Indigenous Australian genomes show deep structure and rich novel variation.

The Indigenous peoples of Australia have a rich linguistic and cultural history. How this relates to genetic diversity remains largely unknown because of their limited engagement with genomic studies. Here we analyse the genomes of 159 individuals from four remote Indigenous communities, including people who speak a language (Tiwi) not from the most widespread family (Pama-Nyungan). This large collection of Indigenous Australian genomes was made possible by careful community engagement and consultation. We observe exceptionally strong population structure across Australia, driven by divergence times between communities of 26,000-35,000 years ago and long-term low but stable effective population sizes. This demographic history, including early divergence from Papua New Guinean (47,000 years ago) and Eurasian groups1, has generated the highest proportion of previously undescribed genetic variation seen outside Africa and the most extended homozygosity compared with global samples. A substantial proportion of this variation is not observed in global reference panels or clinical datasets, and variation with predicted functional consequence is more likely to be homozygous than in other populations, with consequent implications for medical genomics2. Our results show that Indigenous Australians are not a single homogeneous genetic group and their genetic relationship with the peoples of New Guinea is not uniform. These patterns imply that the full breadth of Indigenous Australian genetic diversity remains uncharacterized, potentially limiting genomic medicine and equitable healthcare for Indigenous Australians.

Australian Aboriginal and Torres Strait Islander Collections of Genetic Heritage: The Legal, Ethical and Practical Considerations of a Dynamic Consent Approach to Decision Making.

Dynamic Consent (DC) is both a model and a specific web-based tool that enables clear, granular communication and recording of participant consent choices over time. The DC model enables individuals to know and to decide how personal research information is being used and provides a way in which to exercise legal rights provided in privacy and data protection law. The DC tool is flexible and responsive, enabling legal and ethical requirements in research data sharing to be met and for online health information to be maintained. DC has been used in rare diseases and genomics, to enable people to control and express their preferences regarding their own data. However, DC has never been explored in relationship to historical collections of bioscientific and genetic heritage or to contexts involving Aboriginal and Torres Strait Islander people (First Peoples of Australia). In response to the growing interest by First Peoples throughout Australia in genetic and genomic research, and the increasing number of invitations from researchers to participate in community health and wellbeing projects, this article examines the legal and ethical attributes and challenges of DC in these contexts. It also explores opportunities for including First Peoples' cultural perspectives, governance, and leadership as a method for defining (or redefining) DC on cultural terms that engage best practice research and data analysis as well as respect for meaningful and longitudinal individual and family participation.