Evaluation of forelimb gait variation overground at a walk in sound and lame dogs using a combination of diagnostic techniques.

BACKGROUND: Kinetic and kinematic gait analysis is increasingly practised as a part of lameness evaluation in dogs. The aim of this study was to examine the normal short- and long-term variation in forelimb gait in sound control dogs (CD) at a walk using seven selected variables of objective kinetic and kinematic gait analyses. Also, to compare the findings in CD to a group of forelimb lame dogs with elbow osteoarthritis (OAD). An additional aim was to test a kinetic based graphic method for lameness detection; symmetry squares (SS). A prospective longitudinal study was carried out on client owned CD and OAD. Clinical and orthopaedic evaluations were performed to ensure soundness and detect and grade lameness. Seven kinetic and kinematic variables and SS were tested for lameness evaluation. The CD were divided into two subgroups, CD1 and CD2, and examined twice: CD1 with two months interval and CD2 with 3-4 h interval. The OAD group was evaluated once and compared to the CD groups' first examination. RESULTS: Thirteen CD and 19 OAD were included. For CD1 and CD2, there were no significant differences in any examined variable between examination occasions. Total peak force/impulse symmetry and fore-hind peak force/impulse symmetry differed significantly between OAD and CD. Symmetry squares had a 74% agreement to subjective orthopaedic evaluations. CONCLUSIONS: In CD, no difference in the examined variables was seen between examination occasions. Four out of seven objective variables differed significantly between CD and OAD. The graphic SS method might have diagnostic potential for lameness detection, making it possible to detect a shift from lame to non-lame limbs. Potentially, this might be especially helpful in bilaterally lame dogs, which often represent a clinical challenge in lameness evaluation.

Tissue oxygen saturation is positively correlated with oxygen delivery and cardiac output in a canine hemorrhagic shock and resuscitation model.

OBJECTIVE: To determine if tissue oxygen saturation (StO2) correlates with oxygen delivery (DO2) and/or cardiac output (CO) in a canine hemorrhagic shock model. ANIMALS: 8 healthy purpose-bred dogs. METHODS: Dogs were anesthetized, and hemorrhagic shock was induced by withdrawing up to 60% of total blood volume, targeting a mean arterial pressure (MAP) of 40 mm Hg. The withdrawn blood was returned to the patient in 2 equal aliquots. Data was collected at 4 time points: 10 minutes after MAP was stabilized under anesthesia (time point [TP]-1), 10 minutes after up to 60% of blood volume was removed to target a MAP of 40 mm Hg (TP2), 10 minutes after the return of 50% of shed blood (TP3), and 10 minutes after the return of the remaining 50% of shed blood (TP4). Total blood volume withdrawn, StO2, CO, heart rate, and MAP were recorded, and DO2 was calculated at each TP. RESULTS: Mean StO2 significantly decreased between TP1 (77.8% [± 9.54]) and TP2 (44.8% [± 19.5]; P < .001 vs TP1). Mean StO2 increased to 63.1% (± 9.85) at TP3, but remained significantly lower compared to TP1 (P = .002). There was no difference between mean StO2 at TP4 (82.5% [± 12.6]) versus TP1 (P = .466). StO2 has a strong, positive correlation to both CO (r = 0.80; P < .001) and DO2 (r = 0.75; P < .001). CLINICAL RELEVANCE: A decrease in StO2 may be used in conjunction with physical examination findings and diagnostic parameters to support a diagnosis of shock. The return of shed blood was correlated with increases in StO2, DO2, and CO, suggesting that StO2 may be used as a marker of adequate resuscitation.

Traumatic and iatrogenic sciatic nerve injury in 38 dogs and 10 cats: Clinical and electrodiagnostic findings.

