Converting estimated breeding values from the observed to probability scale for health traits.

Dairy cattle health traits are paramount from a welfare and economic viewpoint; therefore, modern breeding programs prioritize the genetic improvement of these traits. Estimated breeding values for health traits are published as the probability of animals staying healthy. They are obtained using threshold models, which assume that the observed binary phenotype (i.e., healthy or sick) is dictated by an underlying normally distributed liability exceeding or not a threshold. This methodology requires significant computing time and faces convergence challenges as it implies a nonlinear system of equations. Linear models have more straightforward computations and provide a robust approximation to threshold models; thus, they could be used to overcome the mentioned challenges. However, linear models yield estimated breeding values on the observed scale, requiring an approximation to the liability scale analogous to that from threshold models to later obtain the estimated breeding values on the probability scale. In addition, the robustness of the approximation of linear to threshold models depends on the amount of information and the incidence of the trait, with extreme incidence (i.e., ≤ 5%) deviating from optimal approximation. Our objective was to test a transformation from the observed to the liability and then to the probability scale in the genetic evaluation of health traits with moderate and very low (extreme) incidence. Data comprised displaced abomasum (5.1M), ketosis (3.6M), lameness (5M), and mastitis (6.3M) records from a Holstein population with a pedigree of 6M animals, of which 1.7M were genotyped. Univariate threshold and linear models were performed to predict breeding values. The agreement between estimated breeding values on the probability scale derived from threshold and linear models was assessed using Spearman rank correlations and comparison of estimated breeding values distributions. Correlations were at least 0.95, and estimated breeding value distributions almost entirely overlapped for all the traits but displaced abomasum, the trait with the lowest incidence (2%). Computing time was ∼3x longer for threshold than for linear models. In this Holstein population, the approximation was suboptimal for a trait with extreme incidence (2%). However, when the incidence was ≥6%, the approximation was robust, and its use is recommended along with linear models for analyzing categorical traits in large populations to ease the computational burden.

Testicular hypoplasia in Nellore Cattle: Genetic analysis and functional analysis of genome-wide association study results.

Characterized by the incomplete development of the germinal epithelium of the seminiferous tubules, Testicular hypoplasia (TH) leads to decreased sperm concentration, increased morphological changes in sperm and azoospermia. Economic losses resulting from the disposal of affected bulls reduce the efficiency of meat production systems. A genome-wide association study and functional analysis were performed to identify genomic windows and the underlying positional candidate genes associated with TH in Nellore cattle. Phenotypic and pedigree data from 207,195 animals and genotypes (461,057 single nucleotide polymorphism, SNP) from 17,326 sires were used in this study. TH was evaluated as a binary trait measured at 18 months of age. A possible correlated response on TH resulting from the selection for scrotal circumference was evaluated by using a two-trait analysis. Thus, estimated breeding values were calculated by fitting a linear-threshold animal model in a Bayesian approach. The SNP effects were estimated using the weighted single-step genomic BLUP method. Twelve non-overlapping windows of 20 adjacent SNP that explained more than 1% of the additive genetic variance were selected for candidate gene annotation. Functional and gene prioritization analysis of the candidate genes identified genes (KHDRBS3, GPX5, STAR, ERLIN2), which might play an important role in the expression of TH due to their known roles in the spermatogenesis process, synthesis of steroids and lipid metabolism.

Genetic parameter estimation for pre- and post-weaning traits in Brahman cattle in Brazil.

Beef cattle producers in Brazil use body weight traits as breeding program selection criteria due to their great economic importance. The objectives of this study were to evaluate different animal models, estimate genetic parameters, and define the most fitting model for Brahman cattle body weight standardized at 120 (BW120), 210 (BW210), 365 (BW365), 450 (BW450), and 550 (BW550) days of age. To estimate genetic parameters, single-, two-, and multi-trait analyses were performed using the animal model. The likelihood ratio test was verified between all models. For BW120 and BW210, additive direct genetic, maternal genetic, maternal permanent environment, and residual effects were considered, while for BW365 and BW450, additive direct genetic, maternal genetic, and residual effects were considered. Finally, for BW550, additive direct genetic and residual effects were considered. Estimates of direct heritability for BW120 were similar in all analyses; however, for the other traits, multi-trait analysis resulted in higher estimates. The maternal heritability and proportion of maternal permanent environmental variance to total variance were minimal in multi-trait analyses. Genetic, environmental, and phenotypic correlations were of high magnitude between all traits. Multi-trait analyses would aid in the parameter estimation for body weight at older ages because they are usually affected by a lower number of animals with phenotypic information due to culling and mortality.

Feet and legs malformation in Nellore cattle: genetic analysis and prioritization of GWAS results.

