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Copper & Copper Toxicosis
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Copper Toxicosis & DNA tests.
Before giving information on copper toxicosis I feel that it is important that people have an understanding of the role of copper as an essential nutrient. The following information is taken directly from the link below.
The body needs copper for normal growth and health. Copper is needed to help body use iron. It is also important for nerve function, bone growth, and to help the body use sugar. Copper is a component of or a cofactor for approximately 50 different enzymes (cuproenzymes). These enzymes need copper to function properly. Copper is an essential nutrient that plays a role in the production of haemoglobin (blood cells), myelin (essential for the transmission of nerve impulses), collagen (connective tissue such as ligaments, hair and nails), and melanin (dark pigment which has a protective function in regard to skin cancers). Copper also works with vitamin C to help make a component of connective tissue known as elastin. Copper is an essential component of the natural dark pigment, (melanin formed in cells called melanocytes), that colours skin, hair, and eyes. The cupro-enzyme, tyrosinase, is required for the formation of the pigment melanin. Copper is a strong antioxidant, it works together with an antioxidant enzyme, superoxide dismutase (SOD), to protect cell membranes form being destroyed by free radicals. Copper is needed to make adenosine triphosphate (ATP), the energy the body runs on. Copper may play a role in staving off heart rhythm disorders (arrhythmias) and high blood pressure. Copper's anti-inflammatory actions may help in reducing arthritis symptoms.
Copper Toxicosis is an autosomal recessive genetic disease that is known in a number of dog breeds but it is more likely to affect Bedlington Terriers (at this point in time), than other breeds.
Bedlington Terriers that are affected by the disease do not produce the enzyme needed to excrete copper from the liver. Copper Toxicosis is a progressive disease where three distinct “stages” have been identified, as the disease progresses, copper builds up in the liver destroying liver cells and eventually resulting in liver failure.
In recent years Liver Biopsies, DNA linked marker tests and a direct genetic test have been used to determine the disease status of individual dogs.
The earliest methods of identifying dogs with Copper Toxicosis was to take a liver sample through biopsy and, using staining methods, this procedure would identify increased copper levels in the liver. Australian breeders are not using this method of identifying dogs with Copper Toxicosis due to the risks associated with the procedure and the availability of other tests.
The first of the DNA tests (C04107), is a linked marker test where two distinct markers close to the genetic “site” of the disease have been noted. The type 1 markers are usually (over 95%), associated with the normal gene where the type 2 markers are usually associated with the disease gene. To conduct this test a buccal swab is taken to provide a genetic sample which is forwarded to an accredited test facility where the sample is analysed. A certificate is returned to the owner of the dog indicating the result of the test, ie, 1:1, 1:2 or 2:2. In most cases 1:1 dogs will be clear of the disease, 1:2 results generally indicate carriers of the disease 2:2 dogs are most likely to be affected by the disease.
With this test it is important to note that dogs with a 1:1 result have developed Copper Toxicosis. Indeed, it is possible for any of the combinations listed to be clear, carrier or affected.
The most recent test developed is the COMMD1 test which is a direct genetic test. This test identifies a deletion at the MURR1 site on type 2 DNA and allows the positive identification of the Copper Toxicosis status of dogs with type 2 DNA. With this test the sample is collected in the same way as for the previous test and the sample is again analysed at an accredited test facility. A certificate is returned indicating either a “normal” or “abnormal” result. For the COMMD1 test it is important to note that this test will only identify the MURR1 deletion on type 2 DNA.
The following short descriptors of the various stages of the disease have been taken from various internet sites publishing information on Copper Toxicosis.
The livers of dogs in Stage 1 present no clinical abnormalities, and biopsy at this time will indicate that things are normal. However, if liver tissue is stained, using the methods developed by Thornburg et al. (1985), increased levels of copper are revealed.
Stage 2 begins when the hepatic copper concentration reaches 2,000 ppm DW (Thornburg 1985). The dog is still not clinically ill, but a biopsy at this point will reveal hepatitis, and is the only reliable method of diagnosis. Biochemical and toxicologic findings including elevated serum enzyme levels (Alanine Aminotransferase [ALAT] and Alkaline Phosphatase [AP]) may be seen, but do not specifically indicate copper toxicosis.
Finally, in Stage 3, the dog becomes clinically ill, and may have anorexia, depression, vomiting, abdominal pain, polydipsia(drinking frequently), polyuria (urinating often), jaundice (yellowing of the skin or eyes), ascites (abdominal swelling), and encephalopathy, altered mental functioning due to toxins in the blood, (Dill-Macky 1995, Franklin 1988). Weight loss is the predominant indicator, and in some dogs, is the only sign.
If you are considering buying a Bedlington Terrier it is very important that you sight the Copper Toxicosis test results for both the sire and dam of the pup you are intending to buy. The results you will be looking for are;
For C04107 you would like both parents to be 1:1, if one parent is 1:1 and the other is 1:2 it is possible that your pup will be a carrier of the disease. If both parents are 1:2 it is possible that the pups may be clear, carrier or affected. With 1:2 and 2:2 matings statistically, 50% of the pups will be affected and 50%will be carriers. With 2:2 and 2:2 all will be affected. NOTE: there are some dogs that have been identified as having copper toxicosis even though they have two copies of the type 1 markers. It is estimated that significantly less than 5% of 1,1 dogs will be carriers and even less likely that they will be affected. There are also some type 2 dogs that are clear of the disease.
For COMMD1 test results you would be looking for normal/clear for both parents. An abnormal result for this test means that dogs with type 2 markers have been used in the mating and that the MURR1 deletion which causes the disease in type 2 DNA has been detected. If the dog is tested by Genetic Technologies (ANKC endorsed Laboratory in Victoria) the result will indicate CLEAR, CARRIER or AFFECTED. A dog with two type 1 markers will always be identified as clear as this test is not useful for determining CT status on type 1 DNA. If the dog has one or two type two markers you could have a CLEAR result which would reflect 1 (no deletion detected) : 2 (no deletion detected), or 2 (no deletion detected), : 2 (no deletion detected). CARRIER, 1 (no deletion detected),: 2 (deletion detected), or 2 (no deletion detected), : 2 (deletion detected). An AFFECTED dog would have two copies of the type 2 marker with the deletion detected on both copies.
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