NIH funds new centers to expand and diversify the human reference genome

The UC Santa Cruz Genomics Institute will play a leading role in the ambitious new Human Pangenome Reference Sequence Project

Tim Stephens | UCSC | Sep 24, 2019

New grants from the National Institutes of Health (NIH) totaling approximately $29.5 million will enable scientists at the University of California, Santa Cruz, and other collaborating institutions to generate and maintain a completely new and comprehensive reference sequence of the human genome that represents human genetic diversity.

The first human genome sequence, produced by the international Human Genome Project in 2000, was a landmark achievement that gave rise to the burgeoning field of genomic medicine. Improved and annotated over the years, that genome sequence (based mostly on one person’s genome) has been an essential reference for making sense of new genomic data. But the current reference genome is still an incomplete sequence and woefully inadequate as a representation of human diversity and genetic variation.

The new project will address those shortcomings by creating a new “human pangenome reference” based on the complete genome sequences of 350 individuals. The project will be carried out by two new centers funded by the National Human Genome Research Institute (NHGRI), part of the NIH.

“One human genome cannot represent all of humanity. The human pangenome reference will be a key step forward for biomedical research and personalized medicine. Not only will we have 350 genomes representing human diversity, they will be vastly higher quality than previous genome sequences,” said David Haussler, professor of biomolecular engineering at UC Santa Cruz and director of the UC Santa Cruz Genomics Institute.

“It has grown more and more important to have a high-quality, highly usable human genome reference sequence that represents the diversity of human populations,” said Adam Felsenfeld, NHGRI program director in the Division of Genome Sciences. “The proposed improvements will serve the growing basic and clinical genomics research communities by helping them interpret both research and patient genome sequences.”

The two centers—a sequencing center and a reference center—are funded by separate grants. NHGRI has awarded approximately $3.5 million per year over a five-year period to UC Santa Cruz, with major collaborators including the University of Washington in Seattle, Washington University in St. Louis, and Rockefeller University in New York, to form the Human Pangenome Sequencing Center, which will aim to sequence up to 350 diverse human genomes using state-of-the-art technologies to incorporate high-quality sequences that are more broadly representative.

Karen Miga directs the Data Production Center at UCSC for the Human Pangenome Project and is the co-lead of the Telomere-to-Telomere consortium (T2T). Her career has focused on closing the largest, most repetitive gaps that remain in human reference genomes.

NHGRI also awarded $2.5 million per year for five years to three institutions—Washington University in St. Louis (WashU), UC Santa Cruz (UCSC), and the European Bioinformatics Institute (EBI), which will coordinate with the National Center for Biotechnology Information—to form the WashU-UCSC-EBI Human Pangenome Reference Center. The center will provide a next-generation reference sequence of the human genome as a resource for the scientific community.

Human Pangenome Project

Together, these grants initiate a new Human Pangenome Reference Sequence Project, or “Human Pangenome Project.”

Haussler said the project will push the capabilities of current DNA sequencing technology well beyond what has been attempted before. Directing the sequencing center will be Karen Miga, a research scientist at UCSC who co-led a team with Adam Phillippy (NHGRI) that recently achieved the first complete sequence of a human chromosome. This “telomere-to-telomere” assembly (telomeres are the very tips of the chromosomes) of a complete human X chromosome, posted on the bioRxiv server in August, shows that complete chromosome sequences with no gaps are possible using current technologies.

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