Genetics

Our breeds is listed with the Cysturnina and Pyrometra study. It looks like several other breeds have a few good studies also. The French Bulldog club seems very proactive on their grants. The first study listed could also benefit bulldogs.

North Carolina State University (University)
Completed Grant No: 2234:
Basophil/Mast Cell Response to Lectins as a Predictor for Risk of Allergic Disease in Genetically Susceptible Dogs
Disease(s):
Allergies
Sponsor(s):
American Belgian Tervuren Club, Inc., American Miniature Schnauzer Club, Inc., American Sealyham Terrier Club, Bedlington Terrier Club of America, Bichon Frise Club of America, Inc., Bull Terrier Welfare Foundation, Chow Chow Club, Inc., Dalmatian Club of America Foundation, Inc., French Bulldog Club of America, Irish Water Spaniel Club of America, Otterhound Club of America, Rhodesian Ridgeback Club of the United States, Scottish Terrier Club of America Health Trust Fund, Welsh Terrier Club of America, Inc., Westie Foundation of America, Inc.
Researcher(s):
Bruce Hammerberg, DVM, PhD,MS
Breed(s):
All (non-specified), Belgian Tervuren, French Bulldog
Abstract:
Atopic dermatitis or skin allergies is a chronic debilitating disease that is widely distributed among the breeds of dogs. This inherited disease is listed as a high research priority for the following breeds: Bichon Frise, Boston Terrier, Bull Terrier, Cairn Terrier , Dalmatian, Vizsla, Welsh Terrier and West Highland White Terrier. The skin mast cell and circulating basophil are the cells mainly responsible for itching and skin damage seen in atopic dermatitis. This laboratory has just recently discovered that mast cells from atopic dogs release significantly more of the inflammatory mediator, tumor necrosis factor alpha (TNF-¿), than normal dog mast cells when stimulated with lectins that bind glycoproteins on the surface of mast cells. If there is an inherited difference in how surface glycoproteins signal release of TNF-¿, then knowledge of the molecular basis for this difference will lead to being able to identify dogs that will have a higher risk of developing atopic dermatitis. To accomplish this, atopic and nonatopic dogs will be compared with regard to the identity and quantity of the cell surface glycoproteins on basophils that are responsible for signaling immediate TNF-¿ release stimulated by lectins.

University of Utah (University)
Active Grant No: 305:
Histocompatibility Alleles Conferring Susceptibility to Canine Diabetes, Immune-Mediated Thyroiditis and Immune-Mediated Hemolytic Anemia
Disease(s):
Autoimmune Disease
Sponsor(s):
Alaskan Malamute Club of America, Inc., American Belgian Tervuren Club, Inc., American German Shepherd Dog Charitable Foundation, American Spaniel Club Health Foundation, Australian Terrier Club of America, Borzoi Club of America, French Bulldog Club of America Rescue League, Golden Retriever Foundation, Health & Rescue Foundation of the Petit Basset Griffon Vendeen Club of America, Irish Wolfhound Club of America, Inc., Keeshond Club of America, Kerry Blue Terrier Foundation, Pekingese Charitable Foundation, Plum Creek Kennel Club of Colorado, Rottweiler Health Foundation, Samoyed Club of America Education & Research Foundation, Westie Foundation of America, Inc.
Researcher(s):
Wayne Potts, PhD
Breed(s):
All (non-specified), Belgian Tervuren, French Bulldog, German Shepherd Dog, Golden Retriever
Abstract:
Autoimmune diseases cause significant amounts of mortality and debilitating disease in dogs. In humans many autoimmune diseases occur only in individuals expressing one of the few predisposing histocompatibility genes. For example, all cases of type I diabetes in humans are associated with only a few of the many alleleic forms of class II histocompatibility genes. Consequently, if the frequencies of these few alleles were reduced by half, the incidence of diabetes would be reduced by half. Here we propose to characterize histocompatibility susceptibility alleles for three major, heritable canine autoimmune diseases - diabetes, immune-mediated thyroiditis and immune-mediated hemolytic anemia. If any of these three debilitating (or lethal) autoimmune diseases have a restricted number of susceptibility alleles it will allow: (1) development of diagnostic tests for identifying individuals at risk for prophylactic therapy and research and (2) reduction of he incidence of the disease by selective breeding of individuals carrying the predisposing histocompatibility alleles. For each of the three autoimmune diseases, we propose to collect DNA samples from approximately 100 purebred dogs diagnosed with the disease. Histocompatibility genes will be cloned and sequenced for each dog for a total of approximately 1100 sequences. Histocompatiility alleles will be tested for significant associations with each of the autoimmune diseases.

