The epidemiology of upper respiratory tract disorders in a population of insured Swedish dogs (2011-2014), and its association to brachycephaly.

Upper respiratory tract (URT) disorders are common in dogs but neither general nor breed-related epidemiological data are widely reported. This study´s aims were to describe the epidemiology of URT disorders in a Swedish population of dogs and to investigate whether brachycephalic breeds were overrepresented among high-risk breeds. A cohort of dogs insured by Agria Djurförsäkring in Sweden (2011-2014) was used to calculate overall and breed-specific incidence rate (IR), age at first URT diagnosis and relative risk (RR) for URT disorders. For breeds with high RR for URT disorders, co-morbidities throughout the dog's insurance period and age at death were investigated. The cohort included approximately 450,000 dogs. URT disorders had an overall IR of 50.56 (95% CI; 49.14-52.01) per 10,000 dog years at risk. Among 327 breeds, the English bulldog, Japanese chin, Pomeranian, Norwich terrier and pug had highest RR of URT disorders. Eight of 13 breeds with high RR for URT disorders were brachycephalic. The median age at first URT diagnosis was 6.00 years (interquartile range 2.59-9.78). French bulldogs with URT diagnoses had a significantly shorter life span (median = 3.61 years) than other breeds with URT diagnosis (median = 7.81 years). Dogs with high risk for URT disorders had more co-morbidities than average.

Exploration of body weight in 115 000 young adult dogs of 72 breeds.

High body weight (BW), due to large size or excess body fat, has been associated with developmental and metabolic alterations, and degenerative diseases in dogs. Study objectives were to determine mean BW in young adult dogs of different breeds, including changes over a 10-year period. Body weight data from the official Swedish hip dysplasia screening program were used, including data from dogs screened at 1-2.5 years of age, in breeds with ≥ 15 individual observations/year during 2007-2016. Mean BW per breed and sex was established from 114 568 dogs representing 72 breeds. Estimates of breed BW showed significant change in 33 (45%) breeds over the 10-year period. Body weight increased in five breeds (2-14% change) and decreased in 26 breeds (1-8% change). In two breeds, BW increased in male and decreased in female dogs. This observational study provides extensive breed BW data on young adult dogs. The change in breed BW, noted in almost half of the breeds, could be due to changes either in size or in body fat mass. In certain breeds, the change in BW over time might have an impact on overall health. Studies with simultaneous evaluation of BW and body condition over time are warranted.

Transcriptomes from German shepherd dogs reveal differences in immune activity between atopic dermatitis affected and control skin.

Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease with both genetic and environmental risk factors described. We performed mRNA sequencing of non-lesional axillary skin biopsies from nine German shepherd dogs. Obtained RNA sequences were mapped to the dog genome (CanFam3.1) and a high-quality skin transcriptome was generated with 23,510 expressed gene transcripts. Differentially expressed genes (DEGs) were defined by comparing three controls to five treated CAD cases. Using a leave-one-out analysis, we identified seven DEGs: five known to encode proteins with functions related to an activated immune system (CD209, CLEC4G, LOC102156842 (lipopolysaccharide-binding protein-like), LOC480601 (regakine-1-like), LOC479668 (haptoglobin-like)), one (OBP) encoding an odorant-binding protein potentially connected to rhinitis, and the last (LOC607095) encoding a novel long non-coding RNA. Furthermore, high mRNA expression of inflammatory genes was found in axillary skin from an untreated mild CAD case compared with healthy skin. In conclusion, we define genes with different expression patterns in CAD case skin helping us understand post-treatment atopic skin. Further studies in larger sample sets are warranted to confirm and to transfer these results into clinical practice.

Absolute quantification reveals the stable transmission of a high copy number variant linked to autoinflammatory disease.

