UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Bulldog Health Panel

Tests Offered:
CMR1 | DM | HUU

Canine Multifocal Retinopathy 1

Introduction

Canine Multifocal Retinopathy 1 (CMR1) is an inherited eye disease caused by a mutation (c.73C>T) in the Bestrophin 1 gene that results in a shortened, dysfunctional protein. Affected dogs typically present with multiple, discrete circular areas of retinal detachment between 11 and 16 weeks of age. Fluid accumulates under the detached retina resulting in gray, tan, orange or pink “blisters” in the eye. Progression of retinal changes is slow, ceases by 1 year and does not lead to blindness. In some cases, the blisters appear to heal as the dog ages but vision loss has been reported. The disease is inherited in an autosomal recessive fashion thus two copies of the CMR1 mutation must be present to produce the disease. Breeding two carriers is predicted to produce 25% of affected pups


The VGL offers a genetic test for the CMR1 mutation. Genetic screening helps breeders establish the genetic status of breeding stock and select mating pairs appropriately in order to reduce the risk of producing CMR1-affected offspring.


Testing is recommended for: American Bulldog, American Bully, Aussiedoodle, Australian Koolie, Australian Shepherd, Brazilian Terrier, Bulldog, Bullmastiff, Cane Corso, Dogue de Bordeaux, French Bulldog, Great Pyrenees, Havanese, Koolie, Mastiff, Miniature American Shepherd, Miniature Australian Shepherd, Perro de Presa Canario, Shorty Bull, South African Boerboel, Toy Australian Shepherd

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Allow 5-10 business days for results.

Results reported as:

N/N

Normal - no copies of the CMR1 mutation

N/CMR1

Carrier - 1 copy of the CMR1 mutation; dog is normal

CMR1/CMR1

Affected - 2 copies of the CMR1 mutation; dog will develop multifocal retinopathy

References:

Gornik KR, Pirie CG, Duker JS, Boudrieau RJ. 2014. Canine multifocal retinopathy caused by a BEST1 mutation in a Boerboel. Vet Ophthalmol 17(5):368-72. [PubMed: 23998685]


Donner J, Kaukonen M, Anderson H, Moller F, Kyostila K, Sankari S, Hytonen M, Giger U, Lohi H. 2016. Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLoS One 11(8). [PubMed: 27525650]

 

Degenerative Myelopathy

Introduction

Degenerative myelopathy (DM) is an inherited neurologic disorder of dogs similar to Lou Gehrig’s disease in humans and results from a mutation (c.118G>A) in the SOD1 gene. Affected dogs usually present clinical signs of disease in adulthood (at least 8 years of age) with gradual muscle wasting and loss of coordination that typically begins in the hind limbs because of nerve degeneration. Disease progression continues until the dog is unable to walk. Small breed dogs tend to progress more slowly. In late stages of the disease, dogs may become incontinent and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of signs. The disease is inherited in an autosomal recessive fashion with incomplete penetrance. Thus, two copies of the SOD1 mutation (DM/DM) confer increased risk for DM but not all DM/DM dogs across breeds will develop the disease. The variable presentation between breeds suggests that other genetic and environmental factors play a role in disease expression. There is ongoing research to identify other genetic factors that modify risk for DM in different breeds. In addition, similar disease presentation is observed in some animals lacking the SOD1 mutation. Breeding two carriers of the SOD1 mutation together is predicted to produce 25% of pups that may develop DM.


The VGL offers a genetic test for the SOD1 c.118G>A mutation, reported here as DM. Genetic screening helps breeders establish the genetic status of breeding stock and select mating pairs appropriately to reduce the risk of producing DM-affected offspring.

Testing is appropriate for: many breeds

The Degenerative Myelopathy (DM) test is a patented test. The Veterinary Genetics Laboratory is authorized to offer the DM test to residents of the United States, Canada and Australia.

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Allow 5-10 business days for results.

