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The breeding of sport horses to compete in the Olympic disciplines of show jumping, eventing, and dressage is fast becoming a global industry with the increased use of reproductive technologies, including artificial insemination and embryo transfer. Reproductive technologies have facilitated the dissemination of genetics from elite horses across multiple countries and breeds as breeders are no longer limited by location. Due to this increased level of crossbreeding, there is an increased need for estimated breeding values (EBVs) for sport horse performance that can be compared across breeds and countries. However, the implementation of across-breed or across-country genetic evaluations has been limited by the differences in each studbook's individual breeding programs and genetic evaluations. Consequently, the aim of this review was to compare the genetic evaluations for show jumping of sport horse studbooks worldwide. The top sport horse studbooks in the world according to the World Breeding Federation for Sport Horses Studbook Rankings 2019 were contacted by email to request information on their current breeding programs and genetic evaluations. Twenty-six of the 51 studbooks contacted replied to this request but only 18 of these studbooks conducted their own genetic evaluations or were part of a larger genetic evaluation in their country of origin. The other eight studbooks were not involved in genetic evaluations at present but expressed an interest in the implementation of such in the future. Overall, many differences were identified among the genetic evaluations of each studbook or each country. The definition of show jumping performance differed within each evaluation and the methods and models utilized also differed. Despite some stallions and mares being registered in multiple studbooks or having progeny in multiple studbooks, these differences make comparison of EBVs across studbooks difficult. Further transparency and collaboration of sport horse studbooks with organizations such as Interstallion, will be essential to facilitate any future implementation of international genetic evaluations for show jumping performance. [ABSTRACT FROM AUTHOR]

Sexual dimorphism, the phenomenon whereby males and females of the same species are distinctive in some aspect of appearance or size, has previously been documented in cattle for traits such as growth rate and carcass merit using a quantitative genetics approach. No previous study in cattle has attempted to document sexual dimorphism at a genome level; therefore, the objective of the present study was to determine whether genomic regions associated with size and muscularity in cattle exhibited signs of sexual dimorphism. Analyses were undertaken on 10 linear-type traits that describe the muscular and skeletal characteristics of both males and females of five beef cattle breeds: 1,444 Angus (AA), 6,433 Charolais (CH), 1,129 Hereford, 8,745 Limousin (LM), and 1,698 Simmental. Genome-wide association analyses were undertaken using imputed whole-genome sequence data for each sex separately by breed. For each single-nucleotide polymorphism (SNP) that was segregating in both sexes, the difference between the allele substitution effect sizes for each sex, in each breed separately, was calculated. Suggestively (P ≤ 1 × 10−5) sexually dimorphic SNPs that were segregating in both males and females were detected for all traits in all breeds, although the location of these SNPs differed by both trait and breed. Significantly (P ≤ 1 × 10−8) dimorphic SNPs were detected in just three traits in the AA, seven traits in the CH, and three traits in the LM. The vast majority of all segregating autosomal SNPs (86% in AA to 94% in LM) had the same minor allele in both males and females. Differences (P ≤ 0.05) in allele frequencies between the sexes were observed for between 36% (LM) and 66% (AA) of the total autosomal SNPs that were segregating in both sexes. Dimorphic SNPs were located within a number of genes related to muscularity and/or size including the NAB1, COL5A2, and IWS1 genes on BTA2 that are located close to, and thought to be co-inherited with, the MSTN gene. Overall, sexual dimorphism exists in cattle at the genome level, but it is not consistent by either trait or breed. [ABSTRACT FROM AUTHOR]

