genome annotation information into GP. Single nucleotide polymorphisms (SNPs) were annotated to five genomic classes: intergenic, gene, exon, protein coding sequences, and 3′/5′ untranslated region. Haploblocks were constructed for all markers and these five genomic classes by defining a biologically functional unit, and haplotype effects were modeled in both numerical dosage and categorical coding strategies. The first-order epistatic effects among SNPs and haplotypes were modeled using a categorical epistasis model. For all makers, the extension from the SNP-based model to a haplotype-based model improved the accuracy by 5.4–9.8% for carcass weight (CW), live weight (LW), and striploin (SI). For the five genomic classes using the haplotype-based prediction model, the incorporation of gene class information into the model improved the accuracies by an average of 1.4, 2.1, and 1.3% for CW, LW, and SI, respectively, compared with their corresponding results for all markers. Including the first-order epistatic effects into the prediction models improved the accuracies in some traits and genomic classes. Therefore, for traits with moderate-to-high heritability, incorporating genome annotation information of gene class into haplotype-based prediction models could be considered as a promising tool for GP in Chinese Simmental beef cattle, and modeling epistasis in prediction can further increase the accuracy to some degree.

Weighted Single-Step Genome-Wide Association Study for Growth Traits in Chinese Simmental Beef Cattle.

Improving the genetic process of growth traits is one of the major goals in the beef cattle industry, as it can increase meat production and reduce the cost of raising animals. Although several quantitative trait loci affecting growth traits in beef cattle have been identified, the genetic architecture of these economically important traits remains elusive. This study aims to map single nucleotide polymorphisms (SNPs) and genes associated with birth weight (BW), yearling weight (YW), average daily gain from birth to yearling (BYADG), and body weight at the age of 18 months (18MW) in a Chinese Simmental beef cattle population using a weighted, single-step, genome-wide association study (wssGWAS). Phenotypic and pedigree data from 6022 animals and genotypes from 744 animals (596,297 SNPs) were used for an association analysis. The results showed that 66 genomic windows explained 1.01–20.15% of the genetic variance for the four examined traits, together with the genes near the top SNP within each window. Furthermore, the identified genomic windows (>1%) explained 50.56%, 57.71%, 61.78%, and 37.82% of the genetic variances for BW, YW, BYADG, and 18MW, respectively. Genes with potential functions in muscle development and regulation of cell growth were highlighted as candidates for growth traits in Simmental cattle (SQOR and TBCB for BW, MYH10 for YW, RLF for BYADG, and ARHGAP31 for 18MW). Moreover, we found 40 SNPs that had not previously been identified as being associated with growth traits in cattle. These findings will further advance our understanding of the genetic basis for growth traits and will be useful for the molecular breeding of BW, YW, BYADG, and 18MW in the context of genomic selection in beef cattle.

Genomic Prediction and Association Analysis with Models Including Dominance Effects for Important Traits in Chinese Simmental Beef Cattle.

Simple SummaryDominance effects play important roles in determining genetic changes with regard to complex traits. We conducted genomic predictions and genome-wide association studies in order to investigate the effects of dominance on carcass weight, dressing percentage, meat percentage, average daily gain, and chuck roll in 1233 Simmental beef cattle. Using dominance models, we improved the predictive abilities and found several candidate single-nucleotide polymorphisms (SNPs) and genes associated with these traits. Our studies helped us to understand causal mutation mapping and genomic selection models with dominance effects in Chinese Simmental beef cattle.Non-additive effects play important roles in determining genetic changes with regard to complex traits; however, such effects are usually ignored in genetic evaluation and quantitative trait locus (QTL) mapping analysis. In this study, a two-component genome-based restricted maximum likelihood (GREML) was applied to obtain the additive genetic variance and dominance variance for carcass weight (CW), dressing percentage (DP), meat percentage (MP), average daily gain (ADG), and chuck roll (CR) in 1233 Simmental beef cattle. We estimated predictive abilities using additive models (genomic best linear unbiased prediction (GBLUP) and BayesA) and dominance models (GBLUP-D and BayesAD). Moreover, genome-wide association studies (GWAS) considering both additive and dominance effects were performed using a multi-locus mixed-model (MLMM) approach. We found that the estimated dominance variances accounted for 15.8%, 16.1%, 5.1%, 4.2%, and 9.7% of the total phenotypic variance for CW, DP, MP, ADG, and CR, respectively. Compared with BayesA and GBLUP, we observed 0.5–1.1% increases in predictive abilities of BayesAD and 0.5–0.9% increases in predictive abilities of GBLUP-D, respectively. Notably, we identified a dominance association signal for carcass weight within RIMS2, a candidate gene that has been associated with carcass weight in beef cattle. Our results suggest that dominance effects yield variable degrees of contribution to the total genetic variance of the studied traits in Simmental beef cattle. BayesAD and GBLUP-D are convenient models for the improvement of genomic prediction, and the detection of QTLs using a dominance model shows promise for use in GWAS in cattle.

