YTCAF Donor Program

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    YTCA Foundation
    526 N West Avenue PMB 46
    Arlington, WA 98223
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2010 Research Funded by YTCAF


Each year the AKC Canine Health Foundation send the YTCA Foundation a list of grant requests for funding that they have screened and think would be of interest to breeders and owners of Yorkshire Terriers as well as dog fanciers in general. As an independent entity spun off from the Parent club to preserve our tax exempt status, the YTCAF receives no financial support from the YTCA's participating in efforts such as the Purina Circles program. Instead all of our funding comes from memorials made by individual donors and fund raising efforts such as the online auctions and breeding calendar sales. There are currently no matching funds available to increase the size of our donations. Thus our research budget for the remainder of 2010 was limited to $7,000.

In August 2009 fourteen grants were submitted to the YTCA Foundation for consideration. The Board members carefully considered these factors in each of the requests in order to optimize research dollars:

  1. Potential of the research to benefit Yorkshire Terriers in particular and all dogs in general.

  2. Previous research success of the primary investigators

  3. Use of the grant project to help veterinary students, new veterinarians and academicians get started in their chosen field of research (Acorn projects).

After a 2-month investigative process the Board voted to support the following CHF grants for 2010.

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Rabies Challenge Fund

$500

W. Jean Dodds, DVM, Hemopet and Ronald Schultz, DVM, University of Wisconsin

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This is a long term study that is ongoing and studying the long term effects of the rabies vaccine over a consecutive period of time.

There are two concurrent canine rabies vaccine challenge studies (one for 5 years and one for 7 years), a study of canine rabies vaccine adjuvants, and a rabies vaccine adverse reactions reporting system. The primary purpose of the Fund is to improve the safety of canine rabies vaccines and to determine, by challenge, if they confer longer immunity than currently established.

The YTCA Foundation voted to increase funding of this ongoing and important research project by $500. Currently there is an anonymous donor who has committed to match funding up to $10,000 during the month April 2010 and the Foundation took advantage of this offer which makes our matched contribution $1,000.

CHF Grant 1312: Association Mapping Study of Legg-Calves-Perthes Disease in West Highland White Terrier, Yorkshire Terrier, and Miniature Pinscher

$2,500

Clemson University

Keith E. Murphy, PhD and Alison Starr-Moss, PhD

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Project Abstract

Legg-Calve-Perthes Disease (LCPD) is a debilitating developmental disease that affects small breeds of dog, particularly terrier breeds. The only outward indications of this condition are pain, lameness, and muscle atrophy of the hip joint. These signs are not exclusive to LCPD, and are often attributed to minor trauma during the early stages of disease. LCPD is primarily diagnosed by radiographic changes of the femoral head within the hip joint. Due to the developmental nature of the unknown etiology of the disease, LCPD is difficult to predict and prevent. No disease mapping strategies have been employed to date.

This study is using the Affymetrix canine single nucleotide polymorphism (SNP) chip to identify regions that are linked to LCPD in the West Highland White Terrier, Yorkshire Terrier, and Miniature Pinscher breeds.

FINAL REPORT 6-18-14

Legg-Calve’-Perthes Disease (LCPD) is a developmental orthopedic disorder of the coxofemoral joint that is observed in humans and dogs. A loss of vasculature in the developing femoral head leads to necrosis and subsequent microfracture of the capital femoral epiphysis. The resultant articular incongruency reduces joint stability and can cause secondary osteoarthritis. LCPD is among the most common hip disorders diagnosed in children. In humans, private mutations have been identified in COL2a1, but sequencing in dogs did not reveal any causative mutations (Starr-Moss et al. 2012). The etiology of LCPD remains poorly understood, and genetic and environmental factors are expected to play a role in the disease. LCPD most commonly affects breeds of small stature, including the West Highland White Terrier (WHWT), Yorkshire Terrier (YT), Cairn Terrier (CT), Schipperke (SCH) and Poodle (PDL). A multi-breed genome-wide association study was undertaken to identify loci contributing to canine LCPD.

This study aimed to identify genomic regions associated with Legg-Calve-Perthes Disease (LCPD) in terrier breeds, including West Highland White Terriers (WHWY), Yorkshire Terriers, and Cairn Terriers. To this end, we have completed a genetic study using a population of 129 dogs (51 LCPD-affected, 78 controls). Optimally, we hoped to identify a major locus causing LCPD in dogs, and identify a marker that could be reliably used to predict and prevent cases of LCPD.