BACKGROUND: Reports describing sciatic nerve injuries (SNI) and their outcome are scarce in veterinary medicine. HYPOTHESIS: Describe the causes of traumatic and iatrogenic SNI and evaluate which clinical and electrodiagnostic findings predict outcome. ANIMALS: Thirty-eight dogs and 10 cats with confirmed SNI referred for neurologic and electrodiagnostic evaluation. METHODS: Clinical and electrodiagnostic examination results, including electromyography (EMG), motor nerve conduction studies, muscle-evoked potential (MEP), F-waves, sensory nerve conduction studies, and cord dorsum potential (CDP), were retrospectively evaluated. Quality of life (QoL) was assessed based on owner interviews. RESULTS: Surgery (42%) and trauma (33%) were the most common causes of SNI; in dogs, 24% were caused by bites from wild boars. Ability to flex and extend the tarsus was significantly associated with positive outcome in dogs. Mean time from onset of clinical signs until electrodiagnostic evaluation was 67 ± 65 (range, 7-300) days and 65 ± 108 (range, 7-365) days for dogs and cats, respectively. A cut-off amplitude of 1.45 mV for compound motor action potentials (CMAP) was predictive of positive outcome in dogs (P = .01), with sensitivity of 58% and specificity of 100%. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical motor function predicts recovery better than sensory function. Electrodiagnostic findings also may play a role in predicting the outcome of SNI. Application of the proposed CMAP cut-off amplitude may assist clinicians in shortening the time to reassessment or for earlier suggestion of salvage procedures. Owners perceived a good quality of life (QoL), even in cases of hindlimb amputation.

Use of machine learning and Poincaré density grid in the diagnosis of sinus node dysfunction caused by sinoatrial conduction block in dogs.

BACKGROUND: Sinus node dysfunction because of abnormal impulse generation or sinoatrial conduction block causes bradycardia that can be difficult to differentiate from high parasympathetic/low sympathetic modulation (HP/LSM). HYPOTHESIS: Beat-to-beat relationships of sinus node dysfunction are quantifiably distinguishable by Poincaré plots, machine learning, and 3-dimensional density grid analysis. Moreover, computer modeling establishes sinoatrial conduction block as a mechanism. ANIMALS: Three groups of dogs were studied with a diagnosis of: (1) balanced autonomic modulation (n = 26), (2) HP/LSM (n = 26), and (3) sinus node dysfunction (n = 21). METHODS: Heart rate parameters and Poincaré plot data were determined [median (25%-75%)]. Recordings were randomly assigned to training or testing. Supervised machine learning of the training data was evaluated with the testing data. The computer model included impulse rate, exit block probability, and HP/LSM. RESULTS: Confusion matrices illustrated the effectiveness in diagnosing by both machine learning and Poincaré density grid. Sinus pauses >2 s differentiated (P < .0001) HP/LSM (2340; 583-3947 s) from sinus node dysfunction (8503; 7078-10 050 s), but average heart rate did not. The shortest linear intervals were longer with sinus node dysfunction (315; 278-323 ms) vs HP/LSM (260; 251-292 ms; P = .008), but the longest linear intervals were shorter with sinus node dysfunction (620; 565-698 ms) vs HP/LSM (843; 799-888 ms; P < .0001). CONCLUSIONS: Number and duration of pauses, not heart rate, differentiated sinus node dysfunction from HP/LSM. Machine learning and Poincaré density grid can accurately identify sinus node dysfunction. Computer modeling supports sinoatrial conduction block as a mechanism of sinus node dysfunction.

Mobility, functionality and functional mobility: A review and application for canine veterinary patients.

Mobility is an essential aspect of a dog's daily life. It is defined as the ability to move freely and easily and deviations from an animals' normal mobility capabilities are often an indicator of disease, injury or pain. When a dog's mobility is compromised, often functionality (ability to perform activities of daily living [ADL]), is also impeded, which can diminish an animal's quality of life. Given this, it is necessary to understand the extent to which conditions impact a dog's physiological ability to move around their environment to carry out ADL, a concept termed functional mobility. In contrast to human medicine, validated measures of canine functional mobility are currently limited. The aim of this review is to summarise the extent to which canine mobility and functionality are associated with various diseases and how mobility and functional mobility are currently assessed within veterinary medicine. Future work should focus on developing a standardised method of assessing functional mobility in dogs, which can contextualise how a wide range of conditions impact a dog's daily life. However, for a true functional mobility assessment to be developed, a greater understanding of what activities dogs do on a daily basis and movements underpinning these activities must first be established.

Supplemental vibrissal extensions as an alternative to improve the tactile sensitivity of blind dogs - a preliminary approach investigation.

OBJECTIVE: This preliminary study suggests a way to artificially extend vibrissae of blind dogs to assist ambulation and avoiding facial contact with obstacles. PROCEDURES: Fourteen irreversibly blind dogs had 5-6 mystacial vibrissae on each side of the face supplementally extended by attaching carefully chosen adult pig hairs to them and were subjected to a maze test before and after the procedure. In three of these dogs the test was repeated one more time after all the extensions had fallen off. Collision counts and course times with and without extensions were analyzed and compared. A p-value > 0.05 was considered significant. RESULTS: Median number of collisions was significantly higher post-extensions (5 IQR 2.25) and after extensions had fallen off (4 IQR 7.50) compared to pre-extensions (1 IQR 1), p = 0.021. Median times were significantly higher pre-extension (25.6 IQR 8.98) and after the extensions had fallen off, compared to the post-extension performance (22.8 IQR 8.55), p = 0.04. CONCLUSION: Vibrissae play an important role in the tactile perception of blind dogs, and our preliminary results suggest that extending this sensory organ possibly improves obstacle location and their quality of life.

