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Concept: Retriever

642

Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the β-MSH and β-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.

Concepts: Genetics, Labrador Retriever, Dog, Dog breed, Retriever, Golden Retriever, Labradoodle, Guide dog

67

In contrast to European countries, the overwhelming majority of dogs in the U.S. are neutered (including spaying), usually done before one year of age. Given the importance of gonadal hormones in growth and development, this cultural contrast invites an analysis of the multiple organ systems that may be adversely affected by neutering. Using a single breed-specific dataset, the objective was to examine the variables of gender and age at the time of neutering versus leaving dogs gonadally intact, on all diseases occurring with sufficient frequency for statistical analyses. Given its popularity and vulnerability to various cancers and joint disorders, the Golden Retriever was chosen for this study. Veterinary hospital records of 759 client-owned, intact and neutered female and male dogs, 1-8 years old, were examined for diagnoses of hip dysplasia (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA), and mast cell tumor (MCT). Patients were classified as intact, or neutered early (<12 mo) or late (≥12 mo). Statistical analyses involved survival analyses and incidence rate comparisons. Outcomes at the 5 percent level of significance are reported. Of early-neutered males, 10 percent were diagnosed with HD, double the occurrence in intact males. There were no cases of CCL diagnosed in intact males or females, but in early-neutered males and females the occurrences were 5 percent and 8 percent, respectively. Almost 10 percent of early-neutered males were diagnosed with LSA, 3 times more than intact males. The percentage of HSA cases in late-neutered females (about 8 percent) was 4 times more than intact and early-neutered females. There were no cases of MCT in intact females, but the occurrence was nearly 6 percent in late-neutered females. The results have health implications for Golden Retriever companion and service dogs, and for oncologists using dogs as models of cancers that occur in humans.

Concepts: Cancer, Anterior cruciate ligament, Labrador Retriever, Dog, Dog breed, Neutering, Retriever, Golden Retriever

30

Our recent study on the effects of neutering (including spaying) in Golden Retrievers in markedly increasing the incidence of two joint disorders and three cancers prompted this study and a comparison of Golden and Labrador Retrievers. Veterinary hospital records were examined over a 13-year period for the effects of neutering during specified age ranges: before 6 mo., and during 6-11 mo., year 1 or years 2 through 8. The joint disorders examined were hip dysplasia, cranial cruciate ligament tear and elbow dysplasia. The cancers examined were lymphosarcoma, hemangiosarcoma, mast cell tumor, and mammary cancer. The results for the Golden Retriever were similar to the previous study, but there were notable differences between breeds. In Labrador Retrievers, where about 5 percent of gonadally intact males and females had one or more joint disorders, neutering at <6 mo. doubled the incidence of one or more joint disorders in both sexes. In male and female Golden Retrievers, with the same 5 percent rate of joint disorders in intact dogs, neutering at <6 mo. increased the incidence of a joint disorder to 4-5 times that of intact dogs. The incidence of one or more cancers in female Labrador Retrievers increased slightly above the 3 percent level of intact females with neutering. In contrast, in female Golden Retrievers, with the same 3 percent rate of one or more cancers in intact females, neutering at all periods through 8 years of age increased the rate of at least one of the cancers by 3-4 times. In male Golden and Labrador Retrievers neutering had relatively minor effects in increasing the occurrence of cancers. Comparisons of cancers in the two breeds suggest that the occurrence of cancers in female Golden Retrievers is a reflection of particular vulnerability to gonadal hormone removal.

Concepts: Male, Female, Sex, Labrador Retriever, Dog, Dog breed, Retriever, Golden Retriever

24

Two young Labrador retriever dogs with bradycardia-induced syncope resulting from atrial myopathy underwent permanent transvenous pacemaker implantation. Both dogs developed heart failure 3-5 years after pacemaker implantation. Both were managed medically for approximately 7 years after pacemaker implantation and, ultimately, were humanely euthanized due to refractory heart failure signs and quality of life concerns. Long-term management of dogs with atrial myopathy and secondary atrial standstill with pacemaker implantation and medical therapy for heart failure is feasible and prognosis may be better than previously reported or speculated.

Concepts: Medicine, Cardiology, Therapy, Labrador Retriever, Dog, Dog breed, Retriever, Golden Retriever

5

Limber tail is a condition that typically affects larger working breeds causing tail limpness and pain, resolving without veterinary intervention. It is poorly understood and the disease burden has not been well characterised. Data collected from owners of the Dogslife cohort of Labrador Retrievers have been used to describe incidents and a case-control study was undertaken to elucidate risk factors with 38 cases and 86 controls. The cumulative incidence of unexplained tail limpness was 9.7 per cent. Swimming is not a necessary precursor for limber tail, but it is a risk factor (OR=4.7) and working dogs were more susceptible than non-working dogs (OR=5.1). Higher latitudes were shown to be a risk factor for developing the condition and the case dogs were more related to each other than might be expected by chance. This suggests that dogs may have an underlying genetic predisposition to developing the condition. This study is the first, large-scale investigation of limber tail and the findings reveal an unexpectedly high illness burden. Anecdotally, accepted risk factors have been confirmed and the extent of their impact has been quantified. Identifying latitude and a potential underlying genetic predisposition suggests avenues for future work on this painful and distressing condition.

