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Scientists sequence the most complete human genome yet

Tom Hagler by Tom Hagler
01.04.2022
in Technology
Scientists sequence the most complete human genome yet
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A team of almost 100 scientists part of the Telomere-to-Telomere (T2T) Consortium has successfully sequenced the most complete human genome yet. If you’re thinking “Wait a minute — didn’t scientists produce the complete human genome sequence almost two decades ago?” Well, you wouldn’t be wrong. The Human Genome Project finished sequencing 92 percent of the human genome back in 2003, but the techniques available at the time left the remaining 8 percent out of reach until recent years. Thus, 200 million DNA bases remained a mystery for the longest time. 

In a series of papers published in Science, the T2T Consortium has reported how it managed to fill in almost all of the missing spots except for five, leaving only 10 million and the Y chromosome only vaguely understood. After the papers went out, the consortium’s scientists have revealed on Twitter that they have figured out the correct assembly for the Y chromosome and that they will publish another paper with the latest results.

Research lead Evan Eichler from the University of Washington likened sequencing a DNA to solving a jigsaw puzzle. Scientists have to break the DNA into small parts and then use sequencing machines to piece them together. Older tools could only sequence small sections of DNA at once, so it’s like solving those unnecessarily tough puzzles with tens of thousands of repetitive, almost identical pieces. Newer tools can sequence longer segments of DNA, which makes finding the correct sequence much more achievable.

To make the process less complicated, the team used a cell line from a failed pregnancy called a mole, wherein the sperm enters an egg that doesn’t have its own set of chromosomes. That means the team only had to sequence one set of DNA instead of two. Then, they used a technique called Oxford Nanopore to complete assemblies of centromeres, which are dense knobs in the middle of chromosomes. Oxford Nanopore has a relatively high error rate, however, making it less than ideal for sequencing sections with repetitive DNA. For those regions, the team used another technique called PacBio HiFi, which can sequence shorter sections with 99.9 percent accuracy. 

Eichler said the previously unknown genes include ones for immune response that help us survive plagues and viruses, genes that help predict a person’s response to drugs and genes responsible for making human brains larger than other primates’. “Having this complete information will allow us to better understand how we form as an individual organism and how we vary not just between other humans but other species,” Eichler said. 

The consortium’s work cost a few million dollars to achieve, but sequencing is getting cheaper and cheaper with new technologies. Adam Phillippy, another lead author for the studies, said the hope is for individual genome sequencing to cost as little as $1,000 within the next decade. That could make DNA sequencing a part of routine medical tests, which might help doctors create tailor-made treatments for individuals. 

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