Linear type traits describing the skeletal characteristics of an animal are moderately to strongly genetically correlated with a range of other performance traits in cattle including feed intake, reproduction traits and carcass merit; thus, type traits could also provide useful insights into the morphological differences among animals underpinning phenotypic differences in these complex traits. The objective of the present study was to identify genomic regions associated with five subjectively scored skeletal linear traits, to determine if these associated regions are common in multiple beef and dairy breeds, and also to determine if these regions overlap with those proposed elsewhere to be associated with correlated performance traits. Analyses were carried out using linear mixed models on imputed whole genome sequence data separately in 1,444 Angus, 1,129 Hereford, 6,433 Charolais, 8,745 Limousin, 1,698 Simmental, and 4,494 Holstein-Friesian cattle, all scored for the linear type traits. There was, on average, 18 months difference in age at assessment of the beef versus the dairy animals. While the majority of the identified quantitative trait loci (QTL), and thus genes, were both trait-specific and breed-specific, a large-effect pleiotropic QTL on BTA6 containing the NCAPG and LCORL genes was associated with all skeletal traits in the Limousin population and with wither height in the Angus. Other than that, little overlap existed in detected QTLs for the skeletal type traits in the other breeds. Only two QTLs overlapped the beef and dairy breeds; both QTLs were located on BTA5 and were associated with height in both the Angus and the Holstein-Friesian, despite the difference in age at assessment. Several detected QTLs in the present study overlapped with QTLs documented elsewhere that are associated with carcass traits, feed intake, and calving difficulty. While most breeding programs select for the macro-traits like carcass weight, carcass conformation, and feed intake, the higher degree of granularity with selection on the individual linear type traits in a multi-trait index underpinning the macro-level goal traits, presents an opportunity to help resolve genetic antagonisms among morphological traits in the pursuit of the animal with optimum performance metrics. [ABSTRACT FROM AUTHOR]

Background: Linear type traits, which reflect the muscular characteristics of an animal, could provide insight into how, in some cases, morphologically very different animals can yield the same carcass weight. Such variability may contribute to differences in the overall value of the carcass since primal cuts vary greatly in price; such variability may also hinder successful genome-based association studies. Therefore, the objective of our study was to identify genomic regions that are associated with five muscularity linear type traits and to determine if these significant regions are common across five different breeds. Analyses were carried out using linear mixed models on imputed whole-genome sequence data in each of the five breeds, separately. Then, the results of the within-breed analyses were used to conduct an across-breed meta-analysis per trait. Results: We identified many quantitative trait loci (QTL) that are located across the whole genome and associated with each trait in each breed. The only commonality among the breeds and traits was a large-effect pleiotropic QTL on BTA2 that contained the MSTN gene, which was associated with all traits in the Charolais and Limousin breeds. Other plausible candidate genes were identified for muscularity traits including PDE1A, PPP1R1C and multiple collagen and HOXD genes. In addition, associated (gene ontology) GO terms and KEGG pathways tended to differ between breeds and between traits especially in the numerically smaller populations of Angus, Hereford, and Simmental breeds. Most of the SNPs that were associated with any of the traits were intergenic or intronic SNPs located within regulatory regions of the genome. Conclusions: The commonality between the Charolais and Limousin breeds indicates that the genetic architecture of the muscularity traits may be similar in these breeds due to their similar origins. Conversely, there were vast differences in the QTL associated with muscularity in Angus, Hereford, and Simmental. Knowledge of these differences in genetic architecture between breeds is useful to develop accurate genomic prediction equations that can operate effectively across breeds. Overall, the associated QTL differed according to trait, which suggests that breeding for a morphologically different (e.g. longer and wider versus shorter and smaller) more efficient animal may become possible in the future. [ABSTRACT FROM AUTHOR]

Two musicians with chromesthesia (one with and one without absolute pitch) were the subjects of an intensive case study. Musical and neuropsychological interviews and testing were conducted to determine the extent of each individual's aural acuity and synesthesia characteristics, as well as possible neuropsychological characteristics concurrent with this condition. The individual with absolute pitch had aurally-based chromesthesia that was elicited only by sound, with photisms experienced internally and externally for a variety of musical phenomena. The individual without absolute pitch had chromesthesia and grapheme-color synesthesia for days of the week, letters, and numbers. This individual's photisms were experienced internally. Musical phenomena where photisms were elicited consisted of instrument fingering, conducting musical scores and musical sound when the pitch was known. Both participants demonstrated relative deficits in visuoconstruction, attention, and executive functioning on neuropsychological tests, reported attention deficit and compulsive symptoms, and acknowledged auditory-language processing dysfunction, and social, emotional and self-regulation dysfunction. [ABSTRACT FROM AUTHOR]

