HEALTH COMMITTEE UPDATE

Bob McCaskill, DVM and Kay McGuire, DVM
Summer 2007, NEWS

Your help for Westies at work –

Since our beginning in 1998, the Westie Foundation of America granted $144,600 for research to reduce or eliminate Westies disease and conditions that seriously affect the health of the breed. Here’s a look at some of the results from the studies your donations are helping to fund. Together – we are making a difference!

Skin Allergy
Investigator – Thierry Olivry, DrVet, PhD North Carolina State University College of Veterinary Medicine

What is it? Skin Allergy, Atopic Dermatitis, is an immune response to allergens that cause those Westies who are affected to demonstrate allergic signs of itching, feet licking, ear infections, eye infections and hair loss. It is the number one health issue in the breed as indicated by our 1999 and 2007 Health Surveys. The disease causes the Westies body to attempt to destroy the item that he is allergic to by releasing specific cells that produce cellular chemicals. It is these cellular chemicals that cause the Westie’s skin to itch and sting resulting in the signs seen. Current treatment include Allergen specific vaccinations that attempt to build the Westies immune system to respond to the allergens and drugs that either bind or prevent the allergen from attaching to these destructive cells.

How will this study help? Dr. Olivry assembled questionnaires and pedigrees from over 225 Westie owners who either thought their Westies had or didn’t have skin allergies. From this population, there were 147 Westies from 12 family groups (69 ‘atopic’, 38 ‘undetermined’ and 118 ‘normal’ Westies). Next 114 sampling kits were sent out and 109 were returned with usable material (30 atopic, 15 ‘undermined’ and ’64 normal’ Westies). Dr. Olivry samples allowed him to collect atopic and normal blood for DNA isolation and determination of serum allergen-specific IgE (Allergic) antibodies against more than 40 allergens. Dr. Olivry and his team analyzed the results and based on their statistical analysis believe that they have sufficient pedigrees and sample to attempt to find the linkage DNA marker that causes atopic dermatitis in the Westie. If he and his group can find the linkage marker, they will then attempt to find the direct DNA mutated gene that causes this disease. Should this prove to be successful, a test should be able to be developed to allow this disease to be eliminated from the breed.

Critical Orthopedic Inflammatory Disease - CMO
Investigator – Patrick Venta, PhD Michigan State University College of Veterinary Medicine

What is it? CMO (craniomandibular osteopathy) is an inherited noncancerous overgrowth of bone that primarily occurs in the jaw region of affected dogs. Terriers, particularly the Cairn, Scottish and West Highland White terriers are known to have the disease. The disease is treatable and will generally disappear about a year after the initial onset. The disease is rarely fatal, but can cause pain to the puppy and a good deal of distress to the owner.

What is being done ? Dr. Venta and his research team continue to eliminate many candidate genes in their attempt to find the mutated gene that causes this disease. They are using a systematic whole genome linkage approach on the remaining regions of the gene and have eliminated many areas on the genome, including those that have similar phenotypes in human patients. Thus far, they have eliminated the three largest dog chromosomes as the location of the mutant gene. They expect to cover the remaining 35 chromosomes by the end of the year to at least develop a linkage marker for the disease. Once that is accomplished, then the ultimate goal is to identify the specific mutant gene, so that a diagnostic test can be developed to identify carriers and avoid producing affected offspring. That second part (the most important part) will be the subject of a new grant proposal.

Blindness – Hereditary Cataracts
Investigator – D.J.Sidjanin, Ph.D Medical College of Wisconsin

What is it? Cataracts are the leading cause of vision problems in dogs. The West Highland White Terrier is one breed that occasionally develops Juvenile Cataracts. These cataracts typically show up in Westies before three years of age. This is different from cataracts seen in older dogs where the cataracts are associated with the normal aging process. Juvenile Cataracts are thought to be of genetic origin.

What is being done ? Dr. Sidjanin and his team are working very hard on attempting to better understand how genetics plays a part in canine cataracts. They have optimized experimental conditions to evaluate these genes that could harbor mutations responsible for hereditary cataracts in several breeds. Their initial focus is on the Labrador Retriever, however, they are also evaluating Golden Retrievers, Huskies, the Portuguese Water Dog and Spanish Catalan Sheepdogs. All of these breeds are affected by hereditary cataracts. They optimized experimental conditions to evaluate five genes that could be harboring mutations responsible for hereditary cataracts in these breeds. Thus far no mutations have been identified. They will continue their evaluation of additional genes in a hope that they will find a causative mutation for the canine hereditary cataract.

If they are successful, we would hope that their work would correspond to the West Highland White Terrier. Our goal is to ultimately reduce the number of dogs affected by this disease.

