prcd-PRA Gene (Progressive Retinal Atrophy) 

http://www.optigen.com/opt9_test_prcd_pra.html

The genetic disorder, prcd-PRA , 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 “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 be blind. Typically, the clinical disease is recognized first in early adolescence or early adulthood. Since age at onset of disease varies among breeds, you should read specific information for your dog. Diagnosis of retinal disease can be difficult. Conditions that seem to be prcd-PRA might instead be another disease and might not be inherited. OptiGen’s genetic test assists in making the diagnosis. It’s important to remember that not all retinal disease is PRA and not all PRA is the prcd form of PRA. Annual eye exams by a veterinary ophthalmologist will build a history of eye health that will help to diagnose disease. Unfortunately, at this time there is no treatment or cure for PRA. Genetic testing for PRA is available for NSDTR's threw www.optigen.com

CEA Gene (Collie Eye Anomaly)

http://www.optigen.com/opt9_ceatollers.html

Collies share Collie Eye Anomaly (CEA) with several other breeds – it’s not just a problem for collies. CEA is more technically known as Choroidal Hypoplasia (CH). It is a recessively inherited eye disorder that causes abnormal development of the choroid - an important layer of tissue under the retina of the eye. This disease is seen most frequently in U.S. collies, but also worldwide in Rough and Smooth Collies, Border Collies, Australian Shepherds, Lancashire Heelers, Shetland Sheepdogs and Nova Scotia Duck Tolling Retrievers. Since the choroid layer does not develop normally from the start, the primary abnormality can be diagnosed at a very young age. Regrettably, there is no treatment or cure for CEA.

The symptoms and signs – the clinical phenotype – can vary greatly among affected dogs within one breed, between parent and offspring and even within a litter. This creates a difficult situation for the breeder. Learning about the genetic cause and the course of the disease will help you understand how to manage it better and eventually avoid it altogether with genetic testing.

The primary problem is choroidal hypoplasia (CH). There is under-development (hypoplasia) of the eye tissue layer called the choroid. The choroid appears pale and thin, almost transparent, and the blood vessels of the choroid can easily be recognized in those “thin” areas. The ophthalmologist, looking at the back of the eye (the fundus) with an ophthalmoscope, typically will see an area of choroidal thinning that appears like a “window” to the underlying vessels and sclera.

MILD disease: Mild disease is very common in U.S. collies and is present in the other breeds named above. It is easily recognizable on careful ophthalmologic examination as early as 5 to 8 weeks of age. The lesion appears as an area lateral (temporal) to the optic disc with reduction or absence of pigment so that the underlying vessels of the choroid are seen. The choroidal vessels may be reduced in number and of abnormal shape. The underlying white sclera might also be visible. Once the retina changes to its adult color around 3 months of age, the normal pigment sometimes masks the changes in the choroid (so-called “go normal” – read more below). In mildly affected dogs, choroidal thinning is the only detectable abnormality and the dog retains normal vision throughout life. However, dogs with mild disease can produce severely affected offspring.

SEVERE disease: In severely affected dogs, approximately 25% of dogs with CEA/CH, there are related problems with the health of the eye that can result in serious vision loss in some cases. Colobomas are seen at and near the optic nerve head as outpouchings or “pits” in the eye tissue layers. Colobomas can lead to secondary complications such as partial or complete retinal detachments and/or growth of new but abnormal blood vessels with hemorrhage – bleeding inside the eye. This happens in 5-10% of dogs with CEA/CH, generally by 2 years of age, and can affect either one or both eyes. Complications of severe disease can lead to vision loss, although this disorder only rarely threatens total blindness.

CEA/CH is not progressive in the usual sense. The essential features, choroidal hypoplasia and coloboma, are congenital – the abnormalities develop as the eye develops. These features are also stationary once ocular development is complete around 8-12 weeks of life. Retinal detachments and/or aberrant vessel formation can be congenital or develop later, in general only in eyes with colobomas.

