小柯机器人

科学家完成人类X染色体的完整组装
2020-07-16 17:42

美国国立卫生研究院Adam M. Phillippy等研究人员合作完成了人类X染色体的完整组装。2020年7月14日,《自然》杂志在线发表了这项成果。

研究人员报道了超越人类参考基因组(GRCh38)连续性的从头人类基因组装配,以及人类染色体的第一个无间隙、端粒到端粒装配。通过对完整的葡萄胎CHM13基因组进行高覆盖、超长读取的纳米孔测序,并结合用于质量改进和验证的补充技术,研究人员实现这一难点。通过集中于人类X染色体3,研究人员重建了约3.1兆碱基的着丝粒卫星DNA阵列,并消除了当前参考基因组中的全部29个剩余缺口,包括来自人类假常染色体区域和癌症-睾丸两性基因家族(CT-X和GAGE)。这些新的序列将被整合到未来的人类参考基因组版本中。
 
此外,完整的X染色体与超长纳米孔数据相结合,使得研究人员可以首次绘制复杂串联重复序列和卫星阵列的甲基化模式。这些结果表明,整个人类基因组的完成已经触手可及,这些数据将促进人类染色体的完整绘制。
 
据了解,经过二十多年的改进,当前的人类参考基因组(GRCh38)是有史以来最准确、最完整的脊椎动物基因组。然而,没有一条染色体首尾相接,并且数百个未解决的缺口仍然存在。
 
附:英文原文

Title: Telomere-to-telomere assembly of a complete human X chromosome

Author: Karen H. Miga, Sergey Koren, Arang Rhie, Mitchell R. Vollger, Ariel Gershman, Andrey Bzikadze, Shelise Brooks, Edmund Howe, David Porubsky, Glennis A. Logsdon, Valerie A. Schneider, Tamara Potapova, Jonathan Wood, William Chow, Joel Armstrong, Jeanne Fredrickson, Evgenia Pak, Kristof Tigyi, Milinn Kremitzki, Christopher Markovic, Valerie Maduro, Amalia Dutra, Gerard G. Bouffard, Alexander M. Chang, Nancy F. Hansen, Amy B. Wilfert, Franoise Thibaud-Nissen, Anthony D. Schmitt, Jon-Matthew Belton, Siddarth Selvaraj, Megan Y. Dennis, Daniela C. Soto, Ruta Sahasrabudhe, Gulhan Kaya, Josh Quick, Nicholas J. Loman, Nadine Holmes, Matthew Loose, Urvashi Surti, Rosa ana Risques, Tina A. Graves Lindsay, Robert Fulton, Ira Hall, Benedict Paten, Kerstin Howe, Winston Timp, Alice Young, James C. Mullikin, Pavel A. Pevzner, Jennifer L. Gerton, Beth A. Sullivan, Evan E. Eichler, Adam M. Phillippy

Issue&Volume: 2020-07-14

Abstract: After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no one chromosome has been finished end to end, and hundreds of unresolved gaps persist1,2. Here we present a de novo human genome assembly that surpasses the continuity of GRCh382, along with the first gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome3, we reconstructed the ~3.1 megabase centromeric satellite DNA array and closed all 29 remaining gaps in the current reference, including new sequence from the human pseudoautosomal regions and cancer-testis ampliconic gene families (CT-X and GAGE). These novel sequences will be integrated into future human reference genome releases. Additionally, a complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays for the first time. Our results demonstrate that finishing the entire human genome is now within reach and the data presented here will enable ongoing efforts to complete the remaining human chromosomes.

DOI: 10.1038/s41586-020-2547-7

Source: https://www.nature.com/articles/s41586-020-2547-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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