BACKGROUND: Dissecting the role copy number variants (CNVs) play in disease pathogenesis is directly reliant on accurate methods for quantification. The Shar-Pei dog breed is predisposed to a complex autoinflammatory disease with numerous clinical manifestations. One such sign, recurrent fever, was previously shown to be significantly associated with a novel, but unstable CNV (CNV_16.1). Droplet digital PCR (ddPCR) offers a new mechanism for CNV detection via absolute quantification with the promise of added precision and reliability. The aim of this study was to evaluate ddPCR in relation to quantitative PCR (qPCR) and to assess the suitability of the favoured method as a genetic test for Shar-Pei Autoinflammatory Disease (SPAID). RESULTS: One hundred and ninety-six individuals were assayed using both PCR methods at two CNV positions (CNV_14.3 and CNV_16.1). The digital method revealed a striking result. The CNVs did not follow a continuum of alleles as previously reported, rather the alleles were stable and pedigree analysis showed they adhered to Mendelian segregation. Subsequent analysis of ddPCR case/control data confirmed that both CNVs remained significantly associated with the subphenotype of fever, but also to the encompassing SPAID complex (p < 0.001). In addition, harbouring CNV_16.1 allele five (CNV_16.1|5) resulted in a four-fold increase in the odds for SPAID (p < 0.001). The inclusion of a genetic marker for CNV_16.1 in a genome-wide association test revealed that this variant explained 9.7 % of genetic variance and 25.8 % of the additive genetic heritability of this autoinflammatory disease. CONCLUSIONS: This data shows the utility of the ddPCR method to resolve cryptic copy number inheritance patterns and so open avenues of genetic testing. In its current form, the ddPCR test presented here could be used in canine breeding to reduce the number of homozygote CNV_16.1|5 individuals and thereby to reduce the prevalence of disease in this breed.

Naturally Occurring Adrenocortical Insufficiency--An Epidemiological Study Based on a Swedish-Insured Dog Population of 525,028 Dogs.

BACKGROUND: Naturally occurring adrenocortical insufficiency (NOAI) in dogs is considered an uncommon disease with good prognosis with hormonal replacement treatment. However, there are no epidemiological studies with estimates for the general dog population. OBJECTIVES: To investigate the epidemiological characteristics of NOAI in a large population of insured dogs. ANIMALS: Data were derived from 525,028 client-owned dogs insured by a Swedish insurance company representing 2,364,652 dog-years at risk (DYAR) during the period between 1995-2006. METHODS: Retrospective cohort study. Incidence rates, prevalences, and relative risks for dogs with NOAI (AI with no previous claim for hypercortisolism), were calculated for the whole dog population, and for subgroups divided by breed and sex. Mortality rates were calculated and compared in dogs with NOAI and the remaining dogs overall. RESULTS: In total 534 dogs were identified with NOAI. The overall incidence was 2.3 cases per 10,000 DYAR. The relative risk of disease was significantly higher in the Portuguese Water Dog, Standard Poodle, Bearded Collie, Cairn Terrier, and Cocker Spaniel compared with other breeds combined. Female dogs overall were at higher risk of developing AI than male dogs (RR 1.85; 95% CI, 1.55-2.22; P < .001). The relative risk of death was 1.9 times higher in dogs with NOAI than in dogs overall. CONCLUSION AND CLINICAL IMPORTANCE: The data supports the existence of breed-specific differences in incidence rates of NOAI in dogs.

Disease patterns in 32,486 insured German shepherd dogs in Sweden: 1995-2006.

