Human genome sequencing powers personalized, precision medicine

NIH funding has allowed scientists to see the DNA blueprints of human life—completely.

In 2022, the Telomere-to-Telomere Consortium, a group of NIH-funded scientists from research institutions around the world, including Johns Hopkins, achieved a monumental scientific breakthrough: They produced the first fully completed sequence of a human genome.

Our genome sequences play a major role in determining who we are. Contained in our chromosomes, they carry the instructions for our development. Variations in this code influence traits from our hair color to our height and are also one of the main sources of disease risks. Having a fuller picture of the human genome helps scientists better understand genetic risk factors that lead to illnesses like cancer.

A Johns Hopkins geneticist who's part of the T2T Consortium, Rajiv McCoy, explains the importance of this project: "A more complete view of variation within our genomes is foundational to advancing research on cancer, aging, and infertility, as well as countless other aspects of human health. In addition to applications for fundamental research, future clinical genetic tests will be able to target newly resolved regions of the genome, enabling more powerful and accurate approaches for precision medicine."

Sequencing the entire human genome has opened new avenues in genetic research. The T2T Consortium recently finished a complete assembly of a human Y chromosome and non-human ape genomes, and McCoy's lab is currently working to develop additional resources to make those assemblies more practically useful and accessible.

"The lessons and principles learned through these efforts are guiding numerous other genome assembly projects," McCoy says.

The NIH has enabled this research from the beginning, when it established the Office for Human Genome Research in 1988 (later elevated to the National Center for Human Genome Research in 1990 and then the National Human Genome Research Institute in 1997). The NHGRI's original purpose was to support the Human Genome Project, the precursor to the T2T Consortium that aimed to generate the first sequence of the human genome. In 2003, the Human Genome Project got as close to its goal as technology at the time would allow, producing a genome sequence that accounted for more than 90% of the human genome.

This project, as well as its continuation by the T2T Consortium, has made medicine more preventative and treatments more personalized. For example, by knowing which gene mutations cause certain cancers, doctors can identify patients who are at risk and recommend preventative strategies, while scientists can create drugs that target specific genes and proteins.

Advances beyond the initial Human Genome Project would not have been possible without NIH support. "This was a grassroots collaboration involving researchers at many different institutions with diverse and complementary expertise," McCoy says of the T2T Consortium. "The research is supported by numerous grants spanning several institutes of the NIH, with each grant supporting a different aspect of the project (as well as other projects). This funding model illustrates how broad and flexible NIH support enables impactful research in our current era of highly collaborative science."