The first draft of a human “pangenome,” mapping out the different DNA variations in our genes, has been published. The new release builds on the existing human reference genome by adding over 1,000 new gene mutations and almost 120 million base pairs, providing an invaluable resource for future genetic research.
In 2001, the Human Genome Project published the first draft of its human reference genome, with updates adding more detail in the years since until it reached its current version, known as GRCh38. It wasn’t until 2022 that a complete human genome was published, but even that doesn’t tell the whole story.
“Everyone has a unique genome, so using a single reference genome sequence for every person can lead to inequities in genomic analyses,” said Adam Phillippy, a co-author of the new study. “For example, predicting a genetic disease might not work as well for someone whose genome is more different from the reference genome.”
To counter that, a group called the Human Pangenome Reference Consortium is working towards building a more comprehensive atlas of human genetic variety, known as a pangenome, and the first draft has now been published.
This preliminary pass of a pangenome was assembled from DNA from 47 people of a diverse range of ancestries. Compared to the current main reference human genome, it adds 119 million base pairs, and 1,115 new gene duplication mutations, providing multiple options for the same stretch of DNA.
“By using the pangenome reference, we can more accurately identify larger genomic variants called structural variants,” said Mobin Asri, co-first author of the study. “We are able to find variants that were not identified using previous methods that depend on linear reference sequences.”
These structural variants can extend as long as several thousand bases, and play key roles in an individual’s genes, including their risks of diseases. But identifying them has been hard to do with just one main reference genome. Using this pangenome draft has already allowed scientists to more than double the number of structural variants as identified in GRCh38.
And of course, this is just the beginning. This first draft only contains genetic information from 47 people, the Human Pangenome Reference Consortium plans to bump that up to 350 in the final version, expected by mid-2024.
A paper describing the first draft pangenome was published in the journal Nature, along with three other papers that explore early applications of the data.
Source: National Institutes of Health
