RESEARCH PROJECTS FUNDED IN CONJUNCTION WITH THE AKC CANINE HEALTH FOUNDATION

Since its inception, DCAF has helped to fund nearly 20 health research projects. The projects listed below are studies that DCAF either fully funded or helped DCA and other breed clubs support. Note that some of the projects are completed while others are still active.


Current Grant No. 02297-MOU:     Understanding the Genetics of Hepatic Copper Toxicosis in the Dalmatian
Researcher: Principal Investigator: Dr. Andrew Lawrence Mason, PhD; University of Alberta
Program Area: Liver Disease
Grant Period: 12/1/2016 - 11/30/2018
Total Grant Amount: $100,000.00
DCAF Funding:

    Abstract: Copper toxicosis, leading to early death from liver disease, was first described in Bedlington Terriers in 1975, with similar diseases described in other dog breeds including the Labrador Retriever, West Highland White Terrier, Skye Terrier, and Doberman Pinscher. Genes have been linked to copper toxicosis in the Bedlington Terrier and the Labrador Retriever, but the genes differ by breed. In most breeds the genes are not known. Copper toxicosis was considered rare in the Dalmatian but may be more common than previously believed. Symptomatic dogs may be misdiagnosed as having other liver diseases, never appropriately diagnosed or only diagnosed with copper overload at a terminal stage. The investigators aim to identify the faulty gene(s) in Dalmatians using an advanced whole genome sequencing strategy to obtain the genome sequences of carefully selected members of an affected Dalmatian pedigree. Identification of the problem gene is the first step towards genetic testing and to improved breeding practices necessary to eradicate hepatic copper toxicosis from the Dalmatian breed. Gene identification will help raise awareness of copper toxicosis in the Dalmatian breed, lead to more rapid diagnosis of the condition, and support the search for the most effective therapy. Funding for the research is provided through the efforts and generosity of the Dalmatian Club of America/DCA Foundation. The AKC Canine Health Foundation supports the funding of this effort and will oversee administration of funds and scientific progress reports.


Current Grant No. 02263-MOU:     Characterization of Kidney Disease in Dalmatians
Researcher: Dr. Rachel E Cianciolo, VMD, PhD; Ohio State University
Program Area: Renal Disease
Sponsor(s): .
Project Dates: 5/1/2016 to 4/30/2018
Grant Amount: $120,015.00
DCAF Funding: $31,434.00.

    Original Project Description: Chronic kidney disease is a significant progressive problem in dogs. Some breeds (e.g. Dalmatians) are predisposed to developing kidney disease. Two different hereditary diseases of the urinary system have been reported in Dalmatians: urinary stone formation (urolithiasis) and a defect in the glomerulus, which is the filter of the kidney. These two diseases cause distinct clinical signs: urolithiasis leads to urinary tract obstruction while glomerular disease results in protein loss into the urine (proteinuria). The genetic cause of urolithiasis is known while the genetic cause of glomerular disease has not yet been identified. Although one specific type of glomerular disease has been reported in the literature, our preliminary investigations indicate that there are multiple causes of proteinuria in Dalmatians. Evaluation of kidney tissue by the International Veterinary Renal Pathology Service has revealed many diverse types of glomerular diseases in Dalmatians, at least 4 of which might be hereditary. Therefore, the most common disease type is unknown and must first be identified. Here, we propose a detailed review of autopsy and biopsy sample archives that have been previously obtained from Dalmatians with proteinuria. Next, prospective examination of select kidney samples with advanced techniques (electron microscopy and immunofluorscence) will ensure the accurate diagnosis of the glomerular disease. Genetic analysis can then be performed on related dogs that demonstrate similar glomerular lesions. These analyses will include sequencing the genome of dogs so that candidate genes previously associated with glomerular disease can be examined to identify possible mutations.

