The landscape of genomic structural variation in Indigenous Australians

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dc.contributor.authorReis, A.L.M.
dc.contributor.authorRapadas, M.
dc.contributor.authorHammond, J.M.
dc.contributor.authorGamaarachchi, H.
dc.contributor.authorStevanovski, I.
dc.contributor.authorAyuputeri Kumaheri, M.
dc.contributor.authorChintalaphani, S.R.
dc.contributor.authorDissanayake, D.S.B.
dc.contributor.authorSiggs, O.M.
dc.contributor.authorHewitt, A.W.
dc.contributor.authorLlamas, B.
dc.contributor.authorBrown, A.
dc.contributor.authorBaynam, G.
dc.contributor.authorMann, G.J.
dc.contributor.authorMcMorran, B.J.
dc.contributor.authorEasteal, S.
dc.contributor.authorHermes, A.
dc.contributor.authorJenkins, M.R.
dc.contributor.authorNational Centre for Indigenous Genomics,
dc.contributor.authorPatel, H.R.
dc.contributor.authoret al.
dc.date.issued2023
dc.description.abstractIndigenous 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 datasets1-3. 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.
dc.description.statementofresponsibilityAndre L. M. Reis, Melissa Rapadas, Jillian M. Hammond, Hasindu Gamaarachchi, Igor Stevanovski, Meutia Ayuputeri Kumaheri, Sanjog R. Chintalaphani, Duminda S. B. Dissanayake, Owen M. Siggs, Alex W. Hewitt, Bastien Llamas, Alex Brown, Gareth Baynam, Graham J. Mann, Brendan J. McMorran, Simon Easteal, Azure Hermes, Misty R. Jenkins, The National Centre for Indigenous Genomics, Hardip R. Patel, Ira W. Deveson
dc.identifier.citationNature, 2023; 624(7992):602-610
dc.identifier.doi10.1038/s41586-023-06842-7
dc.identifier.issn0028-0836
dc.identifier.issn1476-4687
dc.identifier.orcidLlamas, B. [0000-0002-5550-9176]
dc.identifier.orcidBrown, A. [0000-0003-2112-3918]
dc.identifier.urihttps://hdl.handle.net/2440/140525
dc.language.isoen
dc.publisherSpringer Science and Business Media LLC
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2011277
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2021172
dc.rights© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttp://dx.doi.org/10.1038/s41586-023-06842-7
dc.subjectGenetic variation; Medical genomics; Next-generation sequencing; Structural variation
dc.subject.meshHumans
dc.subject.meshGenetics, Medical
dc.subject.meshGenomics
dc.subject.meshInterspersed Repetitive Sequences
dc.subject.meshMicrosatellite Repeats
dc.subject.meshAlleles
dc.subject.meshGenome, Human
dc.subject.meshAustralia
dc.subject.meshINDEL Mutation
dc.subject.meshGenetic Loci
dc.subject.meshGenomic Structural Variation
dc.subject.meshDNA Copy Number Variations
dc.subject.meshDatasets as Topic
dc.subject.meshAustralian Aboriginal and Torres Strait Islander Peoples
dc.titleThe landscape of genomic structural variation in Indigenous Australians
dc.typeJournal article
pubs.publication-statusPublished online

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