NIH To Provide Grants For Advancing The Reference Sequence Of Human Genome

By Benjamin Ross

October 4, 2019 | The National Human Genome Research Institute (NHGRI), as part of the National Institutes of Health (NIH), will be providing grants totaling approximately $29.5 million to various universities and institutes in order to generate and maintain the most comprehensive reference sequence of the human genome.

The NHGRI said in a statement that the grants come with the end goal being to fund two centers as a part of a new Human Genome Reference Program (HGRP).

The institute's first set of grants will provide $2.5 million per year for five years to Washington University in St. Louis (WashU), University of California, 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 Genome Reference Center. The center will deliver a next-generation reference sequence of the human genome as a resource for the scientific community and support interactions within the genomics community.

The NHGRI, by way of the Human Reference Genome Sequencing Center, will also provide approximately $3.5 million per year over five years to USCS, who, alongside both US and international collaborators, will aim to sequence up to 350 additional diverse human genomes using state-of-the-art technologies to incorporate high-quality sequences that are more broadly representative. Collaborators include Washington University in St Louis, University of Washington School of Medicine, The Rockefeller University, Mt. Sinai, Harvard University, Broad Institute, Coriell Institute for Medical Research, McGill University, University of Cambridge, and the Max Planck Institute.

According to the NHGRI, "The currently available reference sequence of the human genome is becoming obsolete." The funds are "necessary for making advances in DNA sequencing technology and computational methods possible."

Adam Felsenfeld, NHGRI program director in the Division of Genome Sciences, told Bio-IT World in an email exchange that these two awards were made, and that the applicants are deserving of them, due to the peer review process indicating an improvement in interpreting both research and patient genome sequences.

"I am happy to see that the investigators will be scientists that have previously been involved with the Genome Reference Consortium, together with investigators that are newer to this effort and who have appreciation and enthusiasm for the development a pangenome reference," says Felsenfeld.

A pangenome is the complete inventory of genes at a phylogenetic scale. Felsenfeld says the ideal pangenome reference would be an equally useful reference for any individual person's genome.

The additional 350 genomes play a key role when ensuring the accuracy of the pangenome, says Felsenfeld, by choosing samples from people who have diverse ancestry. While unable to predict how universally representative the pangenome will be with the inclusion of these genomes, he believes he will certainly be better than it is currently.

"As a part of this program, I believe that we need to develop better metrics for efficient progress towards a representative pangenome," Felsenfeld says. "This may help focus on ways that samples can be selected for a pangenome, e.g. based on a cheap initial survey of their actual genomic variation, rather than on geographical or ethnic ancestry. I am sure we will learn a lot in the process, including getting a better appreciation of how many genomes, and how diverse, need to be added to approach the ideal, as well as some basic lessons about human genetic variation."

Some of the samples for the genomes will be ones already available from the 1,000 Genomes sample set, Felsenfeld says. New samples will be obtained as part of the efforts of one of the funded grants.