Читать книгу Pet-Specific Care for the Veterinary Team - Группа авторов - Страница 230

Since alleles are inherited from both parents, it would be helpful to know how they combine in individuals and the impact that has on disease susceptibility. Two terms are important in this regard – genotype and phenotype.

Genotype refers to the actual genetic sequence determined in an animal, while phenotype describes what is clinically evident, compared to the normal or typical presentation. So, for any individual genetic trait (T), in which an animal could inherit a typical (T) or variant (t) gene from its parents, there are four combinations possible (TT, Tt, tT, tt) but really only three variants (TT, Tt, tt). If the condition is recessive (such as von Willebrand disease [vWD]) and the heterozygotes (Tt) cannot be clinically distinguished from one of the homozygotes (TT), then clinically there are three variants (TT, Tt, tt) but only two clinical phenotypes – normal (TT or Tt) and abnormal (tt). In the case of a recessive disorder like vWD, we have a genetic test that can tell us genotype (the actual gene pairing in the animal), but without the test we can only determine phenotype – normal versus abnormal, by evidence of bleeding factor tests. So, for a condition like hip dysplasia where currently we cannot identify genotype, we end up making the diagnosis with phenotypic tests such are radiographs or distraction index.

Progressive retinal atrophy in the Irish setter is inherited as an autosomal recessive trait, which means that an affected individual inherits a defective gene (rcd1) from each parent, whereas dogs that inherit a defective gene from only one parent may be difficult to identify, because they appear clinically normal. The good news for veterinary teams, even without a DNA test, is that an electroretinogram can identify affected individuals (with two copies of the abnormal gene) by 6 weeks of age. This identification means the dog can be removed from a breeding program so that it will not contribute its PRA genes to future generations. The bad news for veterinary teams and breeders is that carriers of the trait, those with only one abnormal variant and one normal variant, cannot be identified clinically, even with sophisticated procedures such as electroretinography. Therefore, without genetic testing, genetic counseling is a hit‐or‐miss enterprise until the animal produces affected offspring and we can determine its genotype. With direct DNA testing, though, animals that are affected, clear, or carriers can be identified (see 3.4 Predicting and Eliminating Disease Traits).

That's good news for Labrador retriever breeders; labs are also prone to PRA but a clinical diagnosis cannot be made until the dogs are 4 years old, and an electroretinogram will not identify affected pups until they are 18 months old. DNA testing can identify status early, in pups as young as one day of age. Unfortunately, the specificity of DNA testing is also one of its limitations. The gene that causes PRA in Labrador retrievers (prcd) is different from the one that causes it in Irish setters (rcd1), so the same DNA test cannot be used to diagnose these two forms of the disease (and there are dozens of different genetic forms of PRA). Fortunately, DNA testing for both prcd and rcd1 is now available, and for many other forms of PRA.