Health Issues/Research
Mission Statement
To promote the health and well being of the purebred Shetland Sheepdog. We plan to accomplish this goal through research and public education. We encourage all breeders and owners of Shetland Sheepdogs to be aware of health problems in the breed and to use all resources available to them to ensure the lifelong health and well being of all Shelties in their care. We will function as a public resource and clearing house for information related to health concerns as they pertain to the purebred Shetland Sheepdog.
ASSA Research Committee Chair: Mary Mahaffey
CONTENTS
ASSA Health Activities
Notice on Genetic Diseases in Shelties
Canine Health Information Center (CHIC) Program for Shelties
Shetland Sheepdog Health Survey
CHIC DNA Repository
Current Research Projects
Articles
Current Research Projects
Study on DNA Markers for Female Infertility
Dermatomyositis (DM)
Gallbladder Disease and Hypercholesterolemia Study
Leishmaniasis Research Information
Bladder Cancer Research
Undescended Testicles (Cryptorchidism) Research
Articles
To Test or not to Test?
Considering breeding your Sheltie?
AKC Canine Health Foundation Grants
Grant#748:SNP Association Mapping of Canine Epilepsy
Notice on Genetic Diseases in Shelties
March 2008
Concerned breeders of Shetland Sheepdogs are striving to breed healthy Shelties and decrease the incidence of heritable diseases in the breed. Hip Dysplasia, thyroid disease, eye diseases, Dermatomyositis (Sheltie Skin Syndrome), von Willebrand’s disease (vWD), and epilepsy are some of the known health problems of the breed. Although these problems are NOT COMMON in the breed, the Board of Directors of the American Shetland Sheepdog Association recommends that questions about the health of the dog and its relatives be asked when inquiring about the purchasing of a puppy or adult, use of a stud dog and/or the acceptance of a brood bitch.
Does the dog and its relatives have CERF and OFA or PennHip numbers or an exam form signed by a qualified veterinarian for these tests? Does the Sheltie (adult or puppy) or its relatives have any of the above mentioned problems? Questions should also be asked about abnormal tooth alignment or missing teeth and crypt-orchidism (retained testicle).
The American Shetland Sheepdog Association (ASSA) is NOT advising you not to buy a puppy or breed to a stud dog if these conditions exist, but wants puppy buyers and breeders to be aware of genetic problems in the breed so that informed decisions can be make when buying or planning a breeding.
CanineHealth Information Center (CHIC)
Program for Shetland Sheepdogs
April 2008
Health problems, in general, are not common in Shelties; however, testing of breeding stock is a recommended practice to keep the incidence of certain problems as low as possible. It must be remembered that dogs are animals, not machines, and on average, every dog has 4 to 5 defective genes.1 Congenital and/or hereditary problems will occur no matter how conscientious a breeder is. Nonetheless, breeders should strive to breed Shelties that are a combination of beautiful breed type and good health.
The Canine Health Information Center (CHIC) www.caninehealthinfo.org/chicinfo.html is a canine health database program jointly sponsored by the AKC/Canine Health Foundation (AKC/CHF) and the Orthopedic Foundation for Animals (OFA). Its purpose is to assist breeders in breeding healthy dogs and being a central resource of health information for breeders, owners, and researchers. Over 100 breed clubs participate in the program. The national club for each participating breed recommends health tests to be performed in dogs used for breeding. The number and types of tests are tailored to the needs of each breed. Dogs that have had the required tests will receive a CHIC number, and the CHIC database can be searched for dogs having CHIC numbers. Additional health tests may be recommended, but are considered optional for that breed. Normalcy is not required for participation in the CHIC program; abnormal results of any test are only released to the public with owner permission. As new tests become available, the list of required and optional tests may be altered. Participation in the CHIC program is voluntary.
Breed requirements for Shetland Sheepdogs are as listed below and on the CHIC Shetland Sheepdog web page. www.caninehealthinfo.org/brdreqs.html?breed=SS
Required tests:
- Hip dysplasia (OFA or PennHIP)
- Eye clearance (Canine Eye Registration Foundation, CERF)
- von Willebrand's Disease (VetGen, test results registered with the OFA)
- Multiple drug sensitivity (MDR1) DNA test (Washington State University, results registered with the OFA)
Optional tests:
- Autoimmune thyroiditis (OFA evaluation from an approved laboratory, test results registered with the OFA)
- Collie eye anomaly DNA test (Optigen, test results registered with the OFA)
- Elbow dysplasia (OFA)
- Congenital cardiac database (OFA evaluation by board certified cardiologist or internal medicine specialist)
- American Temperament Testing Society, TT title, (test results registered with the OFA)
Brief Explanation of the Tests
Required tests:
Hip Dysplasia Evaluation – As of March, 2008, Shetland Sheepdogs rank 129th of 150 breeds of dogs evaluated for hip dysplasia by the Orthopedic Foundation for Animals (OFA) www.offa.org. Of 16,223 Shelties evaluated, 4.8% were dysplastic. OFA certification or PennHIP evaluation of the hips (x-ray examination) is on the required list for the CHIC program because hip dysplasia can be a crippling disorder, and one affected influential dog used in breeding programs could increase the incidence in Shelties. OFA hip evaluation results are automatically included in the OFA database with no extra charge. More information can be obtained by clicking on the following link http://www.offa.org/hipinfo.html .
