Genome map that includes more ethnicities could lead to better diagnosis, treatment

Scientists last year finished the momentous task of completely mapping the human genome — an accomplishment that, by comparing it with an individual's genetic information, helps catch problems that might cause disease.

But that original map, known as a reference genome, was based on about 20 individuals. It didn't capture the diversity of the human population and could lead to blind spots in biomedical research. Now, scientists have released a draft of a much more diverse reference genome called a "pangenome."

It includes the genetic material of 47 people from Africa, Asia, the Americas and Europe.

"It's really exciting," said Guillaume Bourque, a professor in the department of human genetics at McGill University in Montreal who is part of the Human Pangenome Reference Consortium that created the first draft of the pangenome.

"People are going to be able to detect new, important genetic mutations that are in these regions that were hidden, and they're going to be able to understand new biology coming from these."

A human genome is the set of DNA instructions found in an individual cell needed to develop and sustain a human being. A pangenome is a digital database of the genome sequences that are meant to represent the diversity of the human species.

Published in a study in Nature in May, the pangenome builds on that first sequencing of the human genome, which was nearly completed more than two decades ago and finished last year.

About 70 per cent of that reference genome was based on an individual of African-American descent, with mixed African and European ancestry. East Asian ancestries were the second-most predominant source, and the rest came from people of mostly European ancestries.

The pangenome, by comparison, contains material from 24 people of African ancestry, 16 from the Americas, six from Asia and one from Europe.

What does this mean for future research?

Genomes slightly differ among individuals, but any two people's genomes are on average 99 per cent identical. However, that one per cent difference could hold a lot of information, says Gagan Gupta, an associate professor at Toronto Metropolitan University who studies functional genomics.

"One genome has billions of pairs of DNA, and one per cent of that is still a great big number that can have many effects on an individual," he said.

For example, with the first genome researchers were able to pinpoint the gene that causes cystic fibrosis — crucial knowledge for developing gene therapies to treat or potentially cure it.

But cystic fibrosis can vary widely in its severity and symptoms, and can mimic other lung diseases such as asthma or bronchitis, making diagnosis challenging.

Gupta's research found it is well-diagnosed in Western countries but often underdiagnosed in India, China and some regions of Africa.

But with the pangenome, Gupta hopes to advance his research and help other scientists diagnose more people.

"We could identify patients in those regions who could respond to the treatments that are available now or patients that may not respond based on this new data," he said.

Lisa Strug, senior genetics scientist at SickKids hospital in Toronto, says many genetic diseases are hard to diagnose with the first reference genome.

"The pangenome will help us to get out those dark regions of the genome that are harbouring variation that's contributing to disease," Strug said.

Cancer diagnosis could also be improved if researchers integrate the pangenome into their research, says Philip Awadalla, a senior investigator at the Ontario Institute for Cancer Research.

"People from different ethnic backgrounds might have different genetic pre-determinants for cancers" he said. "It not only can better diagnosis but also treatment."

Strug says the pangenome could also help identify new avenues for cures for some genetic diseases.

"It can result in potentially new therapies or we could predict who's going to be most susceptible so we could intervene earlier."

More to come

There is a long way to go until the information gleaned from the pangenome can be applied in health-care settings, says Gupta, but the draft is one step forward.

He says this latest step still doesn't encompass everyone, but that will come with more research and time.

"Forty-seven people is still not extremely representative of all the diversity in the human population. So it's still, you know, a relatively small number from which to build a reference human genome," he said.

"We are going to get genomes into the clinic at some point, and how we inform and identify variants in those genomes depend on having proper references and the tools to map them," said Awadalla.

The next part of the consortium's research, expected to be published next year, will include genetic material from 150 areas of the world — more than triple the amount in the current pangenome .

"It's a really important milestone," said Gupta. "Knowing that even more and better is coming is just even more exciting."