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This leaflet gives information about what happens when a sample is sent to a genetics laboratory, the different methods used to perform genetic tests, why some genetic tests take so long and why in some case the laboratory cannot find a result.
Most genetic tests examine DNA, the chemical in our cells that gives our bodies instructions about how to grow, develop and function. DNA is a string of coded messages organised into specific instructions called genes. Humans have 30,000 different genes, arranged on a number of thread-like structures, called chromosomes.
Most genetic tests examine DNA. DNA is a string of coded messages organised into specific instructions called genes.
We inherit our chromosomes from our parents, 23 from our mother and 23 from our father, so we have two sets of 23 chromosomes, or 23 ‘pairs’. One of the ‘pairs’ compromises the X and Y chromosome. The male determining chromosome is the Y chromosome, so men have one Y and one X chromosome in each cell, whilst women have two X chromosomes. If you think of genetics as the book of life, then the DNA are the letters, the genes are words, and the chromosomes are the chapters.
Changes in genes or chromosomes are called mutations. You could think of a mutation as a spelling mistake or a series of words changed in a sentence. Mutations are very common and we all carry a number of them. The effect of a mutation can be good or bad, or it may have no effect at all. This depends on environmental factors, an element of chance, or mutations in other genes.
Changes in genes or chromosomes are called mutations. Mutations are very common and we all carry a number of them.
Mutations can cause problems if they stop the gene or chromosome communicating the correct instructions needed for the body to function properly. Genetic tests therefore aim to find mutations in a particular gene or chromosome. The tests are usually performed on blood or sometimes other tissues. (In some cases it is possible to take a saliva sample to get DNA. However, the scientist will usually need a good amount of high-quality DNA, so this is why a blood sample is normally preferred.) A sample is taken from the patient and sent off to the laboratory so that the genes or chromosomes can be analysed.
Genetics clinics usually have their own genetics laboratory. However, because there are so many genetic tests for so many different conditions, not all laboratories perform every test.
This is particularly the case for tests for the rarer genetic conditions. Therefore, the sample may be sent to another laboratory that specialises in the particular test that the doctor wants performed. It is also worth remembering that a genetic test will usually only provide information about the condition that was tested for.
Clinics do not perform a general test for all genetic conditions. The aim of a genetic test done at the genetics clinic is to provide information about the health of the individual or family.
Genetics clinics do not usually order tests for other issues, such as to check paternity, although information about this may sometimes be revealed in the course of testing. This may change in the future as wide-ranging genetic tests are being developed which test multiple, or all, genes in the person tested. These can be whole exome or whole genome tests, which can diagnose mutations in genes previously not known to cause the person’s disorder. These tests could provide a new diagnosis, but the data from such tests is very complex and hard to analyse, and can sometimes detect harmful mutations in genes which were not expected, resulting in dilemmas as to how to interpret the meaning of the finding, and communicate it to the person tested.
There are two main types of genetics laboratories: cytogenetics laboratories, which look at chromosomes, and molecular genetics laboratories, which look at genes.
If a doctor suspects a genetic condition is caused by a problem on one of the chromosomes, they will ask a cytogenetics laboratory to examine the patient’s chromosomes. Samples taken from blood, skin or the material obtained from amniocentesis and chorionic villus sampling (CVS) tests can be used. First the cells are grown. The cells are then put onto microscope slides and the chromosomes are stained with a dye so that it is easier to see them.
Cytogenetic testing can be a lengthy process.
The cytogeneticist will first check the number of chromosomes. Some conditions are caused because there are additional chromosomes. One of the most common examples of this is Down’s syndrome. People with this condition usually have one additional chromosome in their cells. The cytogeneticist will also check the structure of the chromosomes. Changes in chromosome structure happen when the material in an individual chromosome is broken and rearranged in some way; it may involve the addition or loss of chromosome material. These changes can be so small that they can be hard to detect.
Sometimes a different technique known as fluorescence in situ hybridisation (FISH) is used to detect
changes that are too small to be seen under the microscope or to double check a small change seen under the microscope.
Cytogenetic testing can be a lengthy process. The laboratory first needs to grow the cells and this takes at least a week. It can then take another week or so to prepare the slides and analyse the chromosomes one by one under the microscope.
If a doctor suspects a genetic condition which is caused by a change (mutation) in a gene, they will ask a molecular genetics laboratory to examine the DNA of a particular gene. The instructions within the DNA are written out as a code made up of four letters: A, C, G and T. The molecular genetics laboratory can examine the precise sequence of the code in a particular gene to see if there are any errors.
A single gene, however, may consist of 10,000 or more letters of DNA code. So, a molecular geneticist’s skill lies in being able to read through the code and find the changes. If these changes cause the gene to not give the correct instructions to the body, this can cause a genetic condition. Unlike chromosomes, DNA cannot be seen under a microscope. The molecular geneticist extracts DNA from the cells, and uses the DNA to perform specific chemical reactions to read the code of the gene of interest. Many different techniques are used to detect mutations. Checking the sequence of DNA is one commonly used method.
Genetic test data is always kept confidential and is only released to third parties with the consent of the person tested or their guardians.
Genetics laboratories have a saying that ‘anyone can find a mutation, but not everyone can interpret them.’
