Genomic prediction based on preselected single-nucleotide polymorphisms from genome-wide association study and imputed whole-genome sequence data annotation for growth traits in Duroc pigs.

The use of whole-genome sequence (WGS) data is expected to improve genomic prediction (GP) power of complex traits because it may contain mutations that in strong linkage disequilibrium pattern with causal mutations. However, a few previous studies have shown no or small improvement in prediction accuracy using WGS data. Incorporating prior biological information into GP seems to be an attractive strategy that might improve prediction accuracy. In this study, a total of 6334 pigs were genotyped using 50K chips and subsequently imputed to the WGS level. This cohort includes two prior discovery populations that comprise 294 Landrace pigs and 186 Duroc pigs, as well as two validation populations that consist of 3770 American Duroc pigs and 2084 Canadian Duroc pigs. Then we used annotation information and genome-wide association study (GWAS) from the WGS data to make GP for six growth traits in two Duroc pig populations. Based on variant annotation, we partitioned different genomic classes, such as intron, intergenic, and untranslated regions, for imputed WGS data. Based on GWAS results of WGS data, we obtained trait-associated single-nucleotide polymorphisms (SNPs). We then applied the genomic feature best linear unbiased prediction (GFBLUP) and genomic best linear unbiased prediction (GBLUP) models to estimate the genomic estimated breeding values for growth traits with these different variant panels, including six genomic classes and trait-associated SNPs. Compared with 50K chip data, GBLUP with imputed WGS data had no increase in prediction accuracy. Using only annotations resulted in no increase in prediction accuracy compared to GBLUP with 50K, but adding annotation information into the GFBLUP model with imputed WGS data could improve the prediction accuracy with increases of 0.00%-2.82%. In conclusion, a GFBLUP model that incorporated prior biological information might increase the advantage of using imputed WGS data for GP.

Genetic evaluation for production and body size traits using different animal models in purebred-Duroc pigs.

Duroc pigs are popular crossbred terminal sires, and accurate assessment of genetic parameters in the population can help to rationalize breeding programmes. The principle aim of this study were to evaluate the genetic parameters of production (birth weight, BW; age at 115 kg, AGE; feed conversion ratio, FCR) and body size (body length, BL; body height, BH; front cannon circumference, FCC) traits of Duroc pigs. The second objective was to analyze the fit of different genetic assessment models. The variance components and correlations of BW (28,348 records), AGE (28,335 records), FCR (11,135 records), BL (31,544 records), BH (21,862 records), and FCC (14,684 records) traits were calculated by using DMU and AIREMLF90 from BLUPF90 package. In the common environment model, the heritability of BW, AGE, FCR, BL, BH, and FCC traits were 0.17 ± 0.014, 0.30 ± 0.019, 0.28 ± 0.024, 0.16 ± 0.013, 0.14 ± 0.017, and 0.081 ± 0.016, with common litter effect values of 0.25, 0.20, 0.18, 0.23, 0.19, and 0.16, respectively. According to the results of the Akaike information criterion (AIC) calculations, models with smaller AIC values have a better fit. We found that the common environment model with litter effects as random effects for estimating genetic parameters had a better fit. In this Model, the estimated genetic correlations between AGE with BW, FCR, BL, BH, and FCC traits were -0.28 (0.040), 0.76 (0.038), -0.71 (0.036), -0.44 (0.060), and -0.60 (0.073), respectively, with phenotypic correlations of -0.17, 0.52, -0.22, -0.13 and -0.24, respectively. In our analysis of genetic trends for six traits in the Duroc population from 2012 to 2021, we observed significant genetic trends for AGE, BL, and BH. Particularly noteworthy is the rapid decline in the genetic trend for AGE, indicating an enhancement in the pig's growth rate through selective breeding. Therefore, we believe that some challenging-to-select traits can benefit from the genetic correlations between traits. By selecting easily measurable traits, they can gain from synergistic selection effects, leading to genetic progress. Conducting population genetic parameter analysis can assist us in devising breeding strategies.

Genome-Wide Association Study for Body Length, Body Height, and Total Teat Number in Large White Pigs.