Genome-wide association studies using binned genotypes.

Linear mixed models (LMM) that tests trait association one marker at a time have been the most popular methods for genome-wide association studies. However, this approach has potential pitfalls: over conservativeness after Bonferroni correction, ignorance of linkage disequilibrium (LD) between neighboring markers, and power reduction due to overfitting SNP effects. So, multiple locus models that can simultaneously estimate and test all markers in the genome are more appropriate. Based on the multiple locus models, we proposed a bin model that combines markers into bins based on their LD relationships. A bin is treated as a new synthetic marker and we detect the associations between bins and traits. Since the number of bins can be substantially smaller than the number of markers, a penalized multiple regression method can be adopted by fitting all bins to a single model. We developed an innovative method to bin the neighboring markers and used the least absolute shrinkage and selection operator (LASSO) method. We compared BIN-Lasso with SNP-Lasso and Q + K-LMM in a simulation experiment, and showed that the new method is more powerful with less Type I error than the other two methods. We also applied the bin model to a Chinese Simmental beef cattle population for bone weight association study. The new method identified more significant associations than the classical LMM. The bin model is a new dimension reduction technique that takes advantage of biological information (i.e., LD). The new method will be a significant breakthrough in associative genomics in the big data era.

Accuracies of genomic prediction for twenty economically important traits in Chinese Simmental beef cattle.

SummaryGenomic prediction has been widely utilized to estimate genomic breeding values (GEBVs) in farm animals. In this study, we conducted genomic prediction for 20 economically important traits including growth, carcass and meat quality traits in Chinese Simmental beef cattle. Five approaches (GBLUP, BayesA, BayesB, BayesCπ and BayesR) were used to estimate the genomic breeding values. The predictive accuracies ranged from 0.159 (lean meat percentage estimated by BayesCπ) to 0.518 (striploin weight estimated by BayesR). Moreover, we found that the average predictive accuracies across 20 traits were 0.361, 0.361, 0.367, 0.367 and 0.378, and the averaged regression coefficients were 0.89, 0.86, 0.89, 0.94 and 0.95 for GBLUP, BayesA, BayesB, BayesCπ and BayesR respectively. The genomic prediction accuracies were mostly moderate and high for growth and carcass traits, whereas meat quality traits showed relatively low accuracies. We concluded that Bayesian regression approaches, especially for BayesR and BayesCπ, were slightly superior to GBLUP for most traits. Increasing with the sizes of reference population, these two approaches are feasible for future application of genomic selection in Chinese beef cattle.

A Fast and Powerful Empirical Bayes Method for Genome-Wide Association Studies.

Simple SummaryImproving statistical power and computational efficiency are always the research foci in genome-wide association studies (GWAS). In this study, we proposed a fast empirical Bayes GWAS method, which is based on the linear mixed model framework. The method is called Fast-EB-LMM in short. Results from simulation studies show that the Fast-EB-LMM has the highest power for quantitative trait nucleotides (QTNs) detection, the highest computational efficiency, and the strongest robustness, as compared with the efficient mixed model association (EMMA) and empirical Bayes (EB). Application to beef cattle population also verified the effectiveness of this method. We believe that Fast-EB-LMM is a valuable additional tool for GWAS.Linear mixed model (LMM) is an efficient method for GWAS. There are numerous forms of LMM-based GWAS methods. However, improving statistical power and computing efficiency have always been the research hotspots of the LMM-based GWAS methods. Here, we proposed a fast empirical Bayes method, which is based on linear mixed models. We call it Fast-EB-LMM in short. The novelty of this method is that it uses a modified kinship matrix accounting for individual relatedness to avoid competition between the locus of interest and its counterpart in the polygene. This property has increased statistical power. We adopted two special algorithms to ease the computational burden: Eigenvalue decomposition and Woodbury matrix identity. Simulation studies showed that Fast-EB-LMM has significantly increased statistical power of marker detection and improved computational efficiency compared with two widely used GWAS methods, EMMA and EB. Real data analyses for two carcass traits in a Chinese Simmental beef cattle population showed that the significant single-nucleotide polymorphisms (SNPs) and candidate genes identified by Fast-EB-LMM are highly consistent with results of previous studies. We therefore believe that the Fast-EB-LMM method is a reliable and efficient method for GWAS.

