LITMIR.BIZ

3.11 Integrating Genotypic and Phenotypic Testing

       Lowell Ackerman, DVM, DACVD, MBA, MPA, CVA, MRCVS

       Global Consultant, Author, and Lecturer, MA, USA

BASICS

      3.11.1 Summary

      In pet‐specific care, there is a focus on prevention and early detection. To accomplish early detection, both genotypic and phenotypic tests are needed. Genotypic tests examine an individual's DNA for mutations (variants) or markers that may be correlated with traits and disease risk. Phenotypic tests measure observable features (e.g., blood test results, heart rhythm, body weight, etc.) and diagnostic judgments are made on that basis, and comparisons with so‐called “normal” reference intervals (ranges).

Genotypic tests on their own have value, but they cannot always predict actual risk of diseases. In addition, genotypic tests are available primarily for conditions transmitted as simple Mendelian traits (e.g., von Willebrand disease, progressive rod‐cone dysplasia, mdr1, etc.), mostly controlled by one set of genes. On the other hand, the most common hereditary conditions encountered in veterinary practice (e.g., atopic dermatitis, hip dysplasia, seizure disorders, etc.) have a more complex pattern of inheritance, often influenced by environmental factors and multiple genes, and confirmed principally through phenotypic testing. Because of this, both genotypic and phenotypic testing are needed as part of most early detection schemes.

      3.11.2 Terms Defined

      Genotypic Testing: Testing that determines actual genetic mutations (variants) or markers of traits or conditions.

      Phene: A trait or characteristic that is genetically determined.

      Phenotypic testing: Testing that determines observable features of traits or conditions and compares them to normal or typical values.

MAIN CONCEPTS

Genotypic tests, those that rely on the detection of actual genetic mutations (variants) or markers (Table 3.11.1), have a lot of benefits. They can be detected at an early age, even as early as one day of age. They don't change over time, so if a genetic mutation is present (or not present) when tested, repeat testing is not needed – the results should not change over time. In fact, if the parents have been tested for a specific variant, the status of the offspring can be inferred from such testing. So, if two Labrador retrievers are both “clear” for progressive rod‐cone degeneration (prcd) and they are bred together, theoretically it should not be possible for the pups to develop that specific form of progressive retinal atrophy (PRA) if the testing has been done by a reliable genetic testing facility (http://bit.ly/2YWXBsc or https://dogwellnet.com/ctp). Of course, mistakes do happen. In this instance, the most likely cause for pups testing “affected” for prcd when the parents tested “clear” would be that the breeders made a mistake in identifying which animals were the actual parents. Theoretically, it would also be possible that the pups developed a spontaneous mutation, but this is very rare.

Table 3.11.1 Some of the genotypic tests currently available