It is important to recognize that a solitary reference sequence cannot fully capture the genomic diversity of global populations. It is evident that Asian populations remain underrepresented in the project. For instance, the inclusion of only one Vietnamese individual is inadequate when considering the genetic variation within Vietnam's more than 50 ethnic groups, comprising approximately 100 million people. However, I am hopeful that in the future, collaborations can be established between the project and my team in Vietnam, as well as other locations, to enhance the representativeness of the Pangenome Reference database.

Why is a pangenome so exciting? It includes all the differences between the genomes of the individuals that have been sequenced. All you have to do is look around you to see how different people are. These differences reflect differences in our genomes. Up until now we have used a single genome sequence as a reference for the detection of genetic changes that cause disease. That reference did not include differences between people or populations.

With the pangenome we can now look for genetic changes across many individuals and ultimately the pangenome will grow to include information from thousands and perhaps millions of genome sequences. This means our ability to use genetic information for diagnosis will increase enormously. With the current pangenome from only 45 humans, the accuracy of detection to find genetic changes has gone up by 34% and the number of large, difficult-to-detect changes we now know about has gone up by over 100%! This paper heralds a new age of genetic diagnosis, that will benefit people from all ancestries, unlike our current reference genome that does not reflect all the diversity of humanity.

The publication of the pangenome is a huge step forward in documenting the diversity of the human genetic code in a single map. It aims to record normal variations in the sequence and structure of our genetic code, helping to ensure all races and ethnicities are represented. Such a tool is invaluable for a multicultural society such as Australia. Once finished, the pangenome will be a powerful instrument that will help us diagnose genetic diseases more accurately and discover abnormal genetic variations that can lead to ill-health.

The entire human genome was first published in the early 2000s. This was a significant event that provided genetic researchers and medical doctors a template of ‘normal’ genes to compare other individuals’ DNA to, enabling the discovery of genetic variants that could be causing disease or physical differences.

Of course, there is no such thing as ‘normal’ genes. Humans are wonderfully diverse creatures, with each individual having their own unique collection of genetic variants. A single reference sequence cannot and does not capture the extraordinary genetic diversity of people around the globe. This fact has placed barriers to our ability to fully interpret a person’s genetic sequence. How do we know if a genetic variation is normal or not? How do we know if a variation causes disease, or is commonly found in a particular ethnic group? The pangenome project is helping to answer these important questions to better our understanding of genes and improve the health of all people.

A recent publication in Nature describes the extension of the human genome beyond a single reference to capture more of the variation inherent in our human population. By adding 47 new genomes, they discover over 5% of additional sequence. Researchers also implemented a new representation of these human genomes combined called “pan-genome”.

You can imagine this as a new road map to drop off your kids at school. While you only take the same road every day, your neighbour might take a slightly different road on a side street. While you were never aware of this side road this new approach of a “pan-genome” maps out these alternative routes that make us humans so distinct from each other.

The release of a new pan-genome reference marks a paradigm shift in genetic research. For more than two decades much of human genetic work has relied on the use of a single ‘reference’ through which we then interpret genetic data we collect from individuals. Problems with the reference are well known, for example, the initial reference was hoped to be a composite of 20 diverse donors but approximately 70% came from a single individual (please see article “Is it time to change the reference genome?”, 2019 for more great idiosyncrasies about the human reference!). The pan-genome paper utilises recent advances in sequencing technology to generate ‘references’ from individuals, allowing us to start to break free from the constraints of a single reference and interrogate data with less bias. 

The current pan-genome utilises publicly available samples from broad populations and does not include First Australians. Sovereignty over samples and genetic data is a crucially important aspect for First Australians and current work at the National Centre for Indigenous Genomics (NCIG) is committed to providing and enabling genetic references and data that align with First Australian interests.

While a substantial boon for human genetics the demonstration of this approach will allow those of us working in non-human organisms to implement this into our own research and workflows. Particularly in genetics, not accounting for diversity produces biased and incorrect research outcomes.