Beef cattle affected by feet and legs malformations (FLM) cannot perform their productive and reproductive functions satisfactorily, resulting in significant economic losses. Accelerated weight gain in young animals due to increased fat deposition can lead to ligaments, tendon and joint strain and promote gene expression patterns that lead to changes in the normal architecture of the feet and legs. The possible correlated response in the FLM due to yearling weight (YW) selection suggest that this second trait could be used as an indirect selection criterion. Therefore, FLM breeding values and the genetic correlation between FLM and yearling weight (YW) were estimated for 295,031 Nellore animals by fitting a linear-threshold model in a Bayesian approach. A genome-wide association study was performed to identify genomic windows and positional candidate genes associated with FLM. The effects of single nucleotide polymorphisms (SNPs) on FLM phenotypes (affected or unaffected) were estimated using the weighted single-step genomic BLUP method, based on genotypes of 12,537 animals for 461,057 SNPs. Twelve non-overlapping windows of 20 adjacent SNPs explaining more than 1% of the additive genetic variance were selected for candidate gene annotation. Functional and gene prioritization analysis of candidate genes identified six genes (ATG7, EXT1, ITGA1, PPARD, SCUBE3, and SHOX) that may play a role in FLM expression due to their known role in skeletal muscle development, aberrant bone growth, lipid metabolism, intramuscular fat deposition and skeletogenesis. Identifying genes linked to foot and leg malformations enables selective breeding for healthier herds by reducing the occurrence of these conditions. Genetic markers can be used to develop tests that identify carriers of these mutations, assisting breeders in making informed breeding decisions to minimize the incidence of malformations in future generations, resulting in greater productivity and animal welfare.

Genetic and genomic analyses of testicular hypoplasia in Nellore cattle.

Reproductive performance is a key indicator of the long-term sustainability of any livestock production system. Testicular hypoplasia (TH) is a morphological and functional reproductive disorder that affects bulls around the world and consequently causes major economic losses due to reduced fertility rates. Despite the improvements in management practices to enhance performance of affected animals, the use of hypoplastic animals for reproduction might contribute to expand the prevalence of this disorder. The aim of this study was to identify genomic regions that are associated with TH in Nellore cattle by performing a genome-wide association study (GWAS) and functional analyses. Phenotypic and pedigree data from 47,563 animals and genotypes (500,689 Single Nucleotide Polymorphism, SNPs) from 265 sires were used in this study. TH was evaluated as a binary trait measured at 18 months of age. The estimated breeding values (EBVs) were calculated by fitting a single-trait threshold animal model using a Bayesian approach. The SNP effects were estimated using the Bayes C method and de-regressed EBVs for TH as the response variable (pseudo-phenotype). The top-15 ranking windows (5-adjacent SNPs) that explained the highest proportion of variance were identified for further functional and biological network analyses. The posterior mean (95% highest posterior density) of the heritability for TH was 0.16 (0.08; 0.23). The most important genomic windows were located on BTA1, BTA3, BTA4, BTA5, BTA9, BTA22, BTA23, and BTA25. These windows explained together 22.69% of the total additive genetic variance for TH. Strong candidate genes associated with metabolism and synthesis of steroids, cell survival, spermatogenesis process and sperm motility were identified, which might play an important role in the expression of TH. Our findings contribute to a better biological understanding of TH and future characterization of causal variants might enable improved genomic prediction of this trait in beef cattle.

Genome-wide association study and functional analysis of feet and leg conformation traits in Nellore cattle.

Feet and leg conformation is evaluated as a subset of conformational structure traits in dairy and beef cattle and is related to the feet and leg quality that can compromise the animals' productive performance and longevity. The aim of this study was to perform a genome-wide association study (GWAS) of two traits related to feet and leg conformation in Nellore cattle to identify chromosomal regions related to the expression of these traits. Phenotypic and pedigree data from 104,725 animals and genotypes from 1,435 animals and 407,730 SNPs were used. Feet and leg structure was evaluated as a binary trait (FL1) to identify yearling animals with feet and leg problems or as categorical score (FL2) to assess the overall quality of their feet and leg. The top ten 1-Mb windows that explained the largest proportion of the total genetic variance were identified and functional enrichment analyses were performed. The 10 windows with large effects obtained for FL1 are located on chromosomes 1, 2, 6, 7, 8, 10, and 14, and together explained 8.96% of the additive genetic variance. For FL2, these windows are located on chromosomes 1, 7, 10, 11, 18, 20, 22, 28, and 29, explaining 8.98% of the additive genetic variance. Several candidate genes were identified, including DLX2 which is associated with osteogenic differentiation, IL-1ß and IL-1A associated with some properties of articular cartilage, PiT1 which plays an important role in bone physiology, and CTSL associated with rheumatoid arthritis. The results presented here should contribute to a better understanding of the genetic and physiologic mechanisms regulating both traits, and identifies candidate genes for future investigation of causal mutations.