Eye Certification with the Canine Eye Registration Foundation (CERF) http://www.vmdb.org/cerf.html – Eye abnormalities can occur at any age. Ophthalmic examination can detect a variety of congenital abnormalities, including Progressive Retinal Atrophy (PRA) and Collie eye anomaly (CEA), which also occurs in Shelties. The merling gene may make it difficult to detect mild cases of CEA by ophthalmic examination because merling is normally associated with less pigmentation of the eyegrounds (back of the eye). Also, the CEA lesions (chorioretinal hypoplasia) in some mildly affected dogs may be partially masked as the eye matures, so may be missed at 8-10 weeks of age or later. Thus examination at an early age, about 5-8 weeks of age, is recommended. Because the onset of other eye diseases (such as cataracts and retinal degeneration) can occur at any age, dogs should be reexamined periodically. A more detailed discussion can be found at: http://www.vmdb.org/aug02.html#d xspot . Ideally, each dog should be examined within the preceding 12 mos. of being bred. According to the link above, the likelihood of a genetic problem showing up after age 9 years is low. The test is an eye examination performed by a board certified veterinary ophthalmologist. Results are automatically included in the OFA database with no extra charge.
von Willebrand’s Disease (vWD) DNA Test – vWD is a potentially serious bleeding disorder and one that can be kept from being a major problem in the breed by having this one-time DNA test done. According to the VetGen website (http://www.vetgen.com/canine-vwd3.html ), the incidence of vWD in Shelties as of January, 2005 is: Clear – 92%, Carrier - 7%, Affected – 1%. Dogs “Clear By Parentage” (first generation - see OFA website for detailed policy) would be accepted into the CHIC program. The test can be performed using DNA from cheek brush collection that can be mailed-in by the owner.
Multiple Drug Sensitivity (MDR1 gene) DNA Test – This DNA test identifies dogs that are sensitive to several medications. Shelties, Collies, Australian Shepherds, and Border Collies are a few of the breeds with this genetic mutation. Several commonly used drugs, ex. antiparasitic drugs (some used in heartworm preventatives), tranquilizers (acepromazine), and anti-diarrheal drugs (Imodium®) are a few of the drugs that may affect dogs with this genetic mutation. This test would provide useful, practical knowledge for every Sheltie owner, since knowing the status of each dog as clear, carrier, or affected would help a veterinarian determine which drugs to use or avoid in a particular dog. As of March, 2008, 448 Shelties have been tested (Washington State University) with 11% being heterozygous (carriers) for the MDR1 mutation, and 1 % homozygous for the MDR1 mutation. Heterozygous dogs (carriers) exhibit sensitivity to drugs that is similar to or less than that of homozygous (affected) dogs. A complete list of drugs that may affect dogs with the MDR1 gene can be found at the following link: http://www.vetmed.wsu.edu/depts-VCPL/drugs.aspx. More information on the topic can be found at: http://www.vetmed.wsu.edu/depts-VCPL/ and http://www.ashgi.org/articles/mdr1.htm . Dogs “Clear By Parentage” (first generation - see OFA website for detailed policy) would be accepted into the CHIC program. The test can be performed using DNA from cheek brush collection that can be mailed-in by the owner.
Optional tests:
Autoimmune Thyroiditis – Autoimmune thyroiditis may lead to hypothyroidism. It is generally accepted that autoimmune thyroiditis is inherited; however, studies to determine mode of inheritance either have not been performed or are inconclusive. 2 According to the OFA website, where breed results for the Michigan State University Laboratory are listed, Shetland Sheepdogs are 24th of 140 breeds (in which 100 or more evaluations have been performed) with autoimmune thyroiditis. Of 14,110 Sheltie evaluations, 12.7% were positive for autoimmune thyroiditis. From the OFA website, “Since the majority of affected dogs will have autoantibodies by 4 years of age, annual testing for the first 4 years is recommended. After that, testing every other year should suffice. Unfortunately, a negative result at any one time will not guarantee that the dog will not develop thyroiditis.” The ASSA Research Advisory Committee recommends that, at a minimum, dogs be tested at 2, 4, and 7 years of age. A blood sample is needed for this test. The Committee debated whether or not this test should be on the required list as it should be repeated multiple times over the life of a dog, and it is more expensive than other procedures that should be repeated such as eye certification. More information on autoimmune thyroiditis can be found at the following links: http://www.offa.org/thygeninfo.html and. http://www.upei.ca/~cidd/intro.htm .
Collie Eye Anomaly (CEA or Choroidal Hypoplasia) DNA Test - CEA is a recessively inherited ocular anomaly that affects development of a portion of the eye. Homozygous recessive dogs may have lesions ranging from mild to severe. Heterozygous dogs will be phenotypically normal. Choroidal hypoplasia, coloboma, and retinal detachment are features of the disease. It occurs in Shetland Sheepdogs as well as other herding breeds. The CEA DNA test can distinguish between normal, carrier, and affected dogs. Unlike CERF examination, it is indifferent to the age of the dog or the presence of the merle gene. The ASSA Research Advisory Committee encourages breeders to consider this test for their breeding stock to keep the incidence of this problem as low as possible. A blood sample is needed for this test. This test is for CEA only, so CERF examinations must still be performed to rule out other types of hereditary eye disease such as progressive retinal atrophy. For an excellent discussion on the topic, see the following link www.optigen.com/opt9_test_cea_ch.html .