Our initial goal was to collect blood samples from 200 dogs of the three aforementioned breeds; however, insufficient numbers of study participants were obtained. Two additional breeds, Schipperkes and Fox Terriers, significantly increased the numbers of study participants; seven additional breeds submitted (5 samples. In total samples from 205 dogs were submitted to our laboratory for this work. From these samples, 163 genetic profiles were generated. Our methods were changed midway through this grant period to produce better quality data. While 163 genetic profiles were generated, 39 samples were repeated between the two methods.

LCPD has been proposed to be an autosomal recessive disease. Our study results do not support this hypothesis. LCPD appears to be genetically complex, likely with several genes contributing to the onset of clinical signs.

The analyses of our data did not reveal a major locus shared among the breeds that could explain the onset of LCPD. Individual regions identified from the analyses are being examined further for genotypes that are highly correlated with LCPD and that may be used as predictors of LCPD. There are no immediate candidate genes to sequence, nor is there a test at this time to avoid producing LCPD. One candidate gene identified from human cases of LCPD, COL2A1, was sequenced in affected and control WHWT and excluded as being involved in canine LCPD. Additional analyses with new software programs are being carried out. It is our hope that these secondary analyses will help dissect the complex genetic control of LCPD. Further work remains necessary to elucidate these mechanisms.

Importantly, however, it appears as though there are subclinical LCPD-affected dogs in terrier populations. As samples were collected for this study, a family of fox terriers with three LCPD dogs shared a sire, but occurred in different litters with unrelated dams. After radiographing the littermates and parents of these affected dogs, four additional LCPD-affected dogs were diagnosed, based on characteristic hip changes. In this family, the percentage of affected dogs increased from 12% to 32% after detailed radiographic examination. The 4 previously unknown LCPD dogs had no history of trauma or limping. A manuscript is in preparation describing this family of fox terriers, and recommending the radiographic evaluation of dogs with LCPD relatives, even in the absence of clinical signs.

PUBLICATIONS:

Starr-Moss, A. N., Nowend K. L., Alling, K. M., Zepp, E. J., Murphy, K. E. (2011) Exclusion of COL2A1 in Canine Legg-Calve’-Perthes disease. Animal Genetics. Doi: 10.1111/j. 1365-2052.2011.02215.x

Additional manuscript in preparation.

UPDATE 1-9-13

This study aims to identify genomic regions associated with Legg-Calve-Perthes Disease (LCPD) in terrier breeds, including West Highland White Terrier (WHWT), Yorkshire Terriers (YT), and Cairn Terriers (CT). To this end, we have completed a preliminary association study in a subset of our study population. One candidate gene has been sequenced in WHWT and excluded as being involved in canine LCPD.

Our initial goal was to collect blood samples from 200 dogs of three breeds; however, insufficient numbers of study participants were obtained. Two additional breeds, Schipperkes (Schip) and Fox Terriers, have increased the numbers of study participants from 76 to 179. Relatedness among study participants is currently being assessed; thus the total numberof samples available for the full-scale study are expected to be fewer than the total number presented here. These numbers still may not be sufficient to detect an association, given that LCPD is believed to be genetically complex, and we are examining five breeds as opposed to three. Plans for the remaining grant period include 1) genotyping the remaining WHST, YT, CT, and Schip samples with the illumine SNP array, 2) completing data analysis for the total study population.

UPDATE 6-30-11

This study aims to identify genomic regions associated with Legg-Calve-Perthes Disease (LCPD) in terrier breeds, including West Highland White Terriers (WHWT), Yorkshire Terriers (YT), and Cairn Terriers (CT). To this end, we have completed a preliminary association study in a subset of our study population. One candidate gene has been sequenced in WHWT and excluded as being involved in canine LCPD

Our goal is to collect blood samples from 200 dogs of three breeds: 100 affected and 100 unaffected. To date, we have received 32 affected and 44 unaffected dogs, only about one-third of our desired numbers. The statistical analyses of SNP data from 76 dogs, as opposed to 200 dogs, may not be sufficient to detect an association, given that LCPD is believed to be genetically complex. To help increase study participants numbers, two additional breeds are being considered for inclusion: Fox Terriers (63 samples received) and Schipperkes (21 samples received). Plans for the remaining grant period include 1) genotyping the remaining WHWT, YT, and CT samples with the Affymetrix SNP array, 2) adding the Fox Terrier and Schipperke breeds to the study to increase study participant numbers, and 3) completing data analysis for the total study population.

To help enable this project to fully investigate LCPD as originally designed, please participate in this study by providing DNA samples from affected and unaffected dogs. Interested owners willing to participate can find submission instruction at www.clemson.edu/cgr/. Questions regarding this study should be directed to Dr. Alison Starr-Moss, (astarr@clemson.edu).

