Scientists reveal a more diverse human genome

More than 20 years after scientists first released a draft sequence of the human genome, the book of life has received a long overdue rewrite.

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

Unlike the previous reference – which was largely based on the DNA of a mixed-race man from Buffalo, with input from several dozen other individuals, mostly of European descent – the new “pangenome” contains nearly complete genetic sequences from 47 men and women of various origins, including African Americans, Caribbean Islanders, East Asians, West Africans, and South Americans.

The revamped genome map is a critical tool for scientists and clinicians seeking to identify genetic variations associated with disease. It also promises to deliver treatments that can benefit all people, regardless of their race, ethnicity or origin, researchers said.

“It’s been needed for a long time — and they’ve done it very well,” said Ewan Birney, a geneticist and deputy director-general of the European Molecular Biology Laboratory, who was not involved in the effort. “This will improve our fine-grained understanding of variation, and then that research will open up new opportunities for clinical applications.”

Powered by the latest DNA sequencing technology, the pan genome aggregates all 47 unique genomes into a single source, providing the most detailed picture yet of the code that powers our cells. Gaps in the earlier reference have now been filled, with nearly 120 million previously missing DNA letters added to the three billion letter code.

Gone is the idea of ​​a totemic strand of DNA that is six feet long when unrolled and stretched in a straight line. Now the rebooted reference resembles a corn maze, with alternate paths and byways that allow scientists to explore a wider range of the genetic diversity found in humans around the world.

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

“We’ve gone from having a really nice blueprint of the Chevy to now having blueprints of 47 representative cars from each of 47 different manufacturers,” he said.

Knowing what to do with this Kelley Blue Book of genomics will involve a steep learning curve. New analytics tools are needed. Coordinate systems need to be redefined. Widespread adoption will take time.

“There’s work to be done to make this user-friendly for the community,” said Heidi Rehm, chief genomics officer at Massachusetts General Hospital in Boston, who was not involved in the project.

But in due time, experts said, the pan genome will revolutionize genomic medicine.

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

The project’s architects are continuing to add more populations, aiming to include at least 350 high-quality genomes spanning most of global human diversity.

“We want to represent all branches of the human tree,” said Ira Hall, a geneticist who directs 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 Health System. If their preliminary DNA data appears to reflect certain underrepresented genetic backgrounds, those individuals will be invited to participate in the pangenome project.

However, some gaps will never be closed in the publicly available reference – by design.

Previous attempts to capture human genetic diversity often drew sequence data from marginalized populations without regard to their needs and preferences. Informed by those ethical missteps, pangenome coordinators are now working with Indigenous groups to develop formal policies around data ownership.

“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 was involved in the project.

In Australia, researchers are incorporating DNA sequences from various Aboriginal peoples into a similar repository that will be combined with the open-source pan genome, but kept behind a firewall. According to Hardip Patel of Australia’s National Center for Indigenous Genomics in Canberra, the scientists plan to consult with community leaders on whether and how to make the data accessible on demand.

Some Indigenous advocates want the pangenome project to move forward. Keolu Fox, a genomics scientist at the University of California, San Diego who is Native Hawaiian, has suggested training the next generation of Native scientists to have more of a say in the genomic data.

“It is finally time that we decentralize power and control and redistribute it to the communities themselves,” said Dr. Fox.