Genome-wide association study considering genotype-by-environment interaction for productive and reproductive traits using whole-genome sequencing in Nellore cattle.

BACKGROUND: The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with genome-wide association studies (GWAS), to map genomic regions related to animal adaptation. Including genetic markers from whole-genome sequencing in reaction norm (RN) models allows us to identify high-resolution candidate genes across environmental gradients through GWAS. Hence, we performed a GWAS via the RN approach using whole-genome sequencing data, focusing on mapping candidate genes associated with the expression of reproductive and growth traits in Nellore cattle. For this purpose, we used phenotypic data for age at first calving (AFC), scrotal circumference (SC), post-weaning weight gain (PWG), and yearling weight (YW). A total of 20,000 males and 7,159 females genotyped with 770k were imputed to the whole sequence (29 M). After quality control and linkage disequilibrium (LD) pruning, there remained ∼ 2.41 M SNPs for SC, PWG, and YW and ∼ 5.06 M SNPs for AFC. RESULTS: Significant SNPs were identified on Bos taurus autosomes (BTA) 10, 11, 14, 18, 19, 20, 21, 24, 25 and 27 for AFC and on BTA 4, 5 and 8 for SC. For growth traits, significant SNP markers were identified on BTA 3, 5 and 20 for YW and PWG. A total of 56 positional candidate genes were identified for AFC, 9 for SC, 3 for PWG, and 24 for YW. The significant SNPs detected for the reaction norm coefficients in Nellore cattle were found to be associated with growth, adaptative, and reproductive traits. These candidate genes are involved in biological mechanisms related to lipid metabolism, immune response, mitogen-activated protein kinase (MAPK) signaling pathway, and energy and phosphate metabolism. CONCLUSIONS: GWAS results highlighted differences in the physiological processes linked to lipid metabolism, immune response, MAPK signaling pathway, and energy and phosphate metabolism, providing insights into how different environmental conditions interact with specific genes affecting animal adaptation, productivity, and reproductive performance. The shared genomic regions between the intercept and slope are directly implicated in the regulation of growth and reproductive traits in Nellore cattle raised under different environmental conditions.

Influence of variance component estimates on genomic predictions for growth and reproductive-related traits in Nellore cattle.

This study aimed to estimate variance components (VCs) for growth and reproductive traits in Nellore cattle using two relationship matrices (pedigree relationship A matrix and pedigree plus genomic relationship H matrix), and records collected before and after genomic selection (GS) implementation. The study also evaluated how genomic breeding values (GEBV) are affected by variance components and discarding old records. The analysed traits were weight at 120 days (W120), weight and scrotal circumference at 450 days (W450 and SC450, respectively). Three datasets were used to estimate VCs, including all phenotypic information (All) or records for animals born before or after GS implementation (Before or After datasets, respectively). Both relationship matrices were considered for VC estimation, the A matrix was used in all three datasets and VC from each combination were named as A_Before, A_After, and A_All). The H was used in two datasets: H_All and H_After. Different VCs were used for GEBV prediction through ssGBLUP. This step used two possible Datasets, using all available phenotypic data (Dataset 1) or just records collected since GS implementation (Dataset 2). Validation was conducted using accuracy, bias and dispersion according to the LR method and prediction accuracy from corrected phenotypes. The heritability of all traits increased from A_Before to A_After, while estimates for A_All were intermediary. In the previous order, the estimates were 0.16, 0.17, and 0.15 for W120; 0.31, 0.39, and 0.35 for W450; 0.35, 0.47, and 0.41 for SC. For W450 and SC, using the H matrix reduced the heritability (0.33 and 0.32 for W450; 0.41 and 0.38 for SC for H_After and H_All, respectively). For W120, Dataset1 and VCs from A_After showed the highest accuracy for direct and maternal GEBV (0.953 and 0.868). For W450, Dataset 1 and VC from H_After allowed the highest accuracy (0.854) but use Dataset 2 and same VC source yield similar value (0.846). For SC, Dataset 2 with VC from H_After showed the highest accuracy (0.925). To use Dataset 2 does not cause important changes in bias or dispersion with respect to Dataset 1. The VC and genetic parameters changed for W120, W450, and SC450, using records before or after the GS implementation. For W450 and SC450, genetic variance and heritability estimates increased with the use of GS. For W120, genomic predictions were more accurate using A for VC estimation. Accuracy gains were observed for W450 and SC450 using H in VC estimation and/or discarding records before GS. It is possible to discard phenotypic records before GS implementation without generating bias or dispersion in the GEBV of young candidates.

Meta-analysis across Nellore cattle populations identifies common metabolic mechanisms that regulate feed efficiency-related traits.

