International researchers have released the first draft of a reference 'pangenome' - a collection of DNA sequences from 47 people. 

The reference pangenome is intended to better reflect the diversity of the human population and can be used as a comparison to study genetic disorders and other human DNA sequences. 

To understand the differences that make people unique, scientists create a reference genome sequence that other DNA sequences can be compared to. But until now that standard reference genome was limited in its ability to reflect human diversity as it was based on the DNA of only 20 people and most of it came from only one person. 

The new “pangenome” reference includes genome sequences of 47 people from diverse ancestries, with researchers hoping to increase that number to 350 by mid-2024.

The pangenome includes all the differences between the genomes of the individuals that have been sequenced. 

Up until now, researchers 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, they 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 the ability to use genetic information for diagnosis will increase enormously. 

Experts at the Human Pangenome Reference Consortium have presented the first draft human pangenome reference and findings from studies that use this reference as a basis for new genetic research. 

The pangenome was developed from a cohort of 47 ancestrally diverse individuals and adds 119 million base pairs and 1,115 gene duplications (mutations in which a region of DNA containing a gene is duplicated) to the current reference human genome (GRCh38). 

Use of this draft increased the number of structural variants detected by 104 per cent compared to GRCh38, providing a more complete picture of genetic diversity within the human genome.

Additionally, researchers have developed a map of single-nucleotide variations (SNVs) within segmental duplications (blocks of DNA that occur at more than one site in a genome and share a high level of sequence identity), characterising millions of previously unmapped SNVs and mutational properties that differ from unique DNA. 

They have been able to observe patterns of recombination between the short arms of heterologous acrocentric (where the centromere is located near one end of the chromosome) chromosomes, providing observational evidence for a mechanism of DNA exchange between these chromosomes that had previously been speculated on but not observed, due to the lack of suitable data.

These results are only an interim stage of the envisioned human pangenome, which aims to capture genetic diversity of 350 individuals. 

Experts have highlighted the importance of these advancements, but note that continued improvements are needed to overcome some remaining challenges, such as the need for even more diverse sampling. 

“This will ultimately make it easier to discover genetic variants that mediate physical and clinical traits, and - it is to be hoped - will eventually lead to better health outcomes for many people”, they write.

More details are accessible here.