The First Human Pangenome: A New Reference For Genomics

Thursday - May 11 2023, 10:50 UTC - 1 year ago

The Human Pangenome Reference Consortium, comprising of UCSC professors and students, have released a draft of the first ever human pangenome—which combines data from 47 diverse DNA sources—to provide a more accurate understanding of worldwide genomic diversity. This new pangenome adds 119 million DNA bases to the existing reference genome, increasing the detection of variants in the human genome, making it more accurate, complete and usable. The project will continue until 2024, when a final pangenome with genomic information from 350 individuals is planned for release.

University of California, Santa Cruz scientists, along with a consortium of researchers, have released a draft of the first human pangenome—a new, usable reference for genomics that combines the genetic material of 47 individuals from different ancestral backgrounds to allow for a deeper, more accurate understanding of worldwide genomic diversity.

Insert .

By adding 119 million bases—the "letters" in DNA sequences—to the existing genomics reference, the pangenome provides a representation of human genetic diversity that was not possible with a single reference genome. It is highly accurate, more complete and dramatically increases the detection of variants in the human genome, as shown in a collection of groundbreaking papers published today (May 10, 2023) in the journals Nature, Genome Research, Nature Biotechnology, and Nature Methods.

The pangenome was produced by the Human Pangenome Reference Consortium (HPRC), which is co-led by UCSC’s Associate Professor of Biomolecular Engineering Benedict Paten and Assistant Professor of Biomolecular Engineering Karen Miga and is now available for use in an assembly hub on the UCSC Genome Browser. More than a dozen UCSC researchers and students are contributors to this project, which will continue into 2024 when the researchers plan to release a final pangenome with genomic information from 350 individuals."We are introducing more diversity and equity into the reference by sampling diverse human beings and including them in this structure that everyone can use," said Paten, who is the senior author on the main marker paper. "One genome isn’t enough to represent everybody—the pangenome will ultimately be something that is inclusive and representative."Insert .

Each person’s genome varies slightly—by about 0.4 percent compared to the next person, on average—and understanding these differences can provide insight into their health, help to diagnose disease, predict medical outcomes, and guide treatments. Using the pangenome reference will improve scientists’ ability to detect and understand variation in future studies.Typically when scientists and clinicians study an individual’s genome to look for variation, they compare that individuals’ DNA to that of a standard reference to determine where there are differences of one or more base pairs. Until now, the reference genome has primarily been represented by a single sequence for each human chromosome, mostly sourced from one individual. But, this reference is nearly 20 years old and fundamentally limited in that it can not represent the wealth of genetic variations present in the human population.