BACKGROUND: Feed efficiency (FE) related traits play a key role in the economy and sustainability of beef cattle production systems. The accurate knowledge of the physiologic background for FE-related traits can help the development of more efficient selection strategies for them. Hence, multi-trait weighted GWAS (MTwGWAS) and meta-analyze were used to find genomic regions associated with average daily gain (ADG), dry matter intake (DMI), feed conversion ratio (FCR), feed efficiency (FE), and residual feed intake (RFI). The FE-related traits and genomic information belong to two breeding programs that perform the FE test at different ages: post-weaning (1,024 animals IZ population) and post-yearling (918 animals for the QLT population). RESULTS: The meta-analyze MTwGWAS identified 14 genomic regions (-log10(p -value) > 5) regions mapped on BTA 1, 2, 3, 4, 7, 8, 11, 14, 15, 18, 21, and 29. These regions explained a large proportion of the total genetic variance for FE-related traits across-population ranging from 20% (FCR) to 36% (DMI) in the IZ population and from 22% (RFI) to 28% (ADG) in the QLT population. Relevant candidate genes within these regions (LIPE, LPL, IGF1R, IGF1, IGFBP5, IGF2, INS, INSR, LEPR, LEPROT, POMC, NPY, AGRP, TGFB1, GHSR, JAK1, LYN, MOS, PLAG1, CHCD7, LCAT, and PLA2G15) highlighted that the physiological mechanisms related to neuropeptides and the metabolic signals controlling the body's energy balance are responsible for leading to greater feed efficiency. Integrated meta-analysis results and functional pathway enrichment analysis highlighted the major effect of biological functions linked to energy, lipid metabolism, and hormone signaling that mediates the effects of peptide signals in the hypothalamus and whole-body energy homeostasis affecting the genetic control of FE-related traits in Nellore cattle. CONCLUSIONS: Genes and pathways associated with common signals for feed efficiency-related traits provide better knowledge about regions with biological relevance in physiological mechanisms associated with differences in energy metabolism and hypothalamus signaling. These pleiotropic regions would support the selection for feed efficiency-related traits, incorporating and pondering causal variations assigning prior weights in genomic selection approaches.

Integration analyses of structural variations and differential gene expression associated with beef fatty acid profile in Nellore cattle.

This study aimed to integrate analyses of structural variations and differentially expressed genes (DEGs) associated with the beef fatty acid (FA) profile in Nellore cattle. Copy numbers variation (CNV) detection was performed using the penncnv algorithm and CNVRuler software in 3794 genotyped animals through the High-Density Bovine BeadChip. In order to perform the genomic wide association study (GWAS), a total of 963 genotyped animals were selected to obtain the intramuscular lipid concentration and quantify the beef FA profile. A total of 48 animals belonging to the same farm and management lot were extracted from the 963 genotyped and phenotyped animals to carry out the transcriptomic and differentially expressed gene analyses. The GWAS with extreme groups of FA profiles was performed using a logistic model. A total of 43, 42, 66 and 35 significant CNV regions (p < 0.05) for saturated, monounsaturated, polyunsaturated and omega 3 and 6 fatty acids were identified respectively. The paired-end sequencing of 48 samples was performed using the Illumina HiSeq2500 platform. Real-time quantitative PCR was used to validate the DEGs identified by RNA-seq analysis. The results showed several DEGs associated with the FA profile of Longissimus thoracis, such as BSCL2 and SAMD8. Enriched terms as the cellular response to corticosteroid (GO:0071384) and glucocorticoid stimulus (GO:0071385) could be highlighted. The identification of structural variations harboring candidate genes for beef FA must contribute to the elucidation of the genetic basis that determines the beef FA composition of intramuscular fat in Nellore cattle. Our results will contribute to the identification of potential biomarkers for complex phenotypes, such as the FA profile, to improve the reliability of the genomic predictions including pre-selected variants using differentiated weighting in the genomic models.

Imputation accuracy to whole-genome sequence in Nellore cattle.