The aims of this retrospective study were to describe the morbidity and mortality in German shepherd dogs (GSD) in Sweden, based on insurance data, and to test the hypothesis that GSDs are predisposed to immune-related diseases. Morbidity was defined as incidence rates and based on veterinary care events. Mortality was defined as mortality rates and based on life insurance data. The study included 445,336 dogs, 7.3 per cent GSDs, covered by both veterinary care and life insurance between 1995 and 2006 in the Swedish insurance company Agria (Agria Insurance Company, Stockholm, Sweden). For veterinary care events (morbidity) GSDs were most over-represented for immunological disease, with a relative risk (RR) of 2.7, compared with the risk in all other breeds combined. The most common disease category (morbidity) in GSDs was skin disorders with an incidence rate of 346.8 cases per 10,000 dog years at risk. The highest RR for cause of death in GSDs compared with all other breeds was for skin conditions (RR=7.8). Locomotor disorders were the most common cause of death in GSDs. The GSD is predisposed to immune-related disorders, such as allergies, circumanal fistulae and exocrine pancreatic atrophy, with significantly increased risk compared with all other breeds.

Lifestyle risk factors for progesterone-related diabetes mellitus in elkhounds - a case-control study.

OBJECTIVES: This study aims to investigate lifestyle risk factors for the development of progesterone-related diabetes mellitus in female elkhounds. METHODS: Owners of 48 diabetic elkhounds and 58 healthy elkhounds were interviewed by phone concerning lifetime diet and exercise routines. A logistic model was developed to assess the impact of diet and exercise on diabetes diagnosis. The agreement between lifetime owner-perceived body condition score (BCS) and veterinary-perceived BCS at inclusion was estimated in healthy control dogs using the Kappa statistic. RESULTS: The model showed that diabetic dogs had increased odds for having been overweight (before diagnosis) compared with controls (OR=2·8, 95% confidence interval 1·1-7·5, P=0·034). Although feeding other food than commercial dog feed was associated with diabetes case status, the effect was not significant after BCS was entered into the model. The overall agreement between lifetime owner- and veterinary-perceived BCS at inclusion in the study was 75% and had a Kappa statistic of 0·16 (P=0·12). CLINICAL SIGNIFICANCE: This study indicates that a high owner-perceived lifetime BCS is associated with progesterone-related diabetes in elkhounds.

Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia.

The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60-100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480-3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage.

Diabetes mellitus in elkhounds is associated with diestrus and pregnancy.

BACKGROUND: Female Elkhounds are shown to be at increased risk for diabetes mellitus, and occurrence of diabetes during pregnancy has been described in several cases. HYPOTHESIS: Onset of diabetes mellitus in Elkhounds is associated with diestrus. ANIMALS: Sixty-three Elkhounds with diabetes mellitus and 26 healthy controls. METHODS: Medical records from 63 Elkhounds with diabetes were reviewed and owners were contacted for follow-up information. Blood samples from the day of diagnosis were available for 26 dogs. Glucose, fructosamine, C-peptide, growth hormone (GH), insulin-like growth factor-1, progesterone, and glutamate decarboxylase isoform 65-autoantibodies were analyzed and compared with 26 healthy dogs. Logistic models were used to evaluate the association of clinical variables with the probability of diabetes and with permanent diabetes mellitus after ovariohysterectomy (OHE). RESULTS: All dogs in the study were intact females and 7 dogs (11%) were pregnant at diagnosis. The 1st clinical signs of diabetes mellitus occurred at a median of 30 days (interquartile range [IQR], 3-45) after estrus, and diagnosis was made at a median of 46 days (IQR, 27-62) after estrus. Diabetes was associated with higher concentrations of GH and lower concentrations of progesterone compared with controls matched for time after estrus. Forty-six percent of dogs that underwent OHE recovered from diabetes with a lower probability of remission in dogs with higher glucose concentrations (odds ratio [OR], 1.2; P=.03) at diagnosis and longer time (weeks) from diagnosis to surgery (OR, 1.5; P=.05). CONCLUSIONS: Diabetes mellitus in Elkhounds develops mainly during diestrus and pregnancy. Immediate OHE improves the prognosis for remission of diabetes.

Increased genetic risk or protection for canine autoimmune lymphocytic thyroiditis in Giant Schnauzers depends on DLA class II genotype.

