Hidden DNAs Uncovered as Human Genome is Completely Sequenced

New information was recorded by scientists after finally piecing together the human genome's repetitive regions. These regions accounted for more than eight percent of the genome that was previously left undocumented more than 20 years ago when the first news of human genome sequencing came out.

The repetitive regions were previously found to repeat the same letters of the DNA over and over again which made it impossible for the scientists to assemble the chopped-up sequences in the correct order, thus leaving big gaps in the genomic picture. The idea of getting complete genome sequencing came up when scientists realized that they could sequence just one genome instead of two at a time. Most cells have two genomes, one from each parent. This makes it harder for researchers to conduct the sequencing since sequences from each parent mix together during assembly. But with only one genome to assemble, the task became easier than expected. This was accomplished by using a cell line with only one genome in it, which was a result of a rare glitch in normal development wherein the cells had two copies of the paternal DNA and none of the maternal DNA.

Advanced technology also played a role in the sequencing process. The scientists used a new Nanopore machine that can accurately read a million DNA letters to sequence the genome's hard parts, assemble them and analyze the results. They also used a new Pacific Biosciences machine that produced long-read sequencing reads that were more than 99 percent accurate. These enabled the scientists to fill in more gaps in the sequence.

To assemble the most difficult regions required human factors. Algorithms were found not to be able to handle the complex repetitions. The scientists then analyzed these repetitions by eye as seen on their computer screens. They were able to distinguish tangles among repetitive sequences which they eventually untangled to finally sequence every chromosome in the human DNA.

The scientists regard this event as an early phase of completing variations in hundreds of thousands of other genomes in the future to create a more complete human genome as possible that can represent much more of human diversity.

Learn more about completing the human genome sequence in the full study published by Science and a report from AAAS.