BACKGROUND: A cost-effective strategy to explore the complete DNA sequence in animals for genetic evaluation purposes is to sequence key ancestors of a population, followed by imputation mechanisms to infer marker genotypes that were not originally reported in a target population of animals genotyped with single nucleotide polymorphism (SNP) panels. The feasibility of this process relies on the accuracy of the genotype imputation in that population, particularly for potential causal mutations which may be at low frequency and either within genes or regulatory regions. The objective of the present study was to investigate the imputation accuracy to the sequence level in a Nellore beef cattle population, including that for variants in annotation classes which are more likely to be functional. METHODS: Information of 151 key sequenced Nellore sires were used to assess the imputation accuracy from bovine HD BeadChip SNP (~ 777 k) to whole-genome sequence. The choice of the sires aimed at optimizing the imputation accuracy of a genotypic database, comprised of about 10,000 genotyped Nellore animals. Genotype imputation was performed using two computational approaches: FImpute3 and Minimac4 (after using Eagle for phasing). The accuracy of the imputation was evaluated using a fivefold cross-validation scheme and measured by the squared correlation between observed and imputed genotypes, calculated by individual and by SNP. SNPs were classified into a range of annotations, and the accuracy of imputation within each annotation classification was also evaluated. RESULTS: High average imputation accuracies per animal were achieved using both FImpute3 (0.94) and Minimac4 (0.95). On average, common variants (minor allele frequency (MAF) > 0.03) were more accurately imputed by Minimac4 and low-frequency variants (MAF ≤ 0.03) were more accurately imputed by FImpute3. The inherent Minimac4 Rsq imputation quality statistic appears to be a good indicator of the empirical Minimac4 imputation accuracy. Both software provided high average SNP-wise imputation accuracy for all classes of biological annotations. CONCLUSIONS: Our results indicate that imputation to whole-genome sequence is feasible in Nellore beef cattle since high imputation accuracies per individual are expected. SNP-wise imputation accuracy is software-dependent, especially for rare variants. The accuracy of imputation appears to be relatively independent of annotation classification.

Sliding window haplotype approaches overcome single SNP analysis limitations in identifying genes for meat tenderness in Nelore cattle.

BACKGROUND: Traditional single nucleotide polymorphism (SNP) genome-wide association analysis (GWAA) can be inefficient because single SNPs provide limited genetic information about genomic regions. On the other hand, using haplotypes in the statistical analysis may increase the extent of linkage disequilibrium (LD) between haplotypes and causal variants and may also potentially capture epistastic interactions between variants within a haplotyped locus, providing an increase in the power and robustness of the association studies. We performed GWAA (413,355 SNP markers) using haplotypes based on variable-sized sliding windows and compared the results to a single-SNP GWAA using Warner-Bratzler shear force measured in the longissimus thorasis muscle of 3161 Nelore bulls to ascertain the optimal window size for identifying the genomic regions that influence meat tenderness. RESULTS: The GWAA using single SNPs identified eight variants influencing meat tenderness on BTA 3, 4, 9, 10 and 11. However, thirty-three putative meat tenderness QTL were detected on BTA 1, 3, 4, 5, 8, 9, 10, 11, 15, 17, 18, 24, 25, 26 and 29 using variable-sized sliding haplotype windows. Analyses using sliding window haplotypes of 3, 5, 7, 9 and 11 SNPs identified 57, 61, 42, 39, and 21% of all thirty-three putative QTL regions, respectively; however, the analyses using the 3 and 5 SNP haplotypes, cumulatively detected 88% of the putative QTL. The genes associated with variation in meat tenderness participate in myogenesis, neurogenesis, lipid and fatty acid metabolism and skeletal muscle structure or composition processes. CONCLUSIONS: GWAA using haplotypes based on variable-sized sliding windows allowed the detection of more QTL than traditional single-SNP GWAA. Analyses using smaller haplotypes (3 and 5 SNPs) detected a higher proportion of the putative QTL.

Unraveling genetic sensitivity of beef cattle to environmental variation under tropical conditions.

BACKGROUND: Selection of cattle that are less sensitive to environmental variation in unfavorable environments and more adapted to harsh conditions is of primary importance for tropical beef cattle production systems. Understanding the genetic background of sensitivity to environmental variation is necessary for developing strategies and tools to increase efficiency and sustainability of beef production. We evaluated the degree of sensitivity of beef cattle performance to environmental variation, at the animal and molecular marker levels (412 K single nucleotide polymorphisms), by fitting and comparing the results of different reaction norm models (RNM), using a comprehensive dataset of Nellore cattle raised under diverse environmental conditions. RESULTS: Heteroscedastic RNM (with different residual variances for environmental level) provided better fit than homoscedastic RNM. In addition, spline and quadratic RNM outperformed linear RNM, which suggests the existence of a nonlinear genetic component affecting the performance of Nellore cattle. This nonlinearity indicates that within-animal sensitivity depends on the environmental gradient (EG) level and that animals may present different patterns of sensitivity according to the range of environmental variations. The spline RNM showed that sensitivity to environmental variation from harsh to average EG is lowly correlated with sensitivity from average to good EG, at both the animal and molecular marker levels. Although the genomic regions that affect sensitivity in harsher environments were not the same as those associated with less challenging environments, the candidate genes within those regions participate in common biological processes such as those related to inflammatory and immune response. Some plausible candidate genes were identified. CONCLUSIONS: Sensitivity of tropical beef cattle to environmental variation is not continuous along the environmental gradient, which implies that animals that are less sensitive to harsher conditions are not necessarily less responsive to variations in better environmental conditions, and vice versa. The same pattern was observed at the molecular marker level, i.e. genomic regions and, consequently, candidate genes associated with sensitivity to harsh conditions were not the same as those associated with sensitivity to less challenging conditions.

