Pet-Specific Care for the Veterinary Team. Группа авторов
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 for an animal.
Genomics: The study of the entire genome, and its combined influence on complex diseases and the impact of environmental factors such as diet, exercise, medications, and toxins on genes.
Genotype: An individual's genetic constitution.
Heterozygote: An individual with two different alleles for a given gene.
Homozygote: An individual with two identical alleles for a given gene.
Locus: A fixed position on a chromosome for a gene or marker.
Penetrance: The likelihood of individuals in a population with a given genetic variant (genotype) fully displaying the clinical manifestations (phenotype) of that variant.
Phene: A trait or characteristic that is genetically determined.
Phenotype: Observable characteristics or traits that result from the interaction of genotype with the environment.
Recessive: Heritable characteristics, traits, or diseases that are expressed only when inherited from both parents.
At its simplest, one would suspect that disease outcomes could be readily predicted if only the pattern of inheritance is known. However, things are rarely that simple when it comes to genetics. A few examples of genes, mutations, diseases, and modes of inheritance are in order to help explore the genetics of disease.
Fucosidosis is a rare but devastating lysosomal storage disease of English springer spaniels, transmitted as an autosomal recessive trait, meaning a dog would have to inherit an abnormal gene from each parent to be affected by the disease (see 11.3 Heritable Health Conditions – By Disease). Although the abnormal gene itself does not kill the dog, it codes for an absent or nonfunctional enzyme (alpha‐L‐fucosidase) that can result in clinical problems. If the enzyme is not capable of breaking down its substrate, complex sugars collect within cells and eventually kill them. When the cells are severely compromised by this accumulated substrate, they die, and then the organs (primarily the brain) begin to be compromised, and eventually the situation will lead to the dog's demise. Carriers, who only inherited an abnormal gene from one parent, appear outwardly normal. Their levels of fucosidase enzymes, however, may be lower than normal, but not necessarily low enough to cause expression of the disease.
The same is true for many of the bleeding disorders, in which a defective gene does not produce a fully functioning protein or an enzyme important to clotting. Although carriers appear normal, their level of clotting factor may be lower than normal, just not low enough to cause spontaneous bleeding problems.
Whether a trait/phene is truly recessive depends on how hard one looks at the phenotype (see 3.2 Modes of Inheritance). A dog with fucosidosis typically shows neurological signs early in life and has an abbreviated life span. The affected dog carries two copies of the abnormal gene. If a carrier, with one abnormal gene, has no outward problems as a pup but (theoretically) suffers from dementia and is euthanized