Auburn University (University)
Active Grant No: 257:
Investigation of Predictors of Outcome for Canine Mast Cell Tumors
Disease(s):
Cancer
Sponsor(s):
American German Shepherd Dog Charitable Foundation, Bernese Mountain Dog Club of America, Collie Health Foundation, Doberman Pinscher Club of America, Dog Writers' Educational Trust, French Bulldog Club of America, Irish Wolfhound Club of America, Inc., Labrador Retriever Club, Papillon Club of America, Rhodesian Ridgeback Club of the United States, Soft Coated Wheaten Terrier Club of America, Inc., Staffordshire Bull Terrier Club of America
Researcher(s):
Elizabeth M. Whitley, DVM, PhD
Breed(s):
All (non-specified), French Bulldog, German Shepherd Dog
Abstract:
Mast cell tumors are common and high grade tumors are often deadly in dogs. Treatment for aggressive MCT often fails, in part due to imprecise prediction of aggressiveness when surgical biopsy samples are examined. This project aims to improve the accuracy of prediction by determining the importance of several cellular proteins in relation to the ability of the malignant mast cells (MC) to invade tissue and to metastasize to lymph nodes and to distant organs. We will examine biopsy specimens from previous and current cases of MCT for expression of proteins that have critical functions in adhesion between cells and their environment, in signaling for cell proliferation, and for metastatic capability. Responses of the affected dogs to surgical, radiation and chemotherapies will be compared to protein marker expressions, to try to identify proteins that are associated with aggressiveness. This information can then be used for selection of appropriate therapy. We propose to collect fresh tumor tissue from both aggressive and relatively non-aggressive MCTs and to culture them for use in experiments detailing differences between aggressive and non-aggressive MCT. Cell lines derived from canine MCT also will be useful in future investigations into the basic physiology of canine MC and for use in preclinical testing of drug therapies for MCT.

CNRS (University)
Active Grant No: 336B:
Mapping of the Gene for Malignant Histiocytosis in the Bernese Mountain Dog
Disease(s):
Cancer
Sponsor(s):
Berner Lovers, Bernese Mountain Dog Club of America, Bernese Mountain Dog Club of Northern California, Flat-Coated Retriever Foundation, French Bulldog Club of America, Golden Retriever Foundation, Starlight Fund
Researcher(s):
Francis Galibert, PhD
Breed(s):
Bernese Mountain Dog, Flat-Coated Retriever, French Bulldog, Golden Retriever, Rottweiler
Abstract:
Not Listed

Cornell University (University)
Active Grant No: 415:
Anti-HLA-DR Antibody Therapy in Canine B-cell Lymphoma: Preliminary Clinical Evaluation
Disease(s):
Cancer
Sponsor(s):
Bernese Mountain Dog Club of America, Collie Health Foundation, Doberman Pinscher Club of America, Forsyth Kennel Club, French Bulldog Club of America, Golden Retriever Foundation, Irish Wolfhound Club of America, Inc., Labrador Retriever Club, Rottweiler Health Foundation, Soft Coated Wheaten Terrier Club of America, Inc., Starlight Fund, Vizsla Club of America Welfare Foundation
Researcher(s):
Rodney Page, MS, DVM
Breed(s):
All (non-specified), French Bulldog, Golden Retriever
Abstract:
Canine lymphoma is a frequently occurring, temporarily controllable form of cancer that is similar to high-grade non-Hodgkin¿s lymphoma in people. The best conventional chemotherapy results in rapid improvement, but ultimately relapse and progression occur. Adjustment of current chemotherapy protocols is unlikely to result in substantial gains in survival due to development of multiple mechanisms of drug resistance occurring during treatment. Therefore, new strategies that have demonstrated efficacy in humans are worth developing for dogs. An antibody that recognizes cancer cells and stimulates the patient's immune system to eliminate the cancer is an example of such a strategy. We have determined that an antibody made against human lymphocytes cross-reacts with canine lymphoma and causes cell death. This antibody has been confirmed to be safe in normal dogs. We propose to optimize the administration of this antibody in dogs that have already failed chemotherapy for lymphoma. We will evaluate the safety and potential efficacy of this antibody as a prelude to more extensive testing in dogs with lymphoma. This antibody also recognizes cells from dogs with malignant histiocytosis and may be useful for management of this disorder as well.