Dogs represent an excellent comparative model for autoimmune thyroiditis as several dog breeds develop canine lymphocytic thyroiditis (CLT), which is clinically similar to Hashimoto's thyroiditis in human. We obtained evidence that dog leukocyte antigen (DLA) class II genotype function as either genetic risk factor that predisposes for CLT or as protective factor against the disease. Genetic diversity at their DLA-DRB1, -DQA1, and -DQB1 loci were defined and potential association to major histocompatibility complex II haplotypes and alleles was analyzed. Giant Schnauzers carrying the DLA-DRB1*01201/DQA1*00101/DQB1*00201 haplotype showed an increased risk (odds ratio of 6.5) for developing CLT. The same risk haplotype has, to date, been observed in three different breeds affected by this disease, Giant Schnauzer, Dobermann, and Labrador Retriever, indicating that it is a common genetic risk factor in a variety of breeds affected by this disease. Importantly, protection for development of the disease was found in dogs carrying the DLA-DRB1*01301/DQA1*00301/DQB1*00501 haplotype (odds ratio of 0.3).

Cerebrospinal fluid PCR and antibody concentrations against Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in dogs with neurological signs.

BACKGROUND: The tick-borne bacteria Borrelia burgdorferi sensu lato (sl) and Anaplasma phagocytophilum have been suspected to cause neurological signs in dogs. Diagnosis often has been made based on positive antibody titers in serum of dogs with neurological signs, but a high seroprevalence in dogs in at-risk populations makes diagnosis difficult. OBJECTIVE: To determine if the neurological signs in dogs examined were caused by any of these bacteria. ANIMALS: Fifty-four dogs presented to a board-certified neurologist. METHODS: Prospective study. We divided dogs into 2 groups: those with inflammatory diseases of the central nervous system (CNS) and those with neurological signs from other diseases. Blood and cerebrospinal fluid (CSF) from all dogs were analyzed. RESULTS: Dogs with inflammatory CNS diseases showed no serum antibodies against any of the agents. Among dogs with neurological signs from other diseases, 10.3% had serum antibodies for B. burgdorferi sl and 20.5% for A. phagocytophilum. All blood samples analyzed for bacterial deoxyribonucleic acid (DNA) and all CSF analyzed for antibodies and bacterial DNA for the 2 agents were negative. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on this study, these bacteria are unlikely causes of neurologic disease in dogs and the presence of serum antibodies alone does not document or establish a definitive diagnosis of CNS disease caused by these organisms. Dogs that have neurologic disease and corresponding serum antibodies against these agents should have additional tests performed to assess for other potential etiologies of the signs.

Prevalence of diagnostic characteristics indicating canine autoimmune lymphocytic thyroiditis in giant schnauzer and hovawart dogs.

OBJECTIVES: To investigate prevalence of autoantibodies to thyroglobulin (TgAA) and/or elevated levels of thyroid stimulating hormone (TSH), indicating canine autoimmune lymphocytic thyroiditis (CLT) and/or hypothyroidism, in two high-risk dog breeds. METHODS: A cohort study was conducted in two birth cohorts of giant schnauzer and hovawart dogs. The cohorts were three to four and six to seven years of age at the time of blood sampling and screening for TgAA and TSH levels. Blood sampling was accompanied by one initial and one follow-up questionnaire to the dog owners. A total number of 236 giant schnauzers and 95 hovawarts were included in the study. RESULTS: Seventeen (7.2 per cent) giant schnauzers and three (3.2 per cent) hovawarts had been diagnosed as hypothyroid at the time of sampling. Out of the remaining dogs, 22 giant schnauzers (10.0 per cent) and nine hovawarts (10.1 per cent) had elevated TgAA and/or TSH levels. Prevalence of elevated TgAA and TSH levels varied with age. CLINICAL SIGNIFICANCE: The high prevalence of diagnostic characteristics indicating CLT/hypothyroidism in these two breeds suggests a strong genetic predisposition. It would be advisable to screen potential breeding stock for TSH and TgAA as a basis for genetic health programmes to reduce prevalence of CLT in these breeds.

