Hip Dysplasia is a terrible genetic disease because of the various degrees of arthritis (also called degenerative joint disease, arthrosis, osteoarthrosis) it can eventually produce, leading to pain and debilitation.
The very first step in the development of arthritis is articular cartilage (the type of cartilage lining the joint) damage due to the inherited bad biomechanics of an abnormally developed hip joint. Traumatic articular fracture through the joint surface is another way cartilage is damaged. With cartilage damage, lots of degradative enzymes are released into the joint. These enzymes degrade and decrease the synthesis of important constituent molecules that form hyaline cartilage called proteoglycans. This causes the cartilage to lose its thickness and elasticity, which are important in absorbing mechanical loads placed across the joint during movement. Eventually, more debris and enzymes spill into the joint fluid and destroy molecules called glycosaminoglycan and hyaluronate which are important precursors that form the cartilage proteoglycans. The joint's lubrication and ability to block inflammatory cells are lost and the debris-tainted joint fluid loses its ability to properly nourish the cartilage through impairment of nutrient-waste exchange across the joint cartilage cells. The damage then spreads to the synovial membrane lining the joint capsule and more degradative enzymes and inflammatory cells stream into the joint. Full thickness loss of cartilage allows the synovial fluid to contact nerve endings in the subchondral bone, resulting in pain. In an attempt to stabilize the joint to decrease the pain, the animal's body produces new bone at the edges of the joint surface, joint capsule, ligament and muscle attachments (bone spurs). The joint capsule also eventually thickens and the joint's range of motion decreases.
No one can predict when or even if a dysplastic dog will start showing clinical signs of lameness due to pain. There are multiple environmental factors such as caloric intake, level of exercise, and weather that can affect the severity of clinical signs and phenotypic expression (radiographic changes). There is no rhyme or reason to the severity of radiographic changes correlated with the clinical findings. There are a number of dysplastic dogs with severe arthritis that run, jump, and play as if nothing is wrong and some dogs with barely any arthritic radiographic changes that are severely lame. (http://www.ofa.org/hd_info.html)
Elbow dysplasia is a general term used to identify an inherited polygenic disease in the elbow of dogs. Three specific etiologies make up this disease and they can occur independently or in conjunction with one another. These etiologies include:
Pathology involving the medial coronoid of the ulna (FCP)
Osteochondritis of the medial humeral condyle in the elbow joint (OCD)
Ununited anconeal process (UAP)
Studies have shown the inherited polygenic traits causing these etiologies are independent of one another. Clinical signs involve lameness which may remain subtle for long periods of time. No one can predict at what age lameness will occur in a dog due to a large number of genetic and environmental factors such as degree of severity of changes, rate of weight gain, amount of exercise, etc. Subtle changes in gait may be characterized by excessive inward deviation of the paw which raises the outside of the paw so that it receives less weight and distributes more mechanical weight on the outside (lateral) aspect of the elbow joint away from the lesions located on the inside of the joint. Range of motion in the elbow is also decreased. (http://www.ofa.org/ed_types.html)
Exercise Induced Collapse (EIC)
Dogs affected with EIC can tolerate mild to moderate exercise, but 5 to 20 minutes of strenuous exercise with extreme excitement induces weakness and then collapse. Severely affected dogs may collapse whenever they are exercised to this extent – other dogs only exhibit collapse episodes sporadically.
The first thing noted during an episode is usually a rocking or forced gait. The rear limbs then become weak and unable to support weight. Many affected dogs will continue to run while dragging their back legs. Some of the dogs appear to be uncoordinated, especially in the rear limbs, with a wide-based, long, loose stride rather than the sort stiff strides typically associated with muscle weakness. In some dogs the rear limb collapse progresses to forelimb weakness and occasionally to a total inability to move. Some dogs appear to have a loss of balance and may fall over, particularly as they recover from complete collapse. Most collapsed dogs are totally conscious and alert, still trying to run and retrieve, but as many as 25% of affected dogs will appear stunned or disoriented during the episode. (http://www.vdl.umn.edu/services-fees/canine-neuromuscular-eic/frequently-asked-questions)
Centronuclear Myopathy (CNM), previously known as HMLR, or Hereditary Myopathy, is an autosomal recessive mutation that causes insufficient muscle function in the Labrador Retriever breed. This is due to the centralisation of the nuclei in muscle fibers, caused by a missense insertion in the PTPLA gene.
Puppies are born apparently normal; however, it quickly becomes evident that there is a problem. The puppy will often not gain weight adequately due to decreased muscle tone in the esophagus. Within 2 to 5 months, the disease has usually progressed to display the full range of symptoms, including a loss of muscle tone and control, an awkward gait, and extreme exercise intolerance. This condition is exacerbated in cold conditions.