UPDATE 12-31-10

Objective: This study is using the Affymetrix canine single nucleotide polymorphism (SNP) chip to identify regions that are linked to LCPD in the the West Highland White Terrier, Yorkshire Terrier, and Miniature Pinscher breeds.

Objective 1 of 2: Sample collection and phenotype confirmation. Collect a total of 200 samples with a minimum of 50 per breed.

This study aims to dissect the genetic component(s) of Legg-Calve-Perthes Disease (LCPD) in terrier breeds through genomic analyses. Previous studies have suggested LCPD is transmitted in an autosomal recessive pattern. Our current data suggest the LCPD is inherited in either a dominant or complex fashion. Only with more samples will we begin to understand the genetics controlling LCPD. One candidate gene identified in humans was investigated in canine LCPD, but was not associated with LCPD in West Highland White Terriers.

Interested owners willing to participate in the study are referred to submission instructions found at www.clemson.edu/cgr. Questions regarding this study should be directed to Dr. Alison Starr (astarr@clemson.ed

UPDATE 8-04-10

Legg-Calve-Perthes Disease (LCPD) is a debilitating orthopedic disease that is primarily treated by surgical excision of the affected femoral head and neck of young (<18 months of age ) dogs. At least 26 breeds have reported LCPD occurrence. We are initially focused on the West Highland White Terrier (WHWT), Yorkshire Terrier (YT), and Cairn Terrier (CT) breeds, but our research has the potential to apply to other terrier and small breeds. This study aims to dissect the genetic component(s) of LCPD in terrier breeds through genomic analyses.

Our strategy consists of collecting blood samples from affected and normal terrier breeds, and completing a whole-genome association study using a commercial SNP array. Genotypes for each dog will be assigned using computer algorithms and analyzed using statistical software. Genomic regions that produce statistically significant scores will be further examined for candidate genes. Two hundred samples are anticipated for the completion of this work; 100 normal, and 100 LCPD-affected. Of these, 70 have been collected (42 normal, 28 affected). Preliminary work has commenced with a small number of dogs, however, additional samples from all three breeds - YT and CT, in particular - are required to complete the full-scale analyses. Interested owners willing to participate in the study are referred to submission forms and instructions found at www.clemson.ed/cgr. Questions regarding this study should be directed to Dr. Alison Starr (astarr@clemson.edu). 

YTCAF provides funding support for new Legg-Calve-Perthes Disease (LCPD) Study

In January 2010 the YTCAF voted to provide $2,500 funding support for a new Legg-Calve-Perthes Disease study being conducted by Dr. Keith Murphy, Ph.D. Chair of the Department of Genetics and Biochemistry and Dr. Alison Starr, Ph.D., Research Assistant Professor, both of Clemson University in South Carolina.

LCPD is a bone disease in which the head and neck of the femor (thigh bone) die due to lack of blood supply. Either the left or right leg may be affected or both. It is termed a developmental disease because it is usually seen in young dogs (4-11 months of age) and affected breeds are usually toys or miniatures. Yorkshire Terriers are among the affected breeds. The disease is thought to be caused in part by genetics with both parents contributing a recessive gene. Since either sex may be affected, the mode of transmission is thought to be autosomal recessive. The role of other environmental factors is as yet unclear.

Young dogs who are afflicted usually demonstrate pain, lameness and/or wasting of the muscles at the hip joint. Treatment requires costly surgical intervention via removal of the femoral head or total hip replacement ($1,000-$5,000 minimum cost). LCPD is a condition that has proved difficult to either predict or prevent. Thus finding the cause of LCPD will benefit breeders, owners and the affected dogs alike.

Drs. Murphy and Starr hope to identify the affected genes using DNA analysis and sequencing via 50 blood samples donated from affected pet (25) and normal (25) Yorkshire Terriers in the United States, Canada and other countries around the world. Their ultimate goal is to develop a genetic test that would identify both affected individuals and carriers so that they could be excluded from breeding programs.

CHF Grant 1352-A: Detection of Brucella canis DNA in Canine Urine, Semen and Vaginal Cells via qPCR Analysis

$500

Iowa State University

Lin Kaufman, DVM

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Project Abstract

Brucella canis is a bacteria that causes reproductive disorders in dogs. The number of B. canis cases has been on the increase across the US and specifically the Midwest over the past several years with increasing costs associated with reproduction losses due to disease and euthanasia of infected animals. Prevalence in Oklahoma alone has risen from 2% in 1994-95 to 13% in 2002-03. The potential for human infection from dogs increases concern over this disease. Currently the only available tests for this disease are microbiological cultures and serological testing. Microbiological culture of the blood, vaginal secretions, semen or fetal placenta is the diagnostic gold standard since a positive culture confirms the disease. Unfortunately the organism is hard to culture under the best conditions. Serological tests detect the disease 8-12 weeks postinfection and cannot detect early disease, from the time of infection until when there are detectable levels of anti-Brucella antibodies.