Frequencies Based on CERF Eye Exams in the U.S. from 1991 to 1999
|
Choroidal Hypoplasia |
Coloboma |
Retinal Detachment |
Collies |
66.7% |
8.75% |
1.88% |
Border Collies |
2.12% |
0.57% |
0.06% |
Shelties |
0.39% |
0.79% |
0.05% |
CERF numbers may underestimate the prevalence of the CEA mutation, because of the difficulty of detecting the defect in older dogs and the difficulty in diagnosing in a merled dog. Although the incidence of CEA in American Shelties is relatively low, it occurs in European Shetland Sheepdogs in a significantly greater frequency. For this reason, it is recommended that, at the very least, imported Shelties be tested for the CEA gene. Dogs “Clear By Parentage” (first generation - see OFA website for detailed policy) would be accepted into the CHIC program.
As of July, 2008, OptiGen will send the CEA (Collie eye anomaly) DNA test results for Shelties automatically to OFA. Only normal results will be made public unless an owner notifies OFA that he/she would like abnormal results to be posted. The normal OFA fee of $15 to have the results posted will discounted to $7.50 and collected by OptiGen. For more information see: http://www.optigen.com/
Elbow dysplasia – Of breeds having 100 or more elbow evaluations, Shetland Sheepdogs rank 62nd of 92 breeds with elbow dysplasia. As of March, 2008 there have been 404 Shelties evaluated with 97.3% being normal. More information about elbow dysplasia can be found at the following link: http://www.offa.org/elbowinfo.html . Radiographs (x-rays) are required for this test.
Congenital Cardiac Database – Many congenital cardiac defects have a genetic component, and nearly all common ones produce audible murmurs that can be detected by a veterinarian using a stethoscope. Although not common in Shelties, such defects have been found in the breed. OFA certification for the cardiac database is primarily based on examination by a veterinarian using a stethoscope. Because some veterinarians are more experienced at detecting subtle murmurs than other veterinarians, the ASSA Research Advisory Committee stipulated that the examination must be performed by a board certified veterinary cardiologist or internal medicine specialist. Dogs must be 12 mos. of age to receive a certification number. As of March, 2008 61 Sheltie evaluations have been entered into the OFA database. More information can be obtained at the following link: http://www.offa.org/cardiacinfo.html
American Temperament Testing Society, TT title - The “TT” title isn’t exactly a health test; however, some breeds do include temperament testing in their CHIC test list, and since heredity does play a role in temperament, the ASSA Research Advisory Committee included it on the optional list. Minimum age for a dog to take the test is 18 mos. As of December, 2007, 472 Shelties have been tested. The pass rate was 67.4%. More information on the test can be obtained at the following link: http://www.atts.org/about.html
1. George A. Padgett, DVM, Michigan State University, Prioritizing Genetic Defects, www.lgd.org/library/PadgettDefects.htm
2. Canine inherited disorders database - http://www.upei.ca/~cidd/intro.htm
3. From the OptiGen website: http://www.optigen.com/opt9_test_cea_ch.html
CHIC Program - Questions & Answers
May, 2008
1) For those dogs already meeting the requirements, how long do you think it will take before they show up on the site when one does a search for CHIC Shelties? Within two weeks.
2) Will dogs that have had CERF examinations be included if the exams are out of date? Yes, as long as there is a CERF report on file
3) Once a dog receives a CHIC number, he/she will remain on the CHIC list even if the CERF exam is out of date. Is that correct? Yes, both the CHIC report and website will list WHEN the test was done, as well as the cumulative CERF testing history
4) When submitting the results of the VetGen and MDR-1 tests, one should use the DNA application form (www.offa.org/dnainfo.html). On that form, there is a space for a previous application number. What is that referring to? Would the application number on the OFA certificate be it? Application number is the internal OFA assigned number
5) Is there a Clear by Parentage option available for both the vWD and the MDR-1 gene? The answer is yes. I believe that point is noted on the CHIC webpage for Shelties and on the ASSA website. Concerning the Clear by Parentage issue, I was unable to find any information on the VetGen website concerning the Clear by Parentage option. It may be there, I just didn't find it. I do know that the option is discussed on the OFA website http://offa.org/dnacbp.html . The following is from that page:"For direct mutant gene tests only, the OFA will issue clearances to untested offspring, if the sire and dam have both been DNA tested ?clear,? if the sire and dam?s DNA disease test results have been OFA registered, and if all three (sire/dam/offspring) have been DNA identity profiled and parentage verified. The DNA profile paperwork must be submitted along with a completed OFA DNA-based disease test application."
