Sensory Ataxic Neuropathy (SAN) in Golden Retrievers
Sensory ataxic neuropathy is a progressive neurological disorder characterized by involuntary muscle movements and abnormal posture resulting from degeneration of the nerves controlling muscle movement. It affects both sexes but is only inherited maternally.
Phenotype: Sensory Ataxic Neuropathy is a progressive inherited disorder characterized by uncontrolled muscle movement, abnormal posture, and decreased spinal reflex. However, muscle atrophy is not evident.
Mode of Inheritance: Maternal/mitochondrial
Alleles:N = Normal, SAN = sensory ataxic neuropathy variant
Breeds appropriate for testing: Golden Retriever and Golden Retriever crosses
Explanation of Results:
Dogs with N mitotype do not have the variant associated with sensory ataxic neuropathy found in Golden Retrievers.
Dogs with N/SAN mitotype have variant and non-variant alleles. Depending upon the relative ratios, the dog may develop symptoms of disease.
Dogs with SAN mitotype have the associated variant and are at risk to develop sensory ataxic neuropathy. If a male with a SAN mitotype is mated with an N female, none of the puppies are predicted to develop disease. If a female with a SAN mitotype is mated with an N male, all of the puppies are at risk to develop disease.
At least 15 business days; may be delayed beyond 15 business days if sample requires additional testing, or a new sample is requested.
Sensory ataxic neuropathy is a heritable neurodegenerative disease in Golden Retrievers that affects both the central and peripheral nervous system. It is characterized by a lack of muscle control and coordination as well as decreased spinal reflexes without muscle atrophy. Dogs with sensory ataxic neuropathy (SAN) may have difficulty walking or maintaining normal posture, actively avoid slippery surfaces, have an altered gait and male dogs have been reported to urinate without leg lifting. Symptoms appear slowly in puppies and may not be initially obvious. The disease is progressive, and symptoms may become so severe that dogs have a poor quality of life and thus are euthanized.
Sensory ataxic neuropathy is a mitochondrial disorder and is caused by the deletion of a single base pair at position 5,304 in the tRNATyr mitochondrial gene. Male and female dogs can develop the disease, but mitochondrial disorders are thought to only be inherited through the maternal line. The mitochondria is a specialized structure (organelle) of the cell that has its own DNA. This structure is involved in creating energy that the cell uses to perform all functions. The mitochondria are maternally inherited as these organelles in the male reproductive cells (sperm) are usually destroyed after fertilization and so mostly the mitochondria from the egg survive and get passed down to the next generation.
All puppies produced from a female with a SAN mitochondrial variant may develop sensory ataxic neuropathy. A male dog with a SAN mitochondrial variant, mated to an N female, is not predicted to produce puppies with sensory ataxic neuropathy.
The mutation in tRNATyr is thought to be responsible for causing sensory ataxic neuropathy. Although uncommon, mitochondrial disorders can exhibit heteroplasmy, that is when both normal and variant mitochondrial DNA (mtDNA) are present in a cell, and the proportion of one to the other may vary across the body. A high ratio of variant to normal mtDNA may lead to development of sensory ataxic neuropathy, while dogs with an overall low ratio of the tRNATyr variant may be clinically normal. Interactions with other currently unknown genes may also influence the risk of developing sensory ataxic neuropathy.
Testing for sensory ataxic neuropathy can identify dogs that will likely develop symptoms. Dogs reported with a SAN mitochondrial variant should be clinically evaluated. Breeders can use this test to screen their potential breeding female dogs to avoid producing affected dogs.
Note: This test is specific for the variant present in the Golden Retriever. This assay does not detect neuropathies in other breeds.
Normal. Dog does not have the variant associated with sensory ataxic neuropathy found in Golden Retrievers.
The dog has evidence of two different mitochondria (heteroplasmy). The dog has the Golden Retriever sensory ataxic neuropathy variant as well as the normal variant and may exhibit symptoms of disease.
Only the Golden Retriever sensory ataxic neuropathy variant is present.
Jäderlund, K.H., Orvind, E., Johnsson, E., Matiasek, K., Hahn, C.N., Malm, S., & Hedhammar, A. (2007). A neurologic syndrome in Golden Retrievers presenting as a sensory ataxic neuropathy. Journal of Veterinary Internal Medicine, 21(6), 1307-1315. doi: 10.1892/07-005.1
Baranowska, I., Jäderlund, K.H., Nennesmo, I., Holmqvist, E., Heidrich, N., Larsson, N.G., Andersson, G., Wagner, E.G., Hedhammar, A., Wibom, R., & Andersson, L. (2009). Sensory ataxic neuropathy in golden retriever dogs is caused by a deletion in the mitochondrial tRNATyr gene. PLOS Genetics, 5(5): e1000499. doi: 10.1371/journal.pgen.1000499