Post-exercise management of exertional hyperthermia in dogs participating in dog sport (canicross) events in the UK.

Exercise is a common trigger of heat-related illness (HRI) events in dogs, accounting for 74% of canine HRI cases treated under primary veterinary care in the United Kingdom. However, few empirical studies have evaluated the effectiveness of differing cooling methods for dogs with exertional hyperthermia or HRI. This study aimed to prospectively evaluate effects of ambient conditions and post-exercise management practices (cooling methods and vehicular confinement) on the post-exercise temperature change of dogs participating in UK canicross events. Canine temperature was recorded at three intervals post-exercise: as close as possible to 0- (immediately post-exercise), 5-, and 15-min post-exercise. Ambient conditions and post-exercise management were recorded for 115 cooling profiles from 52 dogs. In 28/115 (24.4%) profiles, the dog's temperature increased during the first 5-min post-exercise. Overall, 68/115 (59.1%) profiles included passive cooling (stood or walked outside), 35 (30.4%) active cooling (cold-water immersion or application of a cooling coat), and 12 (10.4%) involved no cooling and were immediately housed in vehicles. No dogs developed hypothermia during the study and no adverse effects were observed from any cooling method. In hyperthermic dogs, overall post-exercise body temperature change was significantly negatively associated (i.e. the dogs cooled more) with 0-min post-exercise body temperature (ß = -0.93, p < 0.001), and not being housed in a vehicle (ß = -0.43, p = 0.013). This study provides evidence cold-water immersion (in water at 0.1-15.0 °C) can be used to effectively and safely cool dogs with exertional hyperthermia. Progressive temperature increases in many dogs - even after exercise has terminated - supports the message to "cool first, transport second" when managing dogs with HRI. When transporting dogs post-exercise or with HRI even after active cooling, care should be taken to cool the vehicle before entry and promote air movement around the dog during transport to facilitate ongoing cooling and prevent worsening of hyperthermia during travel.

Assessment of left and right ventricular systolic function in dogs with multicentric lymphoma.

OBJECTIVE: Myocardial dysfunction in cardio-oncology is generally thought to be related to the cardiotoxicity of chemotherapy treatment. However, it is known that some tumors have direct effects on myocardial function. These effects have already been studied in man, but there are no publications of these of the effects in dogs. Novel advanced echocardiographic techniques may allow early detection of myocardial dysfunction when compared to conventional echocardiographic techniques. This study aims to assess myocardial systolic function in dogs with multicentric lymphoma prior to initiation of chemotherapy. ANIMALS: Fifteen dogs with multicentric lymphoma and nineteen healthy dogs. METHODS: Case-control study. Dogs with multicentric lymphoma and healthy control dogs underwent physical examination, electrocardiography, systolic blood pressure measurement, standard and speckle tracking echocardiography to assess biventricular systolic function. RESULTS: There were no differences between groups in terms of ejection fraction, fractional shortening, left ventricular systolic and diastolic diameter, tricuspid annular plane systolic excursion, mitral annular plane systolic excursion and fractional area change of the right ventricle (RV). However, there was a reduction in the values of global circumferential strain (p = 0.0003), RV strain (p = 0.01) and RV tissue motion annular displacement (p < 0.05) in the dogs with lymphoma when compared to the control group. CONCLUSIONS: Speckle tracking techniques appear to demonstrate early systolic dysfunction, primarily affecting the RV, in dogs with lymphoma prior to chemotherapy treatment.

Pulse-wave analysis during routine blood pressure measurement shows potential to distinguish between sinus and nonsinus rhythm.