6) I had assumed that if the parents' results were registered by the OFA that the offspring would automatically be given the CBP clearance if the owner submitted the appropriate form and fee, but after reading the above, I see that there are additional requirements that, I think, will cause many owners to balk. Why not just accept that AKC registration papers are correct rather than requiring DNA profiles of all 3 individuals? For the MDR-1 test, it would be cheaper to get the test done on the offspring than to get the CBP done. Please let me know if I am understanding the situation correctly. The OFA Board discussed the CBP policy at the spring 2008 board meeting, and decided the policy should stand. The rationale is that the OFA is going out on a limb and issuing the clearance to an untested dog. In doing so, the board wants absolute confidence that the dog is in fact the offspring of the cleared parents. DNA profiling should not be viewed as a cost of the clearance, but a regular cost of breeding dogs. Responsible breeders should be profiling their dogs regardless for the integrity of the stud book.
7) Must a dog be permanently identified (tattoo or microchip) in order to have genetic test results posted on the OFA or CHIC website? On the OFA submission form, there is a place on the form for a veterinarian to certify that the DNA sample was correctly collected and that he/she had verified the permanent identification of the dog tested. If this is not done, you can still submit the test results. The inofmation may be listed as "no permanent identification" as is done for hip reports. If a veterinarian does not sign the OFA DNA form that goes with vWD and MDR-1 test results, there is another form, "Verification of Permanent Identification" http://offa.org/apps.html . It is suggested that you download and read that form to understand why it may be required in some instances.
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The Shetland Sheepdog Health Survey
September 2008
The Shetland Sheepdog health survey is available through the generosity of the Orthopedic Foundation for Animals(OFA), www.offa.org, and is the result of a collaborative effort between the OFA and the ASSA Research Advisory Committee. It became active October, 2008 and the data seen in the results section is cumulative since that time. Anyone owning a Sheltie may participate in the survey, and it it hoped that many owners will do so. Owners may input information for as many dogs as he/she wishes including information on normal and abnormal dogs, dogs already deceased and, of course, those still alive. If information changes for a dog already in the system, just re-enter that dog with the new information. Eventually, the numbers of dogs in the system will be so great that additional information on a dog already in the system will not make a significant difference in the overall percentages. This will not be a scientifically accurate survey, but it should give us a general idea of which health problems are more common and will guide us in selecting research projects for future support.
The first time you try to enter a dog into the Health Survey, consider clicking on all of the disease categories for the question: "Has your dog been diagnosed with any of the following health issues?", so you can see all of the options. A problem might be located in a different section than where you thought it might be. For instance, the MDR-1 genetic mutation is listed under "Neurologic disorders" since many of the adverse reactions associated with that trait cause neurological symptoms. If you dog doesn't have any problems in a given section, just leave that section blank. After you become familiar with the options, you can just click on the appropriate disease categories when entering additional dogs.
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CHIC DNA Repository
The CHIC DNA Repository is co-sponsored by the OFA and the AKC/Canine Health Foundation. Its purpose is to collect and store canine DNA samples along with pedigree and phenotypic information to facilitate future research and testing with the goal of reducing the incidence of inherited disease in dogs. The ASSA Board of Directors encourages participation in this DNA bank. For more information, visit: http://www.caninehealthinfo.org/dnabank.html.
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Current Research Projects
Study on DNA Markers for Female Infertilityy
March 8, 2008
DOGenes, a company operated under the guidance of Mary Whiteley, Ph. D., is searching for DNA markers for female dog infertility. If you are interested in participating in the study, go to the following link and click on the link to join the study. https://www.dogenes.com/research.html
Update, February 21, 2009: Participants are still needed for this study.
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DM Research - A Search for Potential Genetic Cause
Updated, March, 2008
Blood samples from DM positive Shelties are needed for the current DNA research sponsored by ASSA. All you would provide is 6 cc of whole blood in a purple topped EDTA tube, a copy of a 3-5 generation pedigree and a copy of the dermatomyositis positive biopsy diagnosis. This should all be sent over night with a cold pack to:
Dr. Christine Rees
Texas A&M University
College of Veterinary Medicine
Department of Small Animal Medicine and Surgery
College Station , TX 77843-4474
979-845-2351
Prior to sending the samples, it is suggested you notify Sherry Lindsey, RN, BSN at shalainetx@aol.com or 830-620-6661 or one of her colleagues to be expecting the samples. If you explain the purpose of the blood draw, most veterinarians will draw blood at no charge or a reduced amount.
Thanks to all who support the DM research.
Sherry Lindsey RN BSN
DM information: www.shalaine.com/dm/dm.html
DM Research - New Treatment Study
Updated, March, 2008
Three to 5 Shelties are needed for a study to evaluate a new drug, Dapsone, which is an oral medication found to be effective in the treatment of DM in humans. These dogs would be donated to the study and then altered, if needed, and placed in permanent adoptive homes following the drug study. Please see contact information below if you are interested in donating a DM affected Sheltie to the study. It may be altered or intact, with or without registration papers, as long as it is a purebred Sheltie.
Contact for Dr Christine Rees, DVM and Sherry Lindsey RN BSN:
Dr. Christine Rees, DVM, DACVD
Texas A&M University
Small Animal Clinic
College Station, TX
979-845-2351
CREES@cvm.tamu.edu
Sherry Lindsey, RN BSN
PO BOX 310233
New Braunfels, TX 78131-0233
830-620-6661
shalainetx@aol.com
Biopsy specimens: For both of the above studies, we suggest that DM biopsy specimens be submitted to Dr. Joanne Mansell who is collaborating in the DM research on Shelties. Her dermatohistopathology submission form, complete with mailing address and cost, is on the DM website, http://www.shalaine.com/DM/DM.html , at the "Biopsy Information for Vets" page.