At present, laws make canine brucellosis a reportable disease subject to quarantine. In some states this mean testing all breeding animals and euthanasia of infected animals. The economical impact of quarantine and repeated testing is such that there is potential for individuals to have their dogs tested out of state to avoid quarantine, sell known infected animals and/or to medically treat potentially infected animals to avoid detection with current tests. Brucella canis has infection potential to humans, especially the very young, elderly and immunocompromised individuals. Currently there is no early detection testing available for this disease. Early detection of disease would shorten the quarantine period and would add a measure of safely for buyers of puppies or breeding stock. The goal of this project is to use the Polymerase Chain Reaction (qPCR) based assay to detect Brucella sp. in field samples of suspect B. canis urine (male), semen and vaginal cells and compare how well this test works verses traditional culture and serology.

UPDATE 7-31-10

Brucella canis, a bacteria that causes reproductive disorders in dogs, has been on the increase across the US. This goes hand in hand with increasing costs associated with reproduction losses due to disease and euthanasia of infected animals. The potential for human infection from dogs increases concern over this infectious disease. Currently the only available tests for this disease are not great. The bacteria is hard to culture and serological tests detect the disease 8-12 weeks post-infection but cannot detect early disease. Present laws make canine brucellosis a reportable disease subject to quarantine. In some states this means testing all breeding animals and euthanasia of infected animals. Early detection of disease could shorten the quarantine period and would add a measure of safety for buyers of puppies or breeding stock. The goal of this project is to use Polymerase Chain Reaction (qPCR) assay to detect Brucella sp. in samples of suspect B. canis urine (male), semen and vaginal cells (female) and compare how this test works vs. traditional culture and serology.

To find a more specific and timely diagnostic, this study assessed the ability of qPCR analysis to detect B. canis Omp25 DNA in a variety of samples (blood, urine, vaginal swab) and compared those results against current detection methods for B. canis infection in dogs (serology). qPCR analysis identified the presence of B. canis Omp25 DNA in multiple dogs prior to seroconversion. Non-invasive samples from the genito-urinary tract, including vaginal swabs and urine, were found to be the most sensitive for detection of B. canis Omp25 DNA via qPCR. Use of these samples would make collection of diagnostic samples within the ability of some dog owners and breeders.

The results of this study are very encouraging for use of B. canis Omp25-specific qPCR as a diagnostic screening tool for B. canis. The potential of this assay qPCR for early detection could be very valuable for elimination of B. canis from kennels without having to wait for seroconversion. Additionally, Omp25 qPCR could be a valuable screening tool for B. canis in newly purchased dogs prior to adding these dogs into a new home or kennel. B. canis is a reemerging infectious disease in the canine breeding industry.  A better screening and detection method will be very useful to prevent further spread of this insidious disease. B. canis Omp25 qPCR may be this critical diagnostic component to decrease economic effects of canine brucellosis on the canine breeding industry and prevalence of canine brucellosis in the US.

YTCAF Board's Assessment

The bacterium Brucella canis causes major canine reproductive problems, and the incidence has been on the rise in recent years. It is a major concern to both breeders and purchasers of dogs because current tests to detect its presence take between 2 and 3 months to complete. Concurrently brucellosis is a zoonosis and spreads easily to humans. For this reason it is a reportable disease and affects dogs have to be either quarantined or euthanized. Dr. Kauffman is seeking to use an assay based on the Polymerase Chain Reaction (qPCR) technique (which is very fast) as a detection tool and compare these results with standard test results to see if this new technology would be a more accurate and faster method of testing dogs for the presence of B. canis. Previously Dr. Kauffman has been a featured speaker on the CHF Genome Barks podcasts.

Amount Funded by YTCAF = $500. Rationale for support of this grant:

The YTCAF voted to support this research because of its importance to all dogs including Yorkshire Terriers. Breeders are aware of the disastrous consequences of having breeding stock infected with B. canis. Additionally this bacterium can cause serious illness in humans.

