Assessment of glial fibrillary acidic protein and anti-glial fibrillary acidic protein autoantibody concentrations and necrotising meningoencephalitis risk genotype in dogs with pug dog myelopathy.

BACKGROUND: Pugs commonly present with thoracolumbar myelopathy, also known as pug dog myelopathy (PDM), which is clinically characterised by progressive signs involving the pelvic limbs, no apparent signs of pain and, often, incontinence. In addition to meningeal fibrosis and focal spinal cord destruction, histopathology has confirmed lymphohistiocytic infiltrates in the central nervous system (CNS) in a considerable number of pugs with PDM. Lymphohistiocytic CNS inflammation also characterises necrotising meningoencephalitis (NME) in pugs. This study aimed to investigate the potential contribution of an immunological aetiology to the development of PDM. METHODS: The concentrations of glial fibrillary acidic protein (GFAP) in serum and CSF and of anti-GFAP autoantibodies in CSF were measured with an ELISA. In addition, a commercial test was used for genetic characterisation of the dog leukocyte antigen class II haplotype, which is associated with NME susceptibility. RESULTS: This study included 87 dogs: 52 PDM pugs, 14 control pugs, four NME pugs and 17 dogs of breeds other than pugs that were investigated for neurological disease (neuro controls). Anti-GFAP autoantibodies were present in 15 of 19 (79%) of the PDM pugs tested versus six of 16 (38%) of the neuro controls tested (p = 0.018). All 18 PDM pugs evaluated had detectable CSF GFAP. Serum GFAP was detected in two of three (67%) of the NME pugs and in two of 11 (18%) of the control pugs but not in any of the 40 tested PDM pugs. Male pugs heterozygous for the NME risk haplotype had an earlier onset of clinical signs (70 months) compared to male pugs without the risk haplotype (78 months) (p = 0.036). LIMITATIONS: The study was limited by the lack of healthy dogs of breeds other than pugs and the small numbers of control pugs and pugs with NME. CONCLUSIONS: The high proportion of PDM pugs with anti-GFAP autoantibodies and high CSF GFAP concentrations provide support for a potential immunological contribution to the development of PDM.

Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines.

Introduction: The correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for variant classification. This study aims to apply these guidelines to six genetic variants associated with hypertrophic cardiomyopathy (HCM) in certain cat breeds and to propose a modified criterion for variant classification. Methods: Genetic samples were sourced from five cat breeds: Maine Coon, Sphynx, Ragdoll, Devon Rex, and British Short- and Longhair. Allele frequencies were determined, and in the subset with phenotypes available, odds ratios to determine the association with HCM were calculated. In silico evaluation followed with joint evidence and data from other publications assisting in the classification of each variant. Results: Two variants, MYBPC3:c.91G > C [A31P] and MYBPC3:c.2453C > T [R818W], were designated as pathogenic. One variant, MYH7:c.5647G > A [E1883K], was found likely pathogenic, while the remaining three were labeled as variants of unknown significance. Discussion: Routine genetic testing is advised solely for the MYBPC3:c.91G > C [A31P] in the Maine Coon and MYBPC3:c.2453C > T [R818W] in the Ragdoll breed. The human ACMG guidelines serve as a suitable foundational tool to ascertain which variants to include; however, refining them for application in veterinary medicine might be beneficial.

Sonographic features of the uncomplicated postoperative abdomen in dogs treated for pyometra by ovariohysterectomy.

Pyometra is a prevalent disease in intact bitches and the standard treatment is ovariohysterectomy (OHE). Published descriptions of normal sonographic findings after OHE are currently lacking. The aims of this prospective observational study were to describe and compare postoperative abdominal sonographic features for three timepoints following OHE in a group of dogs with pyometra and an uneventful recovery. A total of 22 dogs had sequential focused abdominal ultrasound examinations on days 1, 4-6, and 10-15 postsurgery. Recorded sonographic features for each examination time point and characteristics of the cervical stump and the mesovarium, size, and echogenicity of medial iliac lymph nodes (MILNs), presence of free peritoneal fluid, and pneumoperitoneum. The cervical stump appeared as a heterogenous area with a hypoechoic center surrounded by hyperechogenic tissue in all dogs. The cervical stump transverse-sectional area was larger on day 4-6 compared with day 1 and day 10-15 (P = .0009). Mesovarium ligature reactions were identified as heterogeneous and hyperechoic areas with central and/or edge shadowing in all dogs. The size and echogenicity of MILNs and the mesovarium reactions did not significantly differ among time points. Free peritoneal fluid was detected in 45%, 41%, and 9% and pneumoperitoneum in 95%, 82%, and 14% of dogs at sequential time points. Findings from this sample of dogs with an uneventful recovery following OHE due to pyometra can be used to assist veterinarians in interpreting postoperative abdominal ultrasonographic characteristics in future dogs treated surgically for pyometra.