Concepts: Epidemiology, Labrador Retriever, Dog, Dog breed, Retriever

5

The Golden Retriever Lifetime Study (GRLS) is the first prospective longitudinal study attempted in veterinary medicine to identify the major dietary, genetic and environmental risk factors for cancer and other important diseases in dogs. The GRLS is an observational study that will follow a cohort of 3000 purebred Golden Retrievers throughout their lives via annual online questionnaires from the dog owner and annual physical examinations and collection of biological samples by the primary care veterinarian. The field of comparative medicine investigating naturally occurring disorders in pets is specifically relevant to the many diseases that have a genetic basis for disease in both animals and humans, including cancer, blindness, metabolic and behavioural disorders and some neurodegenerative disorders. The opportunity for the GRLS to provide high-quality data for translational comparative medical initiatives in several disease categories is great. In particular, the opportunity to develop a lifetime dataset of lifestyle and activity, environmental exposure and diet history combined with simultaneous annual biological sample sets and detailed health outcomes will provide disease incidence data for this cohort of geographically dispersed dogs and associations with a wide variety of potential risk factors. The GRLS will provide a lifetime historical context, repeated biological sample sets and outcomes necessary to interrogate complex associations between genes and environmental influences and cancer.

Concepts: Cohort study, Medicine, Longitudinal study, Epidemiology, Labrador Retriever, Dog breed, Retriever, Golden Retriever

4

BACKGROUND: Dogslife is the first large-scale internet-based longitudinal study of canine health. The study has been designed to examine how environmental and genetic factors influence the health and development of a birth cohort of UK-based pedigree Labrador Retrievers. RESULTS: In the first 12 months of the study 1,407 Kennel Club (KC) registered eligible dogs were recruited, at a mean age of 119 days of age (SD 69 days, range 3 days - 504 days). Recruitment rates varied depending upon the study team’s ability to contact owners. Where owners authorised the provision of contact details 8.4% of dogs were recruited compared to 1.3% where no direct contact was possible. The proportion of dogs recruited was higher for owners who transferred the registration of their puppy from the breeder to themselves with the KC, and for owners who were sent an e-mail or postcard requesting participation in the project. Compliance with monthly updates was highly variable. For the 280 dogs that were aged 400 days or more on the 30th June 2011, we estimated between 39% and 45% of owners were still actively involved in the project. Initial evaluation suggests that the cohort is representative of the general population of the KC registered Labrador Retrievers eligible to enrol with the project. Clinical signs of illnesses were reported in 44.3% of Labrador Retrievers registered with Dogslife (median age of first illness 138 days), although only 44.1% of these resulted in a veterinary presentation (median age 316 days). CONCLUSIONS: The web-based platform has enabled the recruitment of a representative population of KC registered Labrador Retrievers, providing the first large-scale longitudinal population-based study of dog health. The use of multiple different methods (e-mail, post and telephone) of contact with dog owners was essential to maximise recruitment and retention of the cohort.

Concepts: Cohort study, Sociology, Labrador Retriever, Dog, Dog breed, Retriever, Aging in dogs

2

Present mechanical devices are unable to achieve recanalisation in up to 20-40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever.

Concepts: Randomized controlled trial, Stroke, Device, Retriever

1

Situations that are emotional and arousing have an effect on cognitive performance. It is thought that beta adrenergic activation and the release of stress hormones enhance memory consolidation and lead to an increase in memorability of emotional events. This beneficial effect has been shown in humans, non-human primates and rodents. Techniques which could enhance memory for learning specific tasks would be highly valuable, especially in dogs, which are extensively trained to aid humans. A pseudo-randomized, counterbalanced, between subject study designs was utilised and 16 Labrador Retrievers ranging from 1 to 9years of age were trained in a 2-choice discrimination paradigm. After task acquisition, either a playful activity intervention (N=8) or a resting period (N=8) took place, lasting for 30min. A range of factors including age, sex, training experience and trials to criterion on each day was subjected to a multiple factor/covariate General Linear Model analysis. The results show that playful activity post-learning improved training performance evidenced by fewer trials needed to re-learn the task 24h after initial acquisition (playful activity group: mean number of trials 26, SD 6; resting group: mean number of trials 43, SD 19, effect size 1.2). Average heart rate, as a measure of arousal, during the intervention was significantly higher in the playful activity group (143beats/min, SD 16) versus the resting group (86beats/min, SD 19, P<0.001). Salivary cortisol did not significantly differ between groups during training, however a significant decrease (T: -4.1 P<0.01) was seen after the playful activity. To our knowledge this is the first evidence that posttraining activity may influence training performance in dogs.

Concepts: Human, Primate, Labrador Retriever, Dog, Dog breed, Canis, Retriever, Golden Retriever

1

The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional variants in ATP7A and ATP7B contributes to the biological understanding of protein function, with relevance for future development of therapy.

Concepts: DNA, Protein, Gene, Genetics, Mutation, Labrador Retriever, Wilson's disease, Retriever