    Report to Grant Sponsor from Investigator:
    The primary goal for this project is to identify and characterize a type of kidney disease in Dalmatians, which might be hereditary. A popular sire was used a few years ago and died with proteinuria, which indicates that he had a type of kidney disease that caused him to lose large amounts of protein in his urine. Since then, many of his progeny have had similar symptoms. Thus there is concern among Dalmatian breeders that this proteinuric kidney disease might have a genetic basis. There has been one previous publication that documented a certain type of hereditary proteinuric kidney disease (known as canine Alports syndrome) in a lineage of Dalmatians in Australia. However, it was unclear whether or not American Dalmatians had the same type of disease. In fact, none of the Dalmatian kidney samples previously submitted to the International Veterinary Renal Pathology Service (IVRPS) had lesions consistent with canine Alports syndrome. Therefore, the first step for this project is to diagnose the type of changes that occur in kidneys of proteinuric Dalmatians. After characterizing the disease types, we can then evaluate the pedigrees to determine the best candidate genes (and/or dogs) for genetic testing. This will also help us determine which type of genetic analysis would be the most suitable. Collection of kidney tissue, serum and urine are all routine steps in the diagnosis of proteinuric kidney disease. We plan to collect "archived" samples from Dalmatians that were autopsied or biopsied prior to the commencement of the study. We will re-analyze the glass slides of these samples with special stains. As of yet, we have re-examined 8 Dalmatian kidney samples that were archived at the Ohio State University since 2005. At Texas A&M University, 16 Dalmatians have been autopsied since 2005 and re-examination of those samples is ongoing. We have created a flyer to advertise this part of our study of archived tissue (and submitted pedigree) from any Dalmatian owner whose dog died with kidney disease. This reexamination of tissue will be at no cost to the owner. We also need to examine prospectively collected kidney, urine, serum and whole blood from newly diagnosed Dalmatians. Although we encourage owners to allow kidney biopsies to be obtained from their proteinuric Dalmatians (so we can try to detect the early stages of disease), we accept autopsied kidney samples as well. We anticipate that submission of minimally invasive samples (blood and urine) will represent many more dogs/pedigrees than the kidney biopsies. Urine and blood samples can also be submitted from proteinuric Dalmatians that cannot be biopsied and from dogs related to those affected by kidney disease, whose owners would be willing to consent to sample collection. These samples will help us to create an extensive pedigree of affected and unaffected Dalmatians. As mentioned previously, biopsied kidney tissue, urine and serum are all considered routine diagnostic samples, which will help guide therapy for the dog. However, whole blood for DNA isolation is not considered to be a sample used for diagnosis of kidney disease. We obtained approval from the IACUC at Texas A&M, where the whole blood will be processed to harvest DNA. Upon this approval, we created a flyer to distribute to Dalmatian breeders and owners, as well as all veterinarians that submit samples to the IVRPS. We have worked hand in hand with the Dalmatian Club of America Foundation (DCAF) to distribute the flyer and have already received inquiries about sample submission. To date, we have examined kidney tissue, urine and serum from one proteinuric Dalmatian as well as urine and serum from 2 additional Dalmatians. Once the study is in full swing, we anticipate many more samples to be submitted for evaluation, and our conversations with the DCAF have indicated that many breeders and owners have been discussing the logistics of submitting samples. The last part of our study is dependent on the results from these first steps. If we identify a specific type of proteinuric kidney disease that demonstrates a pattern of inheritance, then we will select the best candidate dogs for genetic sequencing. This last step will be done in conjunction with analysis of the pedigree and the guidance of the geneticist for our study. This type of informed approach will ensure that we are examining DNA from Dalmatians that are affected by a similar disease process.


Current Grant No. 02172-MOU:     Hereditary Deafness in Dogs -- Genomic Studies in Australian Cattle Dogs and Dalmatians Using Full Sibling Pairs
Researcher: Dr. George M. Strain, PhD; Louisiana State University
Program Area: Neurology
Sponsor(s): .
Project Dates: 11/1/2015 to 10/31/2017
Grant Amount: $120,015.00
DCAF Funding: $30,003.75.

    Abstract: Hereditary deafness associated with white pigmentation occurs in numerous dog breeds. Because of quality-of-life concerns and in an effort to reduce the prevalence of deafness within breeds, many bilaterally deaf puppies are euthanized by breeders. The breeds most affected are the Dalmatian (Dal, 22% unilaterally deaf, 8% bilaterally deaf) and the Australian cattle dog (ACD, 11.4% and 3%). The mechanism of inheritance is unknown, but does not appear to be simple Mendelian: breeding of two bilaterally deaf Dals produced puppies that heard in both ears. Numerous studies to determine the mode of inheritance and locate the causative gene(s) have thus far failed. The proposed work will use a modified twin study approach. Full-sibling littermates will be identified within the two breeds, where one puppy has normal hearing and one is deaf. Like human twins, full siblings should have very similar DNA, which will reduce the variability of the DNA samples when compared to studies of unrelated dogs. Using the Illumina CanineHD Beadchip, which contains 172,115 DNA markers (SNPs) spread uniformly across the canine chromosomes, activity at the markers will be compared between the sibling pairs, and differences in activity between siblings at individual markers will be identified. These differences will be tallied for 50 Dal pairs and 50 ACD pairs. The chromosome locations of the markers are known, and genes located close to each marker are known because of the sequencing of the canine genome, so candidate deafness genes can be identified and provide the basis for more detailed study.

    Report to Grant Sponsor from Investigator:
    Saliva samples have been collected for DNA isolation from 114 Dalmatians plus 25 samples archived with the OFA, giving 139 samples, above our goal of 100 samples (50 sibling pairs). Saliva samples have been collected for DNA isolation from 87 Australian cattle dogs (ACD) to date, below our goal of 100 (50 sibling pairs), but samples are continuing to be collected. In anticipation of finding a significant marker for deafness in the Dal and ACD dogs, we have also collected saliva samples for DNA isolation from small numbers of dogs in other breeds with pigment-associated deafness to look for a similar significant marker; these include 4 Old English sheepdogs, 4 Dogo Argentinos, and 8 Jack Russell terriers. We will continue to collect as many Dal and ACD samples as possible to increase the statistical power of the DNA analyses in these breeds, and limited numbers of samples from other affected breeds to assess whether one genetic mechanism is associated with hereditary deafness in piebald breeds, or whether multiple mechanisms exist. Identification of a single unified mechanism will significantly increase the impact of the findings on the pure dog breed world. DNA isolation from the collected samples has been completed and the DNA has been delivered to Cornell University where the Illumina microbead array assays will be performed and the subsequent analyses will be performed. Further DNA samples will be conveyed to Cornell as they become available. Genome sequencing studies will be performed with DNA from selected dogs based on findings from the Illumina array analyses.