Genome-wide association between single nucleotide polymorphisms with beef fatty acid profile in Nellore cattle using the single step procedure.

BACKGROUND: Saturated fatty acids can be detrimental to human health and have received considerable attention in recent years. Several studies using taurine breeds showed the existence of genetic variability and thus the possibility of genetic improvement of the fatty acid profile in beef. This study identified the regions of the genome associated with saturated, mono- and polyunsaturated fatty acids, and n-6 to n-3 ratios in the Longissimus thoracis of Nellore finished in feedlot, using the single-step method. RESULTS: The results showed that 115 windows explain more than 1 % of the additive genetic variance for the 22 studied fatty acids. Thirty-one genomic regions that explain more than 1 % of the additive genetic variance were observed for total saturated fatty acids, C12:0, C14:0, C16:0 and C18:0. Nineteen genomic regions, distributed in sixteen different chromosomes accounted for more than 1 % of the additive genetic variance for the monounsaturated fatty acids, such as the sum of monounsaturated fatty acids, C14:1 cis-9, C18:1 trans-11, C18:1 cis-9, and C18:1 trans-9. Forty genomic regions explained more than 1 % of the additive variance for the polyunsaturated fatty acids group, which are related to the total polyunsaturated fatty acids, C20:4 n-6, C18:2 cis-9 cis12 n-6, C18:3 n-3, C18:3 n-6, C22:6 n-3 and C20:3 n-6 cis-8 cis-11 cis-14. Twenty-one genomic regions accounted for more than 1 % of the genetic variance for the group of omega-3, omega-6 and the n-6:n-3 ratio. CONCLUSIONS: The identification of such regions and the respective candidate genes, such as ELOVL5, ESSRG, PCYT1A and genes of the ABC group (ABC5, ABC6 and ABC10), should contribute to form a genetic basis of the fatty acid profile of Nellore (Bos indicus) beef, contributing to better selection of the traits associated with improving human health.

Gene expression profile of intramuscular muscle in Nellore cattle with extreme values of fatty acid.

BACKGROUND: Fatty acid type in beef can be detrimental to human health and has received considerable attention in recent years. The aim of this study was to identify differentially expressed genes in longissimus thoracis muscle of 48 Nellore young bulls with extreme phenotypes for fatty acid composition of intramuscular fat by RNA-seq technique. RESULTS: Differential expression analyses between animals with extreme phenotype for fatty acid composition showed a total of 13 differentially expressed genes for myristic (C14:0), 35 for palmitic (C16:0), 187 for stearic (C18:0), 371 for oleic (C18:1, cis-9), 24 for conjugated linoleic (C18:2 cis-9, trans11, CLA), 89 for linoleic (C18:2 cis-9,12 n6), and 110 genes for α-linolenic (C18:3 n3) fatty acids. For the respective sums of the individual fatty acids, 51 differentially expressed genes for saturated fatty acids (SFA), 336 for monounsaturated (MUFA), 131 for polyunsaturated (PUFA), 92 for PUFA/SFA ratio, 55 for ω3, 627 for ω6, and 22 for ω6/ω3 ratio were identified. Functional annotation analyses identified several genes associated with fatty acid metabolism, such as those involved in intra and extra-cellular transport of fatty acid synthesis precursors in intramuscular fat of longissimus thoracis muscle. Some of them must be highlighted, such as: ACSM3 and ACSS1 genes, which work as a precursor in fatty acid synthesis; DGAT2 gene that acts in the deposition of saturated fat in the adipose tissue; GPP and LPL genes that support the synthesis of insulin, stimulating both the glucose synthesis and the amino acids entry into the cells; and the BDH1 gene, which is responsible for the synthesis and degradation of ketone bodies used in the synthesis of ATP. CONCLUSION: Several genes related to lipid metabolism and fatty acid composition were identified. These findings must contribute to the elucidation of the genetic basis to improve Nellore meat quality traits, with emphasis on human health. Additionally, it can also contribute to improve the knowledge of fatty acid biosynthesis and the selection of animals with better nutritional quality.

Assessing the value of phenotypic information from non-genotyped animals for QTL mapping of complex traits in real and simulated populations.