First of all it is critical that an expert, such as a clinical geneticist, has looked at the patient, their relatives and their family history, and perhaps also the results of any other investigations carried out. This gives the geneticist clues about what gene or chromosome to investigate. So if, for example, the geneticist thinks the patient may have cystic fibrosis because the patient is showing symptoms of the condition, and other family members have had the condition, they will take a sample from the patient and send it off to the laboratory for testing. They will provide the laboratory with all the relevant information about the patient and their family history and tell them to look for the mutations that causes cystic fibrosis. If the laboratory finds two cystic fibrosis mutations, one on each chromosome, then they know that patient has cystic fibrosis.
In some cases a child is affected by a condition but neither of the parents has the mutation. In this case it is likely that the mutation has happened for the first time when that baby was conceived. This is called a ‘de novo’ or new mutation. In some cases a laboratory may not know whether a mutation is disease-causing or not. This may be because the impact of the change in the DNA code is hard to interpret, i.e. it is not clear whether the change in the gene actually alters the function of the gene.
The laboratory will check the details of the variant with databases of mutations in that gene, and other tests on the effect on gene function may be done. Looking to see if the faulty gene is present in other affected individuals in the same family can also help.
The laboratory will usually give some indication as to how likely the mutation is to be damaging after doing these checks. These mutations may be called ‘unclassified variants’ and receiving this result can be frustrating for all involved. However it is extremely important that a laboratory does not say that a mutation is harmful when it is not as this might lead to someone being given an incorrect diagnosis. The laboratory can do other tests to check how likely it is that the variant will be harmful to the gene’s function.
In some situations a test is carried out to find the cause of a problem and no mutation is found. There are a number of reasons as to why this is:
It is important to remember that genetic testing techniques and our knowledge of genetics is advancing rapidly. Therefore, even if a mutation cannot be found now, there is still a possibility that new techniques will enable scientists to find it in the future.
If the laboratory knows exactly what mutation it is looking for, because somebody else in the family has the same condition, or because the laboratory knows which area of the gene to look at, it has a much easier task. The test may then take only a week or two. However if no mutation has previously been found in the family, or if there are a number of genes associated with the condition, it will need more work to get a result. Instead of focusing on one area of a gene the labaratory may need to analyse the whole gene or even more than one gene. This can be a very long process and can take many months. Exactly how long will depend on a number of factors such as how big the gene is and the facilities available at the laboratory. For example, in the case of Duchenne muscular dystrophy, the condition is caused by mutations in a gene called dystrophin, one of the longest genes known. There are thousands of different possible mutations that can occur, and therefore finding a family’s particular mutation can be a very long and laborious process. On the other hand, in the case of Huntington’s disease, mutations in the huntingtin gene always occur in the same small region. Therefore the scientists know exactly where to look in the gene and so the test is fairly easy and much quicker.
The quality of the DNA is also an important factor. Sometimes laboratories first have to check the DNA of someone who is deceased in order to identify the particular mutation. If the DNA from the deceased person is poor quality, this can double or triple the time it takes to find the mutation. In some cases it may not be possible to complete the analysis because there is not enough DNA.
Because genetic tests have very important implications for an individual and their relatives, they are treated very carefully.
Numerous steps are taken to ensure that the correct result is given. If a mutation is found it is always double checked to ensure that the result is correct (although machines are used during many parts of the test, a scientist will still always check the results). Often, scientists will perform another test to ‘cross check’ the first result. Procedures are also in place to make sure that samples do not get mixed up. Additionally, many laboratories take part in Quality Assurance (QA) schemes which helps ensure that they perform good quality, reliable genetic tests.
Unless a patient requests that their sample be discarded after testing, a laboratory will usually store the DNA, and may store chromosome samples. Laboratories will be happy to let you know about your sample, and individuals can request at any time that their DNA be destroyed or returned to them.
Consent may be specifically requested to store the sample. Testing for other conditions is not performed without consent from the patient. As new improved tests are developed, laboratories may perform these tests on stored samples (if for example initial testing did not provide any results), if consent has been given. In this way both patients and clinicians can be reassured that the most up-to-date testing is available. Laboratories may use anonymised DNA samples to help develop new tests, or share them as part of Quality Assurance (QA) schemes, unless an individual specifies that they do not wish their sample to be used in this way. Like any stored clinical samples, DNA is regarded as part of a patient’s medical record and is therefore kept in medical confidence. This means that access to it is only possible through an appropriate healthcare professional.
DNA is regarded as part of a patient’s medical record and is therefore kept in medical confidence.
Some people are concerned about the police accessing their DNA. This is an extremely rare request. If the police should want access to a DNA sample from the genetics laboratory
(as with any other part of a patient’s medical record) then this is only possible on production of a court order.
First published March 2009. Developed by Genetic Alliance UK, London, UK with the help of Dr Ian M Frayling, Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK and Dr Domenico Coviello, Laboratory of Medical Genetics, Fondazione IRCCS, Milan, Italy. Supported by EuroGentest, an EU-FP6 supported NoE contract number 512148.
Reviewed and updated January 2017
with help from Prof. Shirley Hodgson, Emeritus at St. George’s, University of London and members of SWAN UK (syndromes without a name) and Genetic Alliance UK.
To be reviewed in January 2020