Pathologies Associated with the
M D R 1
Multi-Drug Resistance Gene, (MDR) codes for a protein that is responsible for protecting the brain by transporting potentially harmful chemicals away from the brain. In certain breeds, a mutation occurs in the MDR1 gene that causes sensitivity to Ivermectin, Loperamide, and a number of other drugs. Dogs with this mutation have a defect in the P-glycoprotein that is normally responsible for transporting certain drugs out of the brain. The defective protein inhibits the dog's ability to remove certain drugs from the brain, leading to a buildup of these toxins. As a result of the accumulation of toxins, the dog can show neurological symptoms, such as seizures, ataxia, or even death.
Dogs that are homozygous for the MDR1 gene (meaning that they have two copies of the mutation) will display a sensitivity to Ivermectin and other similiar drugs. These dogs will also always pass one copy of the mutation to all potential offspring. Dogs that are heterozygous (meaning they have only one copy of the mutation) can still react to these drugs at higher doses. Also, there is a 50% chance that a dog with one copy of the mutation will pass it on to any offspring.
There are many different types of drugs that have been reported to cause problems. The following is a list of some of the drugs:Ivermectin (found in heartworm medications) Loperamide (Imodium over the counter antidiarrheal agent) Doxorubicin, Vincristine, Vinblastine (anticancer agents) Cyclosporin (immunosuppressive agent) Digoxin (heart drug) Acepromazine (tranquiliser) Butorphanol ("Bute" pain control).
The following drugs may also cause problems: Ondansetron, Domperidone, Paclitaxel, Mitoxantrone, Etoposide, Rifampicin, Quinidine, Morphine.
Animal Genetics accepts buccal swab, blood, and dewclaw samples for testing.
Results ADN proves
2 free copies +/+
1 free copie and 1 afected +/-
2 afected copies -/-
Transmision of the genetic anomaly
Degenerative Myelopathy (DM) is a progressive neurological disorder that affects the spinal cord of dogs. Dogs that have inherited two defective copies will experience a breakdown of the cells responsible for sending and receiving signals from the brain, resulting in neurological symptoms.
The disease often begins with an unsteady gait, and the dog may wobble when they attempt to walk. As the disease progresses, the dog's hind legs will weaken and eventually the dog will be unable to walk at all. Degenerative Myelopathy moves up the body, so if the disease is allowed to progress, the dog will eventually be unable to hold his bladder and will lose normal function in its front legs. Fortunately, there is no direct pain associated with Degenerative Myelopathy.
The onset of Degenerative Myelopathy generally occurs later in life starting at an average age of about 10 years. However, some dogs may begin experiencing symptoms much earlier. A percentage of dogs that have inherited two copies of the mutation will not experience symptoms at all. Thus, this disease is not completely penetrant, meaning that while a dog with the mutation is likely to develop Degenerative Myelopathy, the disease does not affect every dog that has the genotype.
C E A
Collie Eye Anomaly (CEA) is a inherited bilateral eye disease common in a number of breeds of dogs. The disorder causes abnormal development in layers of tissue in the eye under the retina called the choroid. These changes cause what is referred to as Choroidal Hypoplasia. The abnormal choroid appears pale and translucent. In most cases CEA is present at birth and can be detected in puppies as young as 4-8 weeks of age. There is currently no treatment for this disease.
Studies have shown that approximately 70 to 97 percent of rough and smooth collies in the United States and Great Britain have at least one copy of the mutation that causes CEA, and approximately 68 percent of Rough Collies in Sweden are affected. Border Collies are also subjected to this disorder, but at a lower percentage. CEA is also seen in Australian Shepherds, Shetland Sheepdogs, Lancashire Heelers, and other herding dogs.
Animal Genetics has developed a panel of six DNA markers called a "haplotype" to test for CEA. Animal Genetics is interested in developing a more comprehensive test to better distinguish those individual animals that may develop a more severe form of CEA from those that do not. Although we do not incorporate the genetic mutation Optigen claims to have an exclusive right to use into our panel, our test results using this haplotype of six DNA markers provides the same result.
P R A - R C D 2
Progressive Rod-cone degeneration, or PRA-prcd, is a form of Progressive retinal Atrophy (PRA) in which the cells in the retina of a dog degenerate and die. PRA is the dog equivalent of retinitis pigmentosa in humans. Most affected dogs will not show signs of vision loss until 3-5 years of age. Complete blindness can occur in older dogs. Progressive Rod-Cone Degeneration is a form of PRA known to affect over 40 different breeds.
The retina is a membrane located in the back of the eye that contains two types of cells known as photoreceptors. These cells take light coming into the eyes and relay it back to the brain as electrical impulses. These impulses are interpreted by the brain as vision. In dogs suffering from PRA-prcd, the photoreceptors begin to degenerate, causing an inability to interpret changes in light resulting in loss of vision. Rod cells, which are normally function in low-light, begin to degenerate first, leading to night-blindness. The cone cells, which normally function in bright-light or daytime conditions, will deteriorate next. This often leads to complete blindness over time.
PRA-prcd is inherited as an autosomal recessive disorder. A dog must have two copies of the mutated gene to be affected by PRA. A dog can have one copy of the mutation and not experience any symptoms of the disease. Dogs with one copy of the mutation are known as carriers, meaning that they can pass on the mutation to potential offspring. If they breed with another carrier, there is a 25% chance that the offspring can inherit one copy of the mutated gene from each parent, and be affected by the disease.
