Canis ISSN: 2398-2942

Inherited diseases: genetic tests

Contributor(s): Cathryn Mellersh, David R Sargan

Introduction

  • A mutation is a permanent alteration to the nucleotide sequence of an organism's DNA. Mutations can be small (involving single nucleotides of DNA) or large (involving many thousands of nucleotides of DNA, and sometimes affecting several adjacent genes). Many mutations, have little or no effect on the health of the individual that carries them, whereas some mutations may even be beneficial - conferring a selective advantage in evolutionary terms or under artificial selection in domestic species. But some mutations are deleterious and can cause reduced fitness or disease. If the mutation occurs in the germline of an individual it will be passed on to offspring of that individual who may also develop the associated disease.
  • Properly, mutation is the act of change in the DNA sequence, whereas once such a change is established it is called a polymorphism. Often in use, changes with no effect on fitness are refered to as polymorphisms whilst disease causing changes retain the name mutation. We shall maintain this usage here.
  • Recessive mutations are those which do not produce a phenotypic effect unless the individual is homozygous (carries two copies) for the mutation - if an individual carries a single copy of the mutation (is heterozygous), on one of the chromosomes it inherited from one of its parents, it will be a carrier of the mutation but will be healthy. Only when an individual inherits a copy of the mutation from both its parents will it suffer the deleterious effects of the mutation.
  • Dominant mutations only need to be present as a single copy within the genome of an individual before that individual suffers the deleterious effects of the mutation.
  • A genetic test assays an individual's DNA for the presence or absence of a mutation that is known to cause an inherited disease/condition or be associated with other types of inherited trait, such as coat color, coat length or the presence/absence of a tail.
  • Mutation-based tests examine an individuals DNA for the presence or absence of the precise mutation that is known to cause a particular disease. Within the limits of human error a well-designed mutation-based test is 100% accurate in detecting the presence of the mutation. Most modern genetic tests are mutation-based.
  • Linkage-based tests, in contrast, do not detect the disease-causing mutation, but instead analyse polymorphic DNA markers that are known to be located very close to the mutation. Because genetic recombination events can occur between the mutation and the markers that are analysed, linkage-based tests are not usually 100% accurate. Rather they vary in accuracy depending on just how close the DNA marker is to the mutation. Commercial linkage-based tests will typically give an accurate result in at least 95% of dogs tested, whilst some are considerably more accurate than this.
  • The results of a genetic test will inform the veterinarian or owner whether the animal being tested carries zero, one or two copies of the mutation being tested for. Depending on the mode of inheritance of the mutation this information will determine whether or not the animal will, or is likely to, become affected by the disease itself and whether it could the mutation onto its offspring.
  • It is important to understand that detecting the presence of a mutation is not always the same as certain prediction of the onset of a condition. There may be influences from the environment or other parts of the genome.
  • Some mutations show only partial penetrance: that is their effects reach clinical sigificance in only a proportion of individuals that have the mutation they carry a risk of disease rather than a certainty of it.
  • Some mutations show a dosage effect, with mild disease (or minor risk of disease) in heterozygous animals, but markedly more severe disease in homozygotes.
  • The link between the test result and disease is dealt with in more detail below.
Print off the owner factsheet on Genetic testing for dogs to give to your client.

How genetic tests are undertaken

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

How to use the information gained from a genetic test

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Limitations of DNA tests

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

What information should be available for each genetic test

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

What genetic tests are currently available?

This article is available in full to registered subscribers

Sign up now to purchase a 30 day trial, or Login

Further Reading

Publications

Refereed papers

  • Recent references from VetMed Resource and PubMed.
  • Mellersh C S, Graves K T, McLaughlin B, Ennis R B, Pettitt L, Vaudin M & Barnett K C (2007) Mutation in HSF4 Associated with Early but Not Late-Onset Hereditary Cataract in the Boston Terrier. J Hered 98, 531-533 PubMed.
  • Mellersh C S, Pettitt L, Forman O P, Vaudin M & Barnett K C (2006) Identification of mutations in HSF4 in dogs of three different breeds with hereditary cataracts. Vet Ophthalmol 9, 369-378 PubMed.

Other sources of information

  • Inherited diseases in Dogs: http://www.vet.cam.ac.uk/idid/
  • Mellersh C & Sargan D (2011) DNA testing in companion animals - what is it and why do it? In Practice 33, 442-453.


ADDED