Based on research done jointly by scientists at Cornell University and at The Fred Hutchinson Cancer Research Center, BOTH the mild and severe forms of CEA/CH disease now are proven to result from the exact same gene and mutation in ALL of the affected breeds named above. This disease gene is located on canine chromosome number 37 and the disease-causing mutation has been identified. The mutation acts like a RECESSIVE mutation. That means, both parents of an affected dog must have at least one copy of the mutation and both parents must have passed a copy of the mutation to the offspring. The affected dog is HOMOZYGOUS RECESSIVE – that is, both copies of the gene are mutant. ALL dogs that are homozygous recessive affected will show at least the mild form of the disease. ALL affected dogs, regardless of the actual severity of the lesions, are homozygous for the same mutant gene.

Hip Dysplasia

http://www.offa.org/hd_info.html

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.

Elbow Dysplasia

http://www.offa.org/ed_types.html

Elbow dysplasia is a condition involving multiple developmental abnormalities of the elbow-joint in the dog, specifically the growth of cartilage or the structures surrounding it. These abnormalities, known as 'primary lesions', give rise to osteoarthritic processes. Elbow dysplasia is a common condition of certain breeds of dogs.

Most primary lesions are related to osteochondrosis, which is a disease of the joint cartilage and specifically Osteochondritis dissecans (OCD or OD), the separation of a flap of cartilage on the joint surface. Other common causes of elbow dysplasia included ununited anconeal process (UAP) and fractured or ununited medial coronoid process (FCP or FMCP).  

Osteochondritis dissecans is difficult to diagnose clinically as the animal may only exhibit an unusual gait. Consequently, OCD may be masked by, or misdiagnosed as, other skeletal and joint conditions such as hip dysplasia. The problem develops in puppyhood although often subclinically, and there may be pain or stiffness, discomfort on extension, or other compensating characteristics. Diagnosis generally depends on X-rays. While cases of OCD of the stifle go undetected and heal spontaneously, others are exhibited in acute lameness. Surgery is recommended once the animal has been deemed lame, before then non-surgical control is usually used.

Luxating Patellas

http://www.offa.org/pl_dx.html

Luxating patella is a condition in which the patella, or kneecap, dislocates or moves out of its normal location. This is a common condition in dogs, particularly small and miniature breeds. The condition usually becomes evident between the ages of 4 to 6 months.

Luxating Patella cannot be present without the knee being loose, but a loose knee is not necessarily slipping out of the joint. Even with Luxating Patella, there may be no symptoms or only mild ones, such as intermittent limping in the rear leg. Physical examination and manual manipulation are the preferred methods for diagnosis. More extreme cases can result in severe lameness. Osteoarthritis typically develops secondarily. There are four diagnostic grades of patellar luxation, each more severe than the previous:

Auto-immune Thyroiditis

(http://www.offa.org/thy_proc.html)

Autoimmune thyroiditis is the most common cause of primary hypothyroidism in dogs. The disease has variable onset, but tends to clinically manifest itself at 2 to 5 years of age. Dogs may be clinically normal for years, only to become hypothyroid at a later date. The marker for autoimmune thyroiditis, thyroglobulin autoantibody formation, usually occurs prior to the occurrence of clinical signs. Therefore, periodic retesting is recommended.

The majority of dogs that develop autoantibodies have them by 3 to 4 years of age. Development of autoantibodies to any time in the dog’s life is an indication that the dog, most likely, has the genetic form of the disease. Using today's technology only a small fraction of false positive tests occur. 

As a result of the variable onset of the presence of autoantibodies, periodic testing will be necessary. Dogs that are negative at 1 year of age may become positive at 6 years of age. Dogs should be tested every year or two in order to be certain they have not developed the condition. Since the majority of affected dogs will have autoantibodies by 4 years of age, annual testing for the first 4 years is recommended. After that, testing every other year should suffice. Unfortunately, a negative at any one time will not guarantee that the dog will not develop thyroiditis.

The registry data can be used by breeders in determining which dogs are best for their breeding program. Knowing the status of the dog and the status of the dogs lineage, breeders and genetic counselors can decide which matings are most appropriate for reducing the incidence of autoimmune thyroiditis in the offspring.

JADD (juvenile Addisons Disease)

http://www.offa.org/dnatesting/jadd.html

Addison’s disease (hypoadrenocorticism) occurs when the adrenal glands stop secreting the natural steroid hormones (glucocorticoid) and hormones (mineralicorticoids) necessary for the regulation of sodium and potassium levels in the blood. Addison’s disease can occur in any breed of dog and it has an average age of onset of 4 years. Addison’s disease is diagnosed by a veterinarian using a blood test called an ACTH stimulation test. The clinical signs of Addison’s disease can include lethargy, inappetance, vomiting and diarrhea.