CHF Grant 1105: Understanding the Dynamics of Canine Influenza Virus Transmission in Dog Populations and Intervention Strategies for Reducing Transmission

$2,500

University of Florida - 2010

Cynda Crawford, DVM PhD

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Project Abstract

Canine influenza is a newly emerging and highly contagious respiratory infection of dogs caused by a novel influenza A virus of the subtype H3N8. The canine influenza virus (CIV) has caused respiratory disease outbreaks in thousands of dogs housed at greyhound race tracks, boarding/training kennels, and shelter facilities across the U.S. Although most dogs recover, many develop a debilitating pneumonia that can be fatal. There is no information on whether dogs housed in different types of premises are more or less at risk for canine influenza. For this study, we will analyze data from previous canine influenza outbreaks to determine if dog populations in different types of premises have different risk for canine influenza. Using the results from this analysis, we will develop a computer model to investigate parameters important to CIV transmission in dog populations at race tracks, boarding/training kennels, shelters facilities, and dog shows. The model will then be used to determine what intervention strategies (vaccination, quarantine, sanitation) are most effective in reducing or preventing virus transmission. The results of this study will provide valuable information to dog show organizers and others responsible for the health of dogs in other settings, to guide development of policies for control and prevention of canine influenza.

UPDATE 12-31-2011

Canine influenza is a highly contagious respiratory infection of dogs caused by a novel inflenza A virus of the subtype H3N8. H3N8 canine influenza virus (H3N8 CIV) has caused respiratory disease outbreaks in thousands of dogs located in 38 states in the U.S. Although most dogs recover from an influenza-like illness, many develop a debilitating pneumonia that can be fatal if not treated under hospital care.

There is little information on risk factors for canine influenza, either for individual dogs or for facilities that house dogs. In our first epidemiological study, location in the Northeast and West regions of the coutnry and housing in animal shelters and boarding facilities were identified as risk factors for H3N8 CIV infection of dogs. We are currently completing a second epidemiological study focused on identifying kennel facility parameters such as population density, source and frequency of introduction of new dogs, sanitation practices, disease surveillance and infection control protocols that may increase the risk for canine influenza outbreaks.

Since shelters are a risk factor for virus exposure, we constructed a mathematical model to simulate H3N8 CIV transmission in shelters to determine factors important to development of outbreaks and establishment of endemic infection. This study identified indirect virus transmission by contaminated fomites and the number of dogs housed in the shelter as the most important factors promoting canine influenza outbreaks. Isolation of sick dogs, vaccination against canine influenza, vaccination and isolation combined, and stopping admission of new dogs were four common intervention strategies applied to the model to determine their effect in reducing or preventing virus transmission. Analyses indicate that neither isolation nor vaccination alone or in combination can completely eliminate virus transmission in a shelter under the modeling conditions employed. However, these strategies can reduce the number of infected dogs during outbreaks. While stopping admissions of new dogs did not prevent outbreaks, this intervention strategy prevented establishment of endemic infection in the shelters.

An individual-based model to simulate H3N8 CIV virus transmission in dog shows was also developed. Overall, the model as constructed had an excess of infectious contacts, thus reducing any one mode of virus transmission did not necessarily have a strong effect on the number of infected dogs leaving the show. The number of infected dogs leaving the show was most affected by the probability of contact between all dogs, either by direct transmission of virus between dogs or indirect virus transmission by fomites, including contaminated judges. Increased efforts to decontaminate judges only caused a slight reduction in the number of infected dogs when at least 90% of the dogs were vaccinated against canine influenza prior to the show.

The overall results of these studies provide valuable information to dog show organizers and kennel facility managers for guiding the formulation of policies for prevention and control of canine influenza.

Update 12-31-2010

Canine influenza is a recently emerging, highly contagious respiratory infections of dogs caused by a novel influenza A virus of the subtype H3N8. Canine influenza H3N8 virus (CIV) has caused respiratory disease outbreaks in thousands of dogs housed at greyhound race tracks, boarding kennels, and shelter facilities across the U. S. Although most dogs recover, many develop a debilitating pneumonia that can be fatal. There is currently no information on risk factors for canine influenza, either at the individual dog or premise level. For this study, we are analyzing data from previous canine influenza outbreaks to determine if individual dog or premise-related factors influence the risk of CIV infection. We are currently working on epidemiological studies to analyze both individual dog factors (age, breed, sex, geographic location) and premise level factors (population density, source and frequency of introduction of new dogs, adequate quarantine facilities, adequate surveillance and infection control protocols, and geographic location of the facility). We are concurrently developing a simulation model to investigate parameters important to CIV transmission in dog populations at shelter facilities, with the intent to extrapolate this model to dog populations at racetracks, boarding kennels, and dog shows. Once the model is complete, we will then assess what intervention strategies (vaccination, quarantine, sanitation) are most effective in reducing or preventing virus transmission in different premise types. The results of this study will provide valuable information to dog show organizers, and those responsible for the health of dogs in other kennel settings, to guide development of policies for control and prevention of canine influenza.

UPDATE 6-30-10

The Report to Grant Sponsor from Investigator is identical to the 12-31-09 update.