Unfortunately, there is no cure for CNM, as the dog will never develop properly functioning muscle tissue. The dog usually has a normal life span but he will always be plagued with the symptoms of Centronuclear Myopathy.
Centronuclear myopathy is a recessive disorder, meaning that the dog must have two copies (CNM/CNM) of the defective gene to suffer from the disease. A dog can also be a carrier (CNM/n) of this disease, and will not display any symptoms. A carrier dog will pass on the mutation that causes CNM to 50% of it's offspring. If mated with another carrier dog, there is a 25% chance of producing an offspring affected by Centronuclear Myopathy. (http://www.animalgenetics.us/Canine/Genetic_Disease/CNM.asp)
Genetic Eye Disease - CERF / OFA CAER
There are currently ten disorders for which there is an unequivocal recommendation against breeding in all breeds. These diagnoses are ineligible for OFA Eye Registry certifications.
These are conditions which frequently result in blindness and for which there is definite evidence of heritability in one or more breeds.
*Note: The prudent approach of these disorders is to assume they are hereditary except in cases specifically known to be associated with trauma, other causes of ocular inflammation, specific metabolic diseases or nutritional deficiencies.
Keratoconjunctivitis sicca (KCS) - Breeding is not recommended for any animal demonstrating keratitis consistent with KCS. The prudent approach is to assume KCS to be hereditary except in cases suspected to be non-genetic in origin. See above note.
Cataract - Breeding is not recommended for any animal demonstrating partial or complete opacity of the lens or its capsuleunless the examiner has also checked the space for “significance of above cataract unknown” or unless specified otherwise for the particular breed. See above note.
Lens luxation or subluxation See above note.
Glaucoma See above note.
Persistent hyperplastic primary vitreous (PHPV)
Retinal detachment See above note.
Retinal dysplasia - geographic or detached forms See above note.
Optic nerve coloboma
Optic nerve hypoplasia
Progressive Retinal Atrophy (PRA) - Breeding is not advised for any animal demonstrating bilaterally symmetric retinal degeneration (considered to be PRA unless proven otherwise.(http://www.offa.org/eye_eligibility.html)
Canine Cystinuria is an autosomal recessive disorder that affects a dog's ability to filter cystine out of urine. Normally, tubules in the kidney are responsible for re-absorption of cystine, filtering it out of the urine. In dogs with Canine Cystinuria, the tubules are unable to transport the cystine, allowing it to accumulate in the urine. Cystine is generally insoluble in the acidic conditions of canine urine, allowing it to crystallize and form caliculi, also known as stones.
Not every dog that has the mutation responsible for Cystinuria will exhibit symptoms. Stones causing inflammation and blockage are often more common in males, due to their long, narrow urethra. Females exhibit symptoms much less frequently and may be completely asymptomatic.
Canine Cystinuria affects over 60 breeds of dogs. Research suggests that Newfoundlands carry a more severe form of this disease than other breeds. In a variety of breeds affected by Canine Cystinuria, symptoms are often not experienced until about 4-5 years in age. However, Newfoundlands may begin experiencing problems as early as 6 months to one year of age. Newfoundlands are much more likely to experience recurring urethral blockages that could require surgical intervention.
In the Newfoundland breed, the cause of Cystinuria is a single nucleotide polymorphism that occurs in the SLC3A1 gene which causes a premature stop codon. Cystinuria is a recessive disorder, meaning that the dog must have two copies of the defective gene to suffer from the disease. Because Cystinuria is a recessive disorder, a dog can also be a carrier of this disease, meaning it carries one copy of the mutation but does not display any symptoms. A carrier dog can pass on this mutation to their offspring and if they mate with another carrier dog, can produce offspring affected by Cystinuria. (http://www.animalgenetics.us/Canine/Genetic_Disease/CY.asp)
Degenerative Myelopathy (DM)
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. (http://www.animalgenetics.us/Canine/Genetic_Disease/DM.asp)
Hereditary Nasal Parakeratosis(HNPK)
Hereditary nasal parakeratosis (HNPK) is an inherited autosomal recessive disorder in Labrador Retrievers. A mutation T>G in the SUV39H2 gene causes the nose to dry out leading to chronic irritation and inflammation of the noses skin.
Symptoms of the disorder generally appear around 6 to 12 months of age. Affected dogs develop dry, rough; gray to brown crusts on the surface and edge of the nose. In some cases, painful cracks around and on the tip of the nose develop and if not treated develop superficial bacterial infections. Over time, the nose often begins to depigment changing skin color from dark to light in color. Although the disorder is nonlife threatening, continuous care to reduce the recurrence of excessive nasal crusting is required throughout the life of the dog.
