In 2003, the Human Genome Project ended with the generation of an essentially complete sequence of the human genome. The project took the practical approach of using the best-available technologies for sequencing DNA and pushing them to their absolute limits. In the end, it delivered a remarkably high-quality human genome sequence that was nearly complete, accounting for an estimated 92% of the human genome. At the time, there were no convincing prospects for efficiently filling in the remaining bits because the technologies for sequencing DNA at that time were clearly not up to the task. The remaining ~8% of the human genome proved to be particularly difficult to sequence because these regions contained highly repetitive DNA. Since the end of the Human Genome Project, more powerful technologies, such as long-read DNA sequencing methods and newer computational tools, aided researchers in sequencing the repeat-rich genomic regions.
These new tools were put to good use, and on April 1, 2022, the Telomere-to-Telomere (T2T) consortium published a collection of papers that report the first truly complete sequence of the human genome. The sequence — over 3 billion base pairs long across 23 chromosomes — is entirely gapless. The T2T consortium further used this newly completed genome sequence as a reference to discover over 2 million additional genomic variants. Such information is valuable for gaining a comprehensive view about how human genomes vary as well as for investigating how these newly discovered variants influence health and disease.
NHGRI played a pivotal part in the success of the T2T consortium’s work. Researchers funded through NHGRI’s Intramural and Extramural Research Programs contributed to the project, highlighting the relevance of the overall effort to the Institute’s mission.
With a now-available truly complete sequence of the human genome, researchers can effectively move forward to develop more expansive views of human genomic diversity. Such efforts will include developing a human genome reference that reflects the full range of global genomic diversity, such as the studies being performed by NHGRI’s Human Genome Reference Program.
The NHGRI Office of Communications has created multiple outreach pieces for the month of April that highlight the various ways in which research and trainee work contributed to the work of the T2T consortium. The “Fully Sequencing the Human Genome” video highlights several reasons why generating the remaining genome sequence was such an arduous task. A feature on NHGRI researcher Adam Phillippy reflects on his early life and career as well as the propelling factors that led to his instrumental work in the T2T consortium.
NHGRI’s official twitter account includes video clips and quotes from trainees and postdoctoral fellows, each discussing what they have learned from this effort and what it means to them for their careers. In the same vein, our Twitter account shares quotes from several Human Genome Project leaders discussing the significance of this accomplishment and what it means for the future of genomics. In our Ask Dr. Genome series, NHGRI director Eric Green, M.D., Ph.D., and T2T consortium co-chair Karen Miga, Ph.D., discuss the technology development that led to completing the human genome sequence. NHGRI’s featured content can also be viewed on the NIH Instagram account, which highlights the T2T consortium effort using entertaining graphics, videos, and memes.