REPORT FROM DR MURPHY, MAY 30, 2007
ASSA and the Collie folks received a proposal from Dr. Keith Murphy of Texas A&M regarding the identification of the gene for DM. I will quote a very small portion of the proposal we received from Texas A&M:
"Our laboratory carried out linkage studies in the Shetland Sheepdog and identified a region of canine chromosome 35 (CFA35) that may harbor a locus having an affect on the DM phenotype. We have also generated a gene expression of DM in the Shetland Sheepdog and identified more than 200 genes that are differentially regulated in diseased dogs. We propose to further investigate genes on CFA35, as well as genes of interest identified using the expression data. Our goal is to (1) identify candidate genes for DM and (2) develop a genetic test for early identification of affected dogs."
The Collie folks had already put in half the money to fund the study - roughly $40,000. The ASSA Board looked at pros and cons of this study, including the fact that Texas A&M might find the gene, might only find a likely marker or might not find anything. However, Dr. Murphy's staff has successfully found the genes for other breeds' diseases.
In the end, THE ASSA BOARD VOTED TO SPEND $40,000 TO FUND THE DM STUDY BY TEXAS A&M.
This was the ENTIRE SUM in the health portion of the ASSA Foundation's money. Donations to the ASSA foundation would be greatly appreciated. For more information on the ASSA foundation click here.
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Leishmaniasis Research
July 2008
Participants needed to trap insects that might be able to carry Leishmaniasis. Basically, Dr. Mendez is asking dog owners to hang insect traps around the home or kennel area for 24-48 hrs and then mail them back to her at her expense. I urge each of you to participate especially since it seems to be an easy thing to do. Just contact her via e-mail (Dr. Susana Mendez, sm457@cornell.edu) telling her that you are interested in participating. Also, please forward this message to all of your "doggie friends" and ask them to participate and forward on to their friends. Letter from Dr. Mendez
Leishmaniasis Information
Best regards,
Mary Mahaffey, DVM Chair,
ASSA Research Advisory Committee
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Investigation of Bladder Cancer in the Shetland Sheepdog
Updated August, 2009
Background: In early 2006, the Ostrander Laboratory at the National Human Genome Research Institute at NIH in collaboration with the Purdue Comparative Oncology Program at Purdue University and the Department of Small Animal Clinical Sciences at Michigan State University began a study on the genetic susceptibility to transitional cell carcinoma (TCC) of the urinary bladder in dogs. TCC is a devastating disease with genetic underpinnings and their ultimate goal is to identify the genetic variants responsible for susceptibility to this disease.
Dr. Elaine Ostrander and her collaborators will be looking across all the dog’s chromosomes to find regions of the genome that may be responsible for susceptibility to TCC. The initial genetic analysis was begun using two closely related breeds, the Scottish Terrier and West Highland White Terrier. The researchers now feel that the addition of an unrelated breed, such as the Shetland Sheepdog, will add valuable data to the research on the genetic susceptibility to TCC. Shetland Sheepdogs are four and one half times more likely to be diagnosed with TCC than other dogs, making them the third most likely of all breeds to get TCC (VMDB, 2006). Too many Shelties die each year as a result of this terrible disease.
Statistical tools will be used to evaluate the data between the affected and unaffected Shelties and to compare the data from Shelties to that collected from the Scottish Terriers and West Highland White Terriers. Of key interest will be the determination of the variant responsible for this disease in the Sheltie and whether different breeds have the same or similar genetic variants responsible for susceptibility to TCC.
Participation: The Ostrander Lab is soliciting blood samples from two groups of dogs.
Group 1: Shetland Sheepdogs with a diagnosis of TCC (bladder cancer)
Group 2: Shetland Sheepdogs age eight and older that currently have no known cancers. Ideally, dogs in this group should not be closely related, i.e., no parents or grandparents in common.
If your dog meets one of these criteria, please contact Donna Viglietti, Ostrander Lab Samples Manager, for a sampling kit by phone (301-451-9390) or email (dog_genome@mail.nih.gov). Each kit contains a one page consent form, a pair of vials for collecting 5-10 cc of blood at your veterinarian’s office, and instructions for handling the blood. The collection kit comes in a small cardboard mailer tube that protects the blood vials. A return address label is included so that the forms and blood can be sent back to the lab conveniently. Blood can be mailed at room temperature without cold packs.
All genetic and contact information collected for each dog will remain confidential. Specifically, your participation in the study, your dog’s pedigree, health information you provide, and any data we get from your dog’s DNA sample will not be disclosed to any breeders, Club personnel, the AKC, or the AKC Canine Health Foundation.
Thank you in advance for your time and effort. The sample you provide will be instrumental in helping to identify the genomic mutations associated with TCC. Determining the genetic cause of this disease is a necessary first step in developing strategies to prevent the cancer and develop therapies for affected dogs.
As always, our work would not be possible without your participation and dedication to this wonderful breed and its health. Please contact Donna Viglietti by phone or email with any questions or concerns you may have.
