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Comprehension of the genetic basis of temperament has been improved by recent advances in the identification of genes and genetic variants. However, due to the complexity of the temperament traits, the elucidation of the genetic architecture of temperament is incomplete. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to analyze candidate genes related to bovine temperament, using bovine as the population, SNPs and genes as the exposure, and temperament test as the outcome, as principal search terms for population, exposure, and outcome (PEO) categories to define the scope of the search. The search results allowed the selection of 36 articles after removing duplicates and filtering by relevance. One hundred-two candidate genes associated with temperament traits were identified. The genes were further analyzed to construct an interaction network using the STRING database, resulting in 113 nodes and 346 interactions and the identification of 31 new candidate genes for temperament. Notably, the main genes identified were SST and members of the Kelch family. The candidate genes displayed interactions with pathways associated with different functions such as AMPA receptors, hormones, neuronal maintenance, protein signaling, neuronal regulation, serotonin synthesis, splicing, and ubiquitination activities. These new findings demonstrate the complexity of interconnected biological processes that regulate behavior and stress response in mammals. This insight now enables our targeted analysis of these newly identified temperament candidate genes in bovines.

Background: Temperament is an important production trait in cattle and multiple strategies had been developed to generate molecular markers to assist animal selection. As nonsynonymous single nucleotide polymorphisms are markers with the potential to affect gene functions, they could be useful to predict phenotypic effects. Genetic selection of less stress-responsive, temperamental animals is desirable from an economic and welfare point of view., Methods and Results: Two nonsynonymous single nucleotide polymorphisms identified in HTR1B and SLC18A2 candidate genes for temperament were analyzed in silico to determine their effects on protein structure. Those nsSNPs allowing changes in proteins were selected for a temperament association analysis in a Brahman population. Transversion effects on protein structure were evaluated in silico for each amino acid change model, revealing structural changes in the proteins of the HTR1B and SLC18A2 genes. The selected nsSNPs were genotyped in a Brahman population (n = 138), and their genotypic effects on three temperament traits were analyzed: exit velocity, pen score, and temperament score. Only the SNP rs209984404-HTR1B (C/A) showed a significant association (P = 0.0144) with pen score. The heterozygous genotype showed a pen score value 1.17 points lower than that of the homozygous CC genotype., Conclusion: The results showed that in silico analysis could direct the selection of nsSNPs with the potential to change the protein. Non-synonymous single nucleotide polymorphisms causing structural changes and reduced protein stability were identified. Only rs209984404-HTR1B shows that the allele affecting protein stability was associated with the genotype linked to docility in cattle., (© 2024. The Author(s).)