No impact of polymorphism in the phosphodiesterase 5A gene in Cavalier King Charles Spaniels on pimobendan-induced inhibition of platelet aggregation response.

BACKGROUND: A variant in the canine phosphodiesterase (PDE) 5A gene (PDE5A:E90K) is associated with decreased concentrations of circulating cyclic guanosine monophosphate (cGMP) and response to PDE5 inhibitor treatment. Pimobendan is a PDE inhibitor recommended for medical treatment of certain stages of myxomatous mitral valve disease (MMVD) in dogs. HYPOTHESIS: PDE5A:E90K polymorphism attenuates the inhibitory effect of pimobendan on in vitro platelet aggregation and increases basal platelet aggregation in Cavalier King Charles Spaniels (CKCS). Selected clinical variables (MMVD severity, sex, age, hematocrit, platelet count in platelet-rich plasma [PRP], and echocardiographic left ventricular fractional shortening [LV FS]) will not show an association with results. ANIMALS: Fifty-two privately owned CKCS with no or preclinical MMVD. METHODS: Using blood samples, we prospectively assessed PDE5A genotype using Sanger sequencing and adenosine diphosphate-induced platelet aggregation response (area under the curve [AUC], maximal aggregation [MaxA], and velocity [Vel]) with and without pimobendan using light transmission aggregometry. Dogs also underwent echocardiography. RESULTS: Pimobendan inhibited platelet function as measured by AUC, MaxA, and Vel at a concentration of 10 µM (P < .0001) and Vel at 0.03 µM (P < .001). PDE5A:E90K polymorphism did not influence the inhibitory effect of pimobendan or basal platelet aggregation response. CONCLUSIONS AND CLINICAL IMPORTANCE: The PDE5A:E90K polymorphism did not influence in vitro basal platelet aggregation response or the inhibitory effect of pimobendan on platelet aggregation in CKCS. Dogs with the PDE5A:E90K polymorphism did not appear to have altered platelet function or response to pimobendan treatment.

Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human.

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis. METHODS: We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts. RESULTS: Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes. CONCLUSIONS: Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.

Mutations in the CYP27B1 gene cause vitamin D dependent rickets in pugs.

Rickets is a disorder of bone development and can be the result of either dietary or genetic causes. Here, related pugs from 2 litters were included. Three pugs had clinical signs including, lameness, bone deformities, and dyspnea. One other pug was found dead. Radiographs of 2 affected pugs, 5 and 6 months old, showed generalized widening, and irregular margination of the physes of both the appendicular and the axial skeleton with generalized decrease in bone opacity and bulbous swelling of the costochondral junctions. Two pugs had low serum calcium and 1,25 (OH)2 D3 concentrations. Test results further indicated secondary hyperparathyroidism with adequate concentrations of 25-hydroxyvitamin D. Necropsy revealed tongue-like projections of cartilage extending into the metaphysis consistent with rickets, loss of metaphyseal mineralization and lung pathology. Vitamin D-dependent rickets was diagnosed. A truncating mutation in the 1α-hydroxylase gene (CYP27B1) was identified by genome sequence analysis of the pugs with VDDR type 1A. Vitamin D-dependent rickets type 1A can occur in young pugs, and if left untreated is a life-threatening condition. Early medical intervention can reverse clinical signs and should be instituted as soon as possible.

Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy.

Pug dogs with thoracolumbar myelopathy (PDM) present with a specific clinical phenotype that includes progressive pelvic limb ataxia and paresis, commonly accompanied by incontinence. Vertebral column malformations and lesions, excessive scar tissue of the meninges, and central nervous system inflammation have been described. PDM has a late onset and affects more male than female dogs. The breed-specific presentation of the disorder suggests that genetic risk factors are involved in the disease development. To perform a genome-wide search for PDM-associated loci, we applied a Bayesian model adapted for mapping complex traits (BayesR) and a cross-population extended haplotype homozygosity test (XP-EHH) in 51 affected and 38 control pugs. Nineteen associated loci (harboring 67 genes in total, including 34 potential candidate genes) and three candidate regions under selection (with four genes within or next to the signal) were identified. The multiple candidate genes identified have implicated functions in bone homeostasis, fibrotic scar tissue, inflammatory responses, or the formation, regulation, and differentiation of cartilage, suggesting the potential relevance of these processes to the pathogenesis of PDM.

