The human genome is now complete

A person's genome contains all of their genetic material carried by the DNA located on the 23 pairs of chromosomes.

A complete, “gap-free” sequence of the human genome has been published by the Telomere to Telomere (T2T) consortium associated with the United States Human Genome Research Institute.

This breakthrough is the subject of six articles published in the magazine Science and a handful of others, published in specialized journals.

The announcement comes nearly 20 years after the announcement of the completion of the first draft of the human genome on April 14, 2003.

At the time, the Human Genome Project was the culmination of a decade of work involving dozens of scientists from six countries and with a budget of around $3 billion. It had made it possible to map around 92% of the genome.

• A person's genome contains all of their genetic material carried by the DNA located on the 23 pairs of inherited chromosomes of his biological parents.
• It can be compared to a 23-chapter instruction book formulating a person's distinctive traits and allowing their body to function properly.
• Genetic material is present in every cell of a person . Thus, the nucleus of each human cell contains between 20,000 and 25,000 sentences (genes) and more than 6 billion letters (these are the letters A, C, G, and T).
• Each cell reads the genes that concern it. For example, a skin cell reads information about skin texture and amount of hair, but does not read instructions about eyes or heart.

The sequencing announced Thursday is equivalent to the 8% that remained to be mapped. It comes to complete the work announced in 2003, but also all the research efforts carried out in the last two decades and which have benefited from new decryption techniques making the sequencing work much less laborious and much more precise.

This percentage mainly corresponds to "holes" in sequences related to the fact that the technology of the time was unable to complete the puzzle at more difficult places in the chromosomes which include areas of DNA sequence repetitions, says Stéphanie Lord-Fontaine, vice-president scientific affairs at Génome Québec.

Thanks to new technologies, researchers have been able to make the genome close to the centromere, the middle of the chromosome, and in the telomeres at the end of the chromosome, notes Stéphanie Lord-Fontaine.

All of these technological breakthroughs have also improved sequencing on a much more practical level. Sequencing a complete human genome today costs $1,000 and can take a few days, she explains.

Having the complete telomere-to-telomere sequence allows us to see the regions that correspond to "dark matter" of the genome that remained hidden. These regions harbor complex DNA variations that hold clues to diseases we've long sought but haven't yet found the answers to, enthused Adam Phillippy, co-chair of T2T, during a press conference marking the announcement.

Specifically, the ability to read larger chunks of DNA sequences has uncovered more than 2 million additional mutations in the human genome.

< p>“We thought there was no relevant information in these areas, but they are actually linked to about 600 genes that would be medically relevant. »

—Stephanie Lord-Fontaine

One of the researchers who participated in the work revives the literary comparison. In the great manuscript of life, we have access to chapters that have never been read before, said Evan Eichler, a physician at the University of California, Santa Cruz.

The work done since the first draft has created a reference sequence of the human genome used by geneticists around the world.

This international standard has, for example , led to several discoveries, particularly in the understanding of rare diseases. It has since been updated a few times.

We can now diagnose thousands of rare diseases that are caused by genetic mutations. In the case of cancer, we realize that we can predict the response to treatment based on the mutations present in the tumors of patients, says Stéphanie Lord-Fontaine.

“We know a lot more about hereditary cancers, such as breast cancer caused by mutations in the BRCA genes. We are even able to sequence tumors and predict the drugs that will be active against certain mutations. »

— Stéphanie Lord-Fontaine

Personalized medicine will be increasingly present in clinical practice in the coming decades.

In light of this announcement, the GRCh38 reference genome used since 2019 is obsolete and will be replaced by a new version based on the completed version.

Several research teams have already started to use a preliminary version of the complete human genome sequence in their research.

This sequence has already led to a better understanding of genome biology, and I look forward to the next decade of discoveries on these newly revealed regions, explained Dr. Karen Miga, also co-chair of the T2T consortium.

< p class="e-p">The new version will be particularly valuable for studying all of human genomic variation, that is, differences between the DNAs of individuals. It will also make it possible to continue and refine the work initiated with the help of previous versions in the field of personalized medicine.

In the not-too-distant future, sequencing a person's genome may provide their genetic portrait and be used in routine clinical care. His doctor will thus be able to adjust his medical interventions according to his information.

Be able to choose the right drug for the right patient at the right time; predict the genetic risks of diseases; predict the response to certain drugs in relation to the metabolism of patients. There is a wide range of applications that can be envisaged, says Ms. Lord-Fontaine.

Ms. Lord is also pleased with the inclusion of personalized medicine and the presence of the term genomics in the Plan to implement the necessary changes in health presented by Christian Dubé, the Minister of Health and Social Services of Quebec. The word genomics appears on page 69. This is a first! It's coming, don't give up.

Génome Québec is currently working to create a Québec reference genome. We have started sequencing a cohort of 2,000 participants as part of the CARTaGENE project, says Ms. Lord-Fontaine.

CARTaGENE is a public research platform made up of both ;biological samples and data on the health and lifestyle of 43,000 Quebecers aged 40 to 69.

The objective is to create a Quebec reference genome which will contain a catalog of genetic variations which will be very useful for interpreting the different mutations present in the population.

A genome is very complex. Clinicians need to have a reference genome for a given population to have an accurate mapping. We can use this map in the diagnosis of patients, concludes Stéphanie Lord-Fontaine.