Current Grant No. 02157-MOU:     Genomics of Deafness in the Dalmatian Stem Cells: Effects of Donor Characteristics and ex vivo Expansion on Cell Pluripotency
Researcher: Dr. Claire M Wade, PhD; University of Sydney
Program Area: Neurology
Sponsor(s): .
Project Dates: 1/1/2015 to 12/31/2016
Grant Amount: $120,960.00
DCAF Funding: $120,960.00.

    Abstract: Congenital deafness is a health issue that has higher prevalence in certain breeds, including the Dalmatian. Other studies in this breed have found the trait to be inherited in a complex, rather than simple Mendelian manner. The aim of this project is to identify mutations underlying the trait of congenital deafness in the Dalmatian breed and to work towards a genetic testing solution for the Dalmatian breeding community. To do this, we will employ the latest genomic technologies and computational analyses. We have on hand a large number of suitable dog samples from animals that have been tested for hearing status using well validated technology. Work has been underway on this project for some time and has already identified target regions for further analysis.

    Grant Objectives:
    To complete our analysis to better understand the genomics of deafness and to provide a genetic testing solution to Dalmatian breeders. 1. That we can identify mutations underlying the risk signals identified by previous analysis of genotyped samples 2. That we can validate already identified loci in a wider cohort of samples and detect loci that confer greater relative-risk of disease 3. That we can ascertain gene frequencies for risk loci within the Dalmatian breed 4. That we can provide genetic tests for one or more risk loci

    Report to Grant Sponsor from Investigator:
    We have continued to collect samples for breed risk analysis via our neurology clinic run by Dr Georgina Child and have successfully acquired a high quality DNA sample from a bilaterally deaf dog along with a number of samples of deaf, unilateral and hearing pups. We are continuing to conduct assays on promising mutations in the vicinities of our identified regions. From the six loci under investigation we are yet to resolve a definitive risk locus but there is growing statistical support for three of the tested loci. We are working to identify and test mutations in the regions of interest. The regions under investigation are quite large and there are many Dalmatian specific mutations present. This makes it difficult to assess which are characteristic of the breed and which are related to disease. We are slowly working through each locus but it is a time consuming task that has been hampered by poor sequencing quality over some interesting candidate genes.


Completed Grant No. 00970:     Tissue Regeneration Using Canine Mesenchymal Stem Cells: Effects of Donor Characteristics and ex vivo Expansion on Cell Pluripotency
Researcher: Dr. Susan W. Volk, VMD PhD; University of Pennsylvania
Program Area: Treatment
Sponsor(s): .
Project Dates: 1/1/2008 to 6/30/2010
Grant Amount: $165,348.00
DCAF Funding: $2,500.00.

    Abstract: Mesenchymal stem cells (MSCs) are attractive candidates for cell-based therapies because of their relative ease of isolation, broad differentiation potential, and ability to be expanded in vitro. Regenerative medicine strategies using MSCs aim to restore function to damaged tissues, particularly for orthopedic, cardiovascular and neurologic diseases. Although tremendous potential for stem cell therapies exists for canine patients, an understanding of the basic biology of canine MSCs is lacking and must be established prior to initiating responsible clinical trials in patients. Importantly, multiple studies have shown that extrapolation of biologic properties of MSCs between species is unreliable. In our Canine Health Foundation sponsored research project, we have investigated the effect of donor age, harvest site and in vitro passage on the ability of the cells to directly contribute to bone, fat, and cartilage. We identified differences in the ability of MSCs to become bone depending on the age of the dog the cells were harvested from as well as the site from which they were obtained. These findings may help direct future clinical trials by choosing to use MSCs which are most effective for therapy. Because expansion of cell numbers is an important part of the process to generate adequate quantities for therapies, understanding how this process affects the capacity of those cells to differentiate into target cells is vital for therapeutic success. Our studies suggest that expansion of cell numbers has a significant effect on these cells and that those who use these cells for clinical applications need to be aware of such effects. Additional studies are on going to further define as well as limit these effects so that efficacy and safety are maximally preserved. A thorough, systematic understanding of the basic biology of canine MSCs will have a significant impact on the design of future stem cell clinical trials. Clinical trials using MSCs in humans are currently underway and provide a basis for exciting new therapies for many of the most common ailments of dogs: heart failure, neurologic conditions, osteoarthritis, kidney and liver diseases and diabetes. MSC-based therapies could have significant positive effects on quality of life for dogs that are affected by a variety of degenerative, genetic and traumatic conditions, their owners, and the veterinarians who treat them.


