Next-gen genomics reveals diversity of Indigenous Australians

Researchers have used next-generation sequencing to reveal the highest-resolution view of the unique genetic diversity in Indigenous Australians to date, finding an abundance of DNA variations — some of which have never been reported anywhere else in the world.

Led by the ANU National Centre for Indigenous Genomics (NCIG) in collaboration with the Garvan Institute of Medical Research, the researchers used a genomics technique called Oxford Nanopore long-read sequencing to gain new insights into the genomic diversity of 159 individuals from four different Aboriginal communities. Their research, published in two papers in the journal Nature, will help identify genes that contribute to diseases, and better treatment options, by establishing genetic reference databases — in which Indigenous ancestries have until now been critically under-represented.

“Genomic information has the power to guide more personalised clinical care, but to do this we need to know what a community’s background genetic variation is, as a point of reference,” said Dr Ira Deveson, leader of the Genomic Technologies Lab at Garvan. “With genomic medicine becoming more and more relevant in clinical practice, we want to make sure Indigenous Australians are not left behind.”

Long-read sequencing is a cutting-edge method that can accurately survey the entire human genome — including at least 10% of the genetic code that cannot be read by conventional sequencing methods — and detect ‘structural genetic variants’ that affect large segments of DNA. These variants, which occur naturally across individuals of a population, account for most of the genetic differences between individuals and may be linked to genetic disease in some families.

“We identified more than 160,000 structural genetic variants, which is more than any previous population-level long-read study to date, and discovered at least 300 structural variants in each individual that appear to be unique to Indigenous Australians,” Deveson said. ANU’s Dr Hardip Patel added that some of these DNA variations appear to be exclusively found in Indigenous Australians, while others were found in just one out of the four Indigenous communities that were investigated.

“These DNA sequences show a level of genetic variation not observed anywhere else in the world outside of Africa, reflecting Aboriginal and Torres Strait Islander peoples’ deep cultural and linguistic diversity and longstanding connection to the Australian continent,” Patel said.

It is hoped that the research will improve health outcomes for Indigenous Australians by enabling tailored treatments for conditions including diabetes, coronary disease and cancer — all of which disproportionately impact Indigenous peoples compared to the rest of the Australian population. Patel noted, “Previously we’ve had to try to utilise the DNA of non-Indigenous populations to help diagnose and treat disease among Indigenous Australians, which has proven difficult and is often less reliable. But now we have a new, more representative genomic dataset to build off.”

“Aboriginal people have long said you can’t treat us the same because we are so different. Having scientific proof to show this is true is remarkable,” added ANU Associate Professor Azure Hermes, a proud Gimuy Walubara Yidinji woman and Deputy Director of NCIG.

“Clinicians must realise treatment options for Indigenous Australians can’t be viewed through a one-model-fits-all lens. We are not a single genetic group and can’t be lumped into one category.”

The team also identified a structural genetic variant known to cause a neurodegenerative condition known as Machado-Joseph Disease in the genome of one Galiwin’ku individual. This disease is more than 100 times more prevalent among Indigenous populations in areas of the Northern Territory than the global average, but can be difficult to diagnose using existing methods. The individual has since been connected with a local genetic counsellor and clinical management services following the genetic findings, highlighting the power of long-read sequencing for the prediction of disease risk and early mitigation.

“By identifying variants linked to higher prevalence of disease, long-read sequencing could play a critical role in boosting local healthcare efforts and represent a step towards more equitable genomic medicine,” Deveson said.

“Our goal is to work with and empower Indigenous Australians to take ownership of their genetic information and show them the power of genomics and the health benefits it can deliver,” Hermes concluded. “It’s taken us almost eight years to get to this point and has only been made possible because of guidance by Indigenous communities, careful consultation, building relationships with communities and understanding their priorities and protocols.”

Image credit: iStock.com/PomInOz