Temperamental cattle tend to yield carcasses of poorer quality, and Brahman cattle are reportedly more temperamental than non-indicus cattle breeds. A potential link between temperament and product quality may be mitochondrial activity. We hypothesized that mitochondrial measures would be greater in temperamental compared with calm heifers and that the relationships between temperament and mitochondria would persist as heifers age. Serum cortisol and skeletal muscle (longissimus thoracis [LT] and trapezius [TRAP]) mitochondrial profiles and antioxidant activities were quantified from the same calm (n = 6) and temperamental (n = 6) Brahman heifers at 8, 12, and 18 mo of age. Data were analyzed using a mixed model ANOVA in SAS (9.4) with repeated measures. Serum cortisol was greater in temperamental compared with calm heifers throughout the study (P = 0.02). Mitochondrial volume density (citrate synthase [CS] activity) increased over time (P < 0.0001) but was similar between temperament and muscle groups. Mitochondrial function (cytochrome c oxidase activity) was greatest in the temperamental LT at 8 mo of age (P ≤ 0.0006), greatest in the temperamental TRAP at 18 mo of age (P ≤ 0.003), and did not differ by temperament at 12 mo of age. Integrative (relative to tissue wet weight) mitochondrial oxidative phosphorylation capacity with complex I substrates (PCI), PCI plus complex II substrate (PCI+II), noncoupled electron transfer system capacity (ECI+II), and E with functional complex II only (ECII) were greater in the TRAP than LT for calm heifers at all ages (P ≤ 0.002), but were similar between muscle groups in temperamental heifers. Overall, calm heifers tended to have greater intrinsic (relative to CS activity) PCI and flux control of PCI+II (P ≤ 0.1) than temperamental heifers, indicating greater utilization of complex I paired with greater coupling efficiency in calm heifers. Within the LT, integrative PCI+II was greater (P = 0.05) and ECI+II tended to be greater (P = 0.06) in temperamental compared with calm heifers. From 8- to 18-mo old, glutathione peroxidase (GPx) activity decreased (P < 0.0001) and superoxide dismutase activity increased (P = 0.02), and both were similar between muscle groups. The activity of GPx was greater in temperamental compared with calm heifers at 8 (P = 0.004) but not at 12 or 18 mo of age. These results detail divergent skeletal muscle mitochondrial characteristics of live Brahman heifers according to temperament, which should be further investigated as a potential link between temperament and product quality., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cattle temperament is a complex and economically relevant trait. The objective of this study was to identify genomic regions and genes associated with cattle temperament. From a Brahman cattle population of 1,370 animals evaluated for temperament traits (Exit velocity-EV, Pen Score-PS, Temperament Score-TS), two groups of temperament-contrasting animals were identified based on their EV-average values ±1/2 standard deviation (SD). To be considered in the calm group, the EV of females ranged between 0.16-1.82 m/s (n = 50) and the EV of males ranged between 0.4-1.56 m/s (n = 48). Females were classified as temperamental if their EV ranged between 3.13-7.66 m/s (n = 46) and males were classified as temperamental if their EV ranged between 3.05-10.83 m/s (n = 45). Selected animals were genotyped using a total of 139,376 SNPs (GGP-HD-150K), evaluated for their association with EV. The Genome-Wide Association analysis (GWAS) identified fourteen SNPs: rs135340276, rs134895560, rs110190635, rs42949831, rs135982573, rs109393235, rs109531929, rs135087545, rs41839733, rs42486577, rs136661522, rs110882543, rs110864071, rs109722627, (P<8.1E-05), nine of them were located on intergenic regions, harboring seventeen genes, of which only ACER3, VRK2, FANCL and SLCO3A1 were considered candidate associated with bovine temperament due to their reported biological functions. Five SNPs were located at introns of the NRXN3, EXOC4, CACNG4 and SLC9A4 genes. The indicated candidate genes are implicated in a wide range of behavioural phenotypes and complex cognitive functions. The association of the fourteen SNPs on bovine temperament traits (EV, PS and TS) was evaluated; all these SNPs were significant for EV; only some were associated with PS and TS. Fourteen SNPs were associated with EV which allowed the identification of twenty-one candidate genes for Brahman temperament. From a functional point of view, the five intronic SNPs identified in this study, are candidates to address control of bovine temperament, further investigation will probe their role in expression of this trait., Competing Interests: The authors have declared that no competing interests exist.

The objective was to estimate genetic parameters of temperament in beef cattle across an age continuum. The population consisted predominantly of Brahman-British crossbred cattle. Temperament was quantified by 1) pen score (PS), the reaction of a calf to a single experienced evaluator on a scale of 1 to 5 (1 = calm, 5 = excitable); 2) exit velocity (EV), the rate (m/s) at which a calf traveled 1.83 m upon exiting a squeeze chute; and 3) temperament score (TS), the numerical average of PS and EV. Covariates included days of age and proportion of Bos indicus in the calf and dam. Random regression models included the fixed effects determined from the repeated measures models, except for calf age. Likelihood ratio tests were used to determine the most appropriate random structures. In repeated measures models, the proportion of B. indicus in the calf was positively related with each calf temperament trait (0.41 ± 0.20, 0.85 ± 0.21, and 0.57 ± 0.18 for PS, EV, and TS, respectively; P < 0.01). There was an effect of contemporary group (combinations of season, year of birth, and management group) and dam age (P < 0.001) in all models. From repeated records analyses, estimates of heritability (h2) were 0.34 ± 0.04, 0.31 ± 0.04, and 0.39 ± 0.04, while estimates of permanent environmental variance as a proportion of the phenotypic variance (c2) were 0.30 ± 0.04, 0.31 ± 0.03, and 0.34 ± 0.04 for PS, EV, and TS, respectively. Quadratic additive genetic random regressions on Legendre polynomials of age were significant for all traits. Quadratic permanent environmental random regressions were significant for PS and TS, but linear permanent environmental random regressions were significant for EV. Random regression results suggested that these components change across the age dimension of these data. There appeared to be an increasing influence of permanent environmental effects and decreasing influence of additive genetic effects corresponding to increasing calf age for EV, and to a lesser extent for TS. Inherited temperament may be overcome by accumulating environmental stimuli with increases in age, especially after weaning.