Completed Grant No. 00975:     Characterization and Modulation of Canine Mast Cell Derived Eicosanoids
Researcher: Dr. Cheryl A. London, DVM PhD; Ohio State University
Program Area: Treatment
Sponsor(s): .
Project Dates: 4/1/2008 to 3/31/2010
Grant Amount: $34,363.00
DCAF Funding: $2,500.00.

    Abstract: Dr. London's research team has been investigating the production of inflammatory mediators (also known as eicosanoids) by canine mast cells that contribute to a variety of diseases such as atopy and arthritis. The purpose of their work is to determine if currently available non-steroidal antiinflammatory drugs (NSAIDs) such as Rimadyl and Zubrin (among others) are capable of modifying their production. The use of NSAIDs would be an attractive alternative to the use of corticosteroids to modulate mast cell function. The preliminary data indicate that Zubrin is very effective at blocking the production of mast cell derived eicosanoids when mast cells are exposed to standard doses of drug. Therefore, results from these studies may provide a new strategy to modify the function of mast cells in several inflammatory disorders.


Completed Grant No. 00762:     The Mapping and Characterization of Canine Epilepsy Loci
Researcher: Dr. Gary S. Johnson, DVM PhD; University of Missouri, Columbia
Program Area: Prevention
Sponsor(s): .
Project Dates: 10/1/2008 to 9/30/2010
Grant Amount: $129,600.00
DCAF Funding: $7,000.00.

    Abstract: The projects investigators collected DNA from nearly 10,000 epileptic dogs and their close relatives and they have assembled epilepsy?family pedigrees in 28 different dog breeds. The investigators have re-contacted the owners of over 2,000 dogs in this collection to obtain additional clinical information or to confirm that the "normal" dogs have remained seizure free. They have used samples from 13 different breeds in 15 different experimental attempts to identify the chromosomal locations of epilepsy?causing genetic mutations. They used an experimental procedure known as a genome?wide association study (GWAS) which is done with a device known as a SNPchip. SNPchips compare the DNAs from epileptic dogs to the DNAs from non-epileptic family members at tens or hundreds sites in all of the chromosomes. Eight of the GWASs were done in collaborations with other laboratories and seven were done at the University of Missouri. Thirteen of the GWASs were applied to epilepsies in which seizures were the only symptoms. None of these studies provided strong evidence about the chromosomal locations of epilepsy-causing mutation; however, some of them provided weak evidence, suggesting possible chromosomal sites for epilepsy mutations. The investigators examined genes at five of these sites, but failed to find any epilepsy?causing mutations. By contrast, both GWAS for diseases with symptoms in addition to seizures successfully identified the chromosomal locations of the responsible locations. The GWASs for the pure epilepsies probably failed because causes of epilepsy in some of the family members were different from the causes in other family members and/or because the epilepsies resulted from a complex combination of genes and acquired factors.


Completed Grant No. 00759:     Investigation of Antigenic Causes of Vaccine- Associated Allergic Reactions in Dogs
Researcher: Dr. George E. Moore, DVM, PhD; Purdue University
Program Area: Prevention
Sponsor(s): .
Project Dates: 1/1/2007 to 12/31/2008
Grant Amount: $31,631.12
DCAF Funding: $1,000.00.

    Abstract: Researchers at Purdue University were funded by the AKC Canine Health Foundation to identify causes of vaccine-induced allergic reactions. Small dogs in general, and several specific breeds, are known to be at higher risk for these reactions. Although the precise cause of allergic reactions in dogs remains unknown, vaccine components residual from the manufacturing process have been incriminated. These vaccine components need to be identified if possible, so that manufacturers can make vaccines safer for dogs. This study compared antibody concentrations in dogs recently experiencing allergic reactions after vaccination to the antibody concentrations in dogs of the same breed that were vaccinated but didn't have reactions. Comparisons were made by measuring the serum antibody (lgE) reactivity against selected vaccine components. Although samples were solicited from several breeds, only Beagles and Dachshunds provided enough samples for breed-specific comparisons. Grouped together without regard to breed, there were no significant differences between the 46 allergic reactors' and the 50 non-reactors' antibody responses to any of the 7 assayed antigens. When evaluated by breed, however, Beagles demonstrating allergic reactions immediately after vaccination had greater serum response to two vaccine components (fibr.onectin and thyroglobulin) compared to the responses of vaccinated asymptomatic littermates. Dachshunds with reactions did not have greater serum response to any of the measured vaccine components, and in two assays the serum response of nonreactors was actually greater than for reactors. As voluntary submissions, however, the Dachshunds in these two groups were not related nor did they receive the same vaccines. The results of this study indicate that different vaccine components can stimulate antibody response immediately after vaccination, but not all dogs with high response show clinical signs of an allergic reaction. This suggests that dogs with post-vaccinal allergic reactions may have a genetic predisposition which affects the release of chemical mediators from mast cells, and there may not be a vaccine component common to all or most allergic reactions. Further information related to the study will be posted at: http://www.vet.purdue.edu/k9vaxrxn/.