Evaluation of cardiac troponin I as a predictor of death in critically ill cats.

BACKGROUND: Abnormally high serum cardiac troponin I (cTnI) concentration, reflecting leakage from or necrosis of cardiomyocytes, is a negative prognosticator for death in dogs. OBJECTIVES: To investigate in critically ill cats whether serum cTnI concentration is abnormally high, identify conditions associated with abnormally high cTnI concentrations, and evaluate cTnI as an independent prognosticator for death and a potential coprognosticator to the acute patient physiologic and laboratory evaluation (APPLE) score in cats. ANIMALS: One hundred nineteen cats admitted to intensive care units (ICU) and 13 healthy cats at 2 university teaching hospitals. METHODS: Prospective study. Clinical examinations were performed, APPLE scores calculated, and serum cTnI and serum amyloid A (SAA) measured within 24 hours after admission. Outcome was defined as death/euthanasia or survival to discharge, 28 and 90 days after ICU-admission. Prognostic capacity of cTnI, APPLE scores and models combining cTnI and scores were evaluated by receiver-operator-characteristic analyses. RESULTS: Median (IQR) serum cTnI concentration was higher in ill (0.63 [0.18-2.65] ng/mL) compared to healthy (0.015 [0.005-0.041] ng/mL) cats (P < .001) and higher in subgroups with structural cardiac disease (2.05 [0.54-16.59] ng/mL; P < .001) or SAA >5 mg/L (0.84 [0.23-2.81] ng/mL; P = .009) than in cats without these characteristics (0.45 [0.12-1.70] and 0.35 [0.015-0.96] ng/mL). The in-hospital case fatality rate was 29%. Neither serum cTnI concentration for all critically ill cats (area-under-the-curve 0.567 [95% CI 0.454-0.680], n = 119) or subgroups (0.625 [0.387-0.863], n = 27; 0.506 [0.360-0.652], n = 86), nor APPLE scores (fast 0.568 [0.453-0.682], full 0.585 [0.470-0.699], n = 100), were significant prognosticators for death. CONCLUSIONS AND CLINICAL IMPORTANCE: Abnormally high serum cTnI concentration was common in critically ill cats. Unlike in dogs, cTnI did not confer prognostic information regarding death.

A Questionnaire Survey on Long-Term Outcomes in Cats Breed-Screened for Feline Cardiomyopathy.

Feline cardiomyopathy (FCM) is an important contributor to feline morbidity and mortality. This explorative follow-up questionnaire study was aimed at investigating the long-term outcome in cats breed-screened for FCM (BS-FCM) in three Nordic countries. Records of cats with ≥1 BS-FCM between 2004−2015 were included. Of the 1113 included cats, 104/1113 (9.3%) had developed FCM at some time-point. Fifty-nine of the 104 (56.7%) FCM cats were diagnosed within the screening program (ScreenFCM), and 33/59 (55.9%) of these were diagnosed at the first BS-FCM. ScreenFCM cats or with an owner-reported FCM diagnosis at a later time-point had a higher risk of cardiac-related death compared to cats that never developed FCM. A shorter lifespan was found in ScreenFCM cats compared to those with normal screen results (p < 0.001). Times to all-cause mortality were shorter (p < 0.001) in cats that developed FCM at any time-point compared to those that did not. Non-cardiac morbidities were similar in all screen classification groups. The large proportion of cats that developed FCM at a later time-point underscores the need for repeated screenings later in life. Cats that developed FCM at any time-point had a shorter lifespan, with a similar proportion and in line with the nature of non-cardiac morbidities, compared to those without FCM.

Cardiac troponin I in healthy Norwegian Forest Cat, Birman and domestic shorthair cats, and in cats with hypertrophic cardiomyopathy.

