The landscape of genomic structural variation in Indigenous Australians.

Autor:	Reis ALM; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia.; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Rapadas M; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia., Hammond JM; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia., Gamaarachchi H; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia.; School of Computer Science and Engineering, University of New South Wales, Sydney, New South Wales, Australia., Stevanovski I; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia., Ayuputeri Kumaheri M; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia., Chintalaphani SR; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia.; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia., Dissanayake DSB; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.; Institute for Applied Ecology, University of Canberra, Canberra, Australian Capital Territory, Australia., Siggs OM; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia.; Department of Ophthalmology, Flinders University, Bedford Park, South Australia, Australia., Hewitt AW; Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia., Llamas B; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.; Australian Centre for Ancient DNA, School of Biological Sciences and Environment Institute, University of Adelaide, Adelaide, South Australia, Australia.; ARC Centre of Excellence for Australian Biodiversity and Heritage, University of Adelaide, Adelaide, South Australia, Australia.; Indigenous Genomics, Telethon Kids Institute, Adelaide, South Australia, Australia., Brown A; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.; Indigenous Genomics, Telethon Kids Institute, Adelaide, South Australia, Australia., Baynam G; Telethon Kids Institute and Division of Paediatrics, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.; Genetic Services of Western Australia, Western Australian Department of Health, Perth, Western Australia, Australia.; Western Australian Register of Developmental Anomalies, Western Australian Department of Health, Perth, Western Australia, Australia., Mann GJ; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia., McMorran BJ; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia., Easteal S; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia., Hermes A; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia., Jenkins MR; Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia., Patel HR; National Centre for Indigenous Genomics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia. hardip.patel@anu.edu.au., Deveson IW; Genomics and Inherited Disease Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. i.deveson@garvan.org.au.; Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Darlinghurst, New South Wales, Australia. i.deveson@garvan.org.au.; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia. i.deveson@garvan.org.au.
Jazyk:	angličtina
Zdroj:	Nature [Nature] 2023 Dec; Vol. 624 (7992), pp. 602-610. Date of Electronic Publication: 2023 Dec 13.
DOI:	10.1038/s41586-023-06842-7
Abstrakt:	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. (© 2023. The Author(s).)
Databáze:	MEDLINE
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