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

Author

Listed:
  • Karen H. Miga

    (University of California Santa Cruz)

  • Sergey Koren

    (Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Arang Rhie

    (Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Mitchell R. Vollger

    (University of Washington School of Medicine)

  • Ariel Gershman

    (Johns Hopkins University)

  • Andrey Bzikadze

    (University of California San Diego)

  • Shelise Brooks

    (National Institutes of Health)

  • Edmund Howe

    (Stowers Institute for Medical Research)

  • David Porubsky

    (University of Washington School of Medicine)

  • Glennis A. Logsdon

    (University of Washington School of Medicine)

  • Valerie A. Schneider

    (National Institutes of Health)

  • Tamara Potapova

    (Stowers Institute for Medical Research)

  • Jonathan Wood

    (Wellcome Sanger Institute)

  • William Chow

    (Wellcome Sanger Institute)

  • Joel Armstrong

    (University of California Santa Cruz)

  • Jeanne Fredrickson

    (University of Washington)

  • Evgenia Pak

    (National Institutes of Health)

  • Kristof Tigyi

    (University of California Santa Cruz)

  • Milinn Kremitzki

    (McDonnell Genome Institute at Washington University)

  • Christopher Markovic

    (McDonnell Genome Institute at Washington University)

  • Valerie Maduro

    (National Institutes of Health)

  • Amalia Dutra

    (National Institutes of Health)

  • Gerard G. Bouffard

    (National Institutes of Health)

  • Alexander M. Chang

    (Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Nancy F. Hansen

    (National Human Genome Research Institute, National Institutes of Health)

  • Amy B. Wilfert

    (University of Washington School of Medicine)

  • Françoise Thibaud-Nissen

    (National Institutes of Health)

  • Anthony D. Schmitt

    (Arima Genomics)

  • Jon-Matthew Belton

    (Arima Genomics)

  • Siddarth Selvaraj

    (Arima Genomics)

  • Megan Y. Dennis

    (University of California Davis)

  • Daniela C. Soto

    (University of California Davis)

  • Ruta Sahasrabudhe

    (University of California Davis)

  • Gulhan Kaya

    (University of California Davis)

  • Josh Quick

    (University of Birmingham)

  • Nicholas J. Loman

    (University of Birmingham)

  • Nadine Holmes

    (University of Nottingham)

  • Matthew Loose

    (University of Nottingham)

  • Urvashi Surti

    (University of Pittsburgh)

  • Rosa ana Risques

    (University of Washington)

  • Tina A. Graves Lindsay

    (McDonnell Genome Institute at Washington University)

  • Robert Fulton

    (McDonnell Genome Institute at Washington University)

  • Ira Hall

    (McDonnell Genome Institute at Washington University)

  • Benedict Paten

    (University of California Santa Cruz)

  • Kerstin Howe

    (Wellcome Sanger Institute)

  • Winston Timp

    (Johns Hopkins University)

  • Alice Young

    (National Institutes of Health)

  • James C. Mullikin

    (National Institutes of Health)

  • Pavel A. Pevzner

    (University of California San Diego)

  • Jennifer L. Gerton

    (Stowers Institute for Medical Research)

  • Beth A. Sullivan

    (Duke University Medical Center)

  • Evan E. Eichler

    (University of Washington School of Medicine
    University of Washington)

  • Adam M. Phillippy

    (Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health)

Abstract

After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist1,2. Here we present a human genome assembly that surpasses the continuity of GRCh382, along with a 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 centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes.

Suggested Citation

  • 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 , 2020. "Telomere-to-telomere assembly of a complete human X chromosome," Nature, Nature, vol. 585(7823), pages 79-84, September.
    • Handle: RePEc:nat:nature:v:585:y:2020:i:7823:d:10.1038_s41586-020-2547-7
    DOI: 10.1038/s41586-020-2547-7
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    Citations

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    Cited by:

    1. Joanna Hård & Jeff E. Mold & Jesper Eisfeldt & Christian Tellgren-Roth & Susana Häggqvist & Ignas Bunikis & Orlando Contreras-Lopez & Chen-Shan Chin & Jessica Nordlund & Carl-Johan Rubin & Lars Feuk &, 2023. "Long-read whole-genome analysis of human single cells," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Sarah Morrison-Smith & Christina Boucher & Aleksandra Sarcevic & Noelle Noyes & Catherine O’Brien & Nazaret Cuadros & Jaime Ruiz, 2022. "Challenges in large-scale bioinformatics projects," Palgrave Communications, Palgrave Macmillan, vol. 9(1), pages 1-9, December.
    3. Gabriel E. Rech & Santiago Radío & Sara Guirao-Rico & Laura Aguilera & Vivien Horvath & Llewellyn Green & Hannah Lindstadt & Véronique Jamilloux & Hadi Quesneville & Josefa González, 2022. "Population-scale long-read sequencing uncovers transposable elements associated with gene expression variation and adaptive signatures in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Tobias T. Schmidt & Carly Tyer & Preeyesh Rughani & Candy Haggblom & Jeffrey R. Jones & Xiaoguang Dai & Kelly A. Frazer & Fred H. Gage & Sissel Juul & Scott Hickey & Jan Karlseder, 2024. "High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Zhikun Wu & Zehang Jiang & Tong Li & Chuanbo Xie & Liansheng Zhao & Jiaqi Yang & Shuai Ouyang & Yizhi Liu & Tao Li & Zhi Xie, 2021. "Structural variants in the Chinese population and their impact on phenotypes, diseases and population adaptation," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    6. Souren Paul & Mark H. Kaplan & Dinesh Khanna & Preston M. McCourt & Anjan K. Saha & Pei-Suen Tsou & Mahek Anand & Alexander Radecki & Mohamad Mourad & Amr H. Sawalha & David M. Markovitz & Rafael Cont, 2022. "Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Kunpeng Li & Peng Xu & Jinpeng Wang & Xin Yi & Yuannian Jiao, 2023. "Identification of errors in draft genome assemblies at single-nucleotide resolution for quality assessment and improvement," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Temitayo A. Olagunju & Benjamin D. Rosen & Holly L. Neibergs & Gabrielle M. Becker & Kimberly M. Davenport & Christine G. Elsik & Tracy S. Hadfield & Sergey Koren & Kristen L. Kuhn & Arang Rhie & Kati, 2024. "Telomere-to-telomere assemblies of cattle and sheep Y-chromosomes uncover divergent structure and gene content," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    9. Mohamed Awad & Xiangchao Gan, 2023. "GALA: a computational framework for de novo chromosome-by-chromosome assembly with long reads," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    10. Xiao Luo & Xiongbin Kang & Alexander Schönhuth, 2022. "VeChat: correcting errors in long reads using variation graphs," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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