Evaluation of GBLUP, BayesB and elastic net for genomic prediction in Chinese Simmental beef cattle.

Chinese Simmental beef cattle are the most economically important cattle breed in China. Estimated breeding values for growth, carcass, and meat quality traits are commonly used as selection criteria in animal breeding. The objective of this study was to evaluate the accuracy of alternative statistical methods for the estimation of genomic breeding values. Analyses of the accuracy of genomic best linear unbiased prediction (GBLUP), BayesB, and elastic net (EN) were performed with an Illumina BovineHD BeadChip on 1,217 animals by applying 5-fold cross-validation. Overall, the accuracies ranged from 0.17 to 0.296 for ten traits, and the heritability estimates ranged from 0.36 to 0.63. The EN (alpha = 0.001) model provided the most accurate prediction, which was also slightly higher (0.2–2%) than that of GBLUP for most traits, such as average daily weight gain (ADG) and carcass weight (CW). BayesB was less accurate for each trait than were EN (alpha = 0.001) and GBLUP. These findings indicate the importance of using an appropriate variable selection method for the genomic selection of traits and suggest the influence of the genetic architecture of the traits we analyzed.

Probe-based association analysis identifies several deletions associated with average daily gain in beef cattle

BackgroundAverage daily gain (ADG) is an important trait that contributes to the production efficiency and economic benefits in the beef cattle industry. The molecular mechanisms of ADG have not yet been fully explored because most recent association studies for ADG are based on SNPs or haplotypes. We reported a systematic CNV discovery and association analysis for ADG in Chinese Simmental beef cattle.ResultsOur study identified 4912 nonredundant CNVRs with a total length of ~ 248.7 Mb, corresponding to ~ 8.9% of the cattle genome. Using probe-based CNV association, we identified 24 and 12 significant SNP probes within five deletions and two duplications for ADG, respectively. Among them, we found one common deletion with 89 kb imbedded in LHFPL Tetraspan Subfamily Member 6 (LHFPL6) at 22.9 Mb on BTA12, which has high frequency (12.9%) dispersing across population. CNV selection test using VST statistic suggested this common deletion may be under positive selection in Chinese Simmental cattle. Moreover, this deletion was not overlapped with any candidate SNP for ADG compared with previous SNPs-based association studies, suggesting its important role for ADG. In addition, we identified one rare deletion near gene Growth Factor Receptor-bound Protein 10 (GRB10) at 5.1 Mb on BTA4 for ADG using both probe-based association and region-based approaches.ConclusionsOur results provided some valuable insights to elucidate the genetic basis of ADG in beef cattle, and these findings offer an alternative perspective to understand the genetic mechanism of complex traits in terms of copy number variations in farm animals.

A rapid and efficient linear mixed model approach using the score test and its application to GWAS

Recent studies have demonstrated that Linear mixed model (LMM) successfully correct for population structure and genetic relatedness in genome-wide association studies (GWAS). However, currently available LMM methods usually suffer from computational inefficiency. Here, we propose a novel method, consisting of an LMM using the score test (LMM-Score). Our method takes advantage of score test that does not require estimation of parameters under the alternative hypothesis or the full model. We performed extensive simulation studies to estimate the statistical power of LMM-Score with various assumptions of sample size or marker size under different trait heritabilities. Although the limited power of simulation studies due to small sample size and conservativeness of Bonferroni correction, LMM-Score reduces the computing time greatly and maintained statistical power when compared with routine LMM method. Therefore, we believe that the LMM-Score is a valuable method for identifying the genetic basis of complex traits. We also applied our approach to real beef cattle data and suggested SOX17, RP1, LYN RPS20, snoU54, U1, MOS, PLAG1, CHCHD7, and SDR16C5 on BTA14 as the most promising candidate genes affecting pure meat weight (PMW), foreshank weight (FSW) and silverside weight (SSW) in Chinese Simmental beef cattle.