Health Archives

The Proper Use of Genetic Tests in Making Breeding Decisions

Publisher’s Note: This lecture was sponsored by The ESSFTA Foundation, Inc.
A lecture presented to the English Springer Spaniel Field Trial Association in Seattle, Washington on February 28, 1998

(Published in Spaniels In The Field Summer 1998)

The development of genetic tests has allowed greater breeder control of desirable genetic traits and undesirable genetic diseases. However, the development and availability of a genetic test does not automatically translate into improvement in the health of purebred dogs. Recommendations for the proper use of genetic tests requires a knowledge of; 1) the dynamics of the breeding population, 2) the characteristics of the genetic disease being controlled, and 3) the specifics and limitations of the genetic test.


The English springer spaniel breeding population includes both conformation and field lines. The breed ranked twenty-fifth in AKC registrations in both 1995 and 1996. (AKC registrations for 1997 will come out in the April 1998 Gazette.) In 1996, 14,715 individual English springer spaniels, and 4,591 litters were registered with the AKC. While conformation and pet lines account for the largest portion of these registrations, field English springer spaniels also have a broad pedigree base and background of genetic diversity. Well managed genetic disease control programs should not adversely impact the genetic diversity of the breed, as can happen with less populous, less genetically diverse breeds.

The character of a genetic disease includes its severity, typical age of onset, mode of inheritance, and genetic spread in the population. Genetic diseases that cause death or significant discomfort, or those that are not treatable, should have a high priority in genetic disease control. Disorders with a late age of onset are more difficult to control, as genetically affected dogs can be bred before becoming clinically affected. A reliable early test for identification of affected dogs and carrier dogs leads to better management of genetic disorders.

The defective gene or genes controlling genetic disorders can be widely spread in the breeding population, and therefore a concern for all breeders. Conversely, a recent mutation may only involve a small portion of the breeding population, In this case, genetic disease control may have to be more stringent, to prevent the defective gene(s) from spreading further in the breed gene pool.

The genetic spread of defective genes does not necessarily relate to the frequency of a gene in the population. Due to the non-random nature of dog breeding, the frequency of a defective gene maybe high or low, with either older dispersed, or recent localized defective genes. Most defective genes in a purebred population originated from a single ancestral source. Therefore, a defective gene that is rare in the population, but present in two distantly related dogs, indicates an older and widely dispersed gene. While an infrequent occurrence it can be found in a wide pedigree range of the breeding population.

The mode of inheritance is an important factor in genetic disease control. Dominant genes with high penetrance are easy to control, as all carriers of the gene are clinically affected. Simple (single gene) recessive disorders can be easier to control with selection if there is a test for carriers. Simple recessive disorders without carrier tests, and polygenic disorders are more difficult to control, because carriers of defective genes can not be identified. The development of genetic tests to identify carriers is an important step to controlling these diseases.

Genetic tests vary on what they are able to identify, and therefore how they can be used in genetic disease control. Some tests measure the phenotype, or what can be seen or measured in the dog. This may not directly relate to the genotype, or the genes regulating the defect that you are trying to control. Phenotypic tests may require a certain age for the test to be valid. Ex: Tests for hip dysplasia. Newer genetic tests, called PCR or polymerase chain reaction, are a direct measurement of the genotype, and can be run at any age, regardless of the age of onset of the disease. Ex: PFK deficiency.

As discussed above, an effective genetic disease control program requires set goals, based on; the breed, the disease, and the genetic tests available. An immediate goal is to decrease the incidence of affected dogs being born. With an established testing program, the breed can monitor the frequency of the defective gene in the breeding population, and work to decrease the percentage of carriers. The total elimination of defective genes will probably be impossible for most breeds.