OBJECTIVE: To investigate whether pulse-wave analysis (PWA) performed by trained evaluators facilitates detection of nonsinus rhythm. ANIMALS: Same-day, high-definition oscillometry pulse-wave data and ECG results of 155 animals (144 dogs and 11 cats) were analyzed. METHODS: In this cross-sectional study, we enrolled 18 participants from various backgrounds, all of whom received PWA training. The ability to distinguish between sinus and nonsinus rhythms was assessed using receiver operating characteristic curve analysis. The pulse-wave datasets were divided into 5 ECG categories. Agreement between ECG diagnoses and PWA-based arrhythmia detection was evaluated using Cohen κ values, and the correlation between the academic year of veterinary students and their κ values was assessed. RESULTS: All cardiology researchers demonstrated satisfactory accuracy in distinguishing pathological rhythms using PWA (area under the curve, 0.704 to 0.761), with the highest accuracy in detecting atrial fibrillation (area under the curve, 0.811 to 0.845). Fair agreement with ECG categorization was achieved by all 3 cardiology researchers, 2 of 5 general practitioners, and 3 of 10 veterinary undergraduates. The veterinary undergraduates' years of study were correlated with their diagnostic performance (Spearman ρ = 0.658; P = .019). CLINICAL RELEVANCE: PWA during routine noninvasive blood pressure measurement showed significant potential for the detection of pathological arrhythmias, notably atrial fibrillation. This approach yielded improved effectiveness when it was used by veterinarians with cardiology experience. Thus, introducing hands-on training courses, particularly those focused on cardiology and interactive workshops, may enable frontline veterinarians to promptly identify arrhythmias using PWA, facilitating timely ECG examinations or referrals.

How avian influenza viruses spill over to mammals.

The H3N2 canine influenza virus - which originally came from birds - is evolving to become more transmissible between dogs.

Evaluation of VEGF-A and CCL2 in dogs with brachycephalic obstructive airway syndrome or canine idiopathic pulmonary fibrosis and in normocephalic dogs.

Brachycephalic obstructive airway syndrome (BOAS) and canine idiopathic pulmonary fibrosis (CIPF) of West Highland White Terriers (WHWTs) often cause intermittent or chronic hypoxemia. Our objective was to evaluate serum and bronchoalveolar lavage fluid (BALF) concentrations of hypoxemia-related proinflammatory mediators vascular endothelial growth factor A (VEGF-A) and chemokine (CC motif) ligand 2 (CCL2) in brachycephalic dogs (BDs) and WHWTs with and without CIPF. Additionally, effects of BOAS severity and ageing on these mediators were assessed. 114 BDs (28 English Bulldogs (EBs), 37 French Bulldogs, 49 Pugs), 16 WHWTs with CIPF, 26 healthy WHWTs, and 39 normocephalic control dogs were included. Fifty-four BDs were re-examined after two to three years. Bead-based immunoassay was used for proinflammatory mediator measurements. Compared with controls, significantly higher serum concentrations of VEGF-A were seen in EBs (P = 0.009) and of CCL2 in CIPF and healthy WHWTs (P < 0.001; P = 0.002). BALF samples were available from controls, EBs, and WHWTs. VEGF-A was significantly lower in EBs (P < 0.001) and in CIPF and healthy WHWTs (P = 0.006; P = 0.007) and CCL2 was higher in CIPF WHWTs (P = 0.01) compared with controls. Between visits, only serum VEGF-A significantly decreased in BDs (P < 0.001), but breed, BOAS severity, or its change had no significant effect. In conclusion, in EBs with BOAS proinflammatory changes in VEGF-A were detected in both serum and BALF. Ageing reduced serum VEGF-A in BDs. In WHWTs, our results confirmed earlier findings of CCL2 as an important biomarker for CIPF.

Characterizing the metabolic role of STAT3 in canine osteosarcoma.

Signal transducer and activator of transcription 3 (STAT3) dysregulation has been characterized in canine OS, with previous data suggesting that constitutive STAT3 activation contributes to survival and proliferation in OS cell lines in vitro. Recently, the contribution of STAT3 to tumour metabolism has been described across several tumour histologies, and understanding the metabolic implications of STAT3 loss may elucidate novel therapeutic approaches with synergistic activity. The objective of this work was to characterize metabolic benchmarks associated with STAT3 loss in canine OS. STAT3 expression and activation was evaluated using western blotting in canine OS cell lines OSCA8 and Abrams. STAT3 was deleted from these OS cell lines using CRISPR-Cas9, and the effects on proliferation, invasion and metabolism (respirometry, intracellular lactate) were determined. Loss of STAT3 was associated with decreased basal and compensatory glycolysis in canine OS cell lines, without modulation of cellular proliferation. Loss of STAT3 also resulted in diminished invasive capacity in vitro. Interestingly, the absence of STAT3 did not impact sensitivity to doxorubicin in vitro. Our data demonstrate that loss of STAT3 modulates features of aerobic glycolysis in canine OS impacting capacities for cellular invasions, suggesting a role for this transcription factor in metastasis.