BACKGROUND: QTL mapping through genome-wide association studies (GWAS) is challenging, especially in the case of low heritability complex traits and when few animals possess genotypic and phenotypic information. When most of the phenotypic information is from non-genotyped animals, GWAS can be performed using the weighted single-step GBLUP (WssGBLUP) method, which permits to combine all available information, even that of non-genotyped animals. However, it is not clear to what extent phenotypic information from non-genotyped animals increases the power of QTL detection, and whether factors such as the extent of linkage disequilibrium (LD) in the population and weighting SNPs in WssGBLUP affect the importance of using information from non-genotyped animals in GWAS. These questions were investigated in this study using real and simulated data. RESULTS: Analysis of real data showed that the use of phenotypes of non-genotyped animals affected SNP effect estimates and, consequently, QTL mapping. Despite some coincidence, the most important genomic regions identified by the analyses, either using or ignoring phenotypes of non-genotyped animals, were not the same. The simulation results indicated that the inclusion of all available phenotypic information, even that of non-genotyped animals, tends to improve QTL detection for low heritability complex traits. For populations with low levels of LD, this trend of improvement was less pronounced. Stronger shrinkage on SNPs explaining lower variance was not necessarily associated with better QTL mapping. CONCLUSIONS: The use of phenotypic information from non-genotyped animals in GWAS may improve the ability to detect QTL for low heritability complex traits, especially in populations in which the level of LD is high.

Genomic prediction of breeding values for carcass traits in Nellore cattle.

BACKGROUND: The objective of this study was to evaluate the accuracy of genomic predictions for rib eye area (REA), backfat thickness (BFT), and hot carcass weight (HCW) in Nellore beef cattle from Brazilian commercial herds using different prediction models. METHODS: Phenotypic data from 1756 Nellore steers from ten commercial herds in Brazil were used. Animals were offspring of 294 sires and 1546 dams, reared on pasture, feedlot finished, and slaughtered at approximately 2 years of age. All animals were genotyped using a 777k Illumina Bovine HD SNP chip. Accuracy of genomic predictions of breeding values was evaluated by using a 5-fold cross-validation scheme and considering three models: Bayesian ridge regression (BRR), Bayes C (BC) and Bayesian Lasso (BL), and two types of response variables: traditional estimated breeding value (EBV), and phenotype adjusted for fixed effects (Y*). RESULTS: The prediction accuracies achieved with the BRR model were equal to 0.25 (BFT), 0.33 (HCW) and 0.36 (REA) when EBV was used as response variable, and 0.21 (BFT), 0.37 (HCW) and 0.46 (REA) when using Y*. Results obtained with the BC and BL models were similar. Accuracies increased for traits with a higher heritability, and using Y* instead of EBV as response variable resulted in higher accuracy when heritability was higher. CONCLUSIONS: Our results indicate that the accuracy of genomic prediction of carcass traits in Nellore cattle is moderate to high. Prediction of genomic breeding values from adjusted phenotypes Y* was more accurate than from EBV, especially for highly heritable traits. The three models considered (BRR, BC and BL) led to similar predictive abilities and, thus, either one could be used to implement genomic prediction for carcass traits in Nellore cattle.

Genome-wide association study of reproductive traits in Nellore heifers using Bayesian inference.

BACKGROUND: An important goal of Zebu breeding programs is to improve reproductive performance. A major problem faced with the genetic improvement of reproductive traits is that recording the time for an animal to reach sexual maturity is costly. Another issue is that accurate estimates of breeding values are obtained only a long time after the young bulls have gone through selection. An alternative to overcome these problems is to use traits that are indicators of the reproductive efficiency of the herd and are easier to measure, such as age at first calving. Another problem is that heifers that have conceived once may fail to conceive in the next breeding season, which increases production costs. Thus, increasing heifer's rebreeding rates should improve the economic efficiency of the herd. Response to selection for these traits tends to be slow, since they have a low heritability and phenotypic information is provided only later in the life of the animal. Genome-wide association studies (GWAS) are useful to investigate the genetic mechanisms that underlie these traits by identifying the genes and metabolic pathways involved. RESULTS: Data from 1853 females belonging to the Agricultural Jacarezinho LTDA were used. Genotyping was performed using the BovineHD BeadChip (777 962 single nucleotide polymorphisms (SNPs)) according to the protocol of Illumina - Infinium Assay II ® Multi-Sample HiScan with the unit SQ ™ System. After quality control, 305 348 SNPs were used for GWAS. Forty-two and 19 SNPs had a Bayes factor greater than 150 for heifer rebreeding and age at first calving, respectively. All significant SNPs for age at first calving were significant for heifer rebreeding. These 42 SNPs were next or within 35 genes that were distributed over 18 chromosomes and comprised 27 protein-encoding genes, six pseudogenes and two miscellaneous noncoding RNAs. CONCLUSIONS: The use of Bayes factor to determine the significance of SNPs allowed us to identify two sets of 42 and 19 significant SNPs for heifer rebreeding and age at first calving, respectively, which explain 11.35 % and 6.42 % of their phenotypic variance, respectively. These SNPs provide relevant information to help elucidate which genes affect these traits.

