Genetic Testing of Australian Shepherds
At Wellington Ranch Aussies we feel that genetic health testing is imperative to the current and future success of our breeding program. As with all breeds there are specific diseases that Australian Shepherds are prone to. We test all of our breeding age dogs for these specific diseases to ensure that they are clear and/or unaffected. Testing is a costly endeavor but we are committed to the health of our dogs and the puppies that they produce. A copy of our dogs genetic health testing will be updated as individual testing is completed and can be found on the individual dogs page. Below you will find detailed information about what we test for, what each test means and the mode of inheritance of each disease.
Collie eye anomaly (CEA) also known as choroidal hypoplasia (CH)
An inherited disease affecting several dog breeds. The choroid is the layer of tissue in the eye responsible for supplying blood and nutrients to the Retina. In dogs affected with CEA, the choroid does not develop properly and is therefore thinner than normal. The severity of the condition can vary from dog to dog. In mild cases, affected dogs may only show signs of collie eye anomaly on eye exam between about 5 and 12 weeks of age, just prior to normal, age-related pigmentation of the retina which often masks the characteristic, disease-related changes. After this time period, mildly affected dogs may be impossible to distinguish from normal dogs on eye exam (a phenomenon often referred to as “going normal”) and may not display obvious vision deficits. In more severely affected dogs, clinical signs include malformations of the eye and/or optic nerve (colobomas), retinal detachment, intraocular bleeding, and subsequent blindness. Both mild and severe forms of CEA are associated with the same NHEJ1 gene Mutation. Therefore, predicting the potential severity of the disease in an affected puppy is difficult as mildly affected parents may produce offspring that are severely affected.
Inheritance
Genetic testing of the NHEJ1 gene will reliably determine whether a dog is a genetic Carrier of Collie eye anomaly. Collie eye anomaly is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the NHEJ1 gene mutation. Reliable genetic testing is important for determining breeding practices. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups.
Cone degeneration (CD)
An inherited eye disease affecting dogs. Affected dogs develop day blindness (blindness in bright light) and Photophobia (light sensitivity) between 8 to 12 weeks after birth due to degeneration of cells in the eye called cone photoreceptors which are responsible for vision in bright light. Affected dogs have normal vision in low light and structures of the inner eye appear normal on eye exam. Normal cone cell function can be seen on Electroretinogram (ERG) before six weeks of age, but becomes abnormal between 6 to 12 weeks of age and is completely absent in affected adult dogs signifying complete loss of Cone Cells. The cells responsible for vision in low light called Rod photoreceptors are not affected and thus, affected dogs will still be able to see normally in low light throughout life.
Inheritance
Genetic testing of the CNGB3 gene will reliably determine whether a dog is a genetic Carrier of cone degeneration. Cone degeneration is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the CNGB3 gene mutation. Reliable genetic testing is important for determining breeding practices. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups.
Degenerative myelopathy (DM)
Disease caused by Mutation of the SOD1 gene is an inherited neurologic disorder of dogs. This mutation is found in many breeds of dog, though it is not clear whether all dogs carrying two copies of the mutation will develop the disease. The variable presentation between breeds suggests that there are environmental or other genetic factors responsible for modifying disease expression. The average age of onset for dogs with degenerative myelopathy is approximately nine years of age. The disease affects the White Matter tissue of the spinal cord and is considered the canine equivalent to amyotrophic lateral sclerosis (Lou Gehrig’s disease) found in humans. Affected dogs usually present in adulthood with gradual muscle Atrophy and loss of coordination typically beginning in the hind limbs due to degeneration of the nerves. The condition is not typically painful for the dog, but will progress until the dog is no longer able to walk. The gait of dogs affected with degenerative myelopathy can be difficult to distinguish from the gait of dogs with hip dysplasia, arthritis of other joints of the hind limbs, or intervertebral disc disease. Late in the progression of disease, dogs may lose fecal and urinary continence and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of symptoms. Affected medium to large breed dogs can be difficult to manage and owners often elect euthanasia when their dog can no longer support weight in the hind limbs. Affected small breed dogs often progress more slowly than affected large breed dogs and owners may postpone euthanasia until the dog is paraplegic.
Interitance
Genetic testing of the SOD1 gene will reliably determine whether a dog is a genetic Carrier of degenerative myelopathy. Degenerative myelopathy is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the SOD1 gene mutation. Reliable genetic testing is important for determining breeding practices. Because symptoms may not appear until adulthood and some at-risk/affected dogs do not develop the disease, genetic testing should be performed before breeding. Until the exact modifying environmental or genetic factor is determined, genetic testing remains the only reliable way to detect neurological disease associated with this mutation prior to death. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups.
