GDCA Research: 


The GDCA has been a regular contributor to research that involves health and welfare issues that affect the Great Dane. The GDCA has a non-profit 501(c) charity, THE CHARITABLE TRUST, to which you can contribute towards health and welfare research, or you can send donations directly to the AKC-CHF, which has a DONOR ADVISED FUND through a partnership with the GDCA that contributes specifically to Great Dane related research.


The following is a historical list of GDCA supported research projects:

Hip Dysplasia
Active Grant No. 1836: Identifying the Genetic Cause of Canine Hip Dysplasia
George Brewer, MD; University of Michigan 
Sponsors: Alaskan Malamute Club of America, Great Dane Club of America, Orthopedic Foundation for Animals, Rottweiler Health Foundation, Samoyed Club of America Research and Education Foundation 
Abstract: Canine Hip Dysplasia is the number one genetic health problem in dogs, with a significant frequency in over 100 breeds. The mode of inheritance may be polygenic (due to more than one gene) which has discouraged some studies of the genetic cause. However, with the proper approach, a polygenic disease can also be solved, and a DNA test or tests can be offered to help get rid of the disease. We propose a comprehensive approach studying 12 breeds and 11 additional candidate genes (beyond 2 already ruled out). Using multiple breeds increases the chance a given candidate gene will score a "hit." When a hit occurs, we will develop a DNA test to detect affected and carriers. In those breeds where the candidate gene search fails, we will do a genome-wide scan to establish linkage, which may allow us to offer a linked marker test, but in the longer run, will lead to gene discovery through homologous mapping. In the end, we expect to have a DNA test for hip dysplasia in most breeds.

Cancer
Completed Grant No. 1626: Significance of Tumor Suppressor Genes in Canine Cancer 
Jaime Modiano, VMD, PhD
AMC Cancer Research Center 
Sponsors: American Boxer Charitable Foundation, Golden Retriever Club of America, Golden Retriever Foundation, Great Dane Club of America, Health Trust Fund Scottish Terrier Club of America, Medallion Rottweiler Club, Rottweiler Health Foundation 
Abstract: The research conducted in this study will provide the basis for future research that may, ultimately, lead to scientists being able to provide a better assessment of individuals' risks for cancer (or for cancer in progeny), as well as determine whether a given dog is a good candidate for a given therapy. This project has helped to broaden the understanding of why tumors happen, so that the abnormalities can be targeted and better therapies devised. Researchers developed and tested gene therapy for melanoma. In a clinical trial involving five dogs with facial or oral melanoma, they found that the gene therapy, in which tumors were injected with modified genes, was both free of adverse effects and effective. 

Autoimmune Hemolytic Anemia

Active Grant No. 1849: Determinants of Risk in Dogs with Immune Mediated Hemolytic Anemia 
Philip H. Kass, DVM, PhD; University of California, Davis 
Sponsor: Anonymous in Memory of Pippin, Great Dane Club of America 
Abstract: Autoimmune or immune-mediated hemolytic anemia (IMHA) is a potentially fatal disorder affecting humans, dogs, mice and occasionally other species. This condition results when an animal's immune system destroys the animal's own red blood cells, resulting in anemia. There are several causes or "triggering events" known to induce this condition in people including drug administration, vaccinations, certain cancers, infections, and transplants. There is speculation that the incidence of the syndrome is increasing in dogs, and there may be identifiable triggering events that account for the increase in cases. However, we do not know how many dogs currently get IMHA, whether these cases differ from cases in the past, or whether we can identify common triggering events if we look. The goals of this study are to: 1) define the characteristics of dogs recently affected (breed, age, gender) and see if these differ from cases over the last twenty years, 2) determine if vaccinations can act as triggering events for the development of IMHA in dogs, 3) determine the incidence in dogs in the Sacramento Valley region, and 4) follow cases for a one year period to find characteristics that can be used to predict the outcome of cases (death, survival, relapses). 

Cardiomyopathy

Completed Grant No. 1428: Inheritance Patterns and Molecular Genetic Analysis of Doberman Pinschers and Boxer Dogs with Familial Dilated Cardiomyopathy 
Kathryn Meurs, DVM, PhD; The Ohio State University 
Sponsors: American Boxer Charitable Foundation, Great Dane Club of America 
Abstract: This study found that ventricular arrhythmias in Boxers are inherited as an autosomal dominant trait. Researchers found that asymptomatic Boxers have frequent ventricular premature complexes (VPCs), a specific type of irregular heartbeat that is a common form of ventricular arrhythmia. They determined that a two- to three-minute electrocardiogram (ECG) is a poorly sensitive indicator of VPCs, and instead recommend the use of a 24-hour ambulatory ECG (Holter monitor), even on asymptomatic Boxers. In studying Doberman Pinschers, they ruled out some potential candidate genes for study by demonstrating that two specific proteins and a specific gene that are abnormal in some humans with dilated cardiomyopathy (DCM)-a primary heart muscle disorder that can cause the heart to beat erratically-are normal in Dobermans with DCM. Linkage analyses for both Boxers and Dobermans continue. 

