prcd-PRA Gene (Progressive Retinal Atrophy) 

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. 

CEA Gene (Collie Eye Anomaly)

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.

UPDATE Discrepancy in the compliance between clinical  and genetic diagnosis...(1/6/16) https://onlinelibrary.wiley.com/doi/abs/10.1111/age.12405#.VuC9m_Dq5Bw

Hip Dysplasia

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

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

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.

Grade 1: Manually the patella easily luxates at full extension of the stifle joint, but returns to the trochlea when released. No crepitation is apparent. The medial, or very occasionally, lateral deviation of the tibial crest (with lateral luxation of the patella) is only minimal, and there is a very slight rotation of the tibia. Flexion and extension of the stifle are in a straight line with no abduction of the hock.

Grade 2:  There is frequent patellar luxation, which, in some cases, becomes more or less permanent. The limb is sometimes carried, although weight bearing routinely occurs with the stifle remaining slightly flexed. Especially under anesthesia, it is often possible to reduce the luxation by manually turning the tibia laterally, but the patella reluxates with ease when manual tension of the joint is released. As much as 30 degrees of medial tibial torsion and a slight medial deviation of the tibial crest may exist. When the patella is resting medially the hock is slightly abducted. If the condition is bilateral, more weight is shifted onto the forelimbs. Many dogs with this grade live with the condition reasonably well for many years, but the constant luxation of the patella over the medial trochlear ridge of the trochlea causes erosion of the articulating surface of the patella and also the proximal area of the medial lip. This results in crepitation becoming apparent when the patella is luxated manually.
 

Grade 3:  The patella is permanently luxated with torsion of the tibia and deviation of the tibial crest of between 30 degrees and 50 degrees from the cranial/caudal plane. Although the luxation is not intermittent, many animals use the limb with the stifle held in a semi-flexed position. The trochlea is very shallow or even flattened.
 

Grade 4:  The tibia is medially twisted and the tibial crest may show further deviation medially with the result that it lies 50 degrees to 90 degrees from the cranial/caudal plane. The patella is permanently luxated. The patella lies just above the medial condyle and space can be palpated between the patellar ligament and the distal end of the femur. The trochlea is absent or even convex. The limb is carried, or the animal moves in a crouched position, with the limb flexed.

Auto-immune Thyroiditis

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)

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.

Note: This is a "probable" test which means not all factors have been confirmed. Since the release of this test there have been some cases of JADD still in tollers. 

Chondrodystrophy (CDDY and IVDD Risk)

Chondrodysdrophy (CDDY) is a trait that defines many dog breeds and is characterized by reduction of long bone length (shorter legs) as a consequence of early changes in the structure of growth plates. CDDY can also impact health of animals through an abnormal process that causes premature degeneration of the intervertebral discs.

The Chondrodysdrophy (CDDY) mutation was recently discovered by researchers in the Bannasch Laboratory at the University of California, Davis (Brown et al. 2017) as a second FGF4-retrogene insertion in dog chromosome 12.  CDDY includes a short-legged phenotype and abnormal premature degeneration of intervertebral discs leading to susceptibility to Hansen’s type I Intervertebral Disc Disease (IVDD). The intervertebral disc, which sits between vertebrae, is composed of an outer fibrous basket (annulus fibrosus) made of 70% collagen and an inner gel-like layer called the nucleus pulposus. These structures allow for flexibility of the vertebral column. In Chondrodystrophic breeds, premature calcification of the nucleus pulposus at early age (from birth to 1 year of age) results in degeneration of all discs in young dogs. These abnormal discs are predisposed to herniation into the spinal canal where the inflammation, and hemorrhage can cause severe pain and neurological dysfunction (myelopathy) termed IVDD. IVDD has high mortality rate and high cost of surgical and medical veterinary care.

Cleft Lip/Palate and Syndactyly (CLPS)

Cleft palate is a hole (cleft) in the roof of the mouth (palate) that occurs during development of the puppy. Puppies are born with cleft palate. Cleft Lip is a split in the lip and can occur on one or both sides of the mouth. Syndactyly is the fusion of the middle two digits of the feet. The NSDTR, or Toller, breed has multiple genetic causes of cleft palate. A mutation test is already available for CP1 in the NSDTR which causes cleft palate. The mutation that causes a second form of cleft lip and cleft palate called CLPS has been recently identified by scientists from the Bannasch Laboratory at the University of California, Davis and the Wade Laboratory from the University of Sydney. This CPLS test is BREED specific and does not apply to any breed except the NSDTR.

Cleft Palate (CP1)

A cleft palate is a birth defect whereby a hole (cleft) in the roof of the mouth (palate) develops in a puppy during gestation. Puppies born with cleft palate can experience difficulty nursing which will greatly increase their risk of developing aspiration pneumonia - a serious life threatening condition. There are multiple genetic causes of cleft palate within the NSDTR breed; however, the most common form has been identified as CP1.

Researchers from the Bannasch Laboratory at the University of California, Davis discovered the genetic cause of CP1 cleft palate in the Nova Scotia Duck Tolling Retriever. Dogs with this form of cleft palate have a large insertion into a gene known to affect the proper development of the palate. This mutation is not present in any other breed based on testing conducted on over 300 individual animals of over 80 different dog breeds.

Note: There are mulitple types of Cleft Palate. This test does not account for other types or mutated forms of the disease.

Cerebellar Degeneration and Myositis Complex (CDMC)

CDMC is a serious condition that can effect the cerebellum region of the brain and lead to a loss of coordination and balance. Affected dogs develop first symptoms at the age between 10 weeks and 6 months.

Cardiac Laminopathy (CLAM)

Cardiac Laminopathy is a fatal heritable condition that results in dilated cardiomyopathy and sudden death in young adult Nova Scotia Duck Tolling Retrievers.  Affected dogs are homozygous for the variant and present with sudden death associated with dilated cardiomyopathy (DCM). No treatment is available at this time and the condition is typically lethal in young adult dogs. Affected dogs studied to date experienced sudden death by 1.5 years of age.  This research is not yet published, however the genetic variant causing this disease was recently discovered by Dr. Bannasch at UC Davis in the School of Veterinary Medicine and she has shared this finding with the VGL pre-publication so that we can more rapidly offer genetic testing to toller breeders as soon as discoveries are made.

Heart Disease

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.