Cattle temperament is a complex trait, and molecular studies aimed at defining this trait are scarce. We used an interaction networks approach to identify new genes (interacting genes) and to estimate their effects and those of 19 dopamine- and serotonin-related genes on the temperament traits of Charolais cattle. The genes proopiomelanocortin (POMC), neuropeptide Y (NPY), solute carrier family 18, member 2 (SLC18A2) and FBJ murine osteosarcoma viral oncogene homologue (FOSFBJ) were identified as new candidates. Their potential to be associated with temperament was estimated according to their reported biological activities, which included interactions with neural activity, receptor function, targeting or synthesis of neurotransmitters and association with behaviour. Pen score (PS) and exit velocity (EV) measures were determined from 412 Charolais cows to calculate their temperament score (TS). Based on the TS, calm (n = 55; TS, 1.09 ± 0.33) and temperamental (n = 58; TS, 2.27 ± 0.639) cows were selected and genotyped using a 248 single-nucleotide variation (SNV) panel. Of the 248 variations in the panel, only 151 were confirmed to be polymorphic (single-nucleotide polymorphisms; SNPs) in the tested population. Single-marker association analyses between genotypes and temperament measures (EV, PS and/or TS) indicated significant associations of six SNPs from four candidate genes. The markers rs109576799 and rs43696138, located in the DRD3 and HTR2A genes, respectively, were significantly associated with both EV and TS traits. Four markers, rs110365063 and rs137756569 from the POMC gene and rs110365063 and rs135155082 located in SLC18A2 and DRD2, respectively, were associated with PS. The variant rs110365063 located in bovine SLC18A2 causes a change in the amino acid sequence from Ala to Thr. Further studies are needed to confirm the association of genetic profile with cattle temperament; however, our study represents important progress in understanding the regulation of cattle temperament by different genes with divergent functions.

The aim of this study was to analyze the allelic frequency distribution and segregation among breeds and/or between different cattle genetic groups of four novel single nucleotide polymorphisms of the bovine DRD1 and DRD5 genes and one reported SNP from the DRD4 gene. One hundred and nine-animals from ten different cattle breeds were genotyped and allelic frequencies for each locus were estimated. There were significant differences in the allelic frequencies (P < 0.05) among breeds for the DRD1 and DRD5 markers. The allelic frequencies for markers DRD1-825A>G and DRD5-378C>T were also significantly different between groups differing in genetic background. Because differences in temperament have been reported between Bos taurus taurus and B. taurus indicus breeds and their crosses, further studies are needed to investigate if any association exists between described markers and cattle behavior traits.

The objective of this study was to estimate the heritability of 3 measures of temperament in Brahman and Brahman-influenced calves (n = 1,209). Individual animal pen scores (PS) were determined by a trained observer who evaluated groups of 5 or 4 calves at a time for willingness to be approached by a human. Exit velocity (EV) was the rate (m/s) at which each calf exited a squeeze chute. Temperament score (TS) was calculated individually as (PS + EV)/2. Temperament was evaluated at 5 different times of record (28 d preweaning, weaning, 28 d postweaning, 56 d postweaning, and yearling). Contemporary groups (n = 34) comprised calves of the same sex born in the same season of the same year. There were an average of 36 calves per contemporary group and group size ranged from 3 to 78 calves. Average weaning age (186 d) ranged from 105 to 304 d. Calves were born from 2002 through 2012. Random effects included additive genetic and the permanent environmental variance. The fixed effects analyzed were age of dam, sex of calf, contemporary group, fraction of Brahman (2 levels: 1 and 0.5), age of calf at record, and weaning age. At weaning, the mean PS was 2.68 ± 0.1, the mean EV was 2.41 ± 0.1, and the mean TS was 2.48 ± 0.1. The PS was affected by fraction of Brahman (P = 0.034) and tended to be affected by age of dam (P = 0.06). The EV was affected by contemporary group (P < 0.001) and tended to be affected by weaning age (P = 0.074). Contemporary group affected TS (P < 0.001). All 3 methods of temperament evaluation were affected by time of record (P < 0.001). The regression coefficients for PS, EV, and TS were 0.0023 ± 0.0014, 0.0022 ± 0.0012, and 0.0015 ± 0.0012 m·s(-1)·d(-1) of age, respectively. Estimates of maternal genetic effects were always 0 and omitted from final models. Estimates of heritability were 0.27 ± 0.1, 0.49 ± 0.1, and 0.43 ± 0.1 for EV, PS, and TS, respectively. Estimates of permanent environmental variances as proportions of phenotypic variance were 0.33 ± 0.1, 0.23 ± 0.1, and 0.33 ± 0.1 for EV, PS, and TS, respectively. There appears to be sufficient additive genetic variance for selective improvement of temperament characteristics in Brahman cattle.