Update! As of August 14, 2009, the researchers have received DNA samples from 40 Shelties with bladder cancer and 45 Shelties in the control group. Sheltie owners have done a great job in answering the call for sample donations thus far, yet more donations are still needed. We thank you for your enthusiastic response and hope we can count on your continued participation to enable this study to progress. Keep up the good work!
To see the original letter on the August update click here.
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Undescended Testicles (Cryptorchidism) Research
November, 2008, Updated May, 2009
There are 2 research groups studying the problem of cryptorchidism (retained testicles) in Shelties. Both research projects are sponsored by the Canine Health Foundation and the ASSA. Although both studies concern the same topic, the investigators are using different approaches to study the problem. Breeders are urged to contribute to both studies if possible.
Dr. Agoulnik, of the Department of Human and Molecular Genetics, College of Medicine, Florida International University (previously at Baylor Medical School), is using a “global” approach to find genes associated with cryptorchidism by looking at larger strands of DNA to find an association with the trait and further pinpointing the genes from there. Because he needs a large quantity of good quality DNA for his work, he must use blood samples or testicular tissue rather than DNA collected using cheek brushes. (Canine Health Foundation Grant No. 882-A)
Dr. Rothschild, a geneticist at Iowa State University, (Canine Health Foundation Grant No. 1018-A) has been studying cryptorchidism in species other than dogs. He is looking to see if the genes that cause the problem in man, pigs, and mice also are associated with the problem in dogs. The fact that DNA from cheek brush samples can be used for this study makes it easy for owners to collect the DNA samples themselves.
Both studies are described below:
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Undescended Testicles (Cryptorchidism) Research
Canine Health Foundation Grant No. 882-A
Cryptorchidism or retained testicles is the most common birth defect in purebred dogs. Two major health consequences of cryptorchidism are infertility at adulthood and significantly increased risk of testicular cancer. Because of the cancer risk, the retained testicles should be removed. Currently, there is no genetic diagnostic test to predict the risk of this disease in a dog’s progeny. The main objective of this study is to develop a DNA test that may predict the risk of a dog to produce cryptorchidism in its male offspring. Blood samples or tissues samples (testicles) removed during surgery from cryptorchid dogs and their normal littermates are needed for the current DNA research sponsored by AKC CHF. The information generated by this study can be used to identify animals with the mutant gene and thus will provide breeders with informative breeding recommendations.
Samples are needed from cryptorchid Shelties and their normal male littermates. (Samples from normal male littermates are not required, but would be helpful.)
Material needed for participation:
- 2-6 cc of whole blood in purple topped EDTA tubes or
- Frozen testicular tissue removed during castration
- AKC registration number and/or pedigree
- Consent form (obtained from Dr. Agoulnik)
This should all be sent over night with a cold pack to:
Alexander I. Agoulnik, Ph.D.
Professor
Department of Human and Molecular Genetics,
College of Medicine
Florida International University
11200 SW 8th Street, HLS I 327
Miami, Florida 33199
Telephone: (305) 348-1483
E-mail: aagoulni@fiu.edu
Prior to collecting the samples, please notify Dr Agoulnik to request the consent form and shipping instructions. If you explain the purpose of the blood draw, most veterinarians will draw the blood sample at no charge or for a reduced amount. The study will pay for shipping costs.
We sincerely thank everybody who helps with our research aimed to benefit all dog breeders.
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Comparative Gene Discovery for Canine Cryptorchidism
Canine Health Foundation Grant No. 1018-A
Dr. Rothschild, the primary investigator, is a geneticist at Iowa State University. He has been studying cryptorchidism in species other than canine. He is looking to see if the genes that cause the problem in man, pigs, and mice also are associated with the problem in dogs. He is currently working with Siberian Huskies but is banking DNA from other breeds.
After being contacted by the ASSA Research Advisory Committee, he agreed to include Shelties in his study. He would be greatly appreciative and could put the samples to good use. Because obtaining sufficient samples from the right sets of dogs (see below) has been a slow, time consuming process with the Siberian Huskies, he asked that one of the ASSA representatives collect the samples and then send them to him once the needed numbers have been obtained. Mary Mahaffey, DVM is willing to take the lead on this. This is what is needed for the study:
- Cheek brush DNA samples from 20 groups of the following: sire, dam, at least one normal male pup and one cryptorchid pup. (Grandparents would be good also if obtainable).
- Pedigree of the puppies.
The fact that cheek brush samples rather than blood samples are used in this study makes it easier to obtain the samples as owners can collect the DNA themselves. Obtaining 20 combinations as described above may not be easy, but can be done. DNA collected on cheek brushes can be kept indefinitely as long as the brushes are dry and kept in paper envelops. Once 20 of the above combinations are obtained, all will be sent to Dr. Rothschild at the same time.
If the owners wish to keep the information confidential, put all the materials for each litter in a large envelope and indicate on the outside of the envelope that DNA samples of the sire, dam, affected and unaffected male offspring are included inside (without listing the dog names). Then put that envelope inside a larger one and mail it to Mary Mahaffey, DVM at the address below.
To participate in the study, contact Mary Mahaffey and she will send you DNA collection kits and instructions.
