Genotype and phenotype

With Labrador retrievers being so popular, I get a lot of calls from people inquiring about puppies. These individuals are wanting a puppy to love and be their companion. Some have done research and know about genetic problems that occur in the breed. There are many problems that occur in all dog breeds, not just in Labradors. Those problems that most frequently occur in Labradors are orthopedic issues such as hip, elbow, shoulder and hock dysplasia and eye problems such as progressive retinal atrophy, retinal dysplasia and cataracts. There are other problems that occur with less frequency but which are of great concern in the breed such as epilepsy, heart conditions, and hypothyroidism. The website for the Orthopedic Foundation for Animals
and the Canine Eye Registration Foundation provide a lot of information on congenital and inherited defects in Labradors.

It's important to distinguish between clearances that are provided with Labradors and the actual genetic make-up of the dog. The OFA provides certificates for hips and elbows that indicate the phenotype (genetic expression) but cannot determine the genotype or genetic make-up of the dog. It is thought that hip and elbow dysplasia are polygenic traits with many genes contributing to the problem. Thus, no one factor is responsible for the development of these structural defects. There is also evidence that certain risk factors play a role in the degree of expression of the defect. Nutrition, size, growth rate, and some environmental factors may influence manifestation of the defect. At the current time, the only means to genetically select against HD and ED is to use radiographs that demonstrate the actual appearance (phenotype) of the hips and elbows at a given age.

There are disorders like RD and gPRA that result from recessive genes. Thus, it is possible that a dog may carry the recessive gene without expressing it. In such a case, the recessive gene is present but "masked" by the dominant gene for normal eye structure and function. When genes are recessive, a dog is a carrier of the disorder. To be affected by the disorder, the dog must receive a recessive gene from both parents. Parents were either “carrier” or affected. A carrier has one disease gene and one normal gene, and is termed “heterozygous” for the disease. A normal dog has no disease gene and is termed “homozygous normal” – both copies of the gene are the same. And a dog with two disease genes is termed “homozygous affected” – both copies of the gene are abnormal.

Recessive genes are difficult to completely eradicate from the gene pool because the carrier may be bred many times before it is realized that the dog does indeed carry the disorder as shown by affected offspring. In order for the disorder to affect offspring, the mate must also be a carrier.

Fortunately, with gPRA there is now a genetic test which determines whether a Labrador is a carrier for that particular eye disorder. It’s been proven that Labradors being tested for prcd-PRA have the same disease caused by the same mutated gene. So even though we know the mode of inheritance, it is now possible with PRA to test dogs before breeding. Identification of dogs that do not carry disease genes is the key. These "clear" dogs can be bred to any mate - even to a prcd-affected dog which may be a desirable breeding prospect for other reasons.

For these reasons it is recommended that dogs suspected of being carriers through expression of the disorder in offspring no longer be allowed to breed. Dominant genes are more easily eradicated from the gene pool because individuals carrying the gene will always express it. However, one complication lies in the fact that some dominant disorders are not observed until later in life, and an individual may be bred prior to discovery of the disorder. Once a hereditary eye disorder has been diagnosed, eliminating the affected individual from the breeding program and alerting owners of offspring to the potential risk may help in preventing future generations of developing hereditary eye disorders.

TVD is a congenital abnormality and is not acquired. Prevention is limited to controlling for genetic predisposition to the disorder. It is suspected that TVD may be an inherited abnormality but the mode of inheritance is unknown. OFA offers a clearance for heart abnormalities but these only indicate that the dog being tested does not present with the symptoms of the disease. Once again, the phenotype is what is known but the genotype and mode of inheritance are not known for these heart ailments.

Although parents may have every clearance that is offered, there are no guarantees that a puppy will not develop congenital defects. A breeder can only attempt to stack the odds in his favor by choosing superior individuals to breed and being familiar with the bloodlines of each; but when it comes down to facts, only Mother Nature can determine the true outcome.