Polymorphisms in TOX and NCOA2 genes and their associations with reproductive traits in cattle.

Reproductive traits are an important component of the economic selection index for beef cattle in the tropics. Phenotypic expression of these traits occurs late because they are measured when the animals reach reproductive age. Association studies using high-density markers have been conducted to identify genes that influence certain traits. The identification of causal mutations in these genes permits the inclusion of these single nucleotide polymorphisms (SNPs) in customised DNA chips to increase efficiency and validity. Therefore, the aim of the present study was to detect causal mutations in the TOX and NCOA2 genes, previously identified by genome-wide association studies of zebu cattle. DNA was extracted from 385 Nellore females and polymorphisms were investigated by polymerase chain reaction sequencing. Five polymorphisms were detected in the NCOA2 gene and four in the TOX gene that were associated with reproductive traits. Analysis of variance showed that SNP 1718 in the NCOA2 gene was significant for early pregnancy probability (P=0.02) and age at first calving (P=0.03), and SNP 2038 in the same gene was significant for days to calving (P=0.03). Studies investigating polymorphisms in other regions of the gene and in other genes should be conducted to identify causal mutations.

Evaluation of the productive and reproductive performance of sexual precocity at different ages in Nellore heifers.

This study aimed to investigate the differences between productive and reproductive performance traits of sexually precocious and non-sexually precocious Nellore heifers and to evaluate the genetic correlation of sexual precocity with traits of economic importance. For this purpose, 300,000 Nellore heifers were evaluated for reproductive traits: heifer pregnancy (HP) at 14 (HP14), 18 (HP18), and 24 (HP24) months; heifer rebreeding (HR); number of progenies up to 53 months (NP53); and probability of the cow remaining in the herd until 76 months with at least 3 progenies (Stay). The growth-related traits evaluated included female yearling weight (YW); average daily gain from weaning to yearling (ADGW-Y); weight at maturity (MW); weaning weight of first progeny (WWprog); and female visual scores at yearling for conformation (Conf), precocity (Prec) and muscling (Musc). The effects of female YW and ADGW-Y in six categories on HP14, HP18, and HP24 were analyzed using Generalized linear mixed models (GLMM). Furthermore, a linear mixed model was used to evaluate the impact of HP on WWprog, MW, and reproductive performance (NP53 and Stay). Genetic correlations of HP evaluated in different months with growth and reproductive traits were estimated using a bivariate animal model. Precocious heifers (HP14) were lighter for YW and MW but had greater ADGW-Y than HP18 and HP24. The probability for HP14, HP18, and HP24 increased as the classes of YW and ADGW-Y increased. However, heifers weighing more than 326 kg had a slight reduction in the probability of becoming pregnant at HP14 and HP18. Precocious heifers (HP14 and HP18) produced their first progeny by 3 % lighter than HP24, although they had a greater NP53. Precocious heifers at 18 months (HP18) were 3 % and 6.8 % more likely to remain in the herd than HP14 and HP24 heifers, respectively. Genetic correlations between growth traits (WW, YW, ADGW-Y, and MW) and heifer pregnancy (HP14, HP18, and HP24) ranged from weak (rg = 0.27 ± 0.05) to moderate (rg = -0.47 ± 0.07). The genetic correlation between HR and HP was stronger for HP24 (0.75) against HP14 (0.58) and HP18 (0.64). Although, the genetic correlation between NP53 and Stay with HP14 was higher (rg = 0.53 and 0.45) than those observed for HP18 (rg = 0.46 and 0.38) and HP24 (rg = 0.35 and 0.39). The genetic correlation estimates between HP and visual scores were moderate and favorable for HP14. Selecting HP14 is beneficial for production systems because it increases the NP53 during the productive life without compromising heifer productivity or reproductive performance. However, attention should be given to improving the HR of heifers who become pregnant early.

Benchmarking machine learning and parametric methods for genomic prediction of feed efficiency-related traits in Nellore cattle.

