How to Apply Genetic Testing to a Breeding Program

Used with permission from Today’s Breeder, Nestl? Purina PetCare Company.

Significant advances have been made in learning about canine genetic health conditions due in part to a greater awareness of these health conditions and
recent advances in the canine and human genome projects.

But for progress to occur that is, for breeders to have information to make good breeding decisions it is important that breeders and veterinarians are
aware of genetic disorders, their distinguishing characteristics and the availability of genetic testing, says Paula Henthorn, Ph.D., associate professor
of medical genetics at the University of Pennsylvania School of Veterinary Medicine.

“With enough information breeders can make appropriate breeding decisions,” she says. “It is important to have an accurate diagnosis, knowledge of the
mode of inheritance and be able to identify asymptomatic carriers of a recessively inherited condition. When these factors are known, the risks of
producing genetically effective offspring can be determined and appropriate breeding decisions made.”

Knowledge of the gene content of the canine genome (sequencing of the canine genome is currently under way) is likely to have a dramatic impact on
our ability to identify carriers of genetic disorders by dramatically increasing the rate at which DNA-based genetic tests are developed, Henthorn
says.

Two types of DNA-based genetic tests are used to identify differences in DNA sequences. A mutation-based test recognizes mutations that cause health conditions,
and a linked-polymorphism test recognizes DNA differences near the gene that cause a disorder. The latter are used to track normal and mutant alleles
(a gene contains a gene copy or allele from each parent) of that gene through pedigrees.

“Though there are differences in how these two types are developed and how they are used, both involve the same basic techniques, based on the availability
of the dog’s DNA and the use of polymerase chain reaction (PCR),” Henthom says. PCR involves performing a series of chemical reactions to make billions
of copies of specific fragments of genomic DNA to identify mutations.

Mutation-based tests recognize the specific DNA mutation that causes a genetic disorder. The normal gene sequence must be known in order for a mutation-based
test to be developed. Once developed, the tests accurately detect carriers and affected dogs. These tests may be breed-specific with different tests
for the same genetic disorder in different breeds.

Linked-polymorphism tests recognize variation in the DNA sequence outside but are closely linked to the gene causing a disorder. Testing relies on the
ability to detect a normal variation in the DNA sequence, the polymorphism, on the same chromosome near the gene involved in a genetic disorder. Linked-polymorphism
tests do not require knowledge of the gene.

However, these tests do require identification of a specific polymorphism. This involves copying and sequencing of a particular piece of DNA and preliminary
gene mapping studies to demonstrate the polymorphism is linked to the disorder. It also is helpful to have DNA from many individuals within a pedigree
in which the disorder segregates, though it is not necessary to know the exact mutation or even the gene involved in the disorder.

“This type of test is most accurate for use in families in which the parents of the dog in question are informative and DNA is available from an affected
full sibling of the dog to be tested,” Henthorn says. “For an animal to be informative, it must be heterozygous, or have two different alleles, at
the linked-marker locus. Though these are not necessities, additional research may be needed to make the tests accurate for an individual dog and often
for use in different breeds.”

The vast majority of genetic disorders with a linked polymorphism-based test will eventually have a mutation-based test, Henthorn says. “The important
issue is to understand the differences between the two types of tests and the resulting differences in how the test results should be used.”

  • The practicality and success of a genetic screening program depends on the following:
  • The health condition occurs with sufficient frequency to be of economic or social importance.
  • The test for the heterozygote is accurate and affordable.
  • Culling of heterozygotes does not deplete key genetic resources.
  • Test and control programs are acceptable to breeders and preceded by educational and public relations programs.
  • Genetic counseling is available to breeders.

Ultimately, cooperation among veterinary professionals, breeders and breed organizations is essential in a successful genetic screening program that allows
effective control of genetic disorders.

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