Results reported as:

N/N

No copies of the DM mutation

N/DM

1 copy of the DM mutation

DM/DM

2 copies of the DM mutation; dog may develop DM disease

Reference:

Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. 2009. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 106(8):2794-2799. [PubMed: 19188595]


Coates JR, March PA, Oglesbee M, Ruaux CG, Olby NJ, Berghaus RD, O'Brien DP, Keating JH, Johnson GS, Williams DA. 2007. Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med. 21(6):1323-1331. [PubMed: 18196743]


Shelton GD, Johnson GC, O’Brien DP, Katz ML, Pesayco JP, Chang BJ, Mizisin AP, Coates JR. 2012. Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh Corgis and Boxers. J Neurol Sci 318(1-2):55-64. [PubMed: 22542607]


Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. 2014. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med 28(2):515-521. [PubMed: 24524809]

Canine Hyperuricosuria

Introduction

Hyperuricosuria (HUU) means elevated levels of uric acid in the urine. This trait predisposes dogs to form stones in their bladders or sometimes kidneys. These stones often must be removed surgically and can be difficult to treat. HUU is inherited as a simple autosomal recessive defect. A mutation in exon 5 of the gene Solute carrier family 2, member 9 (SLC2A9) has been found to be associated with hyperuricosuria in dogs. HUU can occur in any breed but is most commonly found in the Dalmatian, Bulldog and Black Russian Terrier. While traditional Dalmatians are homozygous for HUU (HU/HU), the introduction of “low uric acid” dogs, derived from Dalmatian x Pointer backcrosses, into the purebred gene pool has provided a means for breeders to reduce incidence of the disease and maintain the breed characteristics. Normal (N/N) and carrier (N/HU) Dalmatians are now present in the breed, and trace to the backcross lineage.


A DNA test for the SLC2A9 mutation can determine the genetic status of dogs for HUU. Dogs that carry two copies of the mutation will be affected and susceptible to develop bladder/kidney stones. The SCL2A9 mutation is not the sole cause of urate bladder stones in dogs. Other factors such as liver disease and diet need also be considered in clinical evaluation.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Detailed Hyperuricosuria Information


The VGL offers a DNA test for hyperuricosuria to assist owners and breeders in identifying affected and carrier dogs. The test uses DNA collected from buccal swabs thus avoiding invasive blood collection. Breeders can use results from the test as a tool for selection of mating pairs to avoid producing affected dogs. The test is offered to all breeds, including American Pitbull Terrier, American Staffordshire Terrier, Australian Shepherd, Black Russian Terrier, Bulldog, Catahoula Leopard Dog, Dalmatian, Danish-Swedish Farmdog, French Bulldog, German Hunting Terrier, German Shepherd, Giant Schnauzer, Jack Russel/Parsons Terrier, Kromfohrländer, Labrador Retriever, Lagotto Romagnolo, Large Munsterlander, South African Boerboel, Spaniel de Pont-Audemer, Swedish Vallhund, Vizsla and Weimaraner.


The following chart details the expected outcomes of matings for all possible combinations of hyperuricosuria genotypes.

Female

Male

N/N

N/HU

HU/HU

N/N

100% N/N

50% N/N, 50% N/HU

100% N/HU

N/HU

50% N/N, 50% N/HU

25% N/N, 50% N/HU, 25% HU/HU

50% N/HU, 50% HU/HU

HU/HU

100% N/HU

50% N/HU, 50% HU/HU

100% HU/HU

Results reported as:

N/N

No copies of hyperuricosuria mutation detected. Dog is normal

N/HU

1 copy of hyperuricosuria mutation detected. Dog is a carrier and unaffected. If bred to another carrier, 25% of offspring are predicted to be affected.

HU/HU

2 copies of hyperuricosuria mutation detected. Dog is affected with HUU and susceptible to develop bladder/kidney stones.

We recommend testing any dog that has formed kidney or bladder stones composed of urate or uric acid. If the dog has the mutation then treatment modalities for Dalmatians can be used to treat the dog.

References:

Bannasch D, N Safra, A Young, N Karmi, RS Schaible and GV Ling. 2008. Mutations in the SLC2A9 Gene Cause Hyperuricosuria and Hyperuricemia in the Dog. PLoS Genetics 4(11): e1000246. [PubMed 18989453]


Karmi N, EA Brown, SS Hughes, B McLaughlin, CS Mellersh, V Biourge, and DL Bannasch. 2010. Estimated Frequency of the Canine Hyperuricosuria Mutation in Different Dog Breeds. J Vet Intern Med 24(6):1337–1342. [PubMed 21054540]


Karmi N, Safra N, Young A, Bannasch DL. 2010. Validation of a urine test and characterization of the putative genetic mutation for hyperuricosuria in Bulldogs and Black Russian Terriers. Am J Vet Res 71(8):909-914. [PubMed 20673090]

 

 

 
Veterinary Genetics Laboratory, Tel 530-752-2211, Email VGL