Hereditary cataracts (HC)
An inherited eye disease in dogs. Cataracts are opacities in the lens of the eye caused by structural changes in lens proteins. A normal lens allows light to pass through it to the Retina in the back of the eye. Light cannot pass through the parts of the lens affected by cataracts and vision becomes blurry. Dogs with Hereditary cataracts most commonly present within a few weeks to months after birth with small cataracts that are visible on a veterinary eye exam. Cataracts from this disease will eventually affect the whole lens in both eyes leading to complete blindness between 2-3 years of age. Of note, not all forms of cataracts are inherited and environmental factors such as UV damage can also play a role in the severity of disease.
Inheritance
Genetic testing of the HSF4 gene will reliably determine whether a dog is a genetic Carrier of Hereditary cataracts. Hereditary cataracts is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the HSF4 gene mutation. Reliable genetic testing is important for determining breeding practices. Because symptoms may not appear until adulthood, genetic testing should be performed before breeding. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups.
Hyperuricosuria (HUU)
An inherited condition of the urinary system affecting several breeds of dog. The SLC2A9 gene codes for a protein that allows the kidneys to transport uric acid from the urine. Dogs with mutations in both copies of the SLC2A9 gene are predisposed to have elevated levels of uric acid in the urine, hence the name hyperuricosuria. Uric acid can form crystals and/or stones (uroliths) in the urinary tract. Dogs with hyperuricosuria most commonly present with symptoms of recurrent urinary tract inflammation, which include frequent urination, blood in the urine, and straining to urinate. They may also have loss of appetite, lethargy, weakness, vomiting and pain. Urinary stones in the bladder can cause urinary tract infections or more seriously, blockage of the Urethra. Both male and female dogs can be affected, but obstruction of urine flow is more common in males due to differences in anatomy. Although an x-ray can be used to exclude other types of stones, urate stones cannot typically be seen using x-rays and must be evaluated by ultrasound. Not all dogs with mutations in both copies of the SLC2A9 gene will have symptoms of disease, though they will have increased uric acid excretion in the urine.
Inheritance
Genetic testing of the SLC2A9 gene will reliably determine whether a dog is a genetic Carrier of hyperuricosuria. Hyperuricosuria is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the SLC2A9 gene mutation. Reliable genetic testing is important for determining breeding practices. Because not all affected dogs will have clinical signs associated with hyperuricosuria, genetic testing should be performed before breeding. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups.
Multi-Drug Resistace 1 (MDR1)
An inherited condition affecting several breeds of dogs, especially herding dogs or descendants of herding breeds. The Mutation in the ABCB1 gene associated with MDR1 causes dysfunction of P-glycoprotein, which is responsible for removing certain drugs and toxins from the body. Clinical signs are most commonly associated with distribution of the drug in the central nervous system. MDR1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing adverse reactions to certain medications. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, Carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly. Thus, dogs that have one or two copies of the mutation are considered at-risk for adverse drug reactions. If an at-risk dog is treated with one of several common drugs (see below*), they are at risk of developing neurologic symptoms that could range from tremors, excess salivation, anorexia, and blindness to coma and even death. Because of the defective ability to metabolize specific drugs, these drugs can be lethal even at low doses. The MDR1 mutation does not cause adverse effects in dogs unless the dog is exposed to these drugs. Therefore, veterinarians should be notified when a dog is at risk for multidrug resistance 1 prior to administration of any medications. *Drugs known to cause neurological signs related to the MDR1 mutation: Acepromazine, butorphanol, doxorubicin, emodepside, erythromycin, ivermectin, loperamide, milbemycin, moxidectin, rifampin, selamectin, vinblastine and vincristine. In addition to this list, there are many other drugs known to be removed from the central nervous system via the P-glycoprotein mechanism in humans. However, reports of neurological dysfunction related to drugs other than those listed here are scarce in dogs. Please consult your veterinarian prior to giving drugs to known multidrug resistance carriers, affected dogs, or untested dogs of breeds commonly affected with this condition.In dogs affected with MDR1, the blood brain barrier is comprimised. This gene encodes a protein, P-glycoprotein, that is responsible for pumping many drugs and other toxins out of the brain. Dogs with the mutant gene cannot pump some drugs out of the brain as a normal dog would, which may result in abnormal neurologic signs. The result may be an illness requiring an extended hospital stay--or even death. It is well known that all sizes of Australian Shepherds and related breeds can have adverse reactions to drugs such as ivermectin, loperamide (Imodium®), and others. DNA testing is now available through Washington State University.
