two copies of a disease‐causing gene (one from each parent) are required to cause a specific problem, the trait is said to be recessive. Thus, PRA in Irish setters is recessive because, to manifest the disease, an animal must inherit a defective gene from each parent (i.e., both parents). If the parents of an Irish setter with PRA appear phenotypically normal, they must both be carriers (heterozygous for a recessive character) of the trait because each contributes a disease‐causing gene to their offspring. Because the trait is recessive, both carrier parents appear normal.
When only one copy of a gene is necessary for a trait to be expressed, that trait is said to dominant. In our PRA example, the gene for normal retinal development is dominant, which is why carriers look outwardly normal even though they carry an abnormal allele and a normal one.
In the simplest terms, if one gene pair controls a trait, conventional use is to capitalize the dominant form and use lower case for the recessive form. For example, imagine that the coat color in a fictitious breed, the American car‐chasing terrier (ACCT), is controlled by a single gene pair. The dominant presentation is black (B), and the recessive presentation is brown (b). Because black is dominant over brown in this example, individuals with a heterozygous genotype (Bb) will appear black. Those with a homozygous genotype will be either black (BB) or brown (bb).
If we did not have a genetic test to identify coat‐color genotype, we would have to determine it the old‐fashioned way, by progeny testing. If you were to breed a black dog (we know that at least one allele is B) to a brown dog (bb) and any of the puppies were brown (bb), the black dog would have to be a heterozygote (Bb). If all the pups were black (BB or Bb), the black parent is most likely a homozygote (BB). Similarly, if we were to breed two black dogs and any of the pups were brown, we would know that both parents had to be heterozygotes for the black color gene (Bb).
If only things were this simple! Although we could indeed give many examples of traits that are inherited in a simple fashion, many more are not nearly as easy to determine or the phenotype is the expression of more than one gene pair. Consider a genotype example for Labrador retrievers, in which nine different coat‐color genotypes are possible (from 16 possible gene combinations). Some genes can affect more than one function, such as the genes affecting coat color that can also be associated with deafness, ocular anomalies, or both. When one gene affects two or more traits in the same individual, it is termed pleiotropy.
In addition to all the new information available on coat‐color genetics, distinct mutations in three genes, RSPO2, FGF5, and KRT71 (encoding R‐spondin‐2, fibroblast growth factor‐5, and keratin‐71, respectively), together account for most coat phenotypes in purebred dogs [1].
3.2.4 Cytoplasmic Inheritance
Most DNA is found in the nucleus, but mitochondria in the cytoplasm contain their own DNA, derived entirely from the mother's ovum. Sperm contain few mitochondria, and none survive fertilization. Therefore, defects in mitochondrial DNA can be passed only from the mother but are transferred to both male and female offspring.
Seamus McTigue is a 6‐month‐old neutered male Scottish terrier that has presented with difficulty in chewing and swallowing, and has early evidence of swelling of the mandible. A genetic panel performed at 12 weeks of age indicated that Seamus was homozygous recessive for the craniomandibular osteopathy genetic variant (SLC37A2). Mrs McTigue has confirmed that neither of Seamus' parents had been affected by the condition, which is entirely consistent with a disorder presumed to have autosomal recessive inheritance. Ordinarily Mrs McTigue would have been more alarmed, but since the veterinary team had apprised her of the likelihood of the issue, and had an action plan in place for dealing with it, she felt that Seamus was in good hands and she felt prepared to deal with the situation as needed.
Monogenic traits (those controlled by a single gene pair) are often described as being dominant or recessive, but the actual pattern of inheritance observed may not be clear cut.
Most traits have polygenic inheritance, in which disease manifestations are controlled by a variety of genes, often with environmental influence.
Heritability is the term used to describe how much of a condition is due to genetic influences.
Many more conditions are caused by variants on the autosomes than on the sex chromosomes.
Mitochondria contain their own distinct genes, and genetic diseases caused by mitochondrial DNA variants are transmitted from mothers to both male and female offspring.
Reference
1 1 Cadieu, E., Neff, M., Quignon, P. et al. (2009). Coat variation in the domestic dog is governed by variants in three genes. Science 326: 150–153.
Recommended Reading
1 Ackerman, L. (2011). The Genetic Connection, 2e. Lakewood, CO: AAHA Press.
2 Ackerman, L. (2020). Proactive Pet Parenting: Anticipating pet health problems before they happen. Problem Free Publishing.
3.3 The Genetics of Disease
Lowell Ackerman, DVM, DACVD, MBA, MPA, CVA, MRCVS
Global Consultant, Author, and Lecturer, MA, USA
3.3.1 Summary
Genes do not cause diseases. They code for proteins that may have developmental or maintenance roles. When those proteins fail to function in a manner consistent with “normal,” an animal may be diagnosed with a phene, trait, or disease of a genetic nature. Still, the relationship between genetics and disease is not as clear cut as one might expect.
3.3.2 Terms Defined
Allele: A variant or alternative form of a gene, found at the same location on a chromosome, and which can result in different observable traits.
Dominant: Heritable characteristics, traits, or diseases that are expressed when inherited even from one parent.
Epistasis: The situation in which the action of one gene depends on the action of another gene.
Expressivity: The extent to which a genetic variant (genotype) expresses the so‐called clinical abnormality (phenotype) on an individual level.
Genetics: The study of genes and how traits or conditions are passed from one generation to the next.
Genome: The complete set of genes