Genetic defects are controlled by single, or a handful of genes, compared with the estimated 10,000 to 40,000 genes in the dog genome. Prudent breeding practices dictate that you do not throw the puppy out with the bath water in genetic disease control. A goal of eliminating a defective gene from a breed may cause such a restriction in the gene pool that it causes a significant loss of genetic diversity. However, the individual breeder can use genetic tests to; 1) identify carriers, 2) work to breed away from the defective gene(s), and 3) ensure (through testing) that the defective gene(s) is not reintroduced in future matings. Depending on the frequency of the defective gene(s) in their own breeding dogs, and which desirable dogs are carriers, each breeder will have their own rate of progress.

The major goal in dog breeding is to produce quality dogs, who exhibit positive traits for the breed. With reliable tests for carriers, you can breed carrier dogs with desirable traits to normal dogs. Normal testing offspring who display those desirable traits of form, function, and behavior should be selected for future breeding stock. You may not produce this offspring in a single mating, and may still have to breed another carrier in the next generation, as long as it is again bred to a normal testing dog. As more breeders work away from the defective gene(s), the problem for the breed as a whole diminishes.

A major mistake of some breeders is to think that selection against carriers is unnecessary, as long as affected dogs are not produced. To reach the goal of breeding away from defective genes you should never select more carrier offspring in the next generation than the average frequency of carriers in the population. The average percentage of carriers in normal to carrier matings is 50 percent. By not selecting against carriers in breeding stock, you are selecting for a carrier frequency of 50 percent; much high than most breed averages. This almost guarantees that half the quality dogs in the next generation will be carriers.

Pragmatic breeders know that true quality dogs are few and far between in each litter. If a quality, normal testing dog has not been produced after a number of matings, a decision for the betterment of the breed must be made. We must look to the common experience when a top performer does not reproduce itself well, but a littermate produces far better than itself. When left without quality, genetically normal breeding stock, breeding to an average, but genetically normal littermate may ultimately provide the desirable offspring you want. The proper use of genetic tests is not one that continually multiplies carriers in a breeding program. It should be geared toward producing quality, genetically normal dogs.

The following are examples of genetic diseases reported in the English springer spaniel, and the genetic tests that are available to control them:

Canine Hip Dysplasia (CDH)
This is a classic example of a polygenically controlled hereditary disease. Due to genetically controlled defects in anatomy and joint laxity, affected dogs can become lame, and eventually crippled due to secondary osteoarthritis. The Orthopedic Foundation for Animals (OFA) has a longstanding hip dysplasia registry to attempt to control the disease based on an extended-hip pelvic radiograph (x-ray). For English springer spaniels from the period before 1980, 7.04 were rated excellent, and 20.2% were rated dysplastic. For all dogs born 1987-1988, there were 7.0% rated excellent, and 16.5% rated dysplastic. For those born 1994-1995 ( dogs now being radiographed at 2-3 years of age), there are 10.8% excellent, and 7.2% dysplastic. Critics of the OFA statistics, feel that the data is skewed, and does not represent actual improvements in breed hip conformation. No one argues that the improvement in hip dysplasia over the years in most breeds has been less than anticipated.

The PennHip method of evaluating hip status is based on a measurement of joint laxity different from that recorded on the (OFA) radiograph. The PennHip method applies a uniform force on the hips of an anesthetized dog to measure the maximum distractibility of the hips. To be licensed to do PennHip evaluations, veterinarians must go through training and certification, to insure that the procedure is both safe and verifiable. PennHip studies show a direct correlation between tight hips and a lower incidence of his dysplasia. By computing a breed average of distractibility, and selecting for tighter hips than the breed average, it is thought that the incidence of hip dysplasia should decrease over time.

We all recognize that a pelvic radiograph is a phenotypic measurement, and does not directly represent the genes controlling hip dysplasia. A severely dysplastic dog due to bony abnormalities but tight hips, has his dysplasia caused by different genes than a severely dysplastic dog due to hip luxation. There are pros and cons to both the OFA and PennHip radiographic methods of his dysplasia control. The OFA radiograph documents natural laxity in a hip extended view, as well as anatomical abnormalities ( shallow sockets, early bony changes). The PennHip radiograph documents maximum distractibility, but it is shown that some dogs with increased distractibility develop normal hips ( false positives ), and some dogs with tight hips develop hip dysplasia (false negatives). For both methods, radiographic findings at an early age are highly correlated to dysplasia at a later age. OFA does not give permanent certification until two years of age, but offers preliminary evaluations at any age.