Completed Grant No. 2009: Determination of the Clinical Phenotype and Inherited Nature of Dilated Cardiomyopathy in the Great Dane. Kathryn M. Meurs, DVM, PhD; The Ohio State University. Sponsor: Great Dane Club of America, Great Dane Health Foundation. 

Abstract: Dilated cardiomyopathy is one of the most common heart diseases observed in the dog. Many breeds of dogs have a high risk of developing this disease including Boxers, Doberman pinschers, Great Danes and Cocker Spaniels. Although many breeds of dogs suffer from dilated cardiomyopathy, the disease is unique in each breed with regards to clinical signs, response to treatment and long term prognosis. Unfortunately, in most cases the disease is severe and the dogs die suddenly or die from a progressive congestive heart failure. In most cases, the cause of the disease is unknown, although there is significant evidence that the disease is inherited in Boxers and Doberman Pinschers. Although the disease is reported in the Great Dane, there is very little information regarding the clinical nature of the disease. Furthermore, although Great Dane enthusiasts have suggested a possible familial cause, there is no scientific evidence for this. The objective of this study is to determine the unique clinical attributes of DCM in the Great Dane as well as to begin to evaluate for a familial nature.

Completed Grant No. 1252: Prospective Study of Morphometric, Genetic and Dietary Risk Factors for Bloat. Lawrence Glickman, VMD, PhD; Purdue University 
Sponsors: Akita Club of America, American Bloodhound Club, American Rottweiler Club, Collie Club of America Foundation, Irish Setter Club of America, Irish Wolfhound Club of America, Morris Animal Foundation, New-Pen-Del Newfoundland Club, Weimaraner Club of America, Great Dane Club of America. 

Abstract: In the largest prospective health study ever done involving companion animals, this project identified 1900 healthy dogs of 11 giant and large breeds and collected information from owners. The dogs were followed for five years to measure the incidence of bloat, evaluate the effectiveness of commonly used bloat-prevention practices and determine the relationship between diet and bloat. The researchers found that the risk of bloat increased with increasing age, having a first-degree relative with bloat and increasing chest/width ratio. The breed at the highest risk was the Great Dane. None of the practices usually advised by experts to prevent bloat, such as raising the food bowl and limiting the amount of exercise and water before or after eating, appeared effective. In fact one of these, raising the food bowl, was associated with a higher incidence of bloat. 

Vaccinosis

GDCA Grant for Support of Research Colony of Beagles
Larry Glickman, DVM; Purdue University 

Abstract: Evaluation of Antithyroglobulin Antibodies After Routine Vaccination in Pet and
Research Dogs. Scott-Moncrieff JC, Azcona-Olivera J, Glickman NW, Glickman LT, HogenEsch Published in J Am Vet Med Assoc. 2002 Aug 15;221(4):515-21. 

Objective: To determine whether routine vaccination induces antibodies against bovine thyroglobulin and autoantibodies against canine thyroglobulin in dogs.

Subjects: 20 healthy research Beagles and 16 healthy pet dogs.

Procedure: For the research Beagles, five dogs were vaccinated with a multivalent vaccine and a rabies vaccine, five dogs received only the multivalent vaccine, five dogs received only the rabies vaccine, and five dogs were unvaccinated controls. The multivalent vaccine was administered at 8, 10, 12, 16, 20, 26, and 52 weeks of age and every six months thereafter. The rabies vaccine was
administered at 16 and 52 weeks of age and then once per year. Blood was collected from all dogs at 8, 16, and 26 weeks of age and then four times yearly. Assays for antibodies directed against bovine and canine thyroglobulin were performed prior to and two weeks after each yearly vaccination. For the pet dogs, blood was collected prior to and two weeks after one vaccination. 

Results: In the research Beagles, there was a significant increase in anti-bovine thyroglobulin
antibodies in all vaccinated dogs, compared with control dogs. There was a significant increase in anti-canine thyroglobulin antibodies in the two groups of dogs that received the rabies vaccine but not in the group that received the multivalent vaccine alone. In the pet dogs, there was a significant increase in anti-canine thyroglobulin antibodies after vaccination but no significant change in anti-bovine thyroglobulin antibodies. 

Conclusions and Clinical Relevance: Recent vaccination may result in increased anti-canine thyroglobulin antibodies. Whether these antibodies have a deleterious effect on canine thyroid function is unknown.

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