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Hip Dysplasia as an example of a Polygenic Disorder

Practical Genetics for Bull Terrier Breeders and Owners

Health Seminar presented to the Bull Terrier Club of America, October 10, 2002

Jerold S Bell, DVM, Tufts University School of Veterinary Medicine

Polygenic disorders are more difficult to manage than simple one-gene disorders. For selective pressure against polygenic disorders, they have to be considered as threshold traits. A number of liability genes must combine together to cross a threshold causing the disorder to be expressed. If we consider a theoretical situation where five genes must combine to cross a threshold to produce a dog with hip dysplasia, a mating between a dysplastic dog with 7 dysplasia liability genes, and a normal dog with three genes would be expected to produce a higher than average rate of dysplastic offspring. If two normal dogs produce an affected dog with a polygenic disorder, then BOTH parents must have contributed liability genes to the mating.

Breeders need to break down what you see in the phenotype into traits that may be more closely related to individual genes. For canine hip dysplasia, the pelvic radiograph can tell you much about why a dog received a fair versus good rating, or why it was rated as dysplastic. If the problem is mild laxity, in an otherwise superior dog, breeding to a dog with tight hips may provide a better response. If the problem is a shallow acetabulum, then breeding to a dog with deep hip sockets may provide the genes necessary for better hip conformation.

Some breeders and owners ask about the difference between OFA certification (the ventrodorsal pelvic radiograph) and PennHip certification (hip distracted radiograph). The OFA provides information on the anatomy of the hip joint, bony arthritic changes, as well as passive laxity in the hip extended view. The PennHip method isolates and provides an objective measurement of laxity as a major factor for the development of hip dysplasia. Both methods have similar low levels of false positive and false negative results. While PennHip will certify at an early age, and OFA will only provide preliminary certification before two years of age, both have similar accuracy in each age group in predicting later hip dysplasia. The OFA method provides a grading and allows the owner to evaluate all aspects of the hip conformation. If there is a problem with hip joint laxity, the PennHip method will allow breeders to select for tighter hips through their selective breeding.

There is no OFA excellent gene that breeders can select for. Different dogs have fair, good, excellent, or dysplastic hips due to different genetic reasons. By evaluating a pelvic radiograph with your veterinarian and selecting for the components of the hip that need improvement, you increase the likelihood of improvement in your matings. You should also consider whether there are any clinical signs of hip pain (either presently, or during the growth period of six to eighteen months), and palpable hip laxity under anesthesia to fully evaluate the hip status of a dog.

Environmental factors can affect the expression of polygenic disorders, and this is also true with hip dysplasia. We know that rapid weight gain at an early age can produce “sloppy” hips; where the maturation of the ligament and muscle components does not keep up with bone growth. By switching from puppy food to adult food after 14 weeks of age, or using large breed puppy food, dogs grow at a slower, and more uniform rate. The adult size and stature of a dog is genetically predetermined. How fast a dog reaches its adult size can influence the expression of hip dysplasia.

The most important factor in selecting against polygenic disorders is utilizing the breadth of the pedigree. Most breeders select for depth of pedigree; normal breeding dogs with normal parents. The status of the littermates of the prospective breeding dogs, and littermates of their parents provides the most information on the possible range of genes carried. A normal dog from normal, or mostly normal litters, provides the best evidence of a low genetic load for disease susceptibility genes. Normal dogs with affected littermates probably have a higher genetic load for the disorder.

A “vertical mating” system is a method to control polygenic disorders, recessive disorders without a test for carriers, or disorders without a known mode of inheritance. A dog of quality with high carrier risk should be bred to a dog with lower carrier risk, resulting in a carrier risk in the offspring lower than the average of the breed. Replace the higher-risk parent with a quality, lower-risk offspring. Repeat the process in the next generation. The number of breeding offspring should be limited from such matings. By breeding once and replacing, you are not propagating and disseminating defective genes into the population. Store semen and DNA from quality stud dogs for future use when a genetic test may become available. Even if the dog turns out to be a carrier, his semen can be used on a normal bitch, and the line carried on with genetically normal offspring. A vertical mating scheme retains the good genes of a line, reduces the carrier risk with each generation, and does not add to the overall carrier risk in the population.

As stated earlier, the Bull Terrier breed is diverse, and relatively healthy compared with other breeds. Bull Terrier breeders should concentrate on maintaining and enhancing the quality of the breed, and avoid the popular sire syndrome. Breeders should use genetic tests to identify carriers or high-risk dogs, work to breed away from defective genes, and prevent the reintroduction of the genes in future breedings. Each breeder must assess their own breeding stock, and determine their own rate of progress. A healthy breeding program does not continually multiply carriers, does not limit the genetic diversity of the gene pool, and is geared toward producing quality, genetically normal dogs.

04062006 Reprint for www.btca.com