University of California, Davis (University)
Completed Grant No: 2465:
Identification and Characterization of Genetic Mutations in Canine Mast Cell Tumors
Disease(s):
Cancer
Sponsor(s):
American Boxer Charitable Foundation, American Bullmastiff Association, Chinese Shar-Pei Charitable Trust, Collie Health Foundation, French Bulldog Club of America, Golden Retriever Foundation, Jeffrey Pepper, Rhodesian Ridgeback Club of the United States, Staffordshire Bull Terrier Club of America
Researcher(s):
Cheryl London, DVM, PhD
Breed(s):
All (non-specified), Boxer, Bullmastiff, French Bulldog, Golden Retriever
Abstract:
The most common malignant tumor in dogs is the mast cell tumor (MCT, a form of skin cancer), occurring with an incidence of close to 20 percent in the canine population. MCTs range from relatively benign to extremely aggressive, leading to tumor spread and eventual death. Particular breeds of dog are at risk for the development of this tumor, indicating a role for genetic factors. We have previously identified mutations in the gene c-kit in 30-50 percent of dog MCTs. c-Kit plays a critical role in regulating the growth and function of normal mast cells, and as the mutations we discovered cause uncontrolled function of c-kit, it is likely they influence MCT development in dogs. This proposal will establish a prospective tumor registry of dog MCTs to be used for investigation of the true incidence of c-kit mutations within specific dog breeds. Moreover, the studies outlined in this grant will identify additional genetic mutations present in dog MCTs that can be used for the development of new targeted therapeutics. In summary, this work will provide a much more detailed understanding of dog MCTs, thereby building a framework for the development of new therapies and strategies for disease prevention.

Iowa State University (University)
Active Grant No: 717-A:
Determination of White Spotting Locus in Dogs
Disease(s):
Coat Color
Sponsor(s):
Not Listed
Researcher(s):
Max Rothschild, PhD
Breed(s):
French Bulldog, Newfoundland, Schipperke
Abstract:
The advent of modern genomics has now made it possible to determine underlying gene effects on traits of major importance in the dog. Unlike many other domesticated species, in the dog the cause or causes of white spotting are not known. White spotting is of interest because extreme white spotting has been linked to health disorders including blindness and deafness in several breeds. Using some unique pedigrees selected to demonstrate simple inheritance of white spotting we plan to use two common approaches to find the gene or genes responsible. We will employ a limited genome scan and directed analyses of a number of candidate genes known to be associated with spotting in other mammalian species in specific canine pedigrees. Results of this effort will either identify specific genes and chromosomal regions or exclude them from further study. Results will be published and made available to all dog breeds.

University of Alaska, Fairbanks (University)
Completed Grant No: 2447:
Genetic Determinants of Susceptibility to Hypothyroid Disease in Dogs
Disease(s):
Endocrine Disorders
Sponsor(s):
American Boxer Charitable Foundation, American Miniature Schnauzer Club, Inc., American Spaniel Club Health Foundation, Bull Terrier Welfare Foundation, Bulldog Club of America Charitable Health Fund, Inc., Collie Health Foundation, Flat-Coated Retriever Foundation, Golden Retriever Foundation, Great Dane Club of America, Rhodesian Ridgeback Club of the United States, Scottish Terrier Club of America Health Trust Fund
Researcher(s):
George Happ, PhD
Breed(s):
All (non-specified), Bulldog, Flat-Coated Retriever, Golden Retriever
Abstract:
Canine hypothyroid disease is very similar to Hashimoto¿s disease in humans, which has been shown to be associated with human MHC genes. If we can show in hypothyroid dogs a similar association with canine MHC genes, these could provide useful genetic markers for selective breeding to reduce disease incidence in dogs. Hypothyroid disease is the most common endocrinopathy of dogs, and represents a significant veterinary problem. Definitive diagnosis is difficult since good clinical diagnostic tests are not available. The disease is characterized by low levels of thyroid hormones, but these may result from other diseases and it appears that primary hypothyroid disease is characterized by the presence of autoantibodies to thyroglobulin. It is thought that only 50 percent of dogs with hypothyroid disease have these autoantibodies. We have recently developed an assay to measure thyroglobulin autoantibodies, which will allow us to identify animals with primary disease. There is a clear genetic component to canine hypothyroid disease, and a number of breeds are thought to be more susceptible. The proposed study could lead to a better understanding of this condition and offer new approaches to its reduction in certain breeds.