Body length, body height, and total teat number are economically important traits in pig breeding, as these traits are usually associated with the growth, reproductivity, and longevity potential of piglets. Here, we report a genetic analysis of these traits using a population comprising 2,068 Large White pigs. A genotyping-by-sequencing (GBS) approach was used to provide high-density genome-wide SNP discovery and genotyping. Univariate and bivariate animal models were used to estimate heritability and genetic correlations. The results showed that heritability estimates for body length, body height, and total teat number were 0.25 ± 0.04, 0.11 ± 0.03, and 0.22 ± 0.04, respectively. The genetic correlation between body length and body height exhibited a strongly positive correlation (0.63 ± 0.15), while a positive but low genetic correlation was observed between total teat number and body length. Furthermore, we used two different genome-wide association study (GWAS) approaches: single-locus GWAS and weighted single-step GWAS (WssGWAS), to identify candidate genes for these traits. Single-locus GWAS detected 76, 13, and 29 significant single-nucleotide polymorphisms (SNPs) associated with body length, body height, and total teat number. Notably, the most significant SNP (S17_15781294), which is located 20 kb downstream of the BMP2 gene, explained 9.09% of the genetic variance for body length traits, and it also explained 9.57% of the genetic variance for body height traits. In addition, another significant SNP (S7_97595973), which is located in the ABCD4 gene, explained 8.92% of the genetic variance for total teat number traits. GWAS results for these traits identified some candidate genomic regions, such as SSC6: 14.96-15.02 Mb, SSC7: 97.18-98.18 Mb, SSC14: 128.29-131.15 Mb, SSC17: 15.39-17.27 Mb, and SSC17: 22.04-24.15 Mb, providing a starting point for further inheritance research. Most quantitative trait loci were detected by single-locus GWAS and WssGWAS. These findings reveal the complexity of the genetic mechanism of the three traits and provide guidance for subsequent genetic improvement through genome selection.

Evaluation of Genomic Selection for Seven Economic Traits in Yellow Drum (Nibea albiflora).

Yellow drum (Nibea albiflora) is an important maricultural fish in China, and genetic improvement is necessary for this species. This research evaluated the application of genomic selection methods to predict the genetic values of seven economic traits for yellow drum. Using genome-wide single-nucleotide polymorphisms (SNPs), we estimated the genetic parameters for seven traits, including body length (BL), swimming bladder index (SBI), swimming bladder weight (SBW), body thickness (BT), body height (BH), body length/body height ratio (LHR), and gonad weight index (GWI). The heritability estimates ranged from 0.309 to 0.843. We evaluated the prediction performance of various statistical methods, and no one method provided the highest predictive ability for all traits. We then evaluated and compared the use of genome-wide association study (GWAS)-informative SNPs and random SNPs for prediction and found that GWAS-informative SNPs obviously increased. It only needed 5 and 100 informative SNPs for LHR and BT to achieve almost the same predictive abilities as using genome-wide SNPs, and for BL, SBI, SBW, BH, and GWI, about 1000 to 3000 informative SNPs were needed to achieve whole-genome level predictive abilities. It can be concluded from the test results that breeders can use fewer SNPs to save the breeding costs of genomic selection for some traits.

Genomic prediction using an iterative conditional expectation algorithm for a fast BayesC-like model.

Genomic prediction is feasible for estimating genomic breeding values because of dense genome-wide markers and credible statistical methods, such as Genomic Best Linear Unbiased Prediction (GBLUP) and various Bayesian methods. Compared with GBLUP, Bayesian methods propose more flexible assumptions for the distributions of SNP effects. However, most Bayesian methods are performed based on Markov chain Monte Carlo (MCMC) algorithms, leading to computational efficiency challenges. Hence, some fast Bayesian approaches, such as fast BayesB (fBayesB), were proposed to speed up the calculation. This study proposed another fast Bayesian method termed fast BayesC (fBayesC). The prior distribution of fBayesC assumes that a SNP with probability γ has a non-zero effect which comes from a normal density with a common variance. The simulated data from QTLMAS XII workshop and actual data on large yellow croaker were used to compare the predictive results of fBayesB, fBayesC and (MCMC-based) BayesC. The results showed that when γ was set as a small value, such as 0.01 in the simulated data or 0.001 in the actual data, fBayesB and fBayesC yielded lower prediction accuracies (abilities) than BayesC. In the actual data, fBayesC could yield very similar predictive abilities as BayesC when γ ≥ 0.01. When γ = 0.01, fBayesB could also yield similar results as fBayesC and BayesC. However, fBayesB could not yield an explicit result when γ ≥ 0.1, but a similar situation was not observed for fBayesC. Moreover, the computational speed of fBayesC was significantly faster than that of BayesC, making fBayesC a promising method for genomic prediction.

Prediction of genomic breeding values using new computing strategies for the implementation of MixP.

MixP is an implementation that uses the Pareto principle to perform genomic prediction. This study was designed to develop two new computing strategies: one strategy for nonMCMC-based MixP (FMixP), and the other one for MCMC-based MixP (MMixP). The difference is that MMixP can estimate variances of SNP effects and the probability that a SNP has a large variance, but FMixP cannot. Simulated data from an international workshop and real data on large yellow croaker were used as the materials for the study. Four Bayesian methods, BayesA, BayesCπ, MMixP and FMixP, were used to compare the predictive results. The results show that BayesCπ, MMixP and FMixP perform better than BayesA for the simulated data, but all methods have very similar predictive abilities for the large yellow croaker. However, FMixP is computationally significantly faster than the MCMC-based methods. Our research may have a potential for the future applications in genomic prediction.

Whole-genome single-nucleotide polymorphism (SNP) marker discovery and association analysis with the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in Larimichthys crocea.