Because HNPK is a recessive disorder, a dog must have two copies of the mutation in order for the disease to manifest. This means that a dog can have one copy of the mutation and not experience any signs or symptoms of HNPK; this dog would be known as a carrier. The carrier can then pass on either the normal gene or the mutated gene to any offspring. If two carriers are bred, there is a 25% chance of haveing a dog that recieves two mutated copies of the gene and would be affected by HNPK. (http://www.animalgenetics.us/Canine/Genetic_Disease/HNPK.asp)
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. (http://www.animalgenetics.us/Canine/Genetic_Disease/HUU.asp)
Pyruvate Kinase Deficiency (PKD)
Pyruvate Kinase Deficiency is a disorder that affects red blood cells. Dogs suffering from pyruvate kinase deficiency have a mutated form of pyruvate kinase, an important enzyme in cellular metabolism. This defect causes the red blood cells to die, leading to severe hemolytic anemia. Because red blood cells deliver oxygen to tissues around the body, it is important that dogs are able to maintain an adequate supply of red blood cells, and dogs suffering from PK deficiency typically are chronically anemic.
SSymptoms of PKD usually begin to show between four months to one year. The symptoms can include weakness, lack of energy, rapid heart rate, heart murmurs, pale gums, and stunted growth. As the disease progresses, bones and the liver can be affected, and the disease is ultimately fatal. Dogs with PKD commonly die before 4 years of age. However, longevity is affected by the breed of dog, with some breeds able to survive longer than others. While there is currently no cure for PKD, it is possible for affected dogs to have a reasonable quality of life with palliative care.
Pyruvate Kinase Deficiency (PKD) is an autosomal recessive trait which means both parents of an affected (homozygous) dog must be carriers (heterozygous) for the disorder. Heterozygous dogs are usually asymptomatic, and it may be difficult to detect clinical signs of the condition in inactive homozygous dogs. It is therefore useful to test for the presence of the mutation before breeding.
Canine PKD was originally documented in Basenjis; it has since been reported in other breeds, including Dachshunds, Labrador Retrievers, Pugs, Beagles, Cairn Terrier and West Highland White Terriers. (http://www.animalgenetics.us/Canine/Genetic_Disease/PKD.asp)
Progressive Retinal Atrophy or PRA-prcd
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. (http://www.animalgenetics.us/Canine/Genetic_Disease/PRA-prcd.asp)
Canine Color Charts
A-Locus (Fawn, Sable, Black-and-Tan/Tricolor, Recessive Black)
This chart explains what a dog's phenotype will be based on his genotype. This chart assumes the dog is "n/n" for the K-Locus. Adding in one or more copies of the KB-allele will modify the pigment that is being produced.
B-Locus (Brown, Chocolate, Liver)
The black (B) allele is dominant to the brown (bs, bd, bc) alleles. In this gene are 3 common mutations (bs, bd, bc) which result in brown instead of black eumelanin production. In some breeds, such as the French Bulldog, additional mutations not identified may affect eumelanin production. Below are the known "b" alleles in different breeds of dogs. Please note that there is no difference between these alleles in the coloration of a dog; for example, a dog that is bsbs will not appear different than a dog that is bdbd or bcbc.
D Locus and B Locus
This chart explains the phenotype or appearance of a dog based on the genotype. In this case, the term "basic color" refers to areas that are self-colored, and would be black without any additional modifiers such as the chocolate and dilute loci. For dogs that are fawn or sable, it should taken into account that this may only refer to the nose and foot pads of the dog.
Dogs that are "ee" will only express yellow pigment, so this table holds true for all dogs of that genotype, regardless of the A- and K- loci.
E-Locus (Recessive Yellow) and B-Locus
This chart explains the phenotype or appearance of a dog based on the genotype of the dog for "self-colored" areas of a dog. This refers to areas of a dog that would be black without other modifications (ie a solid Labrador Retriever, or the black part of a black-and-tan dog). It does not affect areas that are colored otherwise, such as fawn or sable.
Dogs that are "ee" will only express yellow pigment, so this table holds true for all dogs of that genotype, regardless of the A- and K- loci.
(S Locus) Parti, Piebald, or Random White Spotting
There is no single basis for white spotted patterns that occur in animals like cats, dogs and horses. In horses random white spotting, or deletion of color, has been determined to be caused by more than half a dozen known genetic factors. In more than 25 different dog breeds, a mutation found in a gene called Microphthalmia Associated Transcription Factor- (MITF) is associated with a piebald spotting. In many breeds piebald behaves as a dosage-dependent trait. This means that dogs with a single copy (Sn) of the MITF variant will express a limited white spotting pattern, while dogs that have 2 copies (SS) of the variant will exhibit more white with very little color. In some breeds dogs that are (SS) are completely white while dogs that are (Sn) have what is referred to as mantle. (http://www.animalgenetics.us/Canine/Canine-color/Color_Index.asp)