Completed Grant No. 00653-A:     Canine Idiopathic Familial Epilepsies are Associated with Ion Channel Mutations
Researcher: Dr. Kate Chandler, DVM, PhD; Royal Veterinary College
Program Area: Treatment
Sponsor(s): .
Project Dates: 7/1/2005 to 6/30/2006
Grant Amount: $10,194.00
DCAF Funding: $1,000.00.

    Abstract: Idiopathic epilepsy is the most common canine brain disorder, and is associated with significant morbidity and mortality. It is extremely distressing for the pet owner and most patients require life-long medication. Only about two-thirds of canine epileptics can be controlled adequately with anti-epileptic drugs, which often have significant adverse effects. Idiopathic epilepsy is suspected to have a genetic basis in most affected dogs. Hereditary epilepsy has been confirmed in several breeds including Beagles, German Shepherd Dogs, Keeshonden, Labrador Retrievers, Golden Retrievers, Bernese Mountain Dogs, Belgian Tervuren, Viszlas and English Springer Spaniels. Recently the first mutation associated with a canine seizure disorder was identified; an expanded repeat was shown to be a causative mutation in Lafora disease in Miniature Wirehaired Dachshunds. The genetic causes of epilepsy are highly likely to be different for each breed, and perhaps even across bloodlines in the same breed. Identifying a genetic basis for these breed-specific epilepsies will assist breeders in reducing the prevalence of the disease through positive selection.


Completed Grant No. 0002304:     Continued Investigation into the Molecular Genetic Causes of Canine Epilepsies
Researcher: Dr. Gary S. Johnson, DVM PhD; University of Missouri, Columbia
Program Area: Prevention
Sponsor(s): .
Project Dates: 5/28/2002 to 6/30/2004
Grant Amount: $100,000.00
DCAF Funding: $6,820.00.

    Abstract:


Completed Grant No. 0002234:     Basophil/Mast Cell Response to Lectins as a Predictor for Risk of Allergic Disease in Genetically Susceptible Dogs
Researcher: Dr. Bruce Hammerberg, DVM PhD; North Carolina State University
Program Area: Treatment
Sponsor(s): .
Project Dates: 3/8/2002 to 3/31/2005
Grant Amount: $89,069.54
DCAF Funding: $1,600.00.

    Abstract:


Completed Grant No. 0002264:     Whole Genome Screens Using Microsatellite Markers in Genetic Analyses of Hereditary Deafness in the Dalmatian and English Setter
Researcher: Dr. Keith E. Murphy, PhD; Texas A&M University
Program Area: Prevention
Sponsor(s): .
Project Dates: 10/1/2001 to 12/31/2003
Grant Amount: $50,000.00
DCAF Funding: $12,500.00.

    Abstract:


Completed Grant No. 0002434:     Recombinant Thyrotropin (TSH): Standard for the Next Generation of Canine TSH Immunoassays with Improved Sensitivity
Researcher: Dr. Duncan Ferguson, DVM PhD; University of Georgia
Program Area: Treatment
Sponsor(s): .
Project Dates: 1/1/2004 to 12/31/2006
Grant Amount: $97,170.74
DCAF Funding: $1,300.00.

    Abstract:


Completed Grant No. 0001840:     Studies of the Host (Canine) Immune Response to the Opportunistic Pathogen Malassezia pachydermatis
Researcher: Dr. Daniel O. Morris, DVM; University of Pennsylvania
Program Area: Treatment
Sponsor(s): .
Project Dates: 7/8/1999 to 1/14/2002
Grant Amount: $18,585.00
DCAF Funding: $500.00.

    Abstract:


Completed Grant No.0001415 :     Traits of Cutaneous Mast Cell Phenotype and Function Associated with Predisposition to Canine Atopic Dermatitis
Researcher: Dr. Bruce Hammerberg, DVM PhD; North Carolina State University
Program Area: Treatment
Sponsor(s): .
Project Dates: 12/2/1997 to 12/1/1999
Grant Amount: $79,812.00
DCAF Funding: $5,000.00.

    Abstract:


Completed Grant No. 1458:     Hereditary Hearing Loss in Dalmatians and Australian Cattle Dogs
Researcher: Vilma Yuzbasiyan-Gurkan, PhD, Michigan State University
Program Area: Prevention
Sponsor(s): Bull Terrier Welfare Foundation, Dalmatian Club of America Foundation, Inc.
Project Dates: 9/12/1997 to 6/23/2000
Grant Amount: $80,000.00
DCAF Funding: $20,000.

    Abstract: The knowledge gained from this research makes an important contribution to the understanding of the biology involved with deafness. This study evaluated several genes that are good candidates to harbor the mutations responsible for hearing loss in the Dalmatian, Australian Cattle Dog, Bull Terrier and several other breeds affected by hereditary deafness. These breeds appear to share common spotting or ticking patterns that may be associated with hereditary deafness. The researchers characterized five candidate genes, and evaluated them in various breeds of dogs with hearing loss: Dalmatians, Australian Cattle Dogs, Boxers, Catahoula Leopard Dogs, Brittanys, Great Danes and Akitas. They have sequenced between 50 and 100 percent of the coding region for affected and normal dogs for each gene, though they have not yet found the mutation.

