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Cited by 765Genomics and Phylogenetic StudiesChromosomal and Genetic VariationsGenomic variations and chromosomal abnormalities

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

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Miga, Karen H., Koren, Sergey, Rhie, Arang, Vollger, Mitchell R., Gershman, Ariel, Bzikadze, Andrey, Brooks, Shelise, Howe, Edmund +45 more·2020·Nature
DOI 10.1038/s41586-020-2547-7PMC PMC7484160

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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 persist 1,2 . Here we present a human genome assembly that surpasses the continuity of GRCh38 2 , 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 chromosome 3 , 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.

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  • These technological advancements led to a new generation of genome alignment and assembly algorithms leveraging new data types.

    “These technological advancements also led to a new generation of genome alignment and assembly algorithms leveraging the new data types (84–89).”

    From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [88]

    The ‘Highly continuous whole-genome assembly’ section (page not provided) describes assembling nanopore and PacBio reads with Canu, and ‘Methods > Manual gap closure’ describes using Minimap2 for read mapping. This supports the paper as an example of alignment and assembly algorithms applied to new sequencing data, but it does not establish that the technological advances led to a new generation of those algorithms. (LLM, conf=0.78)

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Authors
Miga, K. H., Koren, S., Rhie, A., Vollger, M. R., Gershman, A., Bzikadze, A., Brooks, S., Howe, E., Porubsky, D., Logsdon, G. A., Schneider, V. A., Potapova, T., Wood, J., Chow, W., Armstrong, J., Fredrickson, J., Pak, E., Tigyi, K., Kremitzki, M., Markovic, C., Maduro, V., Dutra, A., Bouffard, G. G., Chang, A. M., Hansen, N. F., Wilfert, A. B., Thibaud-Nissen, F., Schmitt, A. D., Belton, J.-M., Selvaraj, S., Dennis, M. Y., Soto, D. C., Sahasrabudhe, R., Kaya, G., Quick, J., Loman, N. J., Holmes, N., Loose, M., Surti, U., Risques, R. A., Graves Lindsay, T. A., Fulton, R., Hall, I., Paten, B., Howe, K., Timp, W., Young, A., Mullikin, J. C., Pevzner, P. A., Gerton, J. L., Sullivan, B. A., Eichler, E. E., & Phillippy, A. M.
Affiliations
  • University of California, Santa Cruz (US)
  • National Institutes of Health (US)
  • University of Washington (US)
  • Johns Hopkins University (US)
  • University of California San Diego (US)
  • Stowers Institute for Medical Research (US)
  • Wellcome Sanger Institute (GB)
  • Washington University in St. Louis (US)
  • Arima Genomics (United States) (US)
  • University of California, Davis (US)
  • University of Birmingham (GB)
  • University of Nottingham (GB)
  • University of Pittsburgh (US)
  • Duke University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Miga, Karen H.
  • Phillippy, Adam M.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2020-07-14
Volume
585
Issue
7823
Pages
79-84
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-020-2547-7
PMC
PMC7484160
OpenAlex
W3042374389
Cited by
765
References
3
Citations by year
2026: 45 · 2025: 67 · 2024: 77 · 2023: 98 · 2022: 162 · 2021: 222 · 2020: 86 · 2019: 7
FWCI
46.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • W. M. Keck Foundation (DT06172015)
  • Stowers Institute for Medical Research
  • Wellcome Trust (212965, 212965/Z/18/Z)
  • National Institute for Health and Care Research
  • Department of Health and Social Care
  • Korea Health Industry Development Institute (HI17C2098)
  • Surgical Reconstruction and Microbiology Research Centre
  • National Institutes of Health (NIH-R01, U54 1U54HG007990, U01 1U01HG010971)
  • Medical Research Council (MR/J014370/1, MR/M501621/1)
  • National Heart, Lung, and Blood Institute (U01HL137183, U01 1U01HL137183, NIH R01)
  • National Institute of Mental Health (DP2MH119424)
  • National Human Genome Research Institute (HG010169, R44HG008118, HG002385, R21HG010548, R21 1R21HG010548-01, HG009190, U01HG010971, U41HG007234, R01HG009190, U01 1U01HG010971, U54HG007990, R01HG002385, R01HG010169)
  • NIH Office of the Director
  • National Cancer Institute (R21CA238758, R01CA181308, P30CA014236)
  • National Institute of General Medical Sciences (GM007445, T32GM007445, R01GM129263, F32GM134558, R01GM124041)
  • U.S. National Library of Medicine (T32LM012419)
  • Common Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
telomere-to-telomere genome assembly, human X chromosome, nanopore sequencing, centromeric satellite DNA, tandem repeats, reference genome
MeSH terms
Centromere, DNA, Satellite, Female, Humans, Hydatidiform Mole, Male, Pregnancy, Testis, Reproducibility of Results, Genome, Human, Telomere, CpG Islands, DNA Methylation, Chromosomes, Human, X

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