Genetic testing allows us to detect discrete genetic variants for diseases and traits, and yet in real life, the manifestations sometimes appear more like shades of gray than black and white (see 3.4 Predicting and Eliminating Disease Traits). If a pet has a genetic variant detected, shouldn't that mean that the clinical result is a foregone conclusion? Like much of medicine, the answer is both yes and no. Here's why.
To understand the situation, we need to go back to a basic tenet of genetics – genetic mutations/variants don't cause disease; they code for proteins that may not be fully functional and it is this dysfunction that is interpreted as disease (see 3.1 Genetic Basics). The body tends to have a lot of redundant systems, so there may be other genes, epigenetic markers, modifiers, suppressors, and environmental factors that all impact the clinical manifestations in the living patient.
Clinical diagnosis also requires that we be able to clinically differentiate between the “normal” gene and the “variant” gene in all cases within a population of animals, and this is referred to as penetrance. Penetrance can be defined as the percentage of individuals in a population with a given genetic variant (genotype) that fully display the clinical manifestations (phenotype), and this is rarely 100%. Because of this, many conditions are described as having incomplete penetrance and this explains why we can't fully predict the clinical situation, even with sophisticated genetic screening. Some disorders may have full (100%) penetrance, but many more do not.
In contradistinction to penetrance, which looks at genetic manifestations on a population level, expressivity measures the extent to which a genetic variant (genotype) actually expresses the so‐called clinical abnormality (phenotype) on an individual level. There can be different degrees of expression of identical variants in different individuals based on other genes present or environmental factors. Because of this, we might describe that there could be variable expressivity for this variant in different individuals.
These features of penetrance and expressivity make genetic counseling as much an art as a science, even given the certainty of genetic screening. It is also a great reason why genetic testing favors the nuanced interpretation by well‐trained veterinary teams to properly counsel pet owners on the benefits of pet‐specific care and the goal of helping pets live long, healthy, and happy lives.
3.3.5 Epistasis
As if penetrance and expressivity didn't add enough variability to the equation, it's important to realize that there may be diseases, phenes, and traits caused by the effects of more than one gene. Some loci have a variety of different alleles that could participate in a gene pair. Nowhere is this more apparent than in coat coloration (Table 3.3.1). Epistasis is when the action of one gene depends on the action of another gene. Epistasis is wonderfully illustrated by the coat colors possible with different combinations of alleles from different loci. All breeds have all the loci mentioned, but they do not necessarily have all the possible alleles mentioned. Even within a given locus, some alleles are dominant over others.
Table 3.3.1 The genetics of coat color
| Locus and allele | Effect |
|---|---|
| Agouti | |
| A | Solid color |
| Ay | Fawn/sable |
| Aw | Gray/wolf |
| as | Saddle |
| at | Bicolor (tan points) |
| a | Recessive black |
| Black | |
| B | Black |
| b | Liver |
| Color | |
| C | Color factor |
| CC | Full color |
| cch | Chinchilla |
| ce | Extreme dilution |
| cd | White with dark eyes |
| cb | Blue eyes |
| c | Albinism |
| Dilution | |
| D | No dilution |
| d | Dilution (e.g., blue Doberman) |
| Extension | |
| Em | Black mask |
| E | Normal extension |
| e | Nonextension (yellow) |
| Graying | |
| G | Born black, turns blue |
| g | Born black, stays black |
| Intensity | |
| INT | Lightest tan |
| intm | Intermediate tan |
| int | Darkest tan |
| Solid | |
| K | Solid color in pigmented areas |
| Br | Brindle |
| Y | Allows yellow pigment to show |
| Merle | |
| M | Merle |
| m | Nonmerle |
| Spotting | |
| S | Solid color |
| si | Irish spotting |
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sp
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