Profile qualitative variables on the dynamics of weight loss programs in dogs.

Obesity is the most common nutritional disorder in dogs and it is associated with many comorbidities. Some obesity risk factors have already been established, however, the evaluation of the effect of different individual variables on weight loss induced by calorie restriction, although very important, is still poorly explored. The weight loss protocol can be updated and improved by more precise and adjusted equations throughout the weight loss program in the clinical routine practice. Therefore, the objective of this study was to analyze weight loss program dynamics in groups according to reproductive status, age, body size, and breed, as well as to define more accurately the amount of calories per target metabolic weight throughout the program. Data of 1,053 cases, presented between 2012 and 2019 at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo (FMVZ-USP) were retrospectively analyzed. A total of 77 obese dogs (body condition scores 8/9 or 9/9) of different ages, breeds, sizes, and reproductive status were selected. These dogs did not have any concomitant illnesses and successfully completed the weight loss program. Statistical analysis was performed and values of p≤0.05 were considered significant. The proposed weight loss program was based on an energy restriction protocol where daily energy intake (in kcal) was estimated as 70 kcal × target weight0.75. The target weight (TW) was defined as 80% of the animal's current weight. The average calorie intake for weight loss (calories x target weight0.75) was lower for spayed females (62.36), differing from intact males (66.14) and neutered males (65.41), while intact females (63.66) showed intermediate values without differing between groups (p = 0.015). There were no differences between weight loss calories according to age (p = 0.473) or body size (p = 0.084), allowing the use of the same mathematical equation for intact and neutered dogs; for dogs older than 1 year and of different body sizes. Regarding the breed, the average calorie intake was lower (p = 0.002) in mixed breed dogs (61.54xTW0.75) when compared to obesity-prone purebred dogs (64.17xTW0.75) and other purebreds (65.27xTW0.75). It was concluded that spayed females and mixed breed dogs have greater difficulty in losing weight, that is, they need fewer calories per metabolic body weight for the weight loss program to succeed. A more accurate equation for energy requirement for weight loss can improve chances of success, therefore improving compliance and helping clinical management of obesity in dogs.

Personalized endoprostheses for the proximal humerus and scapulohumeral joint in dogs: Biomechanical study of the muscles' contributions during locomotion.

Osteosarcoma represents one of the most common bone tumours in dogs. It commonly occurs in the proximal humerus, the most affected anatomic site. Until recently, amputation or limb-sparing surgery leading to an arthrodesis coupled with chemotherapy were the only available treatments, but they often lead to complications, reduced mobility and highly impact dog's quality of life. Prototypes of both articulated and monobloc (no mobility) patient-specific endoprostheses have been designed to spare the limb afflicted with osteosarcoma of the proximal humerus. This study focuses on the biomechanical effects of endoprostheses and shoulder muscle kinematics. For each of the endoprosthesis designs, a minimal number of muscles needed to ensure stability and a certain degree of joint movement during walking is sought. A quasi-static study based on an optimization method, the minimization of the sum of maximal muscle stresses, was carried out to assess the contribution of each muscle to the shoulder function. The identification of the most important muscles and their impact on the kinematics of the prosthetic joint lead to an improvement of the endoprosthesis design relevance and implantation feasibility.

Red cell distribution width, illness severity, and all-cause mortality in dogs admitted to the ICU.

OBJECTIVE: To determine whether red cell distribution width (RDW) can predict illness severity and mortality risk in a heterogenous population of dogs admitted to the ICU. DESIGN: Prospective observational study. SETTING: Large, urban, private teaching hospital. ANIMALS: One hundred eleven dogs consecutively admitted to the ICU between September 2017 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Abbreviated Acute Patient Physiologic and Laboratory Evaluation (APPLEfast ) score and RDW were measured within 6 h of ICU admission. This study did not demonstrate a significant difference in illness severity across patients stratified by RDW. There was no difference in RDW between survivors and nonsurvivors at hospital discharge or at 30 days. CONCLUSIONS: In this study population, RDW did not correspond with illness severity as measured by APPLEfast . Moreover, RDW did not predict in-hospital or 30-day mortality.

Canine coat pigmentation genetics: a review.

