Signaling a landmark milestone in health science, geneticists have unveiled the first complete human genome map. Over 3,500 new human genes have been identified, some of which likely encode information critical to a greater understanding of human development. The entirely-filled human DNA sequence may set the stage for new discoveries and life-improving innovations in human health, including in cancer and birth defect treatment.
The announcement was made on March 31, 2022, in a series of six papers in Science magazine by scientists who are members of the Telomere-to-Telomere Consortium (T2T). T2T, which describes itself as an “open, community-based effort to generate the first complete assembly of a human genome,” consists of scientists from all over the world who dedicated their work to the goal reached last month. Its name references the caps found at the ends of chromosomes, the molecules that carry genetic material.
The existing authoritative genome used by scientists is the product of the Human Genome Project, completed in 2003. Despite decades of effort, that large-scale research project was only able to map 92% of the human genome. The new announcement means that the previously missing 8% has been found using more recent advancements in DNA-sequencing technology. In particular, scientists now have a far better picture of the content of centromeres, the portions of chromosomes at the centers of the “X”-shaped molecules. The new research has also corrected thousands of errors in the original Human Genome map.
Much has changed in the research process since the end of the Human Genome Project almost twenty years ago. Costs have fallen sharply; Human Genome was three billion dollars in scope, but the new map only required a few million dollars to complete. The success is also the result of a pair of breakthroughs, one procedural and one technological.
Each human cell really contains two genomes, one from the mother and one from the father. A major difficulty with genome mapping efforts is the struggle to distinguish whether any given sequence is paternal or maternal. One T2T researcher named Karen Miga described it as “like having two identical puzzles that only vary slightly in the same box.” A clever solution took advantage of a rare kind of tumor – called a hydatidiform mole – that contains only two copies of the paternal genome. By sequencing from these cells, geneticists were able to greatly simplify the mapping process and bring a 100% mapped genome within reach.
Previous efforts were also hampered by limits in the capability of older sequencing machines. It wasn’t until new machines were developed at Oxford Nanopore Technologies and Pacific Biosciences of California that geneticists had the computational power necessary for the task.
Nevertheless, there are certain aspects of the map that remain imperfect. Like the sequence produced by the Human Genome Project, this genome is really an amalgamation of DNA from dozens of different humans rather than a single individual’s genetic code. That means that it can be regarded as falling short of being a true human genome, said geneticist Ting Wang of Washington University in St. Louis.
Yet he’s still optimistic about what this achievement means for human health. “Having a complete genome reference definitely improves biomedical studies.… It’s an extremely useful resource,” he said. Among the genes newly mapped are ones that have been linked to brain evolution and development, autism, immune responses, cancer, and cardiovascular disease.
Even with its founding goal completed, the Telomere-to-Telomere Consortium said that it would be moving on to a new initiative: the “pangenome project.” T2T said it will aim to construct complete genomes of 350 people from different ethnic and geographic backgrounds, addressing perceived homogeneity in existing genome maps.
As for using the full map to improve human health treatment and expand medical knowledge, the race is now on. Doing that will likely take years, but the full map is an exciting milestone, said Wendy Chung, a Columbia University geneticist, commenting that “It gets us to the starting line.”
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