Immunology – Investigation of Antigenic Causes of Vaccine-Associated Allergic Reactions in Dogs

What is it? Allergic reactions are the most commonly reported adverse event associated with canine vaccinations. The West Highland White Terrier is 34 on the list of breeds that are at risk of allergic reactions after vaccination. (Glicman & Moore JAVMA 2005). Laboratory studies have shown that normal dogs make antibodies against many vaccine components, even though they may not show an allergic reaction immediately following vaccination. Although the specific cause of allergic reactions in dogs remains unknown, residual vaccine components from the manufacturing process have been incriminated.

What is being done ? Dr. Moore and his team intends to use serum from dogs of high-risk breeds and compare antibody concentrations in dogs demonstrating allergic reactions versus antibody concentrations in dogs of the same breed that don’t have reactions. (Health Committee continued from page 3) They intend to identify vaccine components that stimulate allergic reactions. They hope to prompt vaccine manufacturers and/or the USDA (as regulating agency) to remove/reduce these substances and improve the safety of canine vaccines.

Cancer – Mapping of the Gene for Transitional Cell Carcinoma in the Scottish Terrier & West Highland White Terrier
Investigator – Deborah Knapp, DVM; Elaine Ostrander, PhD Purdue University and NHGRI/NIH

What is it? Transitional cell carcinoma (TCC) of the urinary bladder is a common form of cancer in Scottish Terriers (ST) and the West Highland White Terrier (WHWT). Within affected breeds incidence is high. Treatment is only partially effective and mortality is usually inevitable.

What is being done ? Drs. Knapp and Ostrander will identify the genetic variants that predispose dogs to developing the disease. They hope to identify cases (WHWTs and STs diagnosed with TCC) and unaffected controls that meet specified criteria and utilize blood samples from these doges to identify DNA variants that are present in affected, but absent in unaffected dogs. Due to the shared history of these breeds, they will analyze the genomes of both breeds independently and together, as it is possible that some terrier breeds have inherited the disease causing mutations from the common ancestor. DNA samples from affected dogs of other breeds will also be collected for later comparisons. Their expected outcome is identification of the genetic variants responsible for TCC in at least two terrier breeds. Eventually they hope that this information can be used to develop a test to determine which dogs are at risk for TCC.

Immunology – Histocompatibility Alleles Conferring Susceptibility to Canine Diabetes, Immune- Mediated Thyroiditis and Immune-Mediated Hemolytic Anemia
Investigator – Wayne Potts, PhD University of Utah

What is it? Autoimmune diseases are a set of rare disease complexes that can affect the West Highland White Terrier. In these diseases, the body’s immune system attacks different organs resulting in the loss of those organs to support body function.

What is being done ? Our researchers are obtaining samples from at least three breeds for each of the three autoimmune disease plus 10 breed-matched controls. To date, they have collected a total of 248 samples and are shy of their targeted 300 samples. Of the three diseases, Immune-Mediated Hemolytic Anemia cases are the most difficult for them to obtain. They are evaluating additional strategies for IMHA after analysis of the first samples are sequenced. They have also nearly completed sequencing 120 dogs for location of the loci on the gene that might cause these diseases. In the next six months, they plan on finishing most of the sequencing of the existing samples and to concentrate on obtaining remaining needed samples.

Endocrine – Establishing a Genetic Linkage Between Addison’s Disease and DNA Markers
Investigator – Anita Oberbauer, PhD University of California – Davis

What is it? Addison’s disease (hyperadrenal cortisolism) is a disease which our foundation has supported research in for several years. Articles on the disease can be found at other locations on our web site.

What is being done ? The final report for this grant has been received and represents the accomplishments and findings of the last four years of works.

Dr. Oberbauer and her team have genomic DNA and data on 367 West Highland White Terrier submissions with 56 designated as affected by Addison’s disease. The DNA was stored and used for a genome wide screening to identify a genetic marker linked to the disease. Heritability estimates and analysis suggest that a single, autosomal recessive locus controls Addison’s disease. No linkage with the disease was detected and future work will use SNP chip identification of the mutant gene that causes this disease. Recruitment of cases for the WHWT were disappointing. Five other breeds (Bearded Collie, Standard Poodle, Portuguese Water Dog, Leonbergers and Great Danes submitted substantially greater samples for analysis.

Our foundation agreed that for 2007 and beyond that we will focus primarily on the top 5 diseases as determined by our most recent Health Survey. We will actively seek research grants on Atopic Dermatitis, Legge Calve Perthes Disease, Luxating Patellas, Inflammatory Bowl Disease, Craniomandibular Osteopathy and continue to support Idiopathic Pulmonary Fibrosis.

Smaller grants that are shared with other breeds will be considered but not actively pursued.