As with any polygenic disorder, the breeder should select for all traits that can be correlated to the genes which cause the disorder. For hip dysplasia, this includes specific of the radiographic anatomy of the hips, palpable and radiographic joint laxity, and clinical signs of lameness or fatigue in the dog. Polygenic disorders are threshold traits. We need to select against enough dysplasia influencing genes, to get below the threshold where dysplasia develops. We also know that the environment has a role in the expression of hip dysplasia. Breeders should evaluate prospective breeding dogs raised under fairly uniform conditions, which neither promote, nor overly protect against hip dysplasia.
The basic reason we have not had great progress with his dysplasia control is that it is being treated as a single gene disease, with a test for carriers. Breeders select for multiple generations of hip normal ancestors, and expect that offspring should follow suit: i.e., OFA excellent dogs should pass on their OFA excellent gene to their offspring. In polygenic disorders, the phenotype of the individual does not directly represent its genotype. As we have learned from farm animal breeding systems, the phenotype of the full and half brothers and sisters more directly represent the range of genes present in the breeding individual. In other words, the breadth of the pedigree is more important than the depth of the pedigree in polygenic disease control. Breeders should be monitoring all of the individuals in a litter as a measurement of the genes of the dog they are selecting. Phenotypically normal dogs from litters with a high incidence of dysplasia are expected to pass on many genes that promote hip dysplasia. By selecting for breadth of phenotypically normal littermates of breeding dogs and of parents of breeding dogs, all breeds should realize a decrease in hip dysplasia.

Ventricular Septal Defect (VSD)
English springer spaniels have an increased risk of being born with a congenital heart defect called ventricular septal defect. Affected dogs are born with a hole in the wall (septum) connecting the left and right major chambers ( ventricles) of the heart. Dogs with small holes may not show clinical signs. The larger the hole in the heart, the greater the clinical signs. Affected dogs may show exercise intolerance, breathing difficulty, congestive heart failure, and death. While the mode of inheritance in English springer spaniels has not been fully investigated, most congenital heart defects are polygenically inherited. The incidence of the defect in English springer spaniels has not been investigated, but all cardiologists whom I have contacted in the United States have seen affected members of the breed. As with our congenital cardiac diseases, the size of the hole in the heart does not necessarily relate to the genetic load of defective genes. Affected dogs should not be bred. As many affected dogs may not show clinical signs, a doppler ultrasound examination by a cardiologist is required to confirm a dog as phenotypically normal. Inviting a cardiologist to a specialty show or field trial to do examinations (like is done for CERF exams or BAER Testing for hearing in other breeds) will help identify the frequency and spread of the genetic defect. As with other polygenic diseases, littermates and parents of phenotypically affected dogs have a higher risk of carrying defective genes controlling the disorder.

There are not genetic tests for VSD. Control must be based on the knowledge of relationships to affected dogs in your pedigree. The veterinary profession has read of the high incidence of the disease in your breed for many years. The Cardiac Registry conducted by the OFA has no English springer spaniels registered by breeders in either the normal or affected categories. The breed should work toward more (ultrasound) monitoring of the disorder, and cooperation with researchers interested in working on genetic tests for VSD.

Idiopathic Epilepsy (Genetic Seizures)
Idiopathic epilepsy causes recurrent seizures, not due to a metabolic (blood sugar, blood ammonia) or structural (brain tumor) cause. The clinical age of onset in the breed is from 6 months to 3 years of age. Affected English springer spaniels usually progress to clustering seizures on a regular basis within 3-5 months of the initial seizures. While epilepsy is usually controlled by anticonvulsant drugs, many English springer spaniels have a form of idiopathic epilepsy that is highly resistant to drug control. Many affected dogs eventually have to be euthanized because of uncontrollable, frequent, severe seizures. This is also a polygenically inherited disease. There are no specific tests to identify carriers, or even affected dogs. The diagnosis is based on the clinical course, pattern of recurrent seizures, and ruling out other causes. As with other breeds, there is a slight preponderance of males over females with the disorder, and the knowledge of affected relatives needs to be used to make breeding decisions. There are researchers working to identify the types of seizures, and genetic tests for idiopathic epilepsy in many breeds. This disease causes seizures, and must be differentiated from breed-related severe dominance aggression (rage syndrome).