OBJECTIVES: The aims of this study were to assess the potential associations between the serum cardiac troponin I (cTnI) concentration in healthy cats and feline characteristics, systolic blood pressure, heart rate (HR), echocardiographic measurements and storage time; and to compare cTnI concentrations in healthy cats with concentrations in cats with hypertrophic cardiomyopathy (HCM), with or without left atrial enlargement (LAE) and in cats with HCM, to assess potential associations between cTnI concentration and echocardiographic variables. METHODS: Cardiac TnI was analysed using an Abbott ARCHITECT ci16200 analyser in serum from prospectively included healthy Norwegian Forest Cat (NF; n = 33), Birman (n = 33) and domestic shorthair (DSH; n = 30) cats, and from 39 cats with HCM, with or without LAE. RESULTS: In healthy cats, higher cTnI concentrations were found in Birman cats than in NF cats (P = 0.014) and in neutered male cats than in intact females (P = 0.032). Cardiac TnI was positively associated with HR (P <0.0001). In cats with HCM, cTnI concentration was positively associated with left ventricular wall thickness and with left atrial-to-aortic root ratio (all P ⩽0.010). Cats with HCM had higher cTnI concentrations than healthy cats, and cTnI concentrations were higher in cats with HCM and LAE than in those with HCM without LAE (all P = 0.0003). CONCLUSIONS AND RELEVANCE: Breed and sex may affect serum cTnI concentrations in healthy cats. The cTnI concentration increased with increasing severity of HCM.

Chronic Enteropathy in Dogs-Epidemiologic Aspects and Clinical Characteristics of Dogs Presenting at Two Swedish Animal Hospitals.

Information about prevalence and breed predisposition of canine chronic enteropathy (CE) is limited. The aim of this retrospective study was to investigate period prevalence, breed disposition, clinical features, diagnostic results, and treatment response of CE in dogs presenting at two Swedish animal hospitals during 2013−2018. A medical record search was performed to identify CE dogs including those with ≥3 visits because of gastrointestinal disease and/or that had undergone gastroduodenoscopy/colonoscopy during 2013−2018. Dog characteristics, case history, physical examination, laboratory variables, therapeutic protocol, and treatment response were recorded. Inclusion criteria for CE were met by 814 dogs. Period prevalence of CE was 1.1% of total number of dogs. Breeds with the highest relative risk included Norwegian Lundehund, West Highland White Terrier, and Miniature Poodle. Median age at presentation was 3.8 (IQR 1.8−6.8) years. French Bulldogs and Miniature Schnauzers presented at a younger age (<2.5 years) compared to other breeds (p < 0.05). In a subset of dogs, serum hypoalbuminemia (116/662, 17.5%), hypocobalaminemia (98/647, 15.1%), and increased C-reactive protein (CRP) concentrations (145/267, 54.3%) were diagnosed. Treatment outcome was classified in 72.9% of dogs and characterized as immunosuppressant-responsive (55.2%), food-responsive (11.4%), non-responsive (5.2%), and antibiotic-responsive (1.1%). Non-responsive dogs were more likely to present with anemia hypoproteinemia/albuminemia, increased CRP, and ascites (p < 0.05). In conclusion, the prevalence of dogs with CE at Swedish hospitals agreed with earlier reports, but risk breeds differed slightly and, compared to other breeds, a younger age of CE onset was found in two breeds. The largest proportion of dogs was immunosuppressant-responsive and the smallest antibiotic-responsive.

The TNNT2:c.95-108G>A variant is common in Maine Coons and shows no association with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common and potentially fatal heart disease in many cat breeds. An intronic variant in TNNT2, c.95-108G>A, was recently reported as the cause of HCM in the Maine Coon. The aim of this study was to determine this variant's allele frequency in different populations and its possible association with HCM. Based on 160 Maine Coon samples collected in Belgium, Italy, Sweden and the USA, the variant's allele frequency was estimated to be 0.32. Analysis of the 99 Lives feline whole genome sequencing database showed that the TNNT2 variant also occurs in other breeds, as well as mixed-breed cats. Comparison of 31 affected and 58 healthy cats did not reveal significantly increased odds for HCM in homozygotes. Based on the combined evidence and in agreement with the standards and guidelines for the interpretation of sequence variants, this variant is currently classified as a variant of unknown significance and should not be used for breeding decisions regarding HCM.

Correction: The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels.

[This corrects the article DOI: 10.1371/journal.pgen.1009726.].

The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels.

Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heart-derived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.

Evaluation of post-operative complications after mastectomy performed without perioperative antimicrobial prophylaxis in dogs.

