The human genome is composed of 20,000 genes. Genes contain information for synthesising all the proteins in our bodies and these proteins carry out various biological functions. The information is contained in regions called exons and they are separated by regions called introns that do not contain any information. The complete set of exons in our genome is known as the exome.
When there are changes to the DNA in these exons, it can make a person ill and this is known as a mutation. Therefore, we need to know which mutation is causing an illness in order to give patients who have a genetic disorder a correct diagnosis. This was very complicated and costly in both time and money until a few years ago because the technology that was available was limited and it only enabled analysis of small DNA fragments, one by one. As a result, analysis of certain genes could take months and be very costly. Things were even more complicated when, potentially, there were mutations in different genes or the genetic cause was unknown. Nowadays, however, next generation sequencing (NGS) means that we are able to analyse many genes or the regions, such as the exons, that are of interest to us both simultaneously and quickly. The cost of doing so is also much lower now and it is much easier to find the mutation responsible for a given illness.
Types of exomes
There are different ways to locate a genetic mutation using an exome analysis. They include:
- CLINICAL TARGETED EXOME SEQUENCING: The analysis is performed on the genes that we know can explain the patient’s symptoms. This type of analysis is recommended when patients have a suspected case of a disorder that is caused by different genes. For example, osteogenesis imperfecta, Charcot-Marie-Tooth disease and deafness.
- CLINICAL WHOLE EXOME SEQUENCING: In this case, the exons that are responsible for disorders are analysed (around 4,800 of them). This type of analysis is recommended when the patient has unspecific symptoms and/or it is not possible to select a concrete group of genes. For example, autism, epilepsy, mental disabilities and multiple congenital malformations.
Exome sequencing can be useful in the following cases:
- When we need to study large genes that are difficult to study using traditional methods
- Complex pathologies in which multiple genes may be the cause of the illness
- For identifying mutations in illnesses about which little is known (the genetic cause is unknown) or illnesses that have unspecific symptoms.
In addition to illnesses, there are certain pathological conditions that can also benefit from these analyses and many of them are linked to fertility, both in women and in men. For example, premature ovarian failure (POF). POF is a premature end to menstruation (< 40 years of age) and, in most cases, the cause is unknown. However, thanks to this new sequencing technology, many of the genes that are the possible causes of the condition are being identified.
These analyses provide a lot of data that needs to be compared with multiple databases and scientific publications in order to reach a conclusion. Often, more than one of the patient’s relatives (for example, the father or mother) or other individuals with the same illness need to be involved in the process in order to be able to identify the mutation that is responsible for it. Exome analysis is, therefore, a complex task and both a laboratory and a specialist team are required.
We have next generation sequencing technology in Instituto Bernabeu. We also have a team of staff with extensive experience in sequencing and data analysis so that our patients can be provided with a correct genetic diagnosis of most illnesses.