Mary Mahaffey, DVM
1611 Cedar Road
Watkinsville, GA 30677
E-mail address: lastly3345@bellsouth.net
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Investigation of Gallbladder Disease and Hypercholesterolemia in Shetland Sheepdogs*
March 2008, Updated December, 2008, May 2009, November 2009
NEWS FLASH!!! Genetic Mutation Found!
Dr. Katrina Mealey, primary investigator of the study, reported to the ASSA Research Advisory Committee in September, 2009 that her group has identified a genetic mutation in Shelties that is strongly associated with gallbladder mucoceles. It is important that the data be reviewed by scientists and veterinarians prior to offering a test for the mutation to Sheltie owners. The work will be submitted for publication soon. Once the work has been validated, a DNA test should be made available. Dr. Mealey’s group is the same one that developed the DNA test for the MDR-1 gene.
Dr. Mealey said, “We sincerely appreciate the cooperation we have received from the American Shetland Sheepdog Association and we will keep you apprised of developments.” Sheltie owners and the ASSA played an important role in providing Dr. Mealey with the material needed to identify the mutation. It was only 18 months from the time the ASSA became involved in distributing information about the study in March of 2008 until the discovery of the mutation was announced in September, 2009! A special thank you to everyone who participated!
Study Background: Gallbladder disease has been recognized with increasing frequency in dogs since the late 1990’s1-3. Whether or not this was the result of a true increase in disease prevalence or simply the result of increased detection is unclear. Some have suggested that incorporation of abdominal ultrasound examination in dogs as a routine diagnostic tool has resulted in increased detection of gallbladder disease2. Several articles describing gallbladder mucoceles (severe distention of the gallbladder caused by a thick mass of sludge and mucus) in dogs suggest a breed predilection for the problem in Shetland Sheepdogs as well as Cocker Spaniels and Miniature Schnauzers. Both Shetland Sheepdogs and Miniature Schnauzers are breeds predisposed to hyperlipidemia (too much lipid or fat in the blood), 4, 5 a factor that is known to contribute to gallbladder disease in people6, 7. A study has confirmed a link between hyperlipidemia and hypercholesterolemia (high blood cholesterol levels) and gallbladder mucocele formation in Shetland Sheepdogs2. Collectively, this suggested the possibility of a genetic defect in a protein responsible for lipid homeostasis (regulation of blood lipid levels). In March, 2008, The Veterinary Clinical Pharmacology Laboratory, led by Dr. Katrina Mealey, at Washington State University began a research study investigating a gene that plays an important role in lipid homeostasis. It was proposed that a defect in that gene could be the underlying cause of gallbladder disease in Shetland Sheepdogs.
The ASSA assisted Dr. Mealey in collection of DNA samples from Shelties with and without hyperlipidemia and gallbladder disease by sending notice of the study through Sheltie related internet message groups and posting the information on the ASSA web page. Nine months after the study began, enough material was obtained, through the generous participation of Sheltie owners, to limit sample collection to dogs with surgically confirmed gallbladder mucoceles and older normal Shelties. As noted above, it was a mere 18 months from the beginning of ASSA participation until the genetic mutation was confirmed. This could not have been accomplished without the enthusiastic participation of Sheltie owners, and of course, without the dedication and expertise of Dr. Mealey
Dr. Mealey said, “I was surprised (in a positive way) on the response!…Thanks for your assistance--for an uncommon disease we were able to collect a good number of samples with complete medical information in a short time period (especially considering this was breed specific!)”. Thanks to everyone who has participated.
THANK YOU Dr. Mealey!!!
Katrina Mealey DVM PhD; Diplomate, ACVIM; Diplomate, ACVCP
Associate Professor and Director, Veterinary Clinical Pharmacology Laboratory
College of Veterinary Medicine
Washington State University
Pullman WA, 99164-6610
EMAIL: kmealey@vetmed.wsu.edu
http://www.vetmed.wsu.edu/depts-VCPL/instructions.aspx
References
Pike FS, Bert J, King NW, et al. Gallbladder mucoceles in dogs: 30 cases (2000-2002). J Am Vet Med Assoc 2004;224:1615-1622.
Aguirre AL, Center SA, Randolph JF, et al. Gallbladder disease in Shetland Sheepdogs: 38 cases (1995-2005). J Am Vet Med Assoc 2007;231:79-88.
Worley DR, Hottinger HA, Lawrency HJ. Surgical management of gallbladder mucoceles in dogs: 22 cases (1999-2003). J Am Vet Med Assoc 2004;225:1418-1422.
Whitney MS, Boon GD, Rebar AH, et al. Ultracentrifugal and electrophoretic characteristics of the plasma lipoproteins of miniature schnauzer dogs with idiopathic hyperlipoproteinemia. J Vet Intern Med 1993; 7:253-260.
Sato K, Agoh H, Kaneshige T, et al. Hypercholesterolemia in Shetland sheepdogs. J Vet Med Sci 2000; 62:1297-1301.
Loria P, Leonardo A, Lombardini S, et al. Gallstone disease in non-alcoholic fatty liver: prevalence and associated risk factors. J Gastroenterol Hepatol 2005; 20:1176-1184.
