Canine Research Foundation *DGR

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2018 Funded Projects

The CRF fundded the following research projects in 2018

 

(1) Towards eliminating canine hip-dysplasia: German Shepherd dogs as a modelDistribution of genetic mutations associated with degenerative myelopathy

(Professor Bill Ballard, University of New South Wales)

Canine hip dysplasia remains the most common heritable orthopedic condition in the dog world, This joint malformation (dysplasia) results in instability of the hip which ultimately causes damage to the articular cartilage and inflammation of the synovial membrane in the hip. Secondary osteoarthritis precipitates the clinical signs of lameness. The disease affects dogs of all breeds with different prevalence. Breed occurrence, as estimated by the Orthopedic Foundation for Animals (OFA), varies widely from 1 % to 75 %. A genetic model that can predict hip dysplasia has now been developed. This model could be our answer to minimising and possibly ridding the dog world of this albatross that is constantly thrown around our neck by the media and general public. However, it needs extensive testing.

We plan for three applications over a three-year period.

• In the first year of the project, our goal is to take 500 samples from German Shepherd dogs that have been radiographed and then see if we can confidently predict OFA results from their DNA.

• In the second year, we plan to extend the project to include 250 Labradors and 250 Golden Retrievers to see if we can confidently predict OFA results from their DNA.

• In the third year, we plan to develop breeding plans for these three breeds. This proposal will likely include less consumable costs but will include travel,

These three independent proposals will culminate in the first ever scientifically based breeding program to improve hip-scores in three common breeds. It will prevent the "throwing the baby out with the bathwater" mentality that has plagued many other DNA testing programs.

 

(2) Assessing the canine uterine microbiome

(Dr Natali Krekeler, The University of Melbourne)

Pyometra is one of the most common, life-threatening reproductive diseases in female intact dogs. The disease process is only incompletely understood. In recent years it has become obvious that bacteria can persist for a prolonged period of time in the bitch's uterus before causing an infection. We have shown last year that Escherichia coli (E. coli) bacteria from bitches affected by pyometra have the potential to form biofilm, enabling them to persist while evading the host's immune response. These bacteria are extremely difficult to diagnose because they often cannot be cultured with conventional methods.  We hypothesize that the uterus of bitches is not a sterile environment, but rather that bacteria often persist but cannot be readily detected. The aim of the present study is to characterize the "microbiome" (the combined genetic material of all present microorganisms) in the canine uterus with gene sequencing technologies. We propose to analyse samples from 10 young (s 4 years) and 10 old (£ 6 years) healthy bitches. They will be further split into two groups (n=5) with and without the uterine abnormalities commonly seen in pyometra. A second aim is to correlate the microbiomes with histological samples from these uteri. The results are aimed to lead to a better understanding of the disease process, which is a very important step in the development of new prevention strategies for canine pyometra and therefore, improved canine health.

(3) The effect of diet on the host and microbiome metabolome

(Assoc Professor Caroline Mansfield, The University of Melbourne)

The gut harbours millions of bacterial organisms, with the genetic potential o( those organisms called the  microbiome, which have an important role in health and disease. In particular, the impact of the gastrointestinal (Gl) microbiome on the metabolic function of the host is immense. In people, the Gl microbiome has been implicated in many metabolic diseases, including diabetes, obesity, depression and auto-immune disorders. To date, there are few studies looking at the metabolic impact of the microbiome in dogs. New analytical methods are now available to determine the metabolic output of the microbes present in the Gl tract, along with assessing the hosts' metabolic status. In this study, we will evaluate the effect of diet change on the metabolome of healthy dogs and their microbiome. By establishing this, we can then extrapolate and develop further studies where specific manipulation of the Gl microbiome can be initiated to combat specific metabolic conditions.

 

(4) Genetic studies of canine glaucoma

(Professor Paul Baird, The University of Melbourne)

Glaucoma is an eye condition that, if left untreated, can result in irreversible blindness. Glaucoma is one of the most common causes of irreversible blindness in purebred dogs. There is little understanding at present as to how glaucoma develops in dogs. If we can understand how genetics influences the disease, we can make a strong impact on how it is treated and managed in the future. Our aim is to undertake genetic studies in glaucoma affected canines to identify novel disease genes associated with canine glaucoma. We have already collected 150 samples from dogs (with and without glaucoma) and now we wish to use a "bead chip" to look at over 170,000

genetic variations scattered across all chromosomes in these samples. A total of 48 dogs across several breeds will be assessed to establish if the same or different glaucoma genes are present in each breed. Using statistical analysis we will be able to identify genetic variations that are only found in those dogs with glaucoma compared to those without glaucoma. As a result, new disease genes will be identified whereby we can improve the management and breeding practices in purebred dogs. Identification of novel genes through this research may also have profound implications in the study of human glaucoma as humans also develop glaucoma and a discovery from our research may help identify a new gene pathway of interest for further exploration in human subjects with glaucoma.

 

(5) Canine lymphoma management by DNA analysis

(Professor Peter Williamson, The University of Sydney)

Many canine cancers have a significant association with genetic background and are more prevalent in certain breeds. This project develops a strategy to manage lymphoma, a relatively common cancer in dogs, using DNA analysis. There are two aims, the first is to evaluate a DNA test developed to inform breeding decisions in Bullmastiff dogs. The second aim capitalises on our experience in working with lymphoma in Bullmastiffs, and investigates the genetics of lymphoma in Border Collies. The expected outcome for the second aim is a DNA test, similar to that developed in the previous aim, that can be used by Border Collie breeders when deciding

mating partners. Overall the goal is to manage cancer in dogs to minimise disease by preventative measures.

(6) Genetics of mitral valve disease in Cavalier King Charles Spaniels

(Assoc Professor Niek Beijerink, The University of Sydney)

Background/Slgnlflcance: Myxomatous mitral valve disease (MMVD) is the most common acquired cardiorespiratory disease In small and medium sized dogs. It is also the most frequent cause of heart failure and heart disease related death. Severity of MMVD is highly variable with some dogs rapidly progressing Into cardlomegaly and CHF, whilst others remain relatively asymptomatic throughout their lives. A progressive nature of MMVD Is clinically recognized, however the underlying pathophysiological reasons are currently undefined or poorly understood. This represents a significant knowledge gap In disease pathogenesis. Heredity Is suspected to play a major role in MMVD transmission. The natural history of this disease suggests prevalence, severity and mortality rates are higher in aged dogs, but there are many cases of severe early onset In certain breeds. The Cavalier King Charles Spaniel (CKCS) is utmost affected dog with prevalence approaching 100% by the age of 11.

Aims: By focusing on MMVD in one dog breed (CKCS), we aim to 1) perform a genome-wlde association to identify candidate genes associated with the disease phenotypes; 2) perform comparative sequencing of positional candidate genes to identify potential causative mutations; 3) evaluate candidate mutations

In an enlarged sample set including a variety of dog breeds.  Expected outcomes: Significance and expected outcomes: The proposed study is of particular importance for canine health. This project has a realistic chance of revealing underlying mutations causing mitral valve disease in CKCS. Genetic tests to screen for risk of developing CHF could be made, giving dog breeders and vets the ultimate tools to make MVD a relative benign/asymptomatic disease in for future generations of dogs. Novel therapies for those dogs that would still suffer from CHF could be developed, possibly reversing this disease.