Abstract
Indigenous Australians harbour rich and unique genomic diversity. However, Aboriginal and Torres Strait Islander ancestries are historically under-represented in genomics research and almost completely missing from reference datasets 1–3. Addressing this representation gap is critical, both to advance our understanding of global human genomic diversity and as a prerequisite for ensuring equitable outcomes in genomic medicine. Here we apply population-scale whole-genome long-read sequencing 4 to profile genomic structural variation across four remote Indigenous communities. We uncover an abundance of large insertion–deletion variants (20–49 bp; n = 136,797), structural variants (50 b–50 kb; n = 159,912) and regions of variable copy number (>50 kb; n = 156). The majority of variants are composed of tandem repeat or interspersed mobile element sequences (up to 90%) and have not been previously annotated (up to 62%). A large fraction of structural variants appear to be exclusive to Indigenous Australians (12% lower-bound estimate) and most of these are found in only a single community, underscoring the need for broad and deep sampling to achieve a comprehensive catalogue of genomic structural variation across the Australian continent. Finally, we explore short tandem repeats throughout the genome to characterize allelic diversity at 50 known disease loci 5, uncover hundreds of novel repeat expansion sites within protein-coding genes, and identify unique patterns of diversity and constraint among short tandem repeat sequences. Our study sheds new light on the dimensions and dynamics of genomic structural variation within and beyond Australia.
Original language | English |
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Pages (from-to) | 602-610 |
Number of pages | 9 |
Journal | Nature |
Volume | 624 |
Issue number | 7992 |
Early online date | 13 Dec 2023 |
DOIs | |
Publication status | Published - 21 Dec 2023 |
Bibliographical note
Funding Information:We acknowledge the Aboriginal and Torres Strait Islander peoples as the first peoples and traditional custodians of the lands and waters where we meet, live, learn and work. We celebrate the rich diversity of Aboriginal and Torres Strait Islander cultures and the ongoing leadership of our First Nations’ peoples and communities who have paved the way. We pay our respects to ancestors of this country, the legacy of elders, the knowledge holders, and leaders of the past, present, and future. This work was conducted primarily on land traditionally owned by the Ngunnawal and Ngambri peoples and the Gadigal people of the Eora Nation. We are indebted to the individuals and communities who participated in this research and the NCIG Governance Board who guided this work in a culturally appropriate manner. We acknowledge the following Community Organizations and individuals: Yarrabah Shire Council, R. Andrews, E. Fourmile and P. Burns; Tiwi Land Council Board members; Yalu Aboriginal Corporation (Galiwin’ku), R. Wunungmurra, E. Djotja, R. Gundjarrangbuy; Titjikala Shire Council and Titjikala Health services. We thank our colleagues A. McCarthy, W. Hoy, S. Foote, J. Matthews, R. Thomson, D. MacArthur, J. Yuan, T. Amos and J. Craig for their various contributions to the project. This project was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government and the Australian National University (ANU). We acknowledge the following facilities that were used during this study: the Garvan Sequencing Platform (GSP) and the Australian Phenomics Facility (APF). We acknowledge the following funding sources: Medical Research Futures Fund (MRFF) grants 2016008, 1173594, 2023126 and 2016124, and National Health and Medical Research Council (NHMRC) grants 2011277 and 2021172.
Funding Information:
We acknowledge the Aboriginal and Torres Strait Islander peoples as the first peoples and traditional custodians of the lands and waters where we meet, live, learn and work. We celebrate the rich diversity of Aboriginal and Torres Strait Islander cultures and the ongoing leadership of our First Nations’ peoples and communities who have paved the way. We pay our respects to ancestors of this country, the legacy of elders, the knowledge holders, and leaders of the past, present, and future. This work was conducted primarily on land traditionally owned by the Ngunnawal and Ngambri peoples and the Gadigal people of the Eora Nation. We are indebted to the individuals and communities who participated in this research and the NCIG Governance Board who guided this work in a culturally appropriate manner. We acknowledge the following Community Organizations and individuals: Yarrabah Shire Council, R. Andrews, E. Fourmile and P. Burns; Tiwi Land Council Board members; Yalu Aboriginal Corporation (Galiwin’ku), R. Wunungmurra, E. Djotja, R. Gundjarrangbuy; Titjikala Shire Council and Titjikala Health services. We thank our colleagues A. McCarthy, W. Hoy, S. Foote, J. Matthews, R. Thomson, D. MacArthur, J. Yuan, T. Amos and J. Craig for their various contributions to the project. This project was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government and the Australian National University (ANU). We acknowledge the following facilities that were used during this study: the Garvan Sequencing Platform (GSP) and the Australian Phenomics Facility (APF). We acknowledge the following funding sources: Medical Research Futures Fund (MRFF) grants 2016008, 1173594, 2023126 and 2016124, and National Health and Medical Research Council (NHMRC) grants 2011277 and 2021172.
Publisher Copyright:
© 2023, The Author(s).