BACKGROUND: Mastectomy is the most common procedure for treatment of mammary tumours. Dogs undergoing mastectomy have a risk of developing surgical site infections (SSI) and other postoperative complications. However, potential risk factors associated with such complications have been sparsely investigated. Thus, the objective of this retrospective study was to determine the incidence of, and identify risk factors for, SSI and non-SSI postoperative complications after mastectomy performed without perioperative antimicrobial prophylaxis in privately owned otherwise clinically healthy dogs. RESULTS: Medical records were reviewed retrospectively for 135 client-owned female dogs, 10-35 kg in weight and three to 10 years of age, which had undergone mastectomy due to mammary tumours at three referral animal hospitals in Sweden over a 3-year period. Twelve (8.9%) dogs developed SSI, and 21 dogs (17.1%) dogs suffered a non-SSI postoperative complication. The incidence of SSI and all complications (SSI and non-SSI) were higher in dogs that had two to three (SSI: P = 0.036 and all complications: P = 0.0039) and four to five (SSI and all complications: P = 0.038) mammary glands excised, compared to dogs that had one mammary gland excised. The incidence of SSI was 1.7% (n = 1/60) in dogs that had one gland removed. The incidence of non-SSI postoperative complications was higher in dogs with a higher body weight (P = 0.02). CONCLUSIONS: The incidence of SSI was lower than or similar to previously reported incidences of SSI in dog populations that have undergone tumour excisional surgery, despite the fact that dogs in the present study had not received perioperative antibiotics. Dogs that had two or more glands excised had an increased risk of developing SSI and non-SSI complications compared to dogs that had one gland excised. Furthermore, higher BW was associated with an increased risk of non-SSI complications. Results from the study indicate that routine use of perioperative antibiotics in tumour excisional surgery can be questioned, at least in single gland mastectomy in otherwise clinically healthy dogs.

Influence of clinical setting and cat characteristics on indirectly measured blood pressure and pulse rate in healthy Birman, Norwegian Forest, and Domestic Shorthair cats.

BACKGROUND: Measured indirect blood pressure (BP) results in cats in a clinical environment might be affected by stress and characteristics of the cats. HYPOTHESIS: To investigate the influence of clinical setting, cat characteristics, and life situation on BP and pulse rate (PR) in healthy cats. ANIMALS: Ninety-four healthy Domestic Shorthair, Birman and Norwegian Forest cats. METHODS: Blood pressure measured by high-definition oscillometry in 3 settings: cat placed in its own carrier with veterinarian present; cat placed in carrier with owner alone present; and cat placed on table with veterinarian present. Statistical analyses were performed using mixed linear models. RESULTS: Systolic BP (SBP) did not differ among settings. Higher mean arterial pressure (MAP), diastolic BP (DBP), and PR were found when measurements were performed with cat placed on table, rather than in carrier. Coefficients of variation (CVs) higher for SBP, MAP, DBP, and PR when measured with cat placed on table than in carrier. Birman cats had lower BP than other breeds. Systolic BP, MAP, DBP, and PR increased with age. Cats allowed outdoors had lower PR than cats living strictly indoors. CONCLUSION AND CLINICAL IMPORTANCE: No difference in SBP was found among settings, but measuring BP with the cat placed on the examination table gave higher MAP, DBP, PR, and CV than measuring BP with the cat in its carrier. Breed affected BP, with lower BP in Birman cats than other breeds. Blood pressure increased with age. Pulse rate was lower in cats allowed outdoors than cats living strictly indoors.

Facial conformation characteristics in Persian and Exotic Shorthair cats.

OBJECTIVES: The primary objectives of the study were to examine the diversity in facial conformation characteristics within a group of Persian (PER) and Exotic Shorthair (EXO) show cats, and to contrast the results to findings within a group of non-purebred domestic shorthair (DSH) and domestic longhair (DLH) cats. The secondary objectives were to determine the PER/EXO show cat owners' perceptions of the breathing status of their cats, and to evaluate if remarks from the cat show judges concerning the cats' head and facial conformation were exclusively related to the aesthetic features of the cats. METHODS: Sixty-four PER and 12 EXO show cats were prospectively examined at five international cat shows, and 20 DSH/DLH cats were examined at an animal hospital. Facial conformation characteristics were evaluated by examining photos of the cats. Owners of the PER/EXO show cats answered a questionnaire concerning their cats' health status, and they were encouraged to send in the judges' score sheets from the cat shows. RESULTS: The PER/EXO show cats had higher diversity in facial conformation characteristics than the DSH/DLH cats, and high incidences of hypoplasia of the nose leather (95%), the nose leather top positioned above the level of the lower eyelid (93%), moderate-to-severe stenotic nares (86%), epiphora (83%) and entropion (32%). Owners of 6/76 PER/EXO show cats stated that their cat had increased respiratory sounds and/or trouble breathing at least once a week. The cat show judges' written comments were exclusively related to aesthetic features of the cats' head and facial conformation details. CONCLUSIONS AND RELEVANCE: Hypoplasia of the nose leather, high position of the nose leather top, stenotic nares, epiphora and entropion were common findings in the PER/EXO show cats but not in the DSH/DLH cats. Few of the cat owners perceived that their cat had problems related to the airways.

