CNN's March 31, 2022 article Scientists sequence the complete human genome for the first time says:
In 2003, the Human Genome Project made history when it sequenced 92% of the human genome. But for nearly two decades since, scientists have struggled to decipher the remaining 8%. Now, a team of nearly 100 scientists from the Telomere-to-Telomere (T2T) Consortium has unveiled the complete human genome -- the first time it's been sequenced in its entirety, the researchers say.
The research, published in the journal Science on Thursday, was previously in preprint, allowing other teams to use the sequence in their own studies.
Until now, it was unclear what these unknown genes coded.
"It turns out that these genes are incredibly important for adaptation," Eichler1 said. "They contain immune response genes that help us to adapt and survive infections and plagues and viruses. They contain genes that are ... very important in terms of predicting drug response."
Eichler also said that some of the recently uncovered genes are even responsible for making human brains larger than those of other primates, providing insight into what makes humans unique.
This remaining 8% of the human genome had stumped scientists for years because of its complexities. For one thing, it contained DNA regions with several repetitions, which made it challenging to string the DNA together in the correct order using previous sequencing methods.
The researchers relied on two DNA sequencing technologies that emerged over the past decade to bring this project to fruition: the Oxford Nanopore DNA sequencing method, which can sequence up to 1 million DNA letters at once but with some mistakes, and the PacBio HiFi DNA sequencing method, which can read 20,000 letters with 99.9% accuracy.
CNN's explanation is helpful as far as it goes, but with Nanopore's error rate of 1% to 3% (1, 2) and the difference between the repeats of some repeated sequences presumably a lot less than that, how was the error-prone Nanopore method combined with the HiFi method to nail the last 8% of the human genome accurately despite the repeated sequence challenges?
Question: What were the challenges to sequencing the last 8% of the human genome that took 20 years to overcome and how was this done? (T2T Consortium)
A premise of the question post is that it was the presence of repetitive sequences that posed the primary challenge, but the CNN article says "...because of its complexities. For one thing, it contained DNA regions with several repetitions..." which suggests there are other important factors as well.
Update: From the March 31, 2022 item in Science Most complete human genome yet reveals previously indecipherable DNA:
In six papers in Science, the Telomere-to-Telomere (T2T) Consortium—named for the chromosomes’ end caps—fills in all but five of the hundreds of remaining problem spots, leaving just 10 million bases and the Y chromosome only roughly known. And today, the T2T consortium announced in a tweet it had deposited a correct sequence assembly of the missing Y.
I think that of the six, the main paper is The complete sequence of a human genome
1Evan Eichler, a Howard Hughes Medical Institute investigator at the University of Washington and the research leader, said Thursday.