Human Genome Sequencing

Scientists complete the sequencing of human genome, say 'The future has arrived'


University of Washington
This image made available by the National Human Genome Research Institute shows the output from a DNA sequencer. (AP via WA Today)

A critical aspect went mostly missed during the celebrations of the human genome's mapping two decades ago: the job wasn't done. Historically, only approximately 92 percent of the nearly 3 billion letters that make up the human genome have been sequenced.

Scientists had exhausted all possibilities with the available technology, and shortly after the turn of the century, they presented their final map. However, portions of the genome remained cryptic, with repeated letters that continued indefinitely, like a needle skipping on a scratched record album. The task of mapping those sections was deferred to a future era when new technologies would complete the job.

That future has come to pass. The Telomere-to-Telomere consortium, a massive collaboration of researchers from government, academia, and corporate organizations, published the first complete, "gapless" human genome in Science.

"Hallelujah, we have finally completed one human genome," Evan Eichler, a geneticist at the University of Washington and one of the project's organizers, said during a news briefing on Thursday, US time.

Additional articles in Science, Nature, and Genome Research expounded on the significance of the milestone and its possible uses.

"If there is one blueprint on this planet that we should know from beginning to end, it is that of humans," said Eric Green, head of the National Human Genome Research Institute.

The accomplishment expands researchers' horizons and may have practical implications in personalized medicine. According to scientists, the newly sequenced regions of the genome contain genes involved in developing several disorders.

The complete human genome will serve as a reference for genetic differences observed in humans, especially when more genomes from varied populations worldwide are fully sequenced and added to the library of blueprints. This will also aid in our understanding of the tree of life, as many species of plants and animals have genomic regions similar to those of the human genome that are difficult to map, according to Karen Miga, a geneticist at the University of California, Santa Cruz and co-founder of the T2T consortium.

Additionally, these newly mapped portions – representing the previously unmapped 8% of the genome – may shed light on the causes of aging, Miga said.

"There are these enormous and persistent gaps in our genome that have existed for decades and represent critically important regions of our genome," she explained. "Without these regions, there would be no life as we know it."

The researchers do not assert that this is "the" human genome and it is, in fact, "a" human genome. This naturally raises the question of whose genome it is, where the story becomes tricky. It is not the genome of a single individual.

Each individual has two copies of their chromosomes, one from each parent. However, this research used a cell line developed decades ago from a rare sort of tumor called a "complete hydatidiform mole" that arose after a single sperm and an ovum fused but lacked the woman's DNA due to a biological quirk. The donors are unknown, according to the NIH.

"This is a one-of-a-kind cell line that represents no person who has ever lived," said Adam Phillippy, a consortium co-founder and head of the National Human Genome Research Institute's Genome Informatics Section.

Green, the NIH officer, previously worked on the earlier Human Genome Project, the decade-long US government project that found itself in a head-to-head competition with a commercial company, Celera Genomics, led by J Craig Ventre, around the turn of the century. The race concluded in a truce, with both teams releasing their initial sequences in February 2001 in the journals Science and Nature, followed by more exact versions two years later.

However, the genome remained incomplete. These were sections that were so redundant that mapping them was difficult. The same letters would repeatedly emerge in exquisite detail. The repetitive areas resembled featureless jigsaw puzzle pieces - similar to a puzzle section depicting the only blue sky. What transpired? The scientists agreed that they would complete the jigsaw puzzle's sky section later.

Several of the gaps were on telomeres, the caps at the ends of chromosomes that have been likened to the aglets on shoelaces. There were also holes on centromeres, a restricted portion of the chromosome that connects two arms.

"There were sections of the human genome that contained DNA that was so repetitive, so rugged, and so difficult to sequence that any of the methods available at the time choked and failed," Green explained.

The enhanced map was enabled by developing new technology for reading huge genome segments. To return to the jigsaw puzzle analogy, larger pieces make the problem easier to assemble.

Additionally, these technologies improved the sequencing's precision. If these techniques could be made more affordable, the researchers added, it would enable clinicians to identify patients more precisely at the genetic level, a significant step forward in "individualized medicine."

Deanna Church, a genome scientist at Inscripta who was not involved in the new research, believes that this sequencing accomplishment is the beginning of a new age in genome analysis.

"We want genomes from a diverse range of people from around the world," Church explained.

Publish : 2022-04-01 08:42:00

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