Impact of equipment and handling on systolic blood pressure measurements in conscious dogs in an animal hospital environment.

BACKGROUND: Situational hypertension and differences between devices complicate interpretations of systolic blood pressure (SBP) measurements in dogs. HYPOTHESIS/OBJECTIVES: To evaluate if time point of in-clinic SBP measurement, type of oscillometric device, and operator affect SBP measurements in conscious dogs. ANIMALS: Sixty-seven privately owned dogs with or without chronic kidney disease, divided into 2 study samples (A and B). METHODS: Cross-sectional diagnostic study. In part A, SBP measurements in dogs were performed using 2 different devices (HDO and petMap) after acclimatization at 3 standardized time points during a clinical visit. In part B, SBP measurements (HDO) were performed in dogs by a trained final year veterinary student and by the owner alone, at the same occasion. RESULTS: For all dogs, there was no difference in mean SBP (mSBP) among the 3 time points for HDO (P = .12) or petMAP (P = .67). However, intraindividual mSBP differences of up to 60 mm Hg between time points were documented. Mean SBP obtained with petMAP was on average 14 (95% CI: 8-20) mm Hg higher than mSBP obtained with HDO, and this difference increased with increasing SBP. Mean SBP measurements obtained by the trained student were 7 (95% CI: 2-11) mm Hg higher than mSBP measurements obtained by the owner. CONCLUSIONS AND CLINICAL IMPORTANCE: According to the results of this study, time point of in-clinic SBP measurement in dogs is of minor importance, and instructing owners to perform measurements might reduce suspected situational hypertension. Differences in mSBP measured with HDO and petMAP underscore the need for validation of BP devices used clinically.

A novel canine reference genome resolves genomic architecture and uncovers transcript complexity.

We present GSD_1.0, a high-quality domestic dog reference genome with chromosome length scaffolds and contiguity increased 55-fold over CanFam3.1. Annotation with generated and existing long and short read RNA-seq, miRNA-seq and ATAC-seq, revealed that 32.1% of lifted over CanFam3.1 gaps harboured previously hidden functional elements, including promoters, genes and miRNAs in GSD_1.0. A catalogue of canine "dark" regions was made to facilitate mapping rescue. Alignment in these regions is difficult, but we demonstrate that they harbour trait-associated variation. Key genomic regions were completed, including the Dog Leucocyte Antigen (DLA), T Cell Receptor (TCR) and 366 COSMIC cancer genes. 10x linked-read sequencing of 27 dogs (19 breeds) uncovered 22.1 million SNPs, indels and larger structural variants. Subsequent intersection with protein coding genes showed that 1.4% of these could directly influence gene products, and so provide a source of normal or aberrant phenotypic modifications.

Deletion in the Bardet-Biedl Syndrome Gene TTC8 Results in a Syndromic Retinal Degeneration in Dogs.

In golden retriever dogs, a 1 bp deletion in the canine TTC8 gene has been shown to cause progressive retinal atrophy (PRA), the canine equivalent of retinitis pigmentosa. In humans, TTC8 is also implicated in Bardet-Biedl syndrome (BBS). To investigate if the affected dogs only exhibit a non-syndromic PRA or develop a syndromic ciliopathy similar to human BBS, we recruited 10 affected dogs to the study. The progression of PRA for two of the dogs was followed for 2 years, and a rigorous clinical characterization allowed a careful comparison with primary and secondary characteristics of human BBS. In addition to PRA, the dogs showed a spectrum of clinical and morphological signs similar to primary and secondary characteristics of human BBS patients, such as obesity, renal anomalies, sperm defects, and anosmia. We used Oxford Nanopore long-read cDNA sequencing to characterize retinal full-length TTC8 transcripts in affected and non-affected dogs, the results of which suggest that three isoforms are transcribed in the retina, and the 1 bp deletion is a loss-of-function mutation, resulting in a canine form of Bardet-Biedl syndrome with heterogeneous clinical signs.