University of Kentucky (University)
Completed Grant No: 2209:
Galactokinase 1: A Candidate Gene for Juvenile Cataracts in Dogs
Disease(s):
Eye Disease
Sponsor(s):
Boston Terrier Club of America Charitable Trust, French Bulldog Club of America, Rhodesian Ridgeback Club of the United States, San Joaquin Kennel Club, Siberian Husky Club of America
Researcher(s):
Kathryn Graves, PhD
Breed(s):
All (non-specified), French Bulldog
Abstract:
Juvenile cataracts occur in a number of breeds and in many cases appear to be inherited as an autosomal recessive trait. This means that it is impossible to eliminate carrier animals solely through removal of affected animals from the breeding population. Due to similarities between patterns of cataract formation in some dog breeds and humans with galactokinase deficiency, we feel that one or more mutations in Galactokinase1 (GALK1) may be responsible for juvenile cataracts in certain dog breeds. We are requesting funding to complete the sequencing of the GALK1 exons (coding regions) in the dog. We will then sequence the eight exons in four breeds of dogs affected with juvenile cataracts. This will be a preliminary study to determine if a mutation in this gene may exist in the Boston Terrier, Australian Terrier, Siberian Husky or Brittany. Regardless of the outcome in these breeds, the ability to sequence the exons of this gene could lead to rapid development of a DNA-based test for carrier animals in other breeds.

University of Tennessee (University)
Pending Grant No: 726-A:
Pharmacokinetics of Topically Applied Ciprofloxacin in Canine Tears
Disease(s):
Eye Disease
Sponsor(s):
Not Listed
Researcher(s):
Diane Hendrix DVM
Breed(s):
All (non-specified), Bulldog, French Bulldog, Lhasa Apso, Pekingese, Pug, Shih Tzu
Abstract:
Ulcerative keratitis (corneal ulceration) occurs very commonly in dogs. Corneal ulcers usually occur secondary to trauma, but may also occur secondary to lack of tear production, eyelid abnormalities or nerve damage. While corneal ulcers occur in all breeds of dogs, brachycephalic breeds such as Pekingese, Lhasa Apsos and Shih Tzus, have a higher incidence of ulceration. Additionally, corneal ulcers in brachycephalic breeds are more likely to become infected than ulcers in mesocephalic or dolicocephalic breeds. The anatomy of brachycephalic dogs with prominent, frontally placed globes leads to corneal exposure. Often concurrent eyelid abnormalities, abnormally low tear production, and increased tear evaporation slow healing, increasing the chances of corneal invasion by bacteria. Infected corneal ulcers can develop rapid stromal dissolution leading to globe perforation and iris prolapse. When this occurs surgery is required to restore globe integrity, but even with prompt surgical intervention, blindness may still occur. Appropriate antibiotic usage is paramount in the prophylactic treatment of non-infected ulcers and for the treatment of infected ulcers where rapid killing of the bacteria helps prevent worsening of the ulcer. No studies have been done to evaluate the pharmacokinetics of ophthalmic antibiotics in the tear film of dogs. Studies in normal humans, rabbits, and horses have shown that ciprofloxacin maintains a concentration greater than the MIC for most bacteria longer than 4 hours. We would like to evaluate the pharmacokinetics in the tear film of normal mesocephalic and brachycephalic dogs. Twenty mesocephalic and 20 brachycephalic dogs will be tested. The study will be carried out on dogs free of active ocular disease. After 35 ¿l (one drop) of ciprofloxacin has been placed on the cornea, a Schirmer tear test strip will be used to collect the tears at multiple time points. The concentration of the antibiotic will then be determined using high performance liquid chromatography (HPLC).