Linear type traits describing the skeletal, muscular, and functional characteristics of an animal are routinely scored on live animals in both the dairy and beef cattle industries. Previous studies have demonstrated that genetic parameters for certain performance traits may differ between breeds; no study, however, has attempted to determine if differences exist in genetic parameters of linear type traits among breeds or sexes. Therefore, the objective of the present study was to determine if genetic covariance components for linear type traits differed among five contrasting cattle breeds, and to also investigate if these components differed by sex. A total of 18 linear type traits scored on 3,356 Angus (AA), 31,049 Charolais (CH), 3,004 Hereford (HE), 35,159 Limousin (LM), and 8,632 Simmental (SI) were used in the analysis. Data were analyzed using animal linear mixed models which included the fixed effects of sex of the animal (except in the investigation into the presence of sexual dimorphism), age at scoring, parity of the dam, and contemporary group of herd-date of scoring. Differences (P < 0.05) in heritability estimates, between at least two breeds, existed for 13 out of 18 linear type traits. Differences (P < 0.05) also existed between the pairwise within-breed genetic correlations among the linear type traits. Overall, the linear type traits in the continental breeds (i.e., CH, LM, SI) tended to have similar heritability estimates to each other as well as similar genetic correlations among the same pairwise traits, as did the traits in the British breeds (i.e., AA, HE). The correlation between a linear function of breeding values computed conditional on covariance parameters estimated from the CH breed with a linear function of breeding values computed conditional on covariance parameters estimated from the other breeds was estimated. Replacing the genetic covariance components estimated in the CH breed with those of the LM had least effect but the impact was considerable when the genetic covariance components of the AA were used. Genetic correlations between the same linear type traits in the two sexes were all close to unity (=0.90) suggesting little advantage in considering these as separate traits for males and females. Results for the present study indicate the potential increase in accuracy of estimated breeding value prediction from considering, at least, the British breed traits separate to continental breed traits. [ABSTRACT FROM AUTHOR]

The breeding of sport horses to compete in show jumping is fast becoming a global industry with the increased use of reproductive technologies, including artificial insemination and embryo transfer, facilitating the dissemination of genetics from elite horses across multiple countries and breeds. Due to this increased level of crossbreeding, there is an increased need for estimate breeding values for sport horse performance that can be compared across breeds and countries. However, the implementation of a cross-breed or across-country genetic evaluations has been limited by the differences in individual breeding programs and genetic evaluations in each studbook. Consequently, the aim of this study was to compare the genetic evaluations for show jumping of sport horse studbooks worldwide. An email was sent to the studbooks included in the World Breeding Federation for Sport Horses Studbook Rankings for show jumping in 2019 to request information on their current breeding programs and genetic evaluations. Twenty-six of the 51 studbooks contacted replied to this request. Only 18 of these studbooks conducted their own genetic evaluations or were part of a larger genetic evaluation in their country of origin. Overall, many differences were identified among the genetic evaluations of each studbook or each country. The definition of show jumping performance differed within each evaluation and the methods and models utilized also differed (Table 1). Despite some stallions and mares being registered in multiple studbooks or having progeny in multiple studbooks, these differences make comparison of estimated breeding values across studbooks difficult. Further transparency and collaboration of sport horse studbooks with organizations such as Interstallion, will be essential to facilitate any future implementation of international genetic evaluations for show jumping performance. [ABSTRACT FROM AUTHOR]

