What is genetic testing?

Genetic testing is a medical examination. It aims to establish the diagnosis of a genetic disease, or to find out in a specific context, whether a person at risk could transmit this disease to their children.  

Genetic testing is to sequence (that is, to decode) DNA – deoxyribonucleic acid – which is in your cells.

More often than not, the analysis is made by taking a blood sample. Some specific situations require a different kind of sampling such as saliva, skin cells or muscle cells.

What is DNA, a gene, a genome, an exome?

The human body is made up of billions of cells. All the genetic material of a person constitutes his/her genome. The genome, located in the nucleus of most cells in the body, is entirely specific to every individual. No two people have exactly the same genome as yours (unless you have a full-twin brother or sister).

The genome is all the DNA that constitutes our chromosomes. DNA is written using a  four-letter alphabet A, C, T and G (A for Adenosine, C for Cytosine, T for Thymine, and G for Guanine). The DNA sequence, or genetic sequence, forms the “detailed plan” containing all the information necessary for the development and the functioning of the body. Consisting of over three billion letters, the genome of a person would fill the equivalent of 400 dictionaries.

A gene is a fragment of this genome. It corresponds to specific genetic information that results in the production in the cell of a compound necessary for its functioning: a protein. There are about 20,000 genes coding for proteins. Each protein has a different function. For example, haemoglobin is the protein that carries oxygen in the blood. Other proteins are involved in the definition of eye colour.

The genes themselves are made up of exons which are the real “construction plan” of the protein that the gene codes. All the exons within the genome are referred to as the exome. While representing less than 1% of the genome, it is in the exome that the majority of known variants responsible for rare diseases are to be found. The rest of the genome is known as non-coding.

What is a genetic disease?

The genome of two people is, on average, 99% identical. There is therefore a 1% difference between them, known as variations. These variations as well as the interaction of the person with the environment in which he/she lives are at the root of the unique characteristics of every human being. They may be common or rare, ranging from a single change of letter in the DNA to the addition or deletion of a chromosome.

Some genetic variations (for example a mutation in a gene or a chromosomal abnormality) may impair the production of proteins. These genetic variations are known as pathogens.

The “construction plan” of the protein is altered, so to speak, leading to the absence or excess or abnormal production of this protein. The protein cannot therefore perform its role properly, which may cause a genetic disease.

The generally rare nature of pathogen variants explains why most genetic diseases are rare. The large number of genes in the genome (20,000) explains why the number of diseases is high (currently over 6,000 rare genetic diseases).

Nevertheless, the presence of a genetic variant in your genome does not always result in a disease, some may go unidentified or only be expressed depending on the environment in which you live. In this case, the presence of such a mutation is associated with a higher risk of developing a disease. Likewise, the disease can occur at different ages.

How does a genetic disease occur?

With only a few exceptions, genes are present in an individual as two copies, called alleles, which are not necessarily the same: an allele from the egg and an allele from sperm cells.

A pathogenic genetic variant may be passed from one generation to another and/or be present in several members of the same family of the same generation. The corresponding diseases are hereditary diseases.

Depending on the genetic mechanism, the disease is not transmitted in the same way. There are two main modes of transmission:

– A copy (allele), cause of the disease, inherited from one of the parents is sufficient for the disease to develop. This is known as dominant inheritance.

– A copy (allele) cause of the disease, must be inherited from both parents for the disease to develop. This is known as recessive inheritance.

The genetic variation that will cause it may occur accidentally, during the production of gametes (sperm, egg) or at an early stage after fertilisation. In this case, the person coming from these gametes or this fertilisation may carry the genetic abnormality in all their cells (including the reproductive cells) and the disease might affect any future descendants.

What is genome/exome sequencing?

The genetic testing that is proposed consists in reading your DNA: this is known as sequencing. It may concern all of the exons (whole exome) or DNA (whole genome). The aim is to identify the genetic variations which might explain your condition.

Sequencing output is in the form of a succession of the four letters that make up the DNA molecule, A, T, G and C. Although the reading of a whole exome or genome is possible today, its interpretation remains difficult and limited to current knowledge. The large volumes of data produced by these new technologies are analysed by means of powerful computing tools, combined with the expertise of bioinformaticians, genetic biologists and clinical geneticists. Given the large number of variants in every individual, the challenge in the case of a genetic disease lies in identifying the variant responsible for the disorder, which amounts to looking for a needle in a haystack. In order to facilitate this interpretation, it is often necessary to study the DNA of relatives and, more rarely, that of other members of the family.

What are the possible outcomes of genetic testing?

