Gene defect - Mutation
A mutation is a change in the genetic information (DNA sequence). A gene defect is a mutation that leads to a defective gene product and can thereby cause a disease or malfunction.
Not every mutation is a gene defect. Many variants have no recognisable effect, others are even desirable: almost all coat colours go back to mutations, for example the colour Blue/Silver in dogs. In technical language, the neutral term variant is therefore used, and variants that cause a disease are called disease-causing (pathogenic) variants.
Consequences of a gene defect
The defective gene product subsequently leads to symptoms of malfunction, which can vary in severity depending on the type of defect and the importance of the affected gene.
How a gene defect shows up in breeding depends on the mode of inheritance:
- Dominant: one copy of the variant is enough for the animal to be affected, for example in Hyperkalemic Periodic Paralysis (HYPP) in horses.
- Recessive: the animal is only affected if it has received the variant from both parents, for example in Severe Combined Immunodeficiency (SCID) in horses. Animals with only one copy are healthy carriers and pass the variant on unnoticed. Mating related animals increases the probability that two copies come together (see Genomic Inbreeding Coefficient).
Gene defects that cause death as early as the embryonic phase (early embryonic death) remain unnoticed and can be one of the reasons for failed pregnancies or smaller litters.
Inherited or acquired
Mutations can be inherited or acquired in the course of life:
- Germline mutations are present in egg or sperm cells and are passed on to the offspring. In most cases, the animal has inherited the variant from its parents. However, it can also have arisen anew in a germ cell of one of the parents; the offspring then carries a variant that cannot be detected in the parents themselves (de novo mutation).
- Somatic mutations arise during life in individual body cells, for example through radiation, toxins or errors in cell division. They only affect the animal itself, for example in the development of tumours, and are not inherited.
Genetic or not?
Some clinical pictures can be caused both by a gene defect and by external influences such as trauma or infection. A non-hereditary condition that resembles a hereditary disease is called a phenocopy.
If it is not clear whether the cause is a gene defect or whether the defect has arisen as a result of trauma or disease, this often leads to exclusion from breeding; the rules for this are set by the breed associations. The purpose is to prevent as yet unidentified or newly arisen gene defects from being introduced into the breeding population.
DNA tests are available for known gene defects. They show whether an animal is clear, a carrier or affected, and make it possible to mate carriers in a targeted way so that no affected offspring are produced.
Useful links - Literature
Lexicon:
- Genomic Inbreeding Coefficient (GIC)
- Popular Sire Syndrom: how gene defects spread through popular sires
- Bayes Theorem: carrier probability in littermates
Further information:
- Online Mendelian Inheritance in Animals (OMIA): database of known inherited disorders and traits in animals