Has published the most complete sequence of the human genome

Six simultaneous scientific articles published this Thursday in the journal Science confirm the publication of the most complete version of the human genome: a set of genetic material that distinguishes Homo sapiens from mouse or mosquito. The announcement came two decades after the Human Genome Project reached its first draft Chemical alphabet What makes up our genetic material? Genes are segments of DNA – the acid that contains the basic units of genetic inheritance – and contain information about the specific characteristics of living organisms, their functioning and development.

“These parts of the human genome, which we have not been able to study for more than 20 years, are important for understanding genome function, genetic disease, human diversity and evolution,” said Karen Miga, an associate professor of engineering. Biomolecular at the University of California, Santa Cruz, and one of the leaders in this project, which is now culminating.

In 2000, the revelation that what was really nothing more than a human genome project became a political event. The satellite broadcast, which was attended by then-US President Bill Clinton and British Prime Minister Tony Blair, was full of bombastic phrases that day, in late June. “We are learning the language in which God created life,” Clinton continued.

At the time, the scientific baton was shared by geneticist Francis Collins and biologist Craig Venter (first from the public sector, second from his company Celera), who even then warned of the preliminary nature of the results and the enormous task. That was ahead. Another battery in July 2021 Documents Scientists have announced this improved version of the monumental project, the results of which are public today. Researchers around the world will finally be able to study 8% of the genome that has yet to be deciphered.

3 billion DNA base

The famous “double helix” of DNA consists of two strands of the base – a kind Chemical letters It is held in place by hydrogen bonds – which spin to form chromosome arms, X-shaped strands located in the nucleus of cells. The human genome consists of approximately 3 billion base pairs of DNA. Researchers’ press releases state that a more complete and unambiguous sequence of genomes is needed to understand “the full range of variation in the human genome and the genetic conditioning of certain diseases.”

The work was carried out by the Telomere to Telomere (T2T) consortium formed in 2019, among others, by members of the National Human Genome Research Institute (NHGRI), which in turn is part of the U.S. National Institutes of Health; The aforementioned University of California, Santa Cruz and University of Washington, Seattle. NHGRI funded most of the project.

Two thousand genes are to be studied

A new reference genome called T2T-CHM13 adds nearly 200 million base pairs of new DNA sequences, including 99 genes that “probably” encode proteins and nearly 2,000 genes that still need further study. It also corrects thousands of structural errors in an earlier reference sequence.

Defects covered by the new sequence include all the short arms of the five human chromosomes and cover some of the most complex regions of the genome. These include reproducible DNA sequences found in important chromosomal structures, such as telomeres (the ends of chromosomes) and centromers (the chromosome narrowing that separates the short arm from the long arm) that coordinate the division of multiplicative chromosomes.

The new sequence also reveals duplication of previously identified segments, often because technology available at the time was unable to do so. These are long strands of DNA that are duplicated and play an important role in both the evolution and development of the disease. The researchers say that many of the newly identified regions have important functions in the genome, even though they do not contain active genes.

“It has a great advantage to see the whole genome as a whole system. It gives us the position to understand how this system works. “

David Hausler
– Director of the Institute of Genomics, University of Santa Cruz, California

“There is a great advantage to seeing the whole genome as a complete system. “It gives us an idea of ​​how this system works.” “We gained a huge understanding of human biology and disease with about 90% of the human genome, but there were many important aspects that remained hidden, beyond the view of science, because we did not have the technology to read these parts. Genome. “Now we can stand on the top of a mountain and look at the whole landscape below and get a complete picture of our human genetic heritage.”

The new T2T reference genome will complement the standard human reference genome known as the Genome Reference Consortium build 38 (GRCh38), which originated from a publicly funded human genome project and has been constantly updated since its first design in 2000 (announced by Clinton and Blair).

Pangenomics: A New Purpose

“We’re adding a second complete genome and then there will be more,” Hausler explains. “The next step is to think that the reference to the human genome is not a single genomic sequence. “It’s a deep transition, a precursor to a new era in which we will finally embrace human diversity impartially.”

The T2T Consortium has now joined the Human Pangenome Reference Consortium, which aims to create a new “Human Pangenome Reference” based on the complete sequence of the genomes of 350 individuals. The pan-genome is a combination of all the genes of a species, both what all individuals have in common and what is different from each other.

“Pangenomics is about recording the diversity of the human population and also ensuring that we get the whole genome adequately,” said Benedict Patten, associate professor of biomolecular engineering at the University of California, co-author and leader of T2T. On the Pangenomics project. “If we do not have a map of these difficult sequence regions of the genome in many individuals, we will miss out on the many variations in our population.”