Genetic testing

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Clinical genetic testing

Clinical genetic testing refers to the laboratory analysis of DNA or RNA to aid in the diagnosis of disease. It is very important to understand that clinical genetic testing is quite different from other types of laboratory tests. Genetic testing is unique in that it can provide definitive diagnosis as well as help predict the likelihood of developing a particular disease before symptoms even appear; it can tell if a person is carrying a specific gene that could be passed on to his or her children; it can inform as to whether some treatments will work before a patient starts therapy. These are definite advantages. However, there are also some qualities of genetic testing that should be carefully thought out and perhaps discussed with a genetic counsellor or clinical geneticist before undergoing any test. These aspects are reviewed in the section titled Pros and cons of genetic testing. In an era of patient responsibility, it is important that both health professionals and patients are educated in these matters to fully appreciate the value as well as the drawbacks of genetic testing.

Testing genetic material
Testing of genetic material is performed on a variety of specimens including blood, urine, saliva, stool, body tissues, bone, or hair. Cells in these samples are isolated and the DNA within them is extracted and examined for possible mutations or alterations. Looking at small portions of the DNA within a gene requires specialized and specific laboratory testing. This is done to pinpoint the exact location of genetic errors. This section will focus on the examination of a person’s genes to look for the one(s) responsible for a particular disease.

There are four basic reasons that genetic material is tested for clinical reasons. Presymptomatic testing identifies the presence of variant genes that cause disease even if the physical abnormalities associated with the disease are not yet present in an individual. Diagnostic genetic testing is performed on a symptomatic individual with symptoms sufficiently suggestive of a genetic disorder. This assists the individual’s physician in making a clear diagnosis.

Testing of genetic material can also be performed as a prenatal screening tool to assess whether two individuals who wish to become parents have an autosomal or X-linked recessive gene that, when combined in a child, will produce a serious disorder in that child. This type of genetic testing is referred to as carrier screening. Prenatal testing refers to genetics testing of the fetus to assess their health status if the fetus is deemed to be at high risk of a particular genetic disorder.

To test DNA for medical reasons, some type of cellular material is required. This material can come from blood, urine, saliva, body tissues, bone marrow, hair, etc. The material can be submitted in a tube, on a swab, in a container, or frozen. If the test requires RNA, the same materials can be used. Once received in the laboratory, the cells are removed from the substance they are in, broken apart, and the DNA in the nuclei is isolated and extracted.

The laboratory professionals who perform and interpret these tests are specially trained pathologists and scientists. The extracted DNA is manipulated in different ways in order for the molecular pathologist or molecular geneticist to see what might be missing or mutated in such a way as to cause disease. Examples of common manipulations of the DNA include amplification, sequencing, or a special procedure called hybridisation. Another more traditional manipulation involves ‘cutting’ the DNA into small pieces using special enzymes. These small pieces are much easier to test than the long strands of uncut DNA, and they contain the genes of interest.

When the results of these different tests are examined and compared with results from a normal person, it is possible to see differences in the genes that might cause a disease.

Specific genetic diseases
There are many diseases that are now thought to be caused by alterations in DNA. These alterations can either be inherited or can occur spontaneously. Some diseases that have a genetic component to them include:


Alzheimer's disease Bone marrow disorders Breast cancer
Chlamydia Colon cancer Cystic fibrosis
Down syndrome Gonorrhoea Haemochromatosis
Herpes HPV Leukaemia
Lupus Lymphoma Osteoarthritis
Ovarian cancer Sickle cell anaemia Thalassaemia


Some of the related tests include:

Apo E genotyping BRCA 1 and 2 Factor V and PT 20210
Her-2/neu HIV viral load HIV resistance

Several things can go wrong with the genes that make up the DNA, resulting in these and other diseases. The section below discusses what can happen to DNA, and specifically to genes, that might lead to a disease.

Genetic variation and mutation
All genetic variations or polymorphisms originate from the process of mutation. Genetic variations occur sometimes during the process of somatic cell division (mitosis). Other genetic variations can occur during meiosis, the cycle of division that a sperm cell or an ovum goes through. Some variations are passed along through the generations, adding more and more changes over the years. Sometimes these mutations lead to disease, other times there is no noticeable effect. Genetic variations can be classified into different categories: stable genetic variations, unstable genetic variations, silent genetic variations, and other types.

Stable genetic variations are caused by specific changes in single nucleotides. These changes are called single nucleotide polymorphisms or SNPs and can include

  • substitutions, in which one nucleotide is replaced by another
  • deletions, in which a single nucleotide is lost, and
  • insertions, in which one or more nucleotides are inserted into a gene.

If the SNP causes a new amino acid to be made, it is called a “missense mutation.” An example of this is in sickle cell anaemia, in which one nucleotide is substituted for another. The genetic variation in the gene causes a different amino acid to be added to a protein, resulting in a protein that doesn’t do its job properly and causes cells to form sickle shapes and not carry oxygen.

Unstable genetic variations occur when a nucleotide sequence repeats itself over and over. These are commonly called "triplet repeats"; a triplet group of nucleotides repeats over and over and is usually present within a normal range, such as in groups of 5-35 repeats. However, if the number of repeats increases too greatly, it is called an "expanded repeat" and has been found to be the cause of many genetic disorders; most of which affect the central nervous system. An example of a disease caused by an expanded repeat is Huntington disease, a severe late onset progressive neurodegenerative disorder which leads to dementia, psychological changes and unusual choreiform movements.

Silent genetic variations are those mutations or changes in a gene that do not change the protein product of the gene. These mutations rarely result in a disease.

Other types of variations occur when an entire gene is duplicated somewhere in a person’s genome. When this occurs, extra copies of the gene are present and makes extra protein product. An example is a disorder that affects peripheral nerves called Charcot-Marie-Tooth disease type 1. Some variations occur in a special part of the gene that controls when DNA is copied to RNA. When the timing of protein production is thrown off, it results in decreased protein production. Other variations include a defect in a gene that makes a protein that serves to repair broken DNA in our cells. This variation can result in many types of diseases, including colorectal cancer and a skin disease called xeroderma pigmentosum.

Testing for products of genetic expression
Many inherited disorders are identified indirectly by examining abnormalities in the genetic end products (proteins or metabolites) that are present in abnormal forms or quantities. As a reminder, genes code for the production of thousands of proteins and, if there is an error in the code, changes can occur in the production of those proteins. So, rather than detecting the problem in the gene, some types of testing look for unusual findings related to the pertinent proteins, such as their absence.

An example of testing for genetic products includes those widely used to screen newborns for a variety of disorders. For example, newborns are tested for phenylketonuria (PKU), an inherited autosomal recessive metabolic disorder caused by a variation in a gene that makes a special enzyme that breaks down phenylalanine, an amino acid. When too much of this substance builds up in blood, it can lead to intellectual disability if not treated early in life with a special, restricted diet. The test uses a blood sample from a baby’s heel to look for the presence of extra phenylalanine, rather than looking for the mutated gene itself. Other examples include blood tests for congenital hypothyroidism, diagnosed by low blood levels or absence of thyroid hormone, and congenital adrenal hyperplasia, a genetic disease that causes the hormone cortisol to be decreased in blood.

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