DNA: Renewed version of the human genome is published – 05/10/2023 – Science

More than 20 years after scientists first released a draft sequence of the human genome, the book of life is undergoing a much-needed revision.

A more accurate and inclusive edition of our genetic code was published today, marking an important step toward a deeper understanding of human biology and personalized medicine for people from a wide variety of racial and ethnic backgrounds.

Unlike the previous reference —which was largely based on the DNA of a mixed-race male from Buffalo, New York, with contributions from a few dozen other individuals, mostly of European descent—, the new “pangenome” incorporates nearly complete genetic sequences from 47 males. and women from diverse backgrounds, including African Americans, Caribbeans, South Americans, East Asians and West Africans.

The renewed genome map represents a crucial tool for scientists and clinicians who wish to identify genetic variations associated with disease. It also promises to offer treatments that can benefit all people, regardless of their race, ethnicity or ancestry, researchers said.

“This has been needed for a long time – and they’ve done a very good job,” said Ewan Birney, a geneticist and deputy director general of the European Molecular Biology Laboratory, who was not involved in the effort. “It will improve our fine-grained understanding of variations, and this research will open up new opportunities for clinical applications.”

Powered by the latest DNA sequencing technology, the pangenome bundles all 47 unique genomes into a single resource, providing the most detailed picture of the code that powers our cells. The gaps in the previous reference are now filled in, with nearly 120 million previously lost DNA letters added to the 3 billion letter code.

Gone is the idea of ​​a totemic strand of DNA that stretches six feet when uncoiled and stretched straight. The revamped reference resembles a maze in a cornfield, with alternate paths and side trails that allow scientists to explore a wider range of genetic diversity found in people around the world.

Dr. Eric Green, director of the National Human Genome Research Institute, the government agency that funded the work, compares the pangenome to a new kind of manual for auto repair shops. Whereas before each mechanic only had the specifications for one type of car, now there is a master plan that spans different makes and models.

“We’ve gone from having a really good Chevy design to now having designs for 47 representative cars from 47 different manufacturers,” he said.

In due time, experts said, the pangenome will revolutionize the field of genomic medicine.

“We’ll have the benefit of really understanding ourselves a lot better as a species,” said Evan Eichler, a genome scientist at the University of Washington. Eichler was among more than 100 scientists and bioethicists who described the new pangenome reference in the journal Nature.

Project architects continue to add population groups, with the goal of including at least 350 high-quality genomes that span most of global human diversity.

“We want to represent every branch of the human tree,” said Ira Hall, a geneticist who leads the Yale Center for Genomic Health.

Some of the new genomes will come from New Yorkers who previously participated in a research program at the Mount Sinai hospital network. If their preliminary DNA data appears to reflect certain underrepresented genetic backgrounds, these individuals will be invited to participate in the pangenome project.

Some gaps may never be filled in the available reference – as envisaged in the design.

Previous attempts to capture human genetic diversity often extracted sequence data from marginalized populations without taking into account their needs and preferences. Informed by these ethical missteps, pangenome coordinators are now collaborating with indigenous groups to develop formal data ownership policies.

“We’re still grappling with the issue of native and tribal sovereignty,” said Barbara Koenig, a bioethicist at the University of California San Francisco who participated in the project.