Gestational diabetes mellitus in 13 dogs.

BACKGROUND: There are few reports on the clinical appearance, prognosis, and risk factors for gestational diabetes mellitus (GDM) in dogs. OBJECTIVE: To describe the clinical characteristics of GDM in dogs. ANIMALS: Thirteen dogs with GDM. METHODS: Retrospective study. Medical records were reviewed and owners and referring veterinarians were contacted for follow-up information. RESULTS: Nordic Spitz breeds (11/13 dogs) were overrepresented in the case material. Diagnosis was established at a median of 50 days after mating (range, 32-64). Median glucose concentration at diagnosis was 340 mg/dL (18.9 mmol/L) (range, 203-587). One dog was euthanized at diagnosis, 5 bitches were treated with insulin until whelping, and in 7 dogs, pregnancy was terminated within 4 days of diagnosis. One dog died after surgery. Tight glycemic control was not achieved in any of the insulin-treated dogs during pregnancy. Diabetes mellitus (DM) resolved in 7 dogs at a median of 9 days after the end of their pregnancies and DM was permanent in 4 dogs. Puppy mortality was increased compared with offspring of healthy dams. CONCLUSION: This report suggests that GDM affects mainly middle-aged bitches in the 2nd half of pregnancy with a breed predisposition toward Nordic Spitz breeds. GDM may resolve within days to weeks after pregnancy has ended. Further research is needed to investigate optimal treatment regimens for dogs with GDM and risk factors for unsuccessful outcome.

Seroprevalence of Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum in dogs with neurological signs.

A retrospective cohort study was carried out to evaluate whether seropositivity for the tick-transmitted bacterial species Borrelia burgdorferi sensu lato and/or Anaplasma phagocytophilum was associated with one or more specific categories of nervous system disorders in dogs. A total of 248 dogs with nervous system disorders were serotested for these agents and categorised into six main diagnostic categories: degenerative diseases of the spine, epilepsy, inflammatory diseases, neoplasia, peripheral neuropathies, and other diseases. Multivariable analysis using logistic regression was used to model whether a dog was diagnosed as being in any of these categories. The independent variables included were sex, age, year of serological testing, and whether the animal tested positive for B burgdorferi sensu lato and/or A phagocytophilum. In one model, a statistically significant association was found between a positive titre for A phagocytophilum and the risk of a dog developing neoplastic disease. Although statistically significant, it was concluded that the association was not of clinical relevance.

A neurologic syndrome in Golden Retrievers presenting as a sensory ataxic neuropathy.

BACKGROUND: A sensory ataxic neuropathy has been observed in Swedish Golden Retrievers recently. ANIMALS: Twenty-one affected Golden Retrievers. METHODS: Clinical and neurologic status, electrophysiologic, and pathologic status as well as pedigree analyses were evaluated. RESULTS: Clinical signs had an insidious onset between 2 and 8 months of age and a slowly progressive course. Affected dogs were ataxic and dysmetric. They had abnormal postural reactions and decreased spinal reflexes but no apparent muscle atrophy. Clinical pathology, radiography, and electrophysiology of motor systems were all within reference values. Sensory nerve conduction results of affected dogs were significantly different from those of a group of control dogs. Necropsy revealed a chronic progressive central and peripheral sensorimotor axonopathy; the proprioceptive pathways were most severely affected. CONCLUSIONS AND CLINICAL IMPORTANCE: This disease in these Golden Retrievers is distinct from other canine breed-related neurodegenerative diseases or hereditary neurodegenerative diseases described in humans. Pedigree analyses indicated a hereditary background, but the mode of inheritance could not be established.

Incidence of and risk factors for atopic dermatitis in a Swedish population of insured dogs.