YTCAF Board's Assessment

The new H3N8 Canine Influenza Virus (CIV) was first observed in greyhound kennels several years ago. It is thought to be a mutation of a horse virus. Since then there have been sporadic outbreaks. While the majority of dogs survive the viral infection, a small proportion die as a result of the subsequent pneumonia. The purpose of this study is to map out the epidemiology of this new virus; how is it transmitted, what parts of the canine population are at greatest risk, and what treatments have been most effective. A compute model will then be created and used to predict what efforts will be most successful at stopping the spread of the Virus and reducing the opportunities for transmission between dogs. This model could then be used by planners of dog events, boarding/show kennels, etc. Dr. Crawford has been studying this virus for the past several years in Florida and currently holds the provisional patent on a new vaccine against H3N8. She hold a PhD in Immunology/Infectious Diseases as well as a DVM.

Amount Funded by YTCAF = $2,500. Rational for support of this grant:

The YTCAF voted to support Dr. Crawford's research because of its direct implications for the planning of all competitive AKC dog events, as well as individual show kennels. Recent outbreaks of H3N8 in New Jersey and Northern Virginia have highlighted the need to know how this virus is spread and which dogs are at greatest risk.

CHF Grant 1341-A: Sample Collection, Pedigree Analysis and Candidate Gene Screen for Protein-Losing Enteropathy in Yorkshire Terriers

$2,000

Cornell University - 2010

Nate Sutter, PhD

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Project Abstract

Protein-losing enteropathy (PLE) is a life threatening condition diagnosed in many breeds including Soft Coated Wheaten Terrier, Basenji, Lundehund, Chinese Sharpei and Yorkshire Terrier.  The syndrome is particularly prevalent in Yorkshire Terriers.  These dogs commonly suffer from chronic diarrhea and lose protein into the intestine.  A variety of abnormalities in the intestinal lining are thought to be involved.  While dietary changes sometimes help, treatment is supportive rather than curative.  As many as half or more of all Yorkshire Terriers diagnosed with PLE ultimately succumb to it.  We want to identify the genetic risk factor or factors that predispose Yorkshire Terriers to this syndrome.  These genetic factors may also be present in other breeds, a hypothesis that can be tested once the factors are identified in Yorkshire Terriers.  Here, we propose to collect blood samples for DNA, pedigrees, and clinical data from affected and unaffected Yorkshire Terriers.  We will analyze the pedigrees for patterns of coancestry.  We will also sequence a gene, syndecan l, that is a key player in PLE in people, as we hypothesize it plays a role in canine PLE.

UPDATE 5-31-10

Yorkshire Terriers and other purebred dogs suffer from a debilitating protein-losing enteropathy (PLE) syndrome of uncertain causes.  The disease presentation frequently includes diarrhea, vomiting, inappetance, panhypoproteinemia, and weight loss.  Intestinal histopathology is dominated by lymphangiectasia.  Recently, crypt 'cysts" containing proteinaceous material have been described (Kenneth Simpson, personal communication), PLE is frequently fatal in Yorkshire Terriers, and the complexity of presenting complaints, as well as the variable age of onset, suggests the syndrome may be under-diagnosed.  The relative risk for Yorkshire Terriers is above 10 and suggests that one or several heritable components predispose members of this breed to PLE. 

We continue to recruit PLE affected and older unaffected Yorkshire Terriers for a pedigree analysis of co-ancestry among affected dogs, DNA collection and medical data analysis.  To date, we have collected 66 out of 100 samples.  The candidate gene screen of syndecan 1 proposed in this project has so far found no evidence that sequence variation at this gene associated with PLE in the Yorkshire Terrier.

YTCAF Board's Assessment

Of the many breeds of dogs that are diagnosed with Protein-Losing Enteropathy (PLE), Yorkshire Terriers are among the most affected.  This condition is characterized by chronic debilitating diarrhea along with the loss of protein from the body  into the intestinal tract where it is passed out in the feces.  There is currently no cure and individual dogs can only be clinically helped with supportive therapy through the use of drugs and special diets.   Because of the high number of Yorkshire Terriers afflicted with PLE, Dr. Sutter will try to establish a genetic link through the collection of blood samples and pedigrees from dogs in our breed.  This information could then be extrapolated for other breeds that are similarly affected.  Dr. Sutter has been studying canine genetics for some time, Particularly the mutations that make dogs susceptible to cancer and other diseases.  Previously he was a Postdoctoral Fellow at the Fred Hutchinson Cancer Research Center and a Research Fellow at the National Human Genome Research Institute at NIH.