The current genetic evaluations of the Irish Sport Horse are undertaken on a single trait called the Lifetime Performance Rating (LPR). The LPR represents the highest level a horse has achieved two double clear rounds in show jumping in both national and international performances. The objective of this study was to compare the method currently used in these evaluations (Model 1, Table 1) to a modified methodology to determine the most accurate method for estimating breeding values (EBV) for the LPR. Genetic parameters and EBVs were generated based on the LPR of 30,355 horses using eight different animal models. Each of the eight models considered the additive genetic variance as the random effect and a combination of following fixed effects: sex, year the highest level was first achieved, age the highest level was achieved, maximum age of the animal in the competition data, Thoroughbred percentage (TB%), and TB% divided into eights. (Table 1). The goodness-of-fit of each model was evaluated using the Akaike's information criteria and the genetic parameters produced by each model. Heritability estimates for LPR ranged from 0.26 to 0.32 depending on the model used (Table 1). The inclusion of age or maximum age in the model decreased the residual variances, and thus, increased the heritability estimates of LPR; these models also performed better than those that did not consider age in any form. The models that considered the effect of TB% were not a significantly better fit than those that did not consider this effect. In conclusion, future genetic evaluations of LPR in the Irish Sport Horse would benefit from using a model that considers either the age or maximum age of performance of each horse, alongside the year the highest level was achieved, and the sex of the horse. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Doyle and Haas (2010). The Angiogenic Response to Skeletal Muscle Overload is not Dependent on Mast Cell Activation. Microcirculation 17(7), 548-556. Abstract Objective: To determine if mast cell activation in skeletal muscle contributes to overload-induced angiogenesis. Methods: Extensor digitorum longus muscle was overloaded through extirpation of the synergist muscle tibialis anterior. Muscles were removed after 1, 2, 4, 7 or 14 days, and mast cell density and degranulation were quantified by histology. The mast cell stabilizer, cromolyn, was administered acutely or chronically to test if mast cell degranulation contributes to overload-induced angiogenesis. Angiogenesis was determined by calculating capillary to muscle Fiber ratio; mast cell density and activation were quantified by histology, MMP-2 levels were assessed by gelatin zymography and VEGF protein levels were assessed by Western blotting. Results: Muscle overload increased mast cell degranulation and total mast cell number within 7 days. Mast cell stabilization with cromolyn attenuated degranulation but did not inhibit the increased mast cell density, MMP-2 activity, VEGF protein levels or the increase in capillary number following muscle overload. Conclusions: Mast cell degranulation and accumulation precede overload-induced angiogenesis, but mast cell activation is not critical to the angiogenic response following skeletal muscle overload. [ABSTRACT FROM AUTHOR]

Persistent elevation in shear stress within conduit or resistance arteries causes structural luminal expansion, which serves to normalize shear stress while maintaining increased flow to the downstream vasculature. Although it is known that this adaptation involves cellular proliferation and remodeling of the extracellular matrix, the specific cellular events underlying these responses are poorly understood. Matrix metalloproteinases (MMPs) contribute to extensive remodeling of the extracellular matrix in conduit vessels and vein grafts exposed to high flow. However, involvement of MMPs in remodeling of small muscular collateral arteries, which are exposed to less severe increases in shear stress, has not been tested. We utilized an established model of outward remodeling in mesenteric collateral arteries to determine whether MMPs were upregulated during the remodeling response and to test whether MMP activity was required for luminal expansion. By 4 days, MMP-2 and membrane type 1 MMP (MT1-MMP), but not MMP-9, protein levels were significantly elevated in collateral arteries, as assessed by gelatin zymography and immunostaining. MMP-2 and MT1-MMP proteins, together with their respective transcriptional activators c-Jun and Egr-1 were localized predominantly to the smooth muscle layer of the collateral arteries. The general MMP inhibitor doxycycline prevented luminal expansion of collateral arteries but did not affect the endothelial cell proliferative or medial growth responses. In conclusion, this study provides evidence that MMP-2 and MT1-MMP are upregulated in collateral arteries exposed to elevated shear stress and that MMP activity is essential for the full remodeling response that leads to outward luminal expansion. [ABSTRACT FROM AUTHOR]