Completed Grant No. 1870:     Genetics of Hereditary Deafness in the Domestic Dog
Researcher: Keith E. Murphy, PhD, Texas A&M University
Program Area: Prevention
Sponsor(s): Dalmatian Club of America Foundation, Inc., English Setter Association of America, Random Individuals
Project Dates: 9/9/1999 to 9/8/2002
Grant Amount: $77,000.00
DCAF Funding: $11,750.

    Abstract: Congenital deafness has been reported for approximately 60 breeds, and can potentially appear in any breed. The disorder is usually associated with pigmentation patterns, where increasing amounts of white in the hair coat increase the likelihood of deafness. Pigment-associated inheritance of deafness is not restricted o dogs. Similar defects have been reported for mice, mink, pigs, horses, cattle, cats and humans. Waardenburg syndrome type 2 (WS2) in humans presents with congenital deafness and hypopigmentation of the eyes and head hair. This is an autosomal dominant disorder with incomplete penetrance, meaning that individuals that inherit the disorder may not show all of the components of the syndrome. Mutations in the mitf gene cause at least twenty percent of cases of WS2. Piebaldism in humans most commonly presents with congenital patches of white skin and hair-lacking melanocytes on certain parts of the body, although deafness is a characteristic of the disorder in an unknown percentage of affected individuals. Mutations in the kit gene are responsible for typical cases of piebaldisms. We believe that deafness is dogs may result from mutations in the canine mitf/kit genes. Examination of these genes and identification of causative mutations will aid in understanding the etiology of deafness.

Completed Grant No. 2304:     Continued Investigation into the Molecular Genetic Causes of Canine Epilepsies
Researcher: Gary S. Johnson, DVM, PhD, University of Missouri, Columbia
Sponsor(s): American Spaniel Club Health Foundation, AWS Partners, Collie Health Foundation, Dalmatian Club of America Foundation, Inc., English Springer Spaniel Field Trial Association Foundation, Greater Swiss Mountain Dog Club of America, Inc., Irish Setter Club of America Foundation, Irish Water Spaniel Club of America, Random Individuals, St. Bernard Club of America, Standard Schnauzer Club of America, Welsh Springer Spaniel Club of America
DCAF Funding: $6,829.

    Abstract: In our on-going study of canine epilepsy, we have found that most canine epilepsy families do not follow the simple inheritance patterns described by Gregor Mendel. This suggests that epilepsy results when a dog inherits mutations in two or more different genes. Mutations involving two or more genes are also thought to be responsible for the vast majority of human epilepsy that occurs in families. Mendelian inheritance is encountered in rare types of human epilepsy and in many of these families the epilepsy-causing mutation has been found by genome mapping. We appear to have found Mendelian inheritance in at least one canine family and if this holds true we will attempt to map the mutation. One unexpected finding that is not seen in the human epilepsy families is the predominance of males among the affected dogs in several dog breeds. A similar inheritance pattern in human disease has been attributed to paired mutations on the X chromosome and in the mitochondrial DNA in these breeds. Our ultimate goal is to produce a DNA marker that breeders can use to avoid matings that will result in new generations of epileptic dogs.

Completed Grant No. 1415:     Traits of Cutaneous Mast Cell Phenotype and Function Associated with Predisposition to Canine Atopic Dermatitis
Researcher: Bruce Hammerberg, DVM, PhD, MS, North Carolina State University
Sponsor(s): Bull Terrier Welfare Foundation, Dalmatian Club of America Foundation, Inc., MB-F, Inc., Random Individuals, Westie Foundation of America, Inc.
DCAF Funding: $5,000.

    Abstract: In this study, researchers found different function and appearance in mast cells of dogs with atopic dermatitis (AD). This finding supports the hypothesis that there is a genetic basis for AD that can be defined with further work, though the genetic component of the issue is most assuredly complex. AD in dogs causes chronically relapsing itchy, inflamed skin, resulting in a miserable dog. The study provided the basis for ontinued research that will help scientists understand the mechanisms of the increased mast cell activity, with the eventual goal of developing a test that can be given to puppies to determine their risk of developing allergic dermatitis in the future. Such a test could help breeders make decisions about the breeding potential of puppies, and arm owners with information that could help them prevent or slow the onset of allergies.

Completed Grant No. 1840:     Studies of the Host (Canine) Immune Response to the Opportunistic Pathogen Malassezia pachydermatis
Researcher: Daniel O. Morris, DVM, University of Pennsylvania
Program Area: Treatment
Sponsor(s): American Spaniel Club Health Foundation, Basset Hound Club of America, Inc., Dalmatian Club of America Foundation, Inc., English Springer Spaniel Field Trial Association Foundation, Random Individuals, Westie Foundation of America, Inc.
Project Dates: 7/8/1999 to 1/14/2002
Grant Amount: $18,585.00
DCAF Funding: $500.