Amount Funded by YTCAF = $2,000.  Rationale for support of this grant:

Almost 50% of Yorkshire Terriers who have PLE die from it.  Currently there is no screening test for this disease that is suspected to have a genetic basis.  The Foundation's support of this grant will hopefully pave the way for the identification of the gene(s) responsible for PLE and the creation of a test to screen breeding stock as well as individual Yorkies for it.

CHF 1160-A: Development of Contract-Enhanced Magnetic Resonance Angiography for the Diagnosis of Congenital Vascular Liver Disease in Dogs

$1,000

University of Pennsylvania - 2010

Wilfried Mai, DVM, PhD

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Project Abstract

Porto-systemic shunts (PSS) are anomalies of the bessels to the liver (abnormal communication between the portal vein, which feeds the liver, and another veine.g. (vena cava). This results in blood from the gut not being detoxified by the liver causing clinical signs (seizures, stunted growth, fluid accumulation in the abdomen...) and ultimately death, if untreated. Most PSS are congenital. Several breeds are predisposed and some hereditary components have been documented (e.g. Maltese, Yorkshire Terriers, Irish Wolfhound, Australian Cattle Dogs, Golden and Labrador Retrievers). Diagnostic imaging techniques such as X-rays, ultrasonography, and scintigraphy are currently used to diagnose this condition, and are crucial not only to diagnose it but also to decide what the best treatment option will be. None of these techniques is perfect and all have major disadvantages so that often, several techniques must be used in conjunction to get the information needed.   magnetic resonance imaging can image blood vessels with the use of a dye --- a technique known as contract-enhanced magnetic resonance angiography (CE-MRA) --- and is now routinely used in people to diagnose many diseases of the vessels.  This technique overcomes many of the inconveniences of the other techniques and our goal is to develop this method to diagnose congenital porto-systemic shunts in dogs.

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NOTE:  Dr. Mai's grant began with CHF 5-01-2008 and is expected to end 4-30-10.

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UPDATE 4-30-10

The proposed research of utilizing contrast-enhanced portal magnetic resonance angiography (CE-MRA) in dogs to diagnose congenital liver vascular diseases was applied to 17 dogs as planned.  In all of them, the technique was easily and successfully performed, and yielded good to excellent quality images in less than 4 minutes total imaging time, which is much shorter than the current method used (singled-slice helical computed tomography angiography).  This in turns shortens total anesthesia time for diagnostic imaging in comparison with computed tomography.  CE-MRA provided diagnostic information in all 17 dogs, with excellent contrast and anatomic detail.  No complications were observed.  The three-dimensional images obtained are easily understood by the surgeons in charge of the patients.  In all 14 animals that underwent treatment through coil embolization or surgery to close-off the anomalous vessel(s), the anomalies seen on CE-MRA were confirmed.  Two of the 17 dogs have not yet undergone this procedure.  The method is very accurate in terms of anatomic depiction of the vascular abnormalities.  13 dogs were diagnosed with intra-hepatic congenital porto-caval shunts, two with an extra-hepatic shunt and one with a rare form of intra-hepatic arterio-venous fistula.  one dog did not have a macroscopic anomalous vessel identified, consistent with hepatic microvascular dysplasia.  The preliminary results were presented at the Annual Conference of the American College of Veterinary Radiology, the British Small Animal Veterinary Association Conference and the European Association of Veterinary Diagnostic Imaging British/Irish Division Conference, where they impressed the audience because of the ease and simplicity of the method, its non-invasive nature and the high-quality and diagnostic value of the images obtained.  Two very small puppies were imaged and despite the challenges associated with imaging such small patients, the studies were diagnostic in both cases and anesthesia well tolerated with uneventful recovery.  In two animals imaged, ultrasonography prior to the MRA by experienced radiologists failed to accurate describe the anatomy of the shunt or to confirm its presence.

Update 10-26-2009

The proposed research of utilizing contrast-enhanced portal magnetic resonance angiography (CE/MRA) in dogs to diagnose congenital liver vascular diseases was applied to 15 dogs so far.  In all of them, the technique was easily and successfully performed, and yielded good to excellent quality images in less than 4 minutes total imaging time, which is much shorter than the current method used (single-slice helical computed tomography angiography).  This in turn shortens total anesthesia time for diagnostic imaging in comparison with computed tomography.  CEMRA provided diagnostic information in all 15 dogs, with excellent contrast and anatomic detail.  No complications were observed.  The three-dimensional images obtained are easily understood by the surgeons in charge of the patients.  In all 11 animals that underwent treatment through coil embolization or surgery to close off the anomalous vessel(s), the anomalies seen on CE/MRA were confirmed.  Four of the 15 dogs have not yet undergone this procedure.  The method is very accurate in terms of anatomic depiction of the vascular abnormalities.  12 dogs were diagosed with intra-hepatic  congenital porto-caval shunts, two with an extrahepatic shunt and one with a rare form of intra-hepatic arterio-venous fistula.  The preliminary results were presented at the Annual Conference of the American College of Veterinary Radiology, where they impressed the audience because of the ease and simplicity of the method, its non-invasive nature and the high quality and diagnostic value of the images obtained.  Two very small puppies were imaged and despite the challenges associated with imaging such small patients, the studies were diagnostic in both cases and anesthesia well tolerated with uneventful recovery.  In two animals imaged, ultrasonography prior to the MRA by experienced radiologists failed to accurate describe the anatomy of the shunt or to confirm its presence.

