澳大利亚加文医学研究所Ira W. Deveson等研究人员合作揭示澳大利亚土著人的基因组结构变异情况。相关论文于2023年12月13日在线发表在《自然》杂志上。

研究人员应用人群规模的全基因组长序列测序来分析了四个偏远土著社区的基因组结构变异。研究人员发现了大量大插入-缺失变异（20-49bp；n=136797）、结构变异（50b-50kb；n=159912）和拷贝数可变区域（>50kb；n=156）。大多数变异由串联重复序列或穿插移动元件序列组成（高达90%），并且以前未被注释过（高达62%）。很大一部分结构变异似乎是澳大利亚土著居民独有的（估计下限为12%），其中大多数变异仅在一个社区中发现，这突出表明需要进行广泛而深入的取样，以获得整个澳大利亚大陆基因组结构变异的全面目录。

最后，研究人员探索了整个基因组中的短串联重复序列，从而确定了50个已知疾病位点的等位基因多样性，发现了蛋白质编码基因中数百个新的重复扩增位点，并确定了短串联重复序列间独特的多样性和限制模式。这项研究为了解澳大利亚境内外基因组结构变异的规模和动态提供了新的视角。

据介绍，澳大利亚原住民拥有丰富而独特的基因组多样性。然而，土著居民和托雷斯海峡岛民血统在基因组研究中的代表性历来不足，在参考数据集中几乎完全缺失。解决这一代表性不足的问题至关重要，这既能促进人们对全球人类基因组多样性的了解，也是确保基因组医学取得公平成果的前提条件。

附：英文原文

Title: The landscape of genomic structural variation in Indigenous Australians

Author: Reis, Andre L. M., Rapadas, Melissa, Hammond, Jillian M., Gamaarachchi, Hasindu, Stevanovski, Igor, Ayuputeri Kumaheri, Meutia, Chintalaphani, Sanjog R., Dissanayake, Duminda S. B., Siggs, Owen M., Hewitt, Alex W., Llamas, Bastien, Brown, Alex, Baynam, Gareth, Mann, Graham J., McMorran, Brendan J., Easteal, Simon, Hermes, Azure, Jenkins, Misty R., Patel, Hardip R., Deveson, Ira W.

Issue&Volume: 2023-12-13

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 (20–49bp; n=136,797), structural variants (50b–50 kb; n=159,912) and regions of variable copy number (>50kb; 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.

DOI: 10.1038/s41586-023-06842-7

Source: https://www.nature.com/articles/s41586-023-06842-7