In the NSDTR, a genetic form of this disease, called JADD, occurs in much younger animals. The average age of puppies affected with JADD is 5 months; however, puppies as young as 8 weeks and as old as 12 months of age have been identified.

Treatment of puppies affected with JADD requires both mineralicorticoid and glucocorticoid replacement therapy. Puppies can have other concurrent diseases including eye problems (corneal edema, conjunctivitis or uveitis) that may require specialized treatment.

JADD is inherited as an autosomal recessive disease meaning that animals have only one mutant copy of the region (N/A) are normal but they are carriers of the disease and they can produce affected puppies if bred to an affected dog (A/A) or another carrier (N/A). At the time that this test was released approximately 20% of Tollers carry JADD (N/A); however, the number of carriers can change with each generation. Dogs that are carriers (N/A) are normal themselves and can be safely bred to N/N dogs in order to maintain diversity within the breed and select for other positive attributes in carrier dogs.

Heart Disease

http://www.offa.org/cardiac_exam.html

Pulmonic stenosis, also known as Pulmonary stenosis, is a dynamic or fixed obstruction of flow from the right ventricle of the heart to the pulmonary artery. It is usually first diagnosed in childhood. Pulmonic stenosis is usually due to isolated valvular obstruction (Pulmonary valve stenosis), but may be due to subvalvular or supravalvular (Stenosis of pulmonary artery) obstruction. It may occur in association with more complicated congenital heart disorders.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of heart disease that usually appears in adulthood. ARVC is a disorder of the myocardium, which is the muscular wall of the heart. This condition causes part of the myocardium to break down over time, increasing the risk of an abnormal heartbeat (arrhythmia) and sudden death.

ARVC may not cause any symptoms in its early stages. However, affected individuals may still be at risk of sudden death, especially during strenuous exercise. When symptoms occur, they most commonly include a sensation of fluttering or pounding in the chest (palpitations), light-headedness, and fainting (syncope). Over time, ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen. If the myocardium becomes severely damaged in the later stages of the disease, it can lead to heart failure.

In Humans, up to half of all cases of ARVC appear to run in families. Most familial cases of the disease have an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder.

Rarely, ARVC has an autosomal recessive pattern of inheritance, which means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Heart Murmurs

Most heart murmurs are innocent: They are caused by blood flowing through healthy valves in a healthy heart and do not require treatment. However, heart murmurs can be caused by blood flowing through a damaged or overworked heart valve. Valvular abnormalities may be present at birth, may occur as part of the normal aging process, or may result from other heart problems, such as rheumatic fever, heart attacks, or infective endocarditis.

Types of Heart Valve Diseases

Mitral valve prolapse: Normally, your mitral valve closes completely when your left ventricle contracts, preventing blood from flowing back into your left atrium. If part of the valve balloons out so that the valve does not close properly, you have mitral valve prolapse. This causes a clicking sound as your heart beats. Often, this common condition is not serious. However, it can lead to regurgitation (backward blood flow through the valve).

Mitral valve or aortic stenosis: Your mitral or aortic valves, both on the left side of your heart, can become narrowed by scarring from infections, such as rheumatic fever, or may be narrow at birth. Such narrowing or constriction is called stenosis. In mitral valve or aortic stenosis, the heart has to work harder to pump enough blood to satisfy your body's oxygen needs. If untreated, stenosis can wear out your heart and can lead to heart failure. Mitral and aortic stenosis can both occur as calcium is deposited on the valves as people age.

Aortic sclerosis: One in three elderly people have a heart murmur due to the scarring, thickening, or stiffening (sclerosis) of the aortic valve, without evidence of narrowing, or stenosis. This condition is generally not dangerous; typically, the valve can function for years after the murmur is detected. Aortic sclerosis is usually seen in people with atherosclerosis, or hardening of the arteries.

Mitral or aortic regurgitation: Regurgitation (backward flow) of blood can occur with mitral valve prolapse or mitral valve or aortic stenosis. To counteract this back flow, the heart must work harder to force blood through the damaged valve. Over time, this can weaken and/or enlarge the heart and can lead to heart failure.