Exome

To understand what the exome is, it is useful to begin by explaining what the genome is. The human genome comprises the entire DNA of an individual and consists of 3 billion nucleotides or “letters” of DNA. 

Of all the DNA, only a small percentage (approx. 1.5%) contains the information needed to produce proteins, the functional actors of the organism. This fraction of the genome is known as the exome. It consists of all the exons of the genome, which are the coding parts of the genes. The term exon is derived from “EXpressed regiON“, as these are the regions that are translated, or expressed as proteins, unlike the intron, or “INTRagenic regiON“, which is not represented in the final protein.

As described in the previous question, the genome comprises the entire DNA of an individual while the exome comprises only the DNA fragments that provide instructions for making proteins. The exome represents 1% of the genome and the function of many of the human genes is now known. The remaining 99% of the DNA was once known as “junk DNA”, but discoveries in recent decades have shown that many of the areas that were considered “junk” play a very important role in gene regulation. It is to be expected that more details about the function of these regions will be uncovered in the coming years.

This question does not have a clear answer.

It is true that the genome allows the detection of variants in non-coding regions and other variants not detectable through the exome (such as structural variants, triplet repeats, inversions, deletions…). However, the significance of much of this information is unknown.

To date, the majority of known disease-causing mutations (approx. 85%) occur in exons and therefore whole exome sequencing is an effective method to identify potential disease-causing mutations.

Experience in recent years has taught us that the exome is a comprehensive approach that is usually the most successful from the beginning and this for three reasons: diagnostic capacity, price and time.

There are other simpler and cheaper options, such as first analysing only the most common mutations (few genes or panels), in the hope of finding the cause. The problem with these options is that if you miss a mutation, you are always left with the question of whether you have a mutation that could not be detected with these simpler tests. This means that further testing (to test for the mutations that were not tested for) is needed to clear up the doubt. This costs more money and more time to get definitive results. In short, an exome analysis can save time and money.

Diagnostic yield will depend on the disease or group of diseases in question, but the identification of pathogenic or likely pathogenic variants can be as high as 40%, for example in cases of autistic spectrum disorders.

In addition, in up to 40% of cases (depending on the disease or group of diseases in question) variants of uncertain significance (VUS) may be obtained, which can be re-evaluated at regular intervals to determine whether or not they are associated with the pathology.

A clinical exome is generally understood as one that sequences and analyses only the exons of the genes classified as responsible for diseases (approx. 4,800 genes).

Whole exome sequences all the exons of an individual. This information can then be used to perform a targeted analysis of a disease (Charcot-Marie-Tooth, Marfan, osteogenesis imperfecta, etc.) or a group of diseases when the symptoms are more unspecific.

The price of the exome at Genosalut is 1,300€ and includes genetic counselling sessions before and after the test.

As a general rule, private insurance does not cover exome analysis. However, there are certain clinical situations in which they do cover the costs.