There are three possible types of results after genetic testing:

1. One or several genetic variants are identified, known as pathogens (commonly referred to as mutations), which might explain the disease.

2. One or several genetic variants are identified but the impact of these on the patient’s health is not clear. In this case, it may be useful to complete the analysis with other genetic tests, or even to continue them with other family members – which involves their consent.

3. No change which could explain the disease has yet been detected. In this situation, if the patient agrees, the data generated by the test will be stored and will be re-used in the context of the same diagnostic approach, depending on the development of scientific knowledge. In which case, the patient will be informed by his geneticist physician.

In any case, the result will be communicated by the physician. The patient’s physician or genetic counsellor will explain and talk about the results to guide the patient in the next steps of his medical procedure.

Furthermore, this test may in some cases lead to the unexpected finding, in the genome, of information which is not linked to the disease for which this sequencing was prescribed, concerning other conditions that might occur later in life, and for which preventive measures or a treatment are available. This information is of medical importance for the patient and the family members but is not the reason for the consultation.

Where appropriate, when the results are communicated, the physician will, with the patient’s consent, inform him/her of these findings. In no case should the physician disclose this information if it is not of the patient’s choosing.

A refusal has no consequence on care in the context of the pathology that led to this test being done.

Should the family be informed and how?

If it is discovered that the patient is a carrier of a genetic abnormality, other members of the patient’s family are also likely to be carriers.

Indeed, genetic heritage, inherited from parents, is partly shared by different members of the same family (brother, sister, cousin, uncle, aunt…).

If the consequences of this genetic alteration can be serious and are subject to measures of prevention or care, the law requires a patient to inform the members of his/her family, also called “the relatives”.

They can then consult a medical geneticist who will advise them on the possibility of carrying out a genetic test. The result of the test will lead to adapting the medical supervision of this person, if necessary.

It is the role of the prescribing physician or the genetic counsellor to define who, in the family, does or does not present a risk of being a carrier of a family genetic disease. This risk is evaluated taking into account the genetic alteration and the degree of relationship.

Who informs the family? Which family members?

If you are diagnosed with a hereditary genetic alteration that can be the cause of a serious condition (related or not to the disease for which you came to consult), for which there are preventive measures, including genetic counselling, or care, you can directly inform the relevant members of your family. If you do not wish to do it, you can ask a health professional to inform them for you.

If you choose to inform them yourself, your physician or your genetic counsellor can help you, for example with the aid of a document explaining the disease and the way it is inherited. If you feel you need support, a psychologist can also guide you through this process. Finally, the contact details of patient associations can be useful to discuss and benefit from their experience. Your physician will be able to guide you.

If you ask your physician to provide this information, he will send a letter to your family which will state neither your identity, nor the diagnosis of the disease, but which will recommend making an appointment for genetic counselling.

This solution, which helps some families, is not however the most suitable; it is better to foster family communication.

In France, if you refuse to have the information transmitted by yourself or by your physician, your civil responsibility might be engaged.

Indeed, family members concerned, not having been able to take steps to benefit from appropriate care, could claim damages.

In addition:

– You can ask not to know the results of your own test and to delegate to the health professional the transmission of information to other family members (this choice can be made when signing the consent form).   

– You can ask for the information to be transmitted anonymously.

– In the particular case where you have previously made a donation of gametes (sperm or eggs), the physician, if you allow him, will transmit this information to the head of the Centre of Medical Assistance for Procreation (which attributed your gametes to (an) infertile couple(s), to take the necessary steps for the children who might be born through this donation.

What is the possible future use for the biological samples and data from this test?

Biological samples

Thanks to the evolution of sequencing technologies, the quantity of biological material (number of cells) required to carry out the test is very small. Therefore, part of the sample taken (blood…) may still be available and can be reused. You can, through the consent form, accept or oppose this storage. By law, if you accept this sample can be reused:

– Either in the context of the same care procedure (use of another technique, confirmation of results: no further consent will be required.

  – Or in the context of research projects. This research may directly concern the pathology for which you came to consult, another pathology of genetic origin or other research. In this case, the researcher is obliged to inform you of his/her research project and to ensure you are not opposed to the use of your samples for this research.


Similarly, data from genetic testing (the sequence of your exome or your genome) are sensitive data for which specific legislation applies:

– In cases where the analysis of your sequence does not provide information about your disease, the data will be stored and will be re-analysed progressively in the light of other information concerning genes potentially involved. No further consent will be requested.

– As for biological samples, the data from sequencing may provide further knowledge  through research protocols, in particular for genetic research. If the researcher wants to use your data for his/her protocol, he/she should also inform you of the nature of the processing of your data and note your absence of objection to their use in this case.