The influence of temperament on the alteration of metabolic parameters in response to a lipopolysaccharide(LPS) challenge was investigated. Brahman bulls were selected based on temperament score. Bulls (10 months; 211±5kg BW; n = 6, 8 and 7 for Calm, Intermediate and Temperamental groups, respectively) were fitted with indwelling jugular catheters to evaluate peripheral blood concentrations of glucose, blood urea nitrogen (BUN),non-esterified fatty acids (NEFA), insulin, epinephrine and cortisol before and after LPS administration (0.5 μg/kg BW LPS). Feed intake was also recorded. Intermediate bulls consumed more feed than the Temperamental bulls during the challenge (p = 0.046). Pre-LPS glucose (p = 0.401) and BUN (p = 0.222) did not differ among the temperament groups. However, pre-LPS insulin (p = 0.023) was lower, whereas pre-LPS NEFA (p < 0.001),cortisol (p < 0.001) and epinephrine (p < 0.001) were greater in Temperamental than in Calm and Intermediate bulls. Post-LPS glucose was increased in Calm and Intermediate bulls but not in Temperamental bulls(p < 0.001). Insulin concentrations post-LPS were greater in Calm than in Intermediate and Temperamental bulls (p < 0.001). Concentrations of NEFA post-LPS were greater in Temperamental than in Calm and Intermediate bulls (p < 0.001). Serum BUN concentration increased post-LPS, with values being greater in Calm and Intermediate than in Temperamental bulls (p = 0.012). Collectively, these data demonstrate that animal temperament is related to the metabolic responses of Brahman bulls following a provocative endotoxin challenge.Specifically, Temperamental bulls may preferentially utilize an alternate energy source (i.e. NEFA) to a greater degree than do bulls of Calm and Intermediate temperaments. The use of circulating NEFA from lipolysis may reduce the negative metabolic consequences of an immune response by allowing for a prompt answer to increasing energy demands required during immunological challenge, compared with the time required for glycogenolysis and gluconeogenesis.

This study was designed to determine the influence of temperament on endotoxin-induced changes in body temperature, sickness behavior, and stress hormone concentrations in cattle. Brahman bulls were selected based on temperament score measured 28 d prior to weaning. In dwelling recording devices were used to monitor rectal temperature, and jugular catheters were used to collect blood samples to determine cortisol and epinephrine concentrations before and after LPS administration (0.5 μg/kg body weight). Temperamental bulls had the lowest peak rectal temperature and sickness behavior scores relative to the Calm and Intermediate bulls. Prior to the administration of LPS, Temperamental bulls had greater cortisol and epinephrine concentrations than Calm or Intermediate bulls. Cortisol concentrations increased following LPS administration but were not affected by temperament. Epinephrine concentrations peaked 1 h after LPS administration in Calm bulls. Temperamental bulls did not exhibit an epinephrine response to LPS challenge. These data demonstrate that the temperament of calves can modulate the physiological, behavioral, and endocrine responses of pre-pubertal Brahman bulls to endotoxin challenge. Specifically, temperament differentially affected the rectal temperature, sickness behavior and epinephrine, but not cortisol, responses to LPS challenge.

