April 6, 2022 – For the first time, the human genome has finally been mapped end-to-end, and the historic milestone has scientists celebrating.
“It’s genuinely a really big and exciting deal both in the genomic community as well in the broader scientific and medical community,” says Benjamin Solomon, MD, clinical director of the National Human Genome Research Institute.
More than 100 scientists have filled in the last 8% of missing human genetic information and published the findings in a series of six papers in the journal Science along with companion papers in other publications.
Solomon says his social media feed “has blown up” in recent days.
The papers announced that the investigators, part of an international consortium called Telomere-to-Telomere (T2T), named for the caps on the end of all chromosomes, had filled in the gaps of missing data and decoded previously unreadable information over the last 2 decades.
Back in 2003, researchers shared that the human genome had been sequenced as part of the Human Genome Project, but there were gaps in the treasure trove of information that were, at the time, impossible to access.
This missing 8% could unlock clues to such mysteries as how cells produce proteins, how people adapt to and survive infectious diseases, why cancers develop, how we metabolize drugs, and why human brains are bigger and better able to process information than those of apes and other species, the scientists say.
Understanding the Human Body
Many benefits will be realized much later, Solomon points out, but among the near-term improvements will be a clearer reference set for comparing gene defects.
He says it’s like playing the children’s game of finding slight differences in two pictures.
With the previous gaps in the genome, the reference set was harder to see clearly, with holes, blurry images, and coding in the wrong locations, so it was harder to understand what was genetically different in a particular patient’s case.
“There will be cases that we can resolve now that we couldn’t before because we have a better map of the reference set of the genome,” Solomon explains.
One of the leaders of the T2T work, Evan Eichler, PhD, a professor of genome sciences at the University of Washington in Seattle, says the missing 8% was made up of largely repetitive human DNA. Called deoxyribonucleic acid, these genetic instructions in some cases repeated thousands of times, making it too difficult for the sequencing technology at the time to untangle it.
New Technology Led to Discovery
Navigating the repetitive genetic information “was like being on a roundabout with no exits,” says Eichler, who was also part of the original Human Genome Project. With advances in the past 2 decades, technology can now sort out the repeating genetics and present the letters in longer, readable strings.
The human genome, with 23 pairs of chromosomes, has 3 billion base pairs, and the recovered 8% add 200 million new base pairs, which is essentially like adding one very large chromosome to scientific discovery, he says.
Among the things a completed map could help explain is a person’s risk for heart disease. Eichler says the new information could help specialists understand the gene called “lipoprotein (a).” Part of that gene is highly repetitive, he says, and those trying to sequence it before simply got lost.
“We haven’t been able to sequence that gene routinely for the last 2 decades largely because the tail end of it – the business end of the molecule – is made up of these long repeats,” he says. “Now we have our first complete copy,” which means scientists can ask questions and come up with tests for the connection between the gene and heart disease risk. “That’s a clear-cut example of where this information will be very, very valuable,” Eichler says.
