Osteosarcoma is the most common bone tumor of dog. This cancer develops in the bone, usually the limbs, and as the tumor grows it becomes progressively more painful for the dog and can result in lameness. Often these tumors metastasize to the lungs. Giant breeds are at the greatest risk for developing osteosarcomas.

Latest Research Update: To date, we have collected ~500 blood samples from dogs diagnosed with OSA and ~1500 healthy dogs over 8 years old. We have localized genetic risk factors that are associated with OSA to three chromosomal regions in greyhounds as well as three chromosomal regions in the Rottweiler breed, and are currently narrowing in on the precise mutations that cause the disease using ten different breeds. The biological effects of the mutations will be studied to better understand the cause and progression of the disease.

Breeds needed for our study: Rottweilers, Greyhounds, Mastiffs, Leonbergers, Golden Retrievers, Irish Wolfhounds, Great Pyrenees, Great Danes, Borzoi, and Scottish Deerhounds

Main collaborators: Kenine Comstock (The University of Michigan), Jaime Modiano (University of Minnesota), Cheryl London (Ohio State University), Elizabeth McNeil (Michigan State University), Matthew Breen (North Carolina State University)

Funding: AKC/CHF

Hemangiosarcomas are rapidly growing and highly invasive, blood-fed tumors. Blood vessels grow from the tumor and often cause death through excessive blood loss due to rupturing of the tumor.

Latest Research Update: After comparing the genomes of ~100 healthy dogs with ~100 dogs with HSA we were able to identify several areas of the genome that were possibly associated to inherited HSA risk factors. Currently, five genes found to be associated with the disease are being searched for mutations. Once the mutations have been identified and their presence in different breeds assessed, this will allow for rapid development of genetic tests for carriers of HSA.

Breeds needed for our study: Golden Retrievers, Labrador Retrievers, Chinese Shar-Peis, Boxers, Pugs, and Rhodesian Ridgebacks

Main collaborator: Chieko Azuma (Tufts University)

Funding: AKC/CHF

MCTs are cancerous proliferations of mast cells. Although they can and will spread throughout the body, the danger from MCTs comes from the secondary damage caused by the release of chemicals the tumors produce. These chemicals can cause systemic problems that include gastric ulcers, internal bleeding, and a range of allergic manifestations.

Latest Research Update: We have compared the genomes of 88 Golden retrievers with MCT and 103 healthy Golden retrievers and are very excited to have identified
several regions of the genome that appear to be inherited risk factors for mast cell tumors in Golden retrievers. We are now validating these results in more dogs and looking to identify the exact gene and mutation which will allow the development of genetic tests and better treatments.

Breeds needed for our study: Golden Retrievers, Labrador Retrievers, German Shepherds, Pugs, Shar-Peis, and Boxers

Main collaborators: Cheryl London (Ohio State University), Lisa Barber (Tufts University)

Funding: Morris Animal Foundation

A cancer of the lymphocytes that can occur in the lymph nodes, spleen, liver, and other organs. Characteristics are high white blood cell count, swollen lymph glands, lethargy, and loss of appetite. It is a treatable cancer, but if left untreated, it will eventually lead to death. A number of B- and T-cell subtypes exist.

Breeds needed for our study: Golden Retrievers, Cocker Spaniels, Rottweilers, and Boxers

Collaborator: Matthew Breen (North Carolina State University)

Funding: Pending

Tumors of the mammary gland are the most common tumors found in unspayed female dogs. Several subtypes exist but may segregate in the same families.

Breeds needed for our study: English Springer Spaniels, Boxers, and Cocker Spaniels

Main collaborators: Henrik von Euler (Swedish University of Agricultural Science), Elizabeth McNeil (Michigan State University)

Funding: Pending

Melanoma is a cancer of melanocytes (the pigment-producing cells of the skin). Irregular cells develop when the melanocytes erratically multiply and invade surrounding tissue. Malignant melanomas can spread from the original tumor and travel through the blood to other vessels and organs.