University of Pennsylvania (University)
Completed Grant No: 2458:
Molecular Genetic Characterization of Canine Cystinuria for the Development of Carrier Tests
Disease(s):
Kidney Disease
Sponsor(s):
American Bullmastiff Association, Bulldog Club of America Charitable Health Fund, Inc., Mastiff Club of America, Scottish Deerhound Club of America
Researcher(s):
Paula S. Henthorn, PhD
Breed(s):
Bulldog, Bullmastiff, Mastiff, Scottish Deerhound
Abstract:
Cystinuria is an inherited disease that has been long recognized in dogs and has been documented in nearly 70 breeds. Our previous studies made significant progress with a form of cystinuria that is clinically manifested at an early age such that we can go from seeing an affected animal in the clinic to a DNA-based test in a matter of weeks. We now have access to sufficient pedigrees to make similar progress for cystinuria that presents at a later age, and probably represents a more common form of the disease. Genetic testing is even more important for a disease that has a later age of onset.
Active Grant No: 639:
Molecular Genetic Characterization of Canine Cystinuria for the Development of Carrier Tests
Disease(s):
Kidney Disease
Sponsor(s):
American Shih Tzu Club, Inc., Bulldog Club of America Charitable Health Fund, Inc., Cardigan Welsh Corgi Club of America, Dr. William R. Newman, Mastiff Club of America
Researcher(s):
Paula S. Henthorn, PhD
Breed(s):
Bulldog, Bullmastiff, Cardigan Welsh Corgi, Dachshund, German Shorthaired Pointer, Irish Setter, Mastiff, Parson Russell Terrier, Pembroke Welsh Corgi, Saluki, Shih Tzu
Abstract:
Cystinuria is an inherited disorder of amino acid transport in dog, man and other animals and has been documented in over 60 breeds of dog. In humans, mutations in the SLC3A1 and SLC719 genes are found in affected individuals. While human cystinuria was originally thought to be inherited as an autosomal recessive trait, more complex inheritance patterns, and their molecular origins, are currently being elucidated. Based on previous work, which developed tests to detect dystinuric, carrier and normal Newfoundlands and Labrador Retrievers, researchers recently identified a third mutant allele in the SLC3A1 gene that may lead to stone formation when present in only a single copy, and they also hypothesized a more complex etiology for cystinuria in breeds where stone formation occurs later in life. Researchers will focus efforts on experiments that will apply the new information concerning human cystinuria to the canine disease.

Washington State University (University)
Completed Grant No: 2416:
Systemic Inflammatory Response Syndrome in Canine Pyometra
Disease(s):
Reproduction
Sponsor(s):
Bulldog Club of America Charitable Health Fund, Inc., Chow Chow Club, Inc., English Setter Association of America
Researcher(s):
Boel Fransson, DVM, MS
Breed(s):
All (non-specified), Bulldog
Abstract:
Early recognition and aggressive treatment of the Systemic Inflammatory Response Syndrome (SIRS) is imperative to avoid a fatal outcome. SIRS is not a disease in itself but is considered as the overwhelming response of the body to a cascade of inflammatory mediators, released after major trauma, pancreatitis, snake bite, heat stroke or bacterial infection of different organs. Pyometra, a common disease in intact female dogs, is considered associated with SIRS. Our cooperation with the Swedish University of Agricultural Science in Sweden, where female dogs are not routinely spayed, gives us an unique opportunity to receive large numbers of samples from dogs with pyometra. Blood samples from 50 dogs have been successfully transported to WSU. Detection of SIRS today is limited to recognition of clinical criteria, defined for SIRS, such as temperature, heart rate, and white blood cell count, but these criteria are not very specific. The proposed study will test if cytokine and acute phase protein levels in the blood are more specific detectors of SIRS than clinical criteria, which could lead to a more accurate and rapid detection of this syndrome. Rapid recognition would enable institution of aggressive treatment earlier in the disease, likely leading to reduced suffering and mortality of these dogs.