Felis ISSN 2398-2950

Inherited diseases: genetic tests

Contributor(s): Leslie A Lyons, Cathryn Mellersh

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 (egg or sperm) of an individual, the mutation may be passed on to offspring of that individual who then may also develop the associated disease.
  • The term "mutation" is the act of change in the DNA sequence, whereas once such a change is established it is called a variant or a polymorphism when is becomes more frequently established in the populations. An individual may be said to have a "mutant allele". The normal allele does not have the mutation, and is often termed wildtype.
  • Often in use, changes with no effect on fitness are referred to as polymorphisms whilst disease causing changes retain the name mutation.
  • 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), thus present on only one of the chromosomes that have been inherited from the parents. If heterozygous, the individual will be a carrier of the mutation but will be healthy, not presenting with any effects of the mutation. Only when an individual inherits a copy of the mutation from both its parents will the individual suffer the deleterious effects of the mutation.
  • Dominant mutations only need to be present as a single copy within the genome, on one chromosome of an individual, for 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 individual's DNA for the presence or absence of the precise mutation that is known to cause a particular disease. Within the limits of human error or known biological complications of testing, a well-designed mutation-based test is nearly 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 animals tested, whilst some are considerably more accurate.
  • 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. Depending on the mode of inheritance of the mutation, this information will predict 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 significance in only a proportion of individuals that have the mutation - they carry a risk of disease rather than a certainty of having disease.
  • Some mutations show a dosage effect, with mild disease (or minor risk of disease) in heterozygous animals, but markedly more severe disease in homozygotes. These types of mutations are often termed co-dominant or semi-dominant.
  • The link between the test result and disease is considered in more detail below.

How genetic tests are undertaken

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How to use the information gained from a genetic test

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Limitations of DNA tests

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What information should be available for each genetic test

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What genetic tests are currently available?

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Further Reading

Publications

Refereed papers
  • Recent references fromPubMed.

Other sources of information

  • http://www.vetmed.ucdavis.edu/Catgenetics/
  • Mellersh C & Sargan D (2011)DNA testing in companion animals - what is it and why do it? In Practice33, 442-453.
  • Lyons L (2010)Feline Genetics: Clinical Applications and Genetic Testing. Topics in Companion Animal Medicine25(4), 203-212.


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