Breeds needed for our study: Scottish Terriers, Cocker Spaniels, Labrador Retrievers, Rottweilers, and other breeds.

Main collaborators: Phil Bergman (Animal Medical Center), Catherine André (Université de Rennes)

Funding: Pending

FSF is a condition that causes dangerously high recurrent fevers, which can be accompanied by swollen hocks and muzzles and can even result in renal and liver failure.

Breeds needed for our study: Chinese Shar-Peis

Main collaborators: Francesca Puppo (National Institutes of Health), Daniel Kastner (National Institute of Arthritis and Musculoskeletal and Skin Diseases)

*Note - sample collection primarily at NIH

Also known as hypoadrenocorticism or adrenal insufficiency, Addison’s is caused by an insufficient production of adrenal hormones by a kidney’s adrenal gland. Symptoms include vomiting, diarrhea, lethargy, poor appetite, pain in the hindquarters, and generalized muscle weakness.

Breeds needed for our study: Poodles and Bearded Collies

Main collaborators: Anita Oberbauer (University of California, Davis), Åke Hedhammar (Swedish University of Agricultural Science)

*Note - sample collection also at UCD and SUAS

Lymphocytic thyroiditis is an immune-related destruction of the thyroid gland that can result in sluggishness, obesity, skin disease, cold intolerance, hair loss, weakness, poor coat, and infertility. This disease is also one of the leading causes of primary hypothyroidism.

Breeds needed for our study: Giant Schnauzers, Doberman Pinschers, and Leonbergers.

Main collaborator: Åke Hedhammar (Swedish University of Agricultural Science)

Our white coat color study serves as proof of principle for association mapping using the canine SNP arrays. Breeding studies in the 1950s by Clarence Little designated the white coat variant as the extreme white, or sw, allele of the major white spotting locus (S). Several other alleles were also suggested to share the same locus, including Irish spotting (si), and piebald spotting (sp).

Latest Research Update: Using ten white and nine solid boxers we were able to find an area of the genome associated with white spotting coat color, specifically an area of the dog genome that contained an important developmental gene called MITF that is associated with pigment and auditory disorders in humans and mice. We then used a larger sample set of dogs from several breeds, which carry the trait for white spotting, to help pinpoint the mutation and we were able to identify the causative mutation to a region that regulates MITF gene activity.

See: "In dogs, a shortcut to mapping disease genes"

Karlsson et al. (2007) Efficient mapping of mendelian traits in dogs through genome-wide association. Nature Genetics DOI:10.1038/ng.2007.10

Breeds needed for our study: Complete

Main collaborators: Leif Andersson (Uppsala University), Göran Andersson (Swedish University of Agricultural Science)

DS is a congenital disorder where, during embryonic development, the tissues that are to become skin to do not properly separate from the tissues that are to become the nervous system. Dermoid sinuses occur as tubular structures of the skin on the middle of the back, which can penetrate into the spinal canal and become infected, painfully swollen and life threatening for the dog.

Latest Research Update:To map the hair ridge trait in Rhodesian ridgebacks we compared the DNA of 12 ridged dogs to 9 ridgeless dogs and were able to identify a
segment of DNA that only occurred in the in the ridged dogs. This segment includes three genes involved in development called fibroblast growth factor (FGF) genes. Through further research we found that the ridge is caused by abnormal duplication of the FGF genes containing region, so that there are more than one copy of each of the three FGF
genes. The same mutation is found in both Rhodesian and Thai ridgeback dogs.

See: "In dogs, a shortcut to mapping disease genes"

Hillbertz et al. (2007) Duplication of FGF3, FGF4, FGF19, and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs. Nature Genetics DOI: 10.1038/ng.2007.4

Breeds needed for our study: Complete

Main collaborators: Göran Andersson (Swedish University of Agricultural Science), Leif Andersson (Uppsala University)

*Note - sample collection at SUAS

DM is a degenerative neurological disease where the dog’s immune system attacks both the myelin and axons of the nerves in the spinal cord (similar to multiple sclerosis in humans). The first signs are hind limb weakness and lack of coordination which can progress to a complete inability to walk.