The incidence of atopic dermatitis was estimated to be 1.7 cases per 1000 dog-years at risk in a population of insured Swedish dogs whose insurance claims for the period 1995 to 2002 were examined. Several factors were found to increase the risk of having a recorded claim, including living in a city or in central or southern Sweden, being born in the autumn, and belonging to a high-risk breed. Bull terriers had the highest risk, with 21 cases per 1000 dog-years at risk, and several other breeds including boxers and West Highland white terriers also had an above average risk. There was no difference in the incidence between the sexes. There was a slight increase in the incidence during the period. In a subset of the data that consisted only of dogs from 15 high-risk breeds, the overall survival appeared to be lower for the dogs that had had an insurance claim for the disease.

Unequal contribution of sexes in the origin of dog breeds.

Dogs (Canis familiaris) were domesticated from the gray wolf (Canis lupus) at least 14,000 years ago, and there is evidence of dogs with phenotypes similar to those in modern breeds 4000 years ago. However, recent genetic analyses have suggested that modern dog breeds have a much more recent origin, probably <200 years ago. To study the origin of contemporaneous breeds we combined the analysis of paternally inherited Y chromosome markers with maternally inherited mitochondrial DNA and biparentally inherited autosomal microsatellite markers in both domestic dogs and their wild ancestor, the gray wolf. Our results show a sex bias in the origin of breeds, with fewer males than females contributing genetically, which clearly differs from the breeding patterns in wild gray wolf populations where both sexes have similar contributions. Furthermore, a comparison of mitochondrial DNA and Y chromosome diversity in dog groups recognized by the World Canine Organization, as well as in groups defined by the breeds' genetic composition, shows that paternal lineages are more differentiated among groups than maternal lineages. This demonstrates a lower exchange of males than of females between breeds belonging to different groups, which illustrates how breed founders may have been chosen.

Mortality in over 350,000 insured Swedish dogs from 1995-2000: I. Breed-, gender-, age- and cause-specific rates.

This study presents data on over 350,000 insured Swedish dogs up to 10 years of age contributing to over one million dog-years at risk (DYAR) during 1995-2000. A total of 43,172 dogs died or were euthanised and of these 72% had a claim with a diagnosis for the cause of death. The overall total mortality was 393 deaths per 10,000 DYAR. Mortality rates are calculated for the 10 most common breeds, 10 breeds with high mortality and a group including all other breeds, crudely and for general causes of death. Proportional mortality is presented for several classifications. Five general causes accounted for 62% of the deaths with a diagnosis (i.e. tumour (18%), trauma (17%), locomotor (13%), heart (8%) and neurological (6%)). Mortality rates for the five most common diagnoses within the general causes of death are presented. These detailed statistics on mortality can be used in breed-specific strategies as well as for general health promotion programs. Further details on survival and relative risk by breed and age are presented in the companion paper (Egenvall et al. 2005).

Mortality in over 350,000 insured Swedish dogs from 1995-2000: II. Breed-specific age and survival patterns and relative risk for causes of death.

This study continues analysis from a companion paper on over 350,000 insured Swedish dogs up to 10 years of age contributing to more than one million dog-years at risk during 1995-2000. The age patterns for total and diagnostic mortality and for general causes of death (trauma, tumour, locomotor, heart and neurological) are presented for numerous breeds. Survival estimates at five, eight and 10 years of age are calculated. Survival to 10 years of age was 75% or more in Labrador and golden retrievers, miniature and toy poodles and miniature dachshunds and lowest in Irish wolfhounds (91% dead by 10 years). Multivariable analysis was used to estimate the relative risk for general and more specific causes of death between breeds accounting for gender and age effects, including two-way interactions. Older females had tumour as a designated cause of death more often than males in most breeds, but not in the Bernese mountain dog. Information presented in this and the companion paper inform our understanding of the population level burden of disease, and support decision-making at the population and individual level about health promotion efforts and treatment and prognosis of disease events.