Angiogenesis, which is essential for the physiological adaptation of skeletal muscle to exercise, occurs in response to the mechanical forces of elevated capillary shear stress and cell stretch. Increased production of VEGF is a characteristic of endothelial cells undergoing either stretch- or shear-stress-induced angiogenesis. Because VEGF production is regulated by hypoxia inducible factors (HIFs), we examined whether HIFs play a significant role in the angiogenic process initiated by these mechanical forces. Rat extensor digitorum longus (EDL) muscles were overloaded to induce stretch, or exposed to the dilator prazosin to elevate capillary shear stress, and capillaries from these muscles were isolated by laser capture microdissection for RNA analysis. HIF-1α and HIF-2α transcript levels increased after 4 and 7 days of stretch, whereas a transient early induction of HIF-1α and HIF-2α transcripts was detected in capillaries from prazosin-treated muscles. Skeletal muscle microvascular endothelial cells exposed to 10% stretch in vitro showed an elevation in HIF-1α and HIF-2α mRNA, which was preceded by increases in HIF-binding activity. Conversely, HIF-1α and HIF-2α mRNA were reduced significantly, and HIF-α proteins were undetectable, after 24 h exposure to elevated shear stress (16 dyn cm−2 (16 ×10−5 N cm−2). Given the disparate regulation of HIFs in response to these mechanical stimuli, we tested the requirement of HIF-α proteins in stretch- and shear-stress-induced angiogenesis by impeding HIF accumulation through use of the geldanamycin derivative 17-DMAG. Treatment with 17-DMAG significantly impaired stretch-induced, but not shear-stress-induced, angiogenesis. Together, these results illustrate that activation of HIF-1α and HIF-2α contributes significantly to stretch- but not to shear-stress-induced capillary growth. [ABSTRACT FROM AUTHOR]

Background: Temperament traits are of high importance across species. In humans, temperament or personality traits correlate with psychological traits and psychiatric disorders. In cattle, they impact animal welfare, product quality and human safety, and are therefore of direct commercial importance. We hypothesized that genetic factors that contribute to variation in temperament among individuals within a species will be shared between humans and cattle. Using imputed whole-genome sequence data from 9223 beef cattle from three cohorts, a series of genome-wide association studies was undertaken on cattle flight time, a temperament phenotype measured as the time taken for an animal to cover a short-fixed distance after release from an enclosure. We also investigated the association of cattle temperament with polymorphisms in bovine orthologs of risk genes for neuroticism, schizophrenia, autism spectrum disorders (ASD), and developmental delay disorders in humans. Results: Variants with the strongest associations were located in the bovine orthologous region that is involved in several behavioural and cognitive disorders in humans. These variants were also partially validated in independent cattle cohorts. Genes in these regions (BARHL2, NDN, SNRPN, MAGEL2, ABCA12, KIFAP3, TOPAZ1, FZD3, UBE3A, and GABRA5) were enriched for the GO term neuron migration and were differentially expressed in brain and pituitary tissues in humans. Moreover, variants within 100 kb of ASD susceptibility genes were associated with cattle temperament and explained 6.5% of the total additive genetic variance in the largest cattle cohort. The ASD genes with the most significant associations were GABRB3 and CUL3. Using the same 100 kb window, a weak association was found with polymorphisms in schizophrenia risk genes and no association with polymorphisms in neuroticism and developmental delay disorders risk genes. Conclusions: Our analysis showed that genes identified in a meta-analysis of cattle temperament contribute to neuron development functions and are differentially expressed in human brain tissues. Furthermore, some ASD susceptibility genes are associated with cattle temperament. These findings provide evidence that genetic control of temperament might be shared between humans and cattle and highlight the potential for future analyses to leverage results between species. [ABSTRACT FROM AUTHOR]