Latest Research Upate: By comparing the DNA of 38 DM-affected Pembroke Welsh corgis to 17 healthy control dogs, we were able to find a gene that predisposes dogs to DM. Through further testing of dogs with and without DM we identified a mutation in the gene that was associated with inherited risk factors for DM in Pembroke Welsh corgis, boxers, Chesapeake Bay retrievers, German shepherd dogs, and Rhodesian ridgebacks. We believe that additional genetic risk factors contribute to DM in dogs and are therefore continuing our association studies with more samples. This research has been submitted for publication.

Breeds needed for our study: Boxers, Corgis, Hovawarts, Nova Scotia duck tolling retrievers and Chesapeake Bay retrievers.

Main collaborator: Joan Coates (University of Missouri)

JRD is an inherited condition affecting the developmental maturation of the kidney. The key clinical signs of JRD include (but are not limited to) excess water intake and urination from a young age (8 weeks to 2 years of age), and small, irregular-shaped kidneys observed by ultrasound examination, often leading to renal failure.

Latest Research Update: A genome-wide scan with ~10 boxer cases and their parents was performed, resulting in no clear risk loci. Sample collection is therefore ongoing to increase sample numbers. Please help!

Breeds needed for our study: Boxers and Shih Tzus

Main collaborator: Åke Hedhammar (Swedish University of Agricultural Science)

DCM is a disease of the heart muscle that can result in enlarged heart chambers, valve leakage and, in turn, weakened contractions and difficulty pumping blood out to the body and lungs. DCM is most commonly seen in large breed dogs, but it can be found in smaller breed dogs.

Breeds needed for our study: Boxers, Doberman Pinschers, and Newfoundlands

Collaborators: Kathryn Meurs (Washington State University), Åke Hedhammar (Swedish University of Agricultural Science)

*Note - sample collection at WSU and SUAS

The occurrence of a sparse coat of hair and abnormally shaped teeth is known as canine ectodermal dysplaysia (CED), and is characteristic of Chinese crested, Mexican and Peruvian hairless dogs.

Latest Research Update: By comparing the genomes of 20 hairless and 19 coated Chinese crested dogs we were able to identify the dog chromosome that was most associated to the CED trait. To pinpoint the location that was most associated to CED we compared 140 hairless dogs with 55 dogs with hair (including Chinese crested dogs, Mexican hairless dogs and Peruvian hairless dogs) and found the gene most associated to hairlessness. With further research we found a mutation within the most associated gene that is involved in hair development.

Drögemüller et al. (2008) A Mutation in Hairless Dogs Implicates FOXI3 in Ectodermal Development. Science DOI: 10.1126/science.1162525

Breeds needed for our study: Complete

Collaborators: Hannes Lohi (University of Helsinki) and Tosso Leeb (University of Bern)

DProgressive retinal atrophy (PRA) causes blindness and is inherited in over 100 breeds. Cone-rod dystrophy (CRD), a type of PRA, is an inherited photoreceptor disease, which results in day blindness.

Latest Research Update: Through comparing 13 different sets of standard wire-haired dachshund siblings (one sibling with CRD and one without) we were able to identify a new gene, nephroretinin (NPHP4), that is involved in early-onset CRD. NPHP4 was found to be shortened and missing the binding site for an important retina protein (RPGRIP1) in all the affected dogs. This is the first eye disease mutation found in NPHP4 that doesn’t also cause kidney disease (humans with NPHP4 mutations have both). Further studies will allow us to find the molecular mechanism of this retinopathy and develop potential therapies. Tests are now being offered for progressive rod cone dystrophy (contact: Frode Lingaas)

Wiik et al. (2008) A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund. Genome Res. doi:10.1101/gr.074302.107

Breeds needed for our study: Complete

Collaborators: Frode Lingaas (Norwegian School of Veterinary Science)