The landscape of genomic structural variation in Indigenous Australians

Reis, Andre L. M. and Rapadas, Melissa and Hammond, Jillian M. and Gamaarachchi, Hasindu and Stevanovski, Igor and Ayuputeri Kumaheri, Meutia and Chintalaphani, Sanjog R. and Dissanayake, Duminda S. B. and Siggs, Owen M. and Hewitt, Alex W. and Llamas, Bastien and Brown, Alex and Baynam, Gareth and Mann, Graham J. and McMorran, Brendan J. and Easteal, Simon and Hermes, Azure and Jenkins, Misty R. and Pearson, Glen and Roe, Yvette and Mohamed, Janine and Murray, Ben and Ormond-Parker, Lyndon and Kneipp, Erica and Nugent, Keith and Mann, Graham and Patel, Hardip R. and Deveson, Ira W. (2023) The landscape of genomic structural variation in Indigenous Australians. Nature. ISSN 0028-0836

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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 datasets1,2,3. 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 sequencing4 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 loci5, 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.

Item Type: Article
Subjects: Library Keep > Geological Science
Depositing User: Unnamed user with email support@librarykeep.com
Date Deposited: 14 Dec 2023 10:22
Last Modified: 14 Dec 2023 10:22
URI: http://archive.jibiology.com/id/eprint/2164

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