By using the temperament selection criterion of exit velocity (EV), cattle typically exhibiting hypercortisolism and a blunted response to exogenous corticotrophin-releasing hormone (CRH) can be identified via individual behavioral responses to handling. To further characterize hypothalamic-pituitary-adrenal (HPA) axis dysfunction associated with bovine temperament, the present study compared pituitary and adrenal activity, following stimulation with exogenous vasopressin (VP), in steers with an excitable or calm temperament. Serial blood samples were collected via indwelling jugular cannula for 6h preceding and 6h following administration of a VP bolus. Plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol were quantified by RIA to determine pituitary and adrenal responsiveness within temperament groups. Cortisol concentrations in excitable steers during the pre-challenge period revealed an increased initial adrenal reactivity to interactions with humans. Subsequent acclimation to the experimental surroundings yielded greater baseline cortisol concentrations in the cattle with an excitable temperament. Pituitary stimulation with VP resulted in a greater ACTH output from the excitable compared to the calm animals. The data presented herein provide additional evidence that HPA axis function in cattle of an excitable temperament may be akin to a state of chronic stress. The bovine temperament model may be of further use to both decipher mechanisms associated with HPA dysfunction and to elucidate physiological phenotypes or pathologies that have parallels in other species., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Interrelationships among growth, endocrine, immune, and temperament variables were assessed in neonatal Brahman calves. The velocity upon exiting a working chute (exit velocity) of an animal was measured and used as an objective indicator of temperament to classify calves as calm, intermediate, or temperamental. Calves (n = 116) were weighed weekly between d 0 and 21 to 24, and blood samples were collected for plasma and serum on d 0, 1, 2, 7, 14, and 21 to 24 after birth to measure concentrations of immunoglobulins, cortisol, and epinephrine (EPI). Body weight increased from d 0 through d 21 to 24 (P < 0.001) with bulls (n = 60) having greater BW than heifers (n = 56; P = 0.02). Serum concentrations of cortisol were greatest on d 0 before declining (P < 0.001) over the ensuing 21 to 24 d and were not related to temperament (P = 0.89) or sex (P = 0.97). Concentrations of EPI were affected by time, with an increase in EPI concentrations in temperamental bulls between 2 and 14 d of age (P < 0.008). Concentrations of EPI were not affected by temperament (P = 0.44) or sex (P = 0.68). Serum immunoglobulin concentrations peaked on d 1 before declining (P < 0.01) but were not related to temperament (P = 0.40 to 0.68). Of the stress hormones measured (cortisol and EPI), only cortisol was associated with the early performance of the calf. Calf BW at d 21 to 24 and BW gain were positively associated with serum immunoglobulin concentrations, yet negatively associated with concentrations of cortisol. Serum immunoglobulin concentrations were negatively correlated with cortisol concentrations (r = -0.28; P = 0.003), yet positively associated with EPI concentrations (r = 0.51; P = 0.003). During the neonatal period in this study, there was no relationship of temperament with passive immunity or stress hormone concentrations; however, growth was positively associated with passive immunity and negatively associated with stress hormones. Measuring exit velocity as early in life as d 21 to 24 fails to accurately predict temperament at weaning in over 40% of Brahman calves. Our conclusion is that measurement of exit velocity should be done nearer to the time of weaning than to birth. These data can be beneficial in developing best management practices for young calves.

Hypothalamic-pituitary-adrenal (HPA) axis function, in Brahman heifers of differing temperament, was evaluated using separate challenges with CRH and ACTH. Exit velocity (EV) measurement was used to classify heifer temperament as calm [C; consisted of 6 slowest heifers (EV=1.05+/-0.05 m/s)] or temperamental [T; 6 fastest heifers (EV=3.14+/-0.22 m/s)]. During the 6 h prior to CRH challenge, areas under the ACTH (P=0.025) and cortisol (P<0.001) curves were greater in the temperamental heifers. Baseline cortisol (P<0.001) but not ACTH (P=0.10) differed between temperament groups. Following CRH challenge, areas under the ACTH (P=0.057) and cortisol (P<0.01) response curves were greater in the calm animals. The same animals were subjected to an ACTH challenge 14 d following their utilization in the CRH stimulation experiment. Prior to ACTH challenge, baseline cortisol concentrations were higher (P<0.001) in the temperamental heifers (T=18+/-2.6, C=4.3+/-0.6 ng/mL). Following ACTH administration, area under the cortisol response curve was greater (P=0.07) in the calm heifers. After declining below baseline concentrations during the post-challenge recovery period, cortisol in temperamental animals was again greater (P=0.02) than in the calm heifers. These data demonstrate that cattle with an excitable temperament exhibit increased stress responsiveness to handling, increased baseline adrenal function but not increased basal pituitary function, and a muted responsiveness to pharmacological stimulus. Thus, functional characteristics of the HPA axis vary with animal temperament.