Whole-genome single-nucleotide polymorphism (SNP) markers are valuable genetic resources for the association and conservation studies. Genome-wide SNP development in many teleost species are still challenging because of the genome complexity and the cost of re-sequencing. Genotyping-By-Sequencing (GBS) provided an efficient reduced representative method to squeeze cost for SNP detection; however, most of recent GBS applications were reported on plant organisms. In this work, we used an EcoRI-NlaIII based GBS protocol to teleost large yellow croaker, an important commercial fish in China and East-Asia, and reported the first whole-genome SNP development for the species. 69,845 high quality SNP markers that evenly distributed along genome were detected in at least 80% of 500 individuals. Nearly 95% randomly selected genotypes were successfully validated by Sequenom MassARRAY assay. The association studies with the muscle eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content discovered 39 significant SNP markers, contributing as high up to ∼63% genetic variance that explained by all markers. Functional genes that involved in fat digestion and absorption pathway were identified, such as APOB, CRAT and OSBPL10. Notably, PPT2 Gene, previously identified in the association study of the plasma n-3 and n-6 polyunsaturated fatty acid level in human, was re-discovered in large yellow croaker. Our study verified that EcoRI-NlaIII based GBS could produce quality SNP markers in a cost-efficient manner in teleost genome. The developed SNP markers and the EPA and DHA associated SNP loci provided invaluable resources for the population structure, conservation genetics and genomic selection of large yellow croaker and other fish organisms.

Genomic Selection Using Extreme Phenotypes and Pre-Selection of SNPs in Large Yellow Croaker (Larimichthys crocea).

Genomic selection (GS) is an effective method to improve predictive accuracies of genetic values. However, high cost in genotyping will limit the application of this technology in some species. Therefore, it is necessary to find some methods to reduce the genotyping costs in genomic selection. Large yellow croaker is one of the most commercially important marine fish species in southeast China and Eastern Asia. In this study, genotyping-by-sequencing was used to construct the libraries for the NGS sequencing and find 29,748 SNPs in the genome. Two traits, eviscerated weight (EW) and the ratio between eviscerated weight and whole body weight (REW), were chosen to study. Two strategies to reduce the costs were proposed as follows: selecting extreme phenotypes (EP) for genotyping in reference population or pre-selecting SNPs to construct low-density marker panels in candidates. Three methods of pre-selection of SNPs, i.e., pre-selecting SNPs by absolute effects (SE), by single marker analysis (SMA), and by fixed intervals of sequence number (EL), were studied. The results showed that using EP was a feasible method to save the genotyping costs in reference population. Heritability did not seem to have obvious influences on the predictive abilities estimated by EP. Using SMA was the most feasible method to save the genotyping costs in candidates. In addition, the combination of EP and SMA in genomic selection also showed good results, especially for trait of REW. We also described how to apply the new methods in genomic selection and compared the genotyping costs before and after using the new methods. Our study may not only offer a reference for aquatic genomic breeding but also offer a reference for genomic prediction in other species including livestock and plants, etc.

Comparative analysis of the GBLUP, emBayesB, and GWAS algorithms to predict genetic values in large yellow croaker (Larimichthys crocea).

BACKGROUND: The advances of sequencing technology accelerate the development of theory of molecular quantitative genetics such as QTL mapping, genome-wide association study and genomic selection. This paper was designed to study genomic selection in large yellow croaker breeding. The aims of this study were: (i) to estimate heritability values of traits in large yellow croaker; (ii) to assess feasibility of genomic selection in the traits of growth rate and meat quality; (iii) to compare predictive accuracies affected by different algorithms and training sizes, and to find what training sizes could reach ideal accuracies; (iv) to compare results of GWAS with genomic prediction, and to assess feasibility of pre-selection of significant SNPs in genomic selection. 500 individuals were tested in the trait of body weight and body length, while 176 were tested in the percentage of n-3 highly unsaturated fatty acids (n-3HUFA) in muscle. GBLUP and emBayesB were used to perform genomic prediction. RESULTS: Genotyping-By-Sequencing method was used to construct the libraries for the NGS sequencing and find ~30,000 SNPs. Heritability estimates were 0.604, 0.586 and 0.438 for trait of body weight, body length and n-3HUFA, respectively. The predictive abilities estimated by GBLUP showed higher than that by emBayesB in traits of body weight and body length. However, the result was just the opposite in n-3HUFA. According to fit the curve of predictive accuracy, we estimated that at least 1000 individuals in training set could reach an accuracy of 0.8 in body weight and body length. GBLUP, emBayesB and GWAS could not always find significant SNPs associated with phenotypes consistently. Significant SNPs were selected by emBayesB could obtain the largest proportions to explain total additive genetic variances. CONCLUSIONS: This research showed that genomic selection was feasible in large yellow croaker breeding. We suggest doing a test before deciding to use which algorithm in specific trait in genomic prediction. We estimated required training sizes to reach ideal predictive accuracies and assessed feasibility of pre-selection of SNPs successfully. Because of high mortality rate of fish and high cost in genomic sequencing, genomic selection may be more suitable for applying on some traits which cannot be measured on candidates directly.