Dogs that are affected by MDR1 will have a sensitivity to Ivermenctin and other related drugs. Dogs that are carriers of MDR1 may experience some sensitivity to Ivermectin and other related dogs. Dogs that test clear for MDR1 should not exhibit any drug sensitivities however as Australian Shepherds as are in the herding dog breed we still recommend treating those that are negative for the MDR1 gene to be treated as MDR1 sensitive.
Here is a list of medications that should be avoided if the status of an aussies MDR1 status is not known: Acepromazine (tranquilizer and pre-anesthetic agent) Butorphanol (analgesic and pre-anesthetic agent) Erythromycin Ivermectin (antiparasitic agent) Loperamide (ImodiumTM; antidiarrheal agent) Selamectin, milbemycin, and moxidectin (antaparasitic agents) Vincristine, Vinblastine, Doxorubicin (chemotherapy agents) Domperidone Etoposide Mitoxantrone Ondansetron Paclitaxel Rifampicin
Drugs that are known to be pumped out of the brain by the protein that the MDR1 gene is responsible for producing but appear to be safely tolerated by dogs with the MDR1 mutation: Cyclosporin (immunosuppressive agent) Digoxin (cardiac drug) Doxycycline (antibacterial drug)
Drugs that may be pumped out by the protein that the MDR1 is responsible for producing, but appear to be safely tolerated by dogs with the MDR1 mutation: Morphine, buprenorphine, fentanyl (opioid analgesics or pain medications)
Inheritance
Genetic testing of the ABCB1 gene will reliably determine whether a dog is a genetic Carrier of multidrug resistance 1. Multidrug resistance 1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing the disease. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly. Thus, dogs that have one or two mutant copies of the gene are considered at-risk for adverse drug reactions. When carriers of this Mutation are bred with another dog that also is a carrier of the same mutation, there is risk of having affected pups. For each pup that is born to this pairing, there is a 25% chance that the puppy will inherit two copies of the mutation and a 50% chance that the puppy will inherit one copy of the mutation and, in either case, may be susceptible to having adverse drug reactions. Reliable genetic testing is important for determining breeding practices. Because symptoms do not appear unless dogs are exposed to certain drugs, genetic testing should be performed before breeding. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups when bred to a dog that is also clear for this mutation
Multifocal retinopathy 1 (CMR, CMR1)
An inherited disorder of the Retina affecting several breeds of dog. Affected dogs typically present between 11 and 16 weeks of age with multiple discrete circular areas of retinal detachment with underlying fluid accumulation that are visible on an eye exam performed by a veterinarian. These blister-like lesions are typically found in both eyes and can appear gray, tan, orange or pink and vary in number, size and location. Progression of retinal changes is usually slow and new lesions are not noted after 6 to 12 months of age. Occasionally as affected dogs age, lesions appear to heal and are no longer visible on an eye exam. Generally the dog’s vision is not affected although vision loss has been described in some cases of multifocal retinopathy 1.
Inheritance
Genetic testing of the BEST1 gene will reliably determine whether a dog is a genetic Carrier of multifocal retinopathy 1. Multifocal retinopathy 1 is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the BEST1 gene mutation. Reliable genetic testing is important for determining breeding practices. Because visual deficits are generally not noted and lesions can regress as affected dogs age, genetic testing should be performed before breeding. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups.
Progressive Retinal Atrophy, Progressive Rod-Cone Degeneration (PRA- PRCD)
The genetic disorder Progressive Rod-cone Degeneration-Progressive Retinal Atrophy, causes cells in the retina at the back of the eye to degenerate and die, even though the cells seem to develop normally early in life. The result is declining vision and eventual blindness. The “rod” cells operate in low light levels and are the first to lose normal function. Night blindness results. Then the “cone” cells gradually lose their normal function in full light situations. Most affected dogs will eventually go blind. It’s important to remember that not all retinal disease is PRA and not all PRA is the prcd form of PRA. DNA testing will make the diagnosis, prior to the onset of disease.
Inheritance:
Genetic testing of the PRCD gene will reliably determine whether a dog is a genetic Carrier of PRA-prcd. PRA-prcd is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of being a carrier of the PRCD gene mutation. Reliable genetic testing is important for determining breeding practices. Because symptoms do not appear until adulthood, genetic testing should be performed before breeding. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Dogs that are not carriers of the mutation have no increased risk of having affected pups. However, because there are multiple types of PRA caused by mutations in other genes, a normal result in PRCD does not exclude PRA in a pedigree.
Source
-Paw Print Genetics; www.pawprintgenetics.com