In 2003, the Human Genome Project made history by sequencing 92% of the human genome. But for nearly two decades since then, scientists have struggled to figure out the remaining 8%. Now, a team of nearly 100 scientists from the Telomere-to-Telomere (T2T) Consortium has succeeded in revealing the entire human genome, the first time it has been fully sequenced, according to the researchers.
“Having this complete information will allow us to better understand how we come together as an individual organism and how we vary not only among other humans but among other species,” Evan Eichler, a Howard Hughes Medical Institute investigator at the University of Washington and leader of the study, said Thursday. the investigation.
The new research introduces 400 million letters into previously sequenced DNA, that is, the value of an entire chromosome. The complete genome will allow scientists to analyze how DNA differs between people and whether these genetic variations play a role in disease.
The research, published Thursday in the journal Science, was previously in preprint, allowing other teams to use the sequence in their own studies.
Until now, it was unclear what these unknown genes encoded.
“It turns out that these genes are incredibly important for adaptation,” Eichner said. “They contain immune response genes that help us adapt to and survive infections, plagues and viruses. They contain genes that are … very important in predicting drug response.”
Eichner also said that some of the newly discovered genes are even responsible for human brains being larger than those of other primates, providing insight into what makes humans unique.
The importance of decoding and understanding the human genomeThe remaining 8% of the human genome had left scientists speechless for years due to its complexity. For one thing, it contained regions of DNA with multiple repeats, making it difficult to chain the DNA in the correct order according to previous sequencing methods.
The researchers relied on two DNA sequencing technologies that had emerged in the last decade to carry out this project: the Oxford Nanopore DNA sequencing method, which can sequence up to a million DNA letters at a time but with some errors, and the PacBio HiFi DNA sequencing method, which can read up to 20,000 letters with 99.9% accuracy.
Sequencing DNA is like solving a puzzle, Eichner said. Scientists must first break DNA into smaller parts and then use sequencing machines to put them together in the correct order. Previous sequencing tools could only sequence small sections of DNA at a time.
With a 10,000-piece puzzle, it’s difficult to correctly order small puzzle pieces when they look alike, just as it is to sequence small sections of repetitive DNA. Instead, with a 500-piece puzzle it’s much easier to sort out the larger pieces or, in this case, longer segments of DNA.
A second challenge was finding cells with a single genome.
Standard human cells contain two sets of DNA, one maternal and one paternal copy, but this team used DNA from a group of cells called the complete hydatidiform mole, which contains a duplicate of the paternal DNA set. Complete hydatidiform mole is a rare complication of pregnancy caused by abnormal growth of cells that originate in the placenta.
This approach simplifies the genome so that scientists need to sequence only one set rather than two sets of DNA.
Because the research team used a duplicate set of DNA, the scientists were unable to sequence the Y chromosome originally. According to the lead author of the study, Adam Phillippy, the team has succeeded in sequencing the Y chromosome using a different set of cells.
A complete set of 24 sequenced chromosomes is available from the University of Santa Cruz Genome Browser.
Cracking this gapless sequence comes at a high price. Phillippy, who is also head of the genetic informatics section of the National Human Genome Research Institute, said that, in total, the project cost a few million dollars or more. But that’s a fraction of the nearly $450 million it cost the Human Genome Project to achieve its final sequence in 2003. And with new technology, sequencing is only becoming more accessible.
For now, genome sequencing is too expensive and time-consuming for everyone. But research is being done using this genome to identify whether certain genetic differences are linked to specific cancers. Knowing about genetic variations could also allow doctors to better tailor treatments, said Michael Schatz, another investigator on the team and a professor of computation and biology at Johns Hopkins University.
Phillippy says he hopes that within the next 10 years, sequencing the genome of individuals could become a routine medical test costing less than $1,000. His team continues to work towards that goal.
Charles Rotimi, scientific director of the National Human Genome Research Institute, said in a statement that this scientific achievement “brings us closer to individualized medicine for all humanity.” Rotimi was not involved in the investigation.