Gray Collie Syndrome (G C S)
Cyclic Neutropenia (CN) is a recessive stem cell disorder that affects both smooth and rough collies. Also known as Cyclic Hematopoiesis or "Gray Collie Syndrome," dogs affected by Cyclic Neutropenia appear visibly lighter than non-affected littermates - even from puppies with the Merle coloration.
Cyclic Neutropenia is a disease that affects the neutrophils of a dog, which are an integral part of the dog's immune system. Every 10-12 days, the dog will experience a dramatic drop in the number of neutrophils circulating through his blood stream, leaving him extremely susceptible to infections. The dog will often experience diarrhoea, fever, joint pain or other symptoms associated with eye, respiratory, or skin infections. Bleeding episodes can also occur. Unfortunately, most affected dogs will die as puppies, and even with the best care, the dog will not likely live past 2-3 years of age.
Gray Collie Syndrome is an autosomal recessive mutation, meaning that a dog must have two copies of the mutation in order to display the signs and symptoms associated with this disorder. This also means that a parent can be a carrier of this disorder but not show any signs. A dog that carries the mutation can pass on either the normal or mutant allele to any offspring. Therefore, if two carriers produce a litter of pups, there is a 1 in 4, or 25% chance that an offspring will be affected by the disorder. Additionally, 50% of the pups will be carriers and 25% will be clear.
En estas imágenes se ven claramente Rough Collie recién nacidos afectados por el GCS
Dogs with this genetic mutation metabolize waste products as uric acid in their urine. The uric acid forms into hard stones in the bladder, causing pain and inflammation as the stone moves through the urinary tract.
A dog that has difficulty urinating or appears to have an inflamed bladder may have HUU. Other signs can include blood in the urine and frequent urination. If the dog is unable to pass the urate stones without medical intervention, surgery may be required to remove them. And if the urinary tract is blocked, the condition can be life threatening. Even in the best case scenario, HUU is uncomfortable and painful for the dog.
The mutation is autosomal recessive. Both parents will need to be carriers of the mutation to pass it on to their offspring. Carriers will not show any symptoms of HUU and even affected dogs may not show any signs, so it is important to test dogs for HUU prior to breeding.
In the normal anatomy of the hip joint, the root (the thigh bone) is connected to the pelvis at the hip joint. The almost spherical end of the femur head (the caput, or caput ossis femoris) fits into the acetabulum (a concave socket located in the pelvis). The bony surfaces of the femur head and of the acetabulum are covered by cartilage. While bones provide the strength necessary to support body weight, cartilage ensures a smooth fit and a wide range of motion. Normal hip function can be affected by congenital conditions such as dysplasia, discussed in this article, trauma, and by acquired diseases such as osteoarthritis and rheumatoid arthritis.
In a Dysplastic hip anatomy, the hip could have major contractions or seizures from dysplasias. The caput is not deeply and tightly held by the acetabulum. Insteed of being a snug fit, it is a loose fit, or a partial fit. Secondly, the caput or acetabulum are not smooth and round, but era misshapen, causing abnormal wear and tear or friction within the join as it moves. The body reacts to this several ways. First, the joint itself is continually reparing itself and laying down new cartilage. However, cartilage repair is a relatively slow process, the tissue being avascular, so the joint may suffer degradation due to the abnormal wear and tear, or may not support the body weight as intended. The joint becomes inflamed and a cycle of cartilage damage, inflamation and pain commences. This is a self-fueling process, in that the more the joint becomes damage, the less able it is to resist further damage. The inflamation causes further damage. The bones of the joint may also develop osteoarthritis, visible on a X-ray as small outcrops of bone,
Which further degrade the joint. Osteoarthritis is a degenerative disease marked by the breakdown of cartilage between joints resulting in painful bone to bone contact. The underlying deformity of the joint may get worse over time, or may remain static. A dog may have good X-rays and yet be in the pain, or may have very poor X-rays and have no apparent pain issues. The hip consition is only one factor to determine the extent to which dysplasia is causing pain or affecting the quality of life. In mild to moderate dysplasia it is often the secondary effects of abnormal wear and tear or arthritis, rather than dysplasia itself, which is the direct causes of visible problems.
Dogs might exhibit signs of stiffness or soreness after rising from rest, reluctance to exercise, bunny-hopping or other abnormal gait (legs move more together when running rather than swinging alternately), lameness, pain, reluctance to stand on rear legs, jump up, or climb stairs, subluxation or dislocation of the hip joint, or wasting away of the muscle mass in the hip area. Radiographs (X-rays) often confirm the presence of hip dysplasia, but radiographic features may not be present until two years of age in some dogs. Moreover, many affected dogs do not show clinical signs, but some dogs manifest the problem before seven months of age, while others do not show it until well into adulthood.
In Spain there are two organizations that assesses and certifies the degree of hip dysplasia through radiological study (AVEPA, SETOV).
A: Absence of radiological signs of dysplasia
B: Almost normal hip joints
C: Slight radiological signs of dysplasia
D: Moderate radiological signs of dysplasia
E: Severe radiological signs of dysplasia