In the human genome, most genes are made up of portions called exons, separated by spacer regions called introns. Exons give rise to proteins, while introns have a mysterious spacer function. The set of exons of a genome is called exome.
And why do we sequence the exome? Because we know that more than 80% of the known disease-causing mutations are located in the exons … hence, sequencing the exome has proven to be a very efficient strategy from the diagnostic point of view … But above all, if we now sequence the exome it is because technology has advanced enough for it to be cheap and affordable. Until recently we could only sequence small pieces at a very high cost, this could make finding a mutation a matter of years. Today, it is feasible, in a single experiment and at a relatively low cost, to sequence the exons of the more than 20,000 genes that make up the human genome. This provides us many possibilities to find the mutation that causes the disease we are studying.
My exome (or my offspring’s exome) is going to be studied, what genes will be analyzed?
In most cases, in a first analysis only those genes that are known to cause the disease will be analysed and not the 20,000 genes at once. If in this first analysis no genetic alteration is identified, the rest of the genes will be analysed. Keep in mind that, at this point, we can not predict when, or even if you can identify any alteration in a gene that is responsible for the patient’s illness. In some cases, all the genes will be analysed directly. If this is your case, your doctor will tell you.
What are the possible outcomes of an exome sequencing study?
As a general rule, we can expect four outcomes of a study of this type:
1. One or more genetic alterations are identified in genes that are known to be the cause of the disease we are studying in your case. BINGO!! We already have it! Although it is almost certain that we will have to do additional studies directed to your relatives (parents, siblings and / or children) to reach the definitive genetic diagnosis. In this case, a member of our team will be available to discuss the results with you.
2. One or more genetic alterations are identified but their meaning is not evident. In this case, it will most likely be necessary to study other members of the family to try to determine if this alteration is relevant to explain the disease. It will be in your hands to inform your relatives and / or ask them to participate in the genetic study. No one from our team will contact any member of your family.
3. No alteration that can explain your illness is identified. In these circumstances the study could continue later when new knowledge is available that relates your disease to new genes. You will be informed in case this situation occurs in the future.
4. When all the genes are analyzed, there is a small probability that alterations are identified that are not related to the disease being studied. An example of this type of finding could be the identification of a mutation in a gene that confer high risk of suffering cancer or neurological diseases. This can have important repercussions for both you and your family. You must decide whether or not you want to be informed in the event of these fortuitous findings. In case you decide to be informed, the geneticist / group of geneticists will discuss which of them have a clinical impact relevant enough to be informed.
How is the advance in scientific knowledge managed in relation to the results obtained with the sequencing of your exome?
Knowledge of the function of genes and their relation to diseases has been increasing rapidly in recent years. Thus, it is possible that even if today it is not possible to determine the genetic cause of your disease, this can be possible when the knowledge advances. This means that a genetic alteration that is identified today with the sequencing of the exome and that is classified as of unknown repercussion, can be reclassified in the future as pathogenic when the knowledge advances. Your doctor will contact you if this happens. Even so, it is highly recommended that, in the event that the exome analysis has been inconclusive today, you should contact your doctor (or with us) within a period of two years from the discussion of this study to find out if during this time new information that may be relevant to your case has been generated.
What does the sequencing of an exome require?
To sequence the exome it is necessary to have your DNA. We can obtain it from a blood sample (1 tube, from 3 to 5mL), from a little saliva, from buccal cells, … In some cases it may also be necessary to obtain DNA from other relatives (usually parents). The remaining DNA will be preserved for future validation studies. Even if we keep it, it will always be necessary to give your written consent to make any test with your sample … and you have the right to decline this consent at any time, without the need to give any explanation and without this having any repercussion on the quality of the treatment you need to receive.
The use of exome sequencing results for research purposes
The information that will be obtained from the study of your exome is very important for the study of other genetic diseases. The results of the analyses will be kept completely anonymous and only your doctor will have the key to undo anonymity. In this way, the data obtained can be shared anonymously with other accredited researchers. If, as a result of these investigations, there is any discovery relevant to your genetic condition, your doctor will be informed and he will contact you to transmit this information.
I have more questions about the exome tests. Who can I contact?
Your doctor should be able to inform you about all the details of this test.
However, for any additional questions you may have, you can contact us through our telephone assistance department (93 230 12 70)
or by email to info@qgenomics.com