Washington University School of Medicine in St. Louis will share with collaborating institutions $29.5 million from the National Institutes of Health (NIH) to improve the accuracy and diversity of the reference human genome sequence. The aim is to better reflect the spectrum of human diversity around the world and make the reference genome a more useful tool for researchers.
The new project continues the legacy of the university’s McDonnell Genome Institute, which played a major role in the original Human Genome Project, completed in 2002. The institute contributed 25% of the genetic data needed to spell out — in order — all 3.1 billion units of DNA that make up the human genome. Like the first human genome sequencing program, the new Human Pangenome Reference Sequencing Project is funded by the National Human Genome Research Institute (NHGRI) of the NIH.
“Having the reference human genome has really opened the door to personalized medicine,” said Ting Wang, the co-lead principal investigator of the new program and the Sanford C. and Karen P. Loewentheil Distinguished Professor of Medicine at Washington University. “But the original human genome is from a few volunteers. And for many parts of the reference genome, the sequence is from only one individual. The current reference sequence also has very limited diversity built into it.”
“The goal of this new round of sequencing for the human pangenome project is to incorporate human diversity,” said Wang, also a professor of genetics. “New technology allows us to sequence individual chromosomes from end to end, picking up portions of the sequence that were hard to capture with old methods. So, the new sequencing efforts will be more diverse and more complete as well.”
Said Ira M. Hall, co-lead principal investigator of the new program and an associate professor of medicine at Washington University: “The human reference genome is crucial for biomedical research and precision medicine, but the current version suffers from major limitations. This project is an exciting opportunity to improve the human reference by extending it to include a larger and more diverse set of individuals.”
Washington University and its collaborators will perform whole genome sequencing of 350 individuals from different racial and ethnic backgrounds and make that data available as a reference resource for the scientific community. Wang said the new reference genome will require new and innovative methods to present data, since representing the genomes of 350 people will require more than a linear string of DNA “letters.”
Washington University will lead a collaboration with the University of California at Santa Cruz and the European Bioinformatics Institute to form the WashU-UCSC-EBI Human Pangenome Reference Center. A second center focused on sequencing — the Human Pangenome Sequencing Center — will be led by the University of California at Santa Cruz and includes the McDonnell Genome Institute at Washington University, and the University of Washington in Seattle.
“The original reference human genome has been a vital scientific tool, but it’s incomplete,” said Lucinda Antonacci-Fulton, an instructor in genetics and director of operations at the McDonnell Genome Institute. “Rather than a single volume reference, these new sequencing efforts will create a diverse set of encyclopedias to form the human pangenome, a reference resource that will better reflect the diversity of human populations worldwide.”