Our understanding of canine coat colour genetics and the associated health implications is developing rapidly. To date, there are 15 genes with known roles in canine coat colour phenotypes. Many coat phenotypes result from complex and/or epistatic genetic interactions among variants within and between loci, some of which remain unidentified. Some genes involved in canine pigmentation have been linked to aural, visual and neurological impairments. Consequently, coat pigmentation in the domestic dog retains considerable ethical and economic interest. In this paper we discuss coat colour phenotypes in the domestic dog, the genes and variants responsible for these phenotypes and any proven coat colour-associated health effects.

Increased resting state connectivity in the anterior default mode network of idiopathic epileptic dogs.

Epilepsy is one of the most common chronic, neurological diseases in humans and dogs and considered to be a network disease. In human epilepsy altered functional connectivity in different large-scale networks have been identified with functional resting state magnetic resonance imaging. Since large-scale resting state networks have been consistently identified in anesthetised dogs' application of this technique became promising in canine epilepsy research. The aim of the present study was to investigate differences in large-scale resting state networks in epileptic dogs compared to healthy controls. Our hypothesis was, that large-scale networks differ between epileptic dogs and healthy control dogs. A group of 17 dogs (Border Collies and Greater Swiss Mountain Dogs) with idiopathic epilepsy was compared to 20 healthy control dogs under a standardized sevoflurane anaesthesia protocol. Group level independent component analysis with dimensionality of 20 components, dual regression and two-sample t test were performed and revealed significantly increased functional connectivity in the anterior default mode network of idiopathic epileptic dogs compared to healthy control dogs (p = 0.00060). This group level differences between epileptic dogs and healthy control dogs identified using a rather simple data driven approach could serve as a starting point for more advanced resting state network analysis in epileptic dogs.

Ultrasonographic assessment of renal perfusion in bitches with mammary carcinoma treated with long-term carprofen.

The aim of this study was to evaluate renal hemodynamics, routine clinical and laboratory parameters used to estimate renal function, and clinical evolution during six months in bitches with mammary carcinomas that underwent mastectomy and were treated (TG) or not (CG) with carprofen for three months after surgery. Twenty-six bitches with mammary carcinoma were equally distributed into TG that received carprofen 4.4 mg/kg/day for 90 days and CG that did not receive anti-inflammatory medication. Renal artery Doppler flowmetry, contrast-enhanced ultrasound (CEUS) of renal parenchyma, haematological, biochemical and clinical analyses were obtained once a month. These data were compared between groups and time via analysis of variance (ANOVA) in a completely randomized design with repeated measures (P < 0.05). On B-mode ultrasound, the area of the renal artery was greater (P = 0.0003) in the TG. Regarding laboratory findings, haematocrit and haemoglobin were similar in both groups, showing a significant and gradual increase after three months of treatment; MCV, MHC, and MCHC were increased (P < 0.05) and lymphocyte and band counts decreased (P < 0.05) in the TG. Regarding biochemical tests, ALT was the only parameter with a significant difference, being higher (P = 0.0272) in the treated group. It can be concluded that the use of carprofen for 90 days causes minimal changes in renal perfusion, erythrocyte parameters and ALT activity, and reduces the proportion of blood inflammatory cells. Therefore, use of this medication can be carried out safely in patients who require auxiliary cancer treatment.

Heritability and Genomic Architecture of Episodic Exercise-Induced Collapse in Border Collies.

An episodic nervous system disorder triggered by strenuous exercise, termed border collie collapse (BCC), exists in border collies and related breeds. The genetic basis of BCC is unknown but is believed to be a complex genetic disorder. Our goal was to estimate the heritability (h2SNP) of BCC, define its underlying genetic architecture, and identify associated genomic loci using dense whole-genome single-nucleotide polymorphism (SNP) genotyping data. Genotype data were obtained for ~440,000 SNPs from 343 border collies (168 BCC cases and 175 controls). h2SNP was calculated to be 49-61% depending on the estimated BCC prevalence. A total of 2407 SNPs across the genome accounted for nearly all the h2SNP of BCC, with an estimated 2003 SNPs of small effect, 349 SNPs of moderate effect, and 56 SNPs of large effect. Genome-wide association analyses identified significantly associated loci on chromosomes 1, 6, 11, 20, and 28, which accounted for ~5% of the total BCC h2SNP. We conclude that BCC is a moderately- to highly-heritable complex polygenetic disease resulting from contributions from hundreds to thousands of genetic variants with variable effect sizes. Understanding how much the BCC phenotype is determined by genetics and whether major gene mutations are likely to exist inform veterinarians and working/stock dog communities of the true nature of this condition.