Genomic selection (GS) offers a promising opportunity for selecting more efficient animals to use consumed energy for maintenance and growth functions, impacting profitability and environmental sustainability. Here, we compared the prediction accuracy of multi-layer neural network (MLNN) and support vector regression (SVR) against single-trait (STGBLUP), multi-trait genomic best linear unbiased prediction (MTGBLUP), and Bayesian regression (BayesA, BayesB, BayesC, BRR, and BLasso) for feed efficiency (FE) traits. FE-related traits were measured in 1156 Nellore cattle from an experimental breeding program genotyped for ~ 300 K markers after quality control. Prediction accuracy (Acc) was evaluated using a forward validation splitting the dataset based on birth year, considering the phenotypes adjusted for the fixed effects and covariates as pseudo-phenotypes. The MLNN and SVR approaches were trained by randomly splitting the training population into fivefold to select the best hyperparameters. The results show that the machine learning methods (MLNN and SVR) and MTGBLUP outperformed STGBLUP and the Bayesian regression approaches, increasing the Acc by approximately 8.9%, 14.6%, and 13.7% using MLNN, SVR, and MTGBLUP, respectively. Acc for SVR and MTGBLUP were slightly different, ranging from 0.62 to 0.69 and 0.62 to 0.68, respectively, with empirically unbiased for both models (0.97 and 1.09). Our results indicated that SVR and MTGBLUBP approaches were more accurate in predicting FE-related traits than Bayesian regression and STGBLUP and seemed competitive for GS of complex phenotypes with various degrees of inheritance.

Study of whole genome linkage disequilibrium in Nellore cattle.

BACKGROUND: Knowledge of the linkage disequilibrium (LD) between markers is important to establish the number of markers necessary for association studies and genomic selection. The objective of this study was to evaluate the extent of LD in Nellore cattle using a high density SNP panel and 795 genotyped steers. RESULTS: After data editing, 446,986 SNPs were used for the estimation of LD, comprising 2508.4 Mb of the genome. The mean distance between adjacent markers was 4.90 ± 2.89 kb. The minor allele frequency (MAF) was less than 0.20 in a considerable proportion of SNPs. The overall mean LD between marker pairs measured by r(2) and |D'| was 0.17 and 0.52, respectively. The LD (r(2)) decreased with increasing physical distance between markers from 0.34 (1 kb) to 0.11 (100 kb). In contrast to this clear decrease of LD measured by r(2), the changes in |D'| indicated a less pronounced decline of LD. Chromosomes BTA1, BTA27, BTA28 and BTA29 showed lower levels of LD at any distance between markers. Except for these four chromosomes, the level of LD (r(2)) was higher than 0.20 for markers separated by less than 20 kb. At distances < 3 kb, the level of LD was higher than 0.30. The LD (r(2)) between markers was higher when the MAF threshold was high (0.15), especially when the distance between markers was short. CONCLUSIONS: The level of LD estimated for markers separated by less than 30 kb indicates that the High Density Bovine SNP BeadChip will likely be a suitable tool for prediction of genomic breeding values in Nellore cattle.

Genetic parameters for test-day yield of milk, fat and protein in buffaloes estimated by random regression models.

The test-day yields of milk, fat and protein were analysed from 1433 first lactations of buffaloes of the Murrah breed, daughters of 113 sires from 12 herds in the state of São Paulo, Brazil, born between 1985 and 2007. For the test-day yields, 10 monthly classes of lactation days were considered. The contemporary groups were defined as the herd-year-month of the test day. Random additive genetic, permanent environmental and residual effects were included in the model. The fixed effects considered were the contemporary group, number of milkings (1 or 2 milkings), linear and quadratic effects of the covariable cow age at calving and the mean lactation curve of the population (modelled by third-order Legendre orthogonal polynomials). The random additive genetic and permanent environmental effects were estimated by means of regression on third- to sixth-order Legendre orthogonal polynomials. The residual variances were modelled with a homogenous structure and various heterogeneous classes. According to the likelihood-ratio test, the best model for milk and fat production was that with four residual variance classes, while a third-order Legendre polynomial was best for the additive genetic effect for milk and fat yield, a fourth-order polynomial was best for the permanent environmental effect for milk production and a fifth-order polynomial was best for fat production. For protein yield, the best model was that with three residual variance classes and third- and fourth-order Legendre polynomials were best for the additive genetic and permanent environmental effects, respectively. The heritability estimates for the characteristics analysed were moderate, varying from 0·16±0·05 to 0·29±0·05 for milk yield, 0·20±0·05 to 0·30±0·08 for fat yield and 0·18±0·06 to 0·27±0·08 for protein yield. The estimates of the genetic correlations between the tests varied from 0·18±0·120 to 0·99±0·002; from 0·44±0·080 to 0·99±0·004; and from 0·41±0·080 to 0·99±0·004, for milk, fat and protein production, respectively, indicating that whatever the selection criterion used, indirect genetic gains can be expected throughout the lactation curve.