Retinal Dysplasia & Progressive Retinal Atrophy (PRA)
These are two hereditary disorders that affect the retina, and can cause blindness. They are caused by different simple autosomal recessive genes. Retinal dysplasia is present at birth, and can be identified by a direct opthalmoscopic (CERF) retinal examination. Depending on the involvement of the retina, the disorder can cause no signs, or blindness in one or both eyes. The defective gene controlling retinal dysplasia is widespread, but at a low frequency in the population. Many owners and breeders are not aware of the presence of this disorder in the breed, and are surprised when it is diagnosed. While it is now seen rarely in the breed, breeders should know of its possibility. When identified, appropriate genetic disease control should be instituted. There is no genetic test for carriers of retinal dysplasia.

Progressive retinal atrophy is a disease that has received much publicity, due to the large number of breeds affected, and ongoing genetic research by Dr. Gustavo Aguirre at the Baker Institute at Cornell University. English springer spaniels have a late onset PRA, with clinical signs from two to nine years of age. Affected dogs begin to experience night blindness (decreased vision in dim light), which can eventually progress to total blindness. Dogs with advanced stages of PRA can be identified with a CERT exam, while earlier diagnosis is only possible with a special type of electroretinography (ERG).

There are English springer spaniels identified with a peripheral PRA. There are no studies to support that this form of PRA is different from other English springer spaniels with PRA. There are several genes that cause PRA in different breeds. The majority of dog breeds with late onset PRA have progressive rod cone dysplasia (prcd). Dr. Aguirre has identified a genetic linkage test for prcd, which will be available later this year. While not a direct test of the genotype, this linkage test will identify carriers and affected dogs at an early age, with high correlation. Breeding and linkage studies will be necessary to find out if English springer spaniels have the prcd form of PRA, and can use this test for carrier and affected dog identification.

This is a recessively inherited storage disease, which has been observed mostly in English Springer spaniels in the United Kingdom and Australia. Its clinical signs are of neurological deterioration with behavioral changes. Studies in the UK show the defective gene to be widespread in some pedigree lines. A report of an American bred dog was published in the veterinary literature in 1996. While assumed to be rare, it is not known how prevalent the defective gene is in the American population. Phenotypic enzyme tests can identify affected and carrier dogs. A genetic PCR test was developed in Australia, and may be offered in the future by Dr. Urs Giger at the University of Pennsylvania.

Phosphofructokinase Deficiency (PFK)
This is also a recessively inherited storage disease, which causes abnormalities in red blood cells and muscle cells. Clinical signs include intermittent dark urine post-exercise, anemia, fever, weakness, or muscle fatigue. Dr. Giger has developed a genetic PCR test for carrier and affected dogs. The defective gene is more frequent in field English springer spaniel lines, although carrier dogs from purely conformation lines have also been identified. Ten percent of blood samples assayed by Dr. Giger test as carriers, from widespread pedigree backgrounds. Dr. Giger is looking to perform a demographic study to monitor the true frequency of carriers in the population, and the breadth of the defective gene’s pedigree background. The PCR test for PFK is also run by VetGen. The OFA has begun a PFK registry, which currently has three dogs testing normal.

With the development of good veterinary control of infectious, parasitic, medical, and surgical diseases, genetic disease has become a major factor in canine health. Breed clubs should cooperate with researchers willing to work on identification and testing of genetic diseases. Breeders need to be aware of the tests available to control genetic diseases. These must be used in a manner that will ensure long term control, along with improvement of breed characteristics.

(Permission to reprint was granted by the ESSFTA Foundation, Inc. and the author.)