    Abstract: This study confirmed that the immune system of allergic dogs recognizes a specific yeast as a contributor to allergies that the dog's body is mounting an allergic response to the yeast, not just reacting to a yeast infection. The yeast, Malassezia pachydermatis, is present in many dogs with skin allergies, causing itching, infection and sometimes licking to the point of self-mutilation. The most common symptoms of the yeast are ear canal infections and paw licking. Dogs with the yeast allergy can react to a quantity of yeast that would be considered within normal limits for healthy dogs. This discovery provides evidence and hope that it might be possible to manage that allergic reaction through the development of yeast-specific allergy shots, rather than relying on anti-fungal medications, which carry a possibility of side effects and don't stop the allergic reaction from recurring.

Active Grant No. 2434:     Recombinant Thyrotropin (TSH): Standard for the Next Generation of Canine TSH Immunoassays with Improved Sensitivity
Researcher: Duncan Ferguson, DVM, PhD, University of Georgia
Sponsor(s): Airedale Terrier Club of America, Akita Club of America, Inc., American Belgian Malinois Club, American Boxer Charitable Foundation, American German Shepherd Dog Charitable Foundation, Borzoi Club of America, Clumber Spaniel Club of America, Collie Health Foundation, Dalmatian Club of America Foundation, Inc., English Setter Association of America, Golden Retriever Foundation, Italian Greyhound Club of America, Keeshond Club of America, Komondor Club of America, Miniature Pinscher Club of America, Inc., Norwegian Elkhound Association of America, Inc., Petit Basset Griffon Vendeen Club of America, Portuguese Water Dog Foundation, Random Individuals, Rhodesian Ridgeback Club of the United States, Scottish Terrier Club of America Health Trust Fund
DCAF Funding: $1,300.

    Abstract: Hypothyroidism, a failure of the thyroid gland, is the most common hormonal abnormality in dogs, causing a variety of medical problems in many breeds, including hair loss and skin infections. The measurement of serum levels of the pituitary hormone thyrotropin (TSH) has been used as a reliable and sensitive screening test for thyroid glandular insufficiency in human medicine for many years, but the "first generation" assays for canine TSH (cTSH) are missing as many as 1 out of 4 cases of hypothyroidism, resulting in no improvement in diagnostic sensitivity compared to total T4 measurement. Furthermore, the available assays have not been sensitive enough to distinguish low values of cTSH from those in the normal range. Towards the goal of improving current and future immunoassay sensitivity based upon a pure recombinant canine TSH (cTSH) hormone standard, our laboratory has succeeded in cloning and sequencing the two peptide subunits of canine TSH and have expressed them in small quantities. Using techniques recently developed in our parallel work on equine TSH, we plan to express and purify recombinant canine TSH in high quantities and validate its use as a pure immunoassay standard to facilitate its worldwide use.

Active Grant No. 2234:     Basophil/Mast Cell Response to Lectins as a Predictor for Risk of Allergic Disease in Genetically Susceptible Dogs
Principal Investigator: Bruce Hammerberg, DVM, PhD, North Carolina State University
Sponsors: 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.
DCAF Funding: $1,600.

    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-alpha), 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- alpha, 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 non-atopic 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-alpha release stimulated by lectins.

Active Grant No. 1870:     Genetics of Hereditary Deafness in the Domestic Dog
Principal Investigator: Keith E. Murphy, PhD, Texas ASM University
Sponsor(s): Dalmatian Club of America Foundation, Inc., English Setter Association of America
DCAF Funding: Continuation of initial grant.

    Abstract: Congenial deafness has been reported for approximately 60 breeds, and can potentially appear in any breed. The disorder is usually associated with pigmentation patterns, where increasing amounts of white in the hair coat increase the likelihood of deafness. Pigment-associated inheritance of deafness is not restricted to dogs. Similar defects have been repotted for mice, mink, pigs, horses, cattle, cats and humans. Waardenburg syndrome type 2 (WS2) in humans presents with congenital deafness and hypopigmentation of the eyes and head hair. This is an autosomal dominant disorder with incomplete penetrance, meaning that individuals that inherit the disorder may not show all of the components of the syndrome. Mutations in the mitf gene cause at least twenty percent of cases of WS2. Piebaldism in humans most commonly presents with congenital patches of white skin and hair lacking melanocytes on certain parts of the body, although deafness is a characteristic of the disorder in an unknown percentage of affected individuals. Mutations in the kit gene are responsible for typical cases of piebaldisms. We believe that deafness in dogs may result from mutations in the canine mitf/kit genes. Examination of these genes and identification of causative mutations will aid in understanding the etiology of deafness.

Active Grant No. 2264:     Whole Genome Screens Using Microsatellite Markers in Genetic Analyses of Hereditary Deafness in the Dalmatian and English Setter
Researcher: Keith E. Murphy, PhD, Texas A&M University
Sponsor(s): Dalmatian Club of America Foundation, Inc., English Setter Association of America
DCAF Funding: $12,500.