Andreotti G, Chen J, Gao YT, et al. Serum lipid levels and the risk of biliary tract cancers and biliary stones: A population-based study in China. Int J Cancer (2007 epub)
* This report will be updated when the study is published and when the DNA test becomes commercially available.
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Articles
To Test or Not to Test…
Mary E. Galloway DVM
May, 2008
As ASSA Health chairperson*, people who want to purchase a Sheltie frequently contact me asking what they should know about the breed’s health problems. A recent call highlighted some concerns expressed by both breeders and owners about the current focus on canine health and research and how it reflects on the perceived health of purebred dogs and Shelties in particular.
"I am interested in buying a Sheltie but when I hear about all the tests my puppy’s parents should have it worries me. I see your club is involved in various health research projects and is trying to raise money for further research. Should I look for a healthier breed? When I spoke with one breeder I was told about all the tests her dogs have had for a lot of diseases. I can get a Sheltie from another person who told me they don’t have to test for problems since they don’t have any in their lines. What do you think?"
Testing for diseases and monitoring the occurrence of diseases by breed clubs and breeders does not indicate that problems exist in that breed or line. In fact it is a positive indication that the people who breed these dogs are trying to produce the healthiest puppies they can. As researchers become more aware of the underlying causes for many diseases in our dogs, breeders try to use all the resources available to them to produce healthy dogs. This includes feeding a proper diet, providing proper exercise and housing and may include testing for abnormal conditions or diseases that exist in the breed. Testing for specific conditions will allow only unaffected animals to be used for breeding. The abnormal conditions currently recognized in Shelties are found in low numbers in the breed. Testing will allow these uncommon conditions to remain uncommon or even be eliminated from the breed.
A test may be one that screens for the presence of a condition or disease. This would include eye exams (CERF), radiographs of the hips for hip dysplasia (OFA, PennHip) or a blood test for thyroid disease. When a dog has one of these tests done it will tell the owner whether the condition is present in that dog at that time. Many of these tests need to be repeated throughout the dog’s lifetime since the condition can develop as the animal matures and ages. Some tests are done just once at a predetermined age since it is unlikely the condition will develop after that time. Checking for these conditions will allow breeders to breed only dogs that appear normal. What must be remembered is that although the dog may not show the condition him/herself these tests do not show if the dog is genetically free of the problem. The dog may appear normal but carry recessive genes. When this dog is bred to another dog also carrying recessive genes they may produce animals that will develop the disease. This is how affected animals can come from "normal" parents. The best safeguard we have to reduce or eliminate these problems in our dogs is to screen all breeding stock and breed only from those who are free of the condition. In the case of eye checks and thyroid testing, it must be repeated many times in a dog’s lifetime since these abnormalities may not appear until an animal is older. If all animals in the first 3-4 generations of your puppy’s pedigree have been tested and found normal it is unlikely that your puppy will develop the condition. It is important to point out that many of the disease conditions we recognize as having a genetic basis can also be influenced by the environment. The development of hip dysplasia is a good example. Research has shown diet and exercise as well as growth rates, can influence the development of hip dysplasia. Obesity can cause or aggravate a number of disease conditions in dogs. It is the owner’s responsibility to know how to correctly feed, house and exercise their growing puppy to ensure a healthy adult and to maintain good health in your adult dog.
The only absolute way to know your puppy will not develop a certain disease or condition is through genetic testing. A genetic test allows us to know what is actually coded in the genes of the animal being bred. It is not influenced by environment or outside stresses. It will tell you what genes the dog actually carries and not just which ones are expressed. Research is unlocking the key to many diseases in dogs and people. As these tests are developed and become available, breeders will test their breeding stock and know the genetic makeup of each animal. This will allow breedings to be planned to avoid producing affected offspring and to eventually eliminate the disease from the breed. The only genetic based test currently available for the Shetland Sheepdog is for von Willebrand’s Disease, a bleeding disorder. (As of 2008, additional DNA tests have become available. See the CHIC section above.)
That is why all this research is so important. Projects are underway to study many of the conditions that affect our Shelties today. Funding is needed for other projects that are of equal importance. As we eliminate one disease from our animals there will be others to demand our attention. That is why parent clubs like the ASSA monitor the breed through health surveys. Living creatures including dogs and man are constantly changing. Gene mutations are an ongoing process. Some mutations will produce disease conditions not recognized today. It is said all people carry 5-6 lethal genes as well as numerous genes that can cause the development of many disease conditions. The same is probably true for our dogs. The challenge for breeders is to use all the knowledge available today to avoid breeding animals together that carry the same deleterious genes. There is no dog or line of dogs that is free of all disease causing genes. If testing is not done, breeders may not be aware of problems that exist, but they are still there. It is true some diseases can’t be tested for at this time. They can be unpredictable and the best we can do is not use for breeding animals that develop the condition.
So don’t be afraid of a breed or breeder that is active in health research and testing of their breeding animals. This indicates the acceptance of responsibility and an ongoing effort to produce beautiful healthy Shelties.
* Although Dr. Galloway is not the current Chair of the ASSA Research Advisory Committee (formerly known as the Health Committee), the information in this well-written article is still appropriate and helpful.
Copyright © 1998-2008 American Shetland Sheepdog Association. All Rights Reserved.
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