YTCAF Board's Assessment

Dr. Mai is seeking to modify the technique of using contract-enhanced magnetic resonance angiography (CE-MRA) in humans for use in dogs, particularly those breeds which are known to have abnormalities of the blood vessels (i.e. Vasculature) in the liver.  Traditional methods for diagnosing porto-systemic shunts (PSS) and hepatic microvascular disease (MVD) have included radiographs (X-rays), ultrasound, and other tests like scintigraphy.  These tests often have to be use in combination to obtain an accurate picture of the extent of the problem before treatment options can be obtained.  Hopefully CE-MRA will afford a better diagnostic option for canine liver patients.  Breeds that are particularly affected include Yorkshire Terriers.  Dr. Mai holds a DVM as well as a PhD in Biomedical Engineering/Core Medical Imaging.  He has extensive research experience in the use of different radiology techniques in veterinary medicine.

Amount Funded by YTCAF = $1,000.  Rationale for support of this grant:

This technique may prove to be both superior and less invasive than currently used methods of diagnosis for canine liver disease.  This is important because accurate diagnosis often makes the difference between life and death for these dogs.  Since there is a high prevalence of Yorkshire Terriers affected by either PSS or MVD, the Foundation thought that it was important to support Dr. Mai's research.

CHF 1241-A: Detection of DNA Damage in Response to Cooling Storage in Canine Spermatozoa Using Single-Cell Gel Electrophoresis (Comet Assay)

$500

National University of La Plata - 2010

Cristina Gobello, DVM

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Project Abstract

Semen chilling facilitates damage of spermatozoa genetic pool (DNA) which is associated with poor pregnancy outcome. Knowledge of sperm DNA damage during semen storage may provide a more informed explanation of canine reproductive potential after chilling. We speculate that cool storage in milk-based semen extenders gradually lead to DNA damage which is related to decreasing sperm motility. Ejaculates will be collected from six male dogs, diluted in skimmed milk based extenders with and without egg yolk and stored at 4°C. Progressive motility, and DNA integrity will be assessed in the fresh and then daily in extended cooled semen during 7 days. Obtained data will be statistically analyzed. This project will identify the actual "storage life" of canine sperm cooled a user friendly and low cost extenders. A contribution to improvement of canine reproductive performance will be done.

UPDATE 1-24-11

Our preliminary in vitro (laboratory) results showed that sperm DNA is not severely damaged during cool storage in milk-based extenders. These diluents appear as user friendly, non-expensive and probably effective in dogs. Further in vivo (artificial inseminations) studies are warranted to confirm these promising initial laboratory findings. These preliminary results should be considered confidential until completed and published by the authors.

UPDATE 7-02-10

This project will identify the actual "storage life" of canine semen. Ejaculates have been collected from six male dogs, diluted in skimmed milk based extenders with and without egg yolk and stored at 4°C. Progressive motility decreased in all of the extenders and the DNA damage has yet to be analyzed for the samples.

YTCAF Board's Assessment

Many breeders are increasingly using chilled semen as a means of breeding dogs which are separated geographically. This eliminates the stress of shipping dogs, etc., but often results in reproductive failures. Unfortunately chilling the sperm and storing it with extenders damages the DNA. Dr. Gobello proposes to study the spermatozoa from six male dogs, tacking both the ability of the sperm to move and the integrity of the sperm's DNA, i.e. has it been broken apart or been otherwise damaged, for a period of 7 days. Her study will also investigate the variable of milk-based extenders. The resulting data could provide better guidelines for protecting the viability of chilled canine semen. Dr. Gobello has previously completed research supported by the Morris Animal Foundation. Her major interest is in canine reproductive physiology and endocrinology.

Amount Funded by YTCAF = $500. Rationale for support of this grant:

Because many breeders rely on shipment of chilled sperm to maintain their breeding programs using artificial inseminations, the YTCA Foundation felt that this research would potentially benefit everyone in the dog fancy.