    Abstract: Hereditary deafness has been reported for approximately 60 breeds, and can potentially appear in any breed. The disorder is often associated with pigmentation patterns, with increasing amounts of white in the hair coat increasing the likelihood of deafness. Pigment-associated inheritance of deafness is not restricted to dogs. Similar defects have been reported for mouse, mink, pig, horse, cattle, cat and human. High incidences of deafness are found in the Dalmatian and English Setter. Deafness in these breeds presents unilaterally (with no preference for either ear) or bilaterally and recent research suggests that more than one gene is involved. Therefore, in an effort to identify such genes, we will carry out analysis of the entire genome rather than restricting studies to one or two genes. By using this approach, termed linkage analysis, we hope to identify markers present in affected dogs. Informative markers will allow selection and subsequent examination of candidate genes for mutations that play roles in deafness of the aforementioned breeds. The long-term objectives of this work are to 1) develop marker or gene-based tests to identify carriers and to reduce the incidence of deafness, and 2) understand the etiology of deafness in the Dalmatian and English Setter.


RESEARCH PROJECTS FUNDED EXCLUSIVELY BY DCAF

Active DCAF Grant No. 1:     Studies on Urate Urothiasis in Dalmatians
Researcher: Joseph W. Bartges, DVM, PhD, University of Tennessee
Sponsor(s): Dalmatian Club of America Foundation, Inc.
DCAF Funding: $30,000.

    Urinary stone disease occurs commonly in Dalmatians, and is most often composed of uric acid (urate). Dalmatians have a higher risk for forming urate stones because they metabolize uric acid differently than most other breeds of dogs. Urate stones may be dissolved using special diets and a drug, called allopurinol; however, success is variable, and urate stones are highly recurrent. One problem with urate stones is that they are not usually visible on plain x-rays, which means they may be missed. Some believe many Dalmatians form urate stones in their kidneys, which may be associated with recurrent stone formation, abdominal pain, and possible kidney failure. The proposed study will evaluate two issues: 1) how commonly urate stones occur in kidneys from Dalmatians, and, 2) how effective preventative measures are for urate stones in Dalmatians.


PUBLICATIONS AND EDUCATIONAL ACTIVITIES FUNDED EXCLUSIVELY BY DCAF


Parent Club Health Conference
DCAF has contributed by covering travel expenses and sending a participant to the AKC parent Club conference each year, since the inception of the Parent Club Conference in 2002. We plan to continue this worthwhile endeavor.

DCAF Funding: $900 (Approximate).


Urinary Stone Pamphlet
DCAF funded the printing and mailing of the Urinary Stone Pamphlet to the entire DCA membership. The pamphlet was also sent to Dalmatian Clubs in other countries. The pamphlet has been particularly useful as a hand out to Veterinarians for their use in the explanation of and information on stone disease.

DCAF Funding: $11,000.00 (approximate).


Dalmatian Health Survey
DCAF funded the printing, mailing and the data collection analysis of the Health Survey on Dalmatians. Through this survey we were able to determine the prevalence of various Dalmatian related diseases and disorders. The results from this survey are being used to help us determine which grants to fund.

DCAF Funding: $1,528.00


Dalmatian Health Screening 2005 National Specialty
DCAF is funding a large portion of a comprehensive health screening program that is being conducted in conjunction with the 2005 DCA Centennial National Specialty Show. Included will be screenings for CERF, Thyroid, Bladder Ultrasound, Urinalysis, and BAER.

DCAF Funding: $5,000 (Estimate).


CHIC Hearing Registry
DCAF is funding the hearing database associated with the collection of BAER hearing results on entire litters tested. In order to take part a breeder, after having a litter BAER hearing tested, can send to OFA the results and have the litter registered at no cost to the breeder. This grant should cover all litters registered by DCA members for the next 2 or 3 years.

DCAF Funding: $2,000.


Educational Speakers
DCAF has funded speakers that were invited to address the DCA membership at the National Specialty Show on topics of interest to the fancy.

DCAF Funding: $5,000 (Approximate).


Membership Education Booklet
DCAF has funded the development and publication of a membership education booklet that covers a broad range of health topics related to the Dalmatian, as well as education materials. This booklet was distributed to the entire DCA membership.

DCAF Funding: $3,000 (Approximate).



RECUE ACTIVITIES FUNDED BY DCAF
DCAF, on an ongoing basis, offers financial support to DCARE the Dalmatian Club of America Rescue Education. The goal of DCARE is to help increase the likelihood of successful rescue placements and to ensure that the placements are in the best interest of the public, the dog and the breed. DCAF and DCA Funded $1,000. as seed money for Rescue. Additional contributions allowed for a total of $1,752. to have been spent by DCARE for rescue efforts to date.

CURRENT STUDIES

02297-MOU: Understanding the Genetics of Hepatic Copper Toxicosis in the Dalmatian
Study PDF

Grant 02263-MOU: Characterization of Kidney Disease in Dalmatians
Study PDF

Grant 02172-MOU: Understanding Hereditary Deafness in Dogs
Study PDF

Grant 02157-MOU: Genomics of Deafness in the Dalmatian
Study PDF

This page last updated on December 6, 2016

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