With 100% of the human genome mapped, new genetic diagnostic and disease screening tests may soon be available for clinical laboratories and pathology groups

Utilizing technology developed by two different biotechnology/genetic sequencing companies, an international consortium of genetic scientists claim to have sequenced 100% of the entire human genome, “including the missing parts,” STAT reported. This will give clinical laboratories access to the complete 3.055 billion base pair (bp) sequence of the human genome.

Pacific Biosciences (PacBio) of Menlo Park, Calif., and Oxford Nanopore Technologies of Oxford Science Park, United Kingdom (UK), independently developed the technologies that aided the group of scientists, known collectively as the Telomere-to-Telomere (T2T) Consortium, in the complete mapping of the human genome.

If validated, this achievement could greatly impact future genetic research and genetic diagnostics development. That also will be true for precision medicine and disease-screening testing.

The T2T scientists presented their findings in a paper, titled, “The Complete Sequence of a Human Genome,” published in bioRxiv, an open-access biology preprint server hosted by Cold Spring Harbor Laboratory.

Completing the First “End-to-End” Genetic Sequencing

In June of 2000, the Human Genome Project (HGP) announced it had successfully created the first “working draft” of the human genome. But according to the National Human Genome Research Institute (NHGRI), the draft did not include 100% of the human genome. It “consists of overlapping fragments covering 97% of the human genome, of which sequence has already been assembled for approximately 85% of the genome,” an NHGRI press release noted.

“The original genome papers were carefully worded because they did not sequence every DNA molecule from one end to the other,” Ewan Birney, PhD, Deputy Director General of the European Molecular Biology Laboratory (EMBL) and Director of EMBL’s European Bioinformatics Institute (EMBL-EBI), told STAT. “What this group has done is show that they can do it end-to-end. That’s important for future research because it shows what is possible,” he added.

In their published paper, the T2T scientists wrote, “Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release.”

Tale of Two Genetic Sequencing Technologies

Humans have a total of 46 chromosomes in 23 pairs that represent tens of thousands of individual genes. Each individual gene consists of numbers of base pairs and there are billions of these base pairs within the human genome. In 2000, scientists estimated that humans have only 30,000 to 35,000 genes, but that number has since been reduced to just above 20,000 genes.

According to STAT, “The work was possible because the Oxford Nanopore and PacBio technologies do not cut the DNA up into tiny puzzle pieces.”

PacBio used HiFi sequencing, which is only a few years old and provides the benefits of both short and long reads. STAT noted that PacBio’s technology “uses lasers to examine the same sequence of DNA again and again, creating a readout that can be highly accurate.” According to the company’s website, “HiFi reads are produced by calling consensus from subreads generated by multiple passes of the enzyme around a circularized template. This results in a HiFi read that is both long and accurate.”

Oxford Nanopore uses electrical current in its sequencing devices. In this technology, strands of base pairs are pressed through a microscopic nanopore one molecule at a time. Those molecules are then zapped with electrical currents to enable scientists to determine what type of molecule they are and, in turn, identify the full strand.

The T2T Consortium acknowledge in their paper that they had trouble with approximately 0.3% of the genome, but that, though there may be a few errors, there are no gaps.

Karen Miga

“You’re just trying to dig into this final unknown of the human genome,” Karen Miga (above), Assistant Professor in the Biomolecular Engineering Department at the University of California, Santa Cruz (UCSC), Associate Director at the UCSC Genomics Institute, and lead author of the T2T Consortium study, told STAT. “It’s just never been done before and the reason it hasn’t been done before is because it’s hard.” (Photo copyright: University of California, Santa Cruz.)

Might New Precision Medicine Therapies Come from T2T Consortium’s Research?

The researchers claim in their paper that the number of known base pairs has grown from 2.92 billion to 3.05 billion and that the number of known genes has increased by 0.4%. Through their research, they also discovered 115 new genes that code for proteins.

The T2T Consortium scientists also noted that the genome they sequenced for their research did not come from a person but rather from a hydatidiform mole, a rare growth that occasionally forms on the inside of a women’s uterus. The hydatidiform occurs when a sperm fertilizes an egg that has no nucleus. As a result, the cells examined for the T2T study contained only 23 chromosomes instead of the full 46 found in most humans.

Although the T2T Consortium’s work is a huge leap forward in the study of the human genome, more research is needed. The consortium plans to publish its findings in a peer-reviewed medical journal. In addition, both PacBio and Oxford Nanopore plan to develop a way to sequence the entire 46 chromosome human genome in the future.

The future of genetic research and gene sequencing is to create technologies that will allow researchers to identify single nucleotide polymorphisms (SNPs) that contain longer strings of DNA. Because these SNPs in the human genome correlate with medical conditions and response to specific genetic therapies, advancing knowledge of the genome can ultimately provide beneficial insights that may lead to new genetic tests for medical diagnoses and help medical professionals determine the best, personalized therapies for individual patients.

—JP Schlingman

Related Information

Scientists Say They’ve Finally Sequenced the Entire Human Genome. Yes, All of It.

Researchers Claim They Have Sequenced the Entirety of the Human Genome—Including the Missing Parts

The Complete Sequence of a Human Genome

HiFi Reads for Highly Accurate Long-Read Sequencing

President Clinton Announces the Completion of the First Survey of the Entire Human Genome

Genome the Crowning Achievement of Medicine in 2000

International Human Genome Sequencing Consortium Announces “Working Draft” of Human Genome