Genetic parameters of total milk yield and factors describing the shape of lactation curve in dairy buffaloes.

The objective of this study was to apply factor analysis to describe lactation curves in dairy buffaloes in order to estimate the phenotypic and genetic association between common latent factors and cumulative milk yield. A total of 31 257 monthly test-day milk yield records from buffaloes belonging to herds located in the state of São Paulo were used to estimate two common latent factors, which were then analysed in a multi-trait animal model for estimating genetic parameters. Estimates of (co)variance components for the two common latent factors and cumulated 270-d milk yield were obtained by Bayesian inference using a multiple trait animal model. Contemporary group, number of milkings per day (two levels) and age of buffalo cow at calving (linear and quadratic) as covariate were included in the model as fixed effects. The additive genetic, permanent environmental and residual effects were included as random effects. The first common latent factor (F1) was associated with persistency of lactation and the second common latent factor (F2) with the level of production in early lactation. Heritability estimates for F1 and F2 were 0·12 and 0·07, respectively. Genetic correlation estimates between F1 and F2 with cumulative milk yield were positive and moderate (0·63 and 0·52). Multivariate statistics employing factor analysis allowed the extraction of two variables (latent factors) that described the shape of the lactation curve. It is expected that the response to selection to increase lactation persistency is higher than the response obtained from selecting animals to increase lactation peak. Selection for higher total milk yield would result in a favourable correlated response to increase the level of production in early lactation and the lactation persistency.

Heteroscedastic Reaction Norm Models Improve the Assessment of Genotype by Environment Interaction for Growth, Reproductive, and Visual Score Traits in Nellore Cattle.

The assessment of the presence of genotype by environment interaction (GxE) in beef cattle is very important in tropical countries with diverse climatic conditions and production systems. The present study aimed to assess the presence of GxE by using different reaction norm models for eleven traits related to growth, reproduction, and visual score in Nellore cattle. We studied five reaction norm models (RNM), fitting a linear model considering homoscedastic residual variance (RNM_homo), and four models considering heteroskedasticity, being linear (RNM_hete), quadratic (RNM_quad), linear spline (RNM_l-l), and quadratic spline (RNM_q-q). There was the presence of GxE for age at first calving (AFC), scrotal circumference (SC), weaning to yearling weight gain (WYG), and yearling weight (YW). The best models were RNM_l-l for YW and RNM_q-q for AFC, SC, and WYG. The heritability estimates for RNM_l-l ranged from 0.07 to 0.20, 0.42 to 0.61, 0.24 to 0.42, and 0.47 to 0.63 for AFC, SC, WYG, and YW, respectively. The heteroskedasticity in reaction norm models improves the assessment of the presence of GxE for YW, WYG, AFC, and SC. Additionally, the trajectories of reaction norms for these traits seem to be affected by a non-linear component, and selecting robust animals for these traits is an alternative to increase production and reduce environmental sensitivity.

Milk fatty acid characterization and genetic parameter estimates for milk conjugated linoleic acid in buffaloes.

The objectives of this study were to analyse buffalo milk fat composition, to verify the activity of Delta(9)-desaturase enzyme in the mammary gland, as well as to estimate additive genetic variances for milk, fat and protein yield, and milk cis-9,trans-11 conjugated linoleic acid percentage (cis-9,trans-11 CLA%). A total of 3929 lactation milk yields (MY) records from 2130 buffaloes and 1598 lactation fat (FY) and protein (PY) yield records from 914 buffaloes were analysed. For cis-9,trans-11 CLA%percentage, a total of 661 milk samples from 225 buffaloes, daughters of 8 sires, belonging to 4 herds and calving in 2003 and 2004, were used. The genetic parameters and variance components were estimated by Restricted Maximum Likelihood applying an animal model. The fixed effects considered in the model were: contemporary group (herd, year, calving season) and age at calving (linear and quadratic effects) and lactation length (linear and quadratic effects) as covariables. Additive genetic and permanent environment effects were considered as random. The MY, FY, PY and CLA% means were 1482±355 kg, 90.1±24.6 kg, 56.9±15.2 kg and 0.69±0.16%, respectively. Heritability estimates for MY, FY, PY and CLA% were 0.28±0.05, 0.26±0.11, 0.25±0.11 and 0.35±0.14, respectively. There is enough additive genetic variation for buffalo milk, protein and fat yield to improve these traits through selection. The cis-9,trans-11 CLA% can be enhanced by selection in buffaloes and will contribute to improving human health. The activity and efficiency of Delta(9)-desaturase in the mammary was measured and confirmed.