New Results
The complete sequence of a human genome
Sergey Nurk, Sergey Koren, Arang Rhie, Mikko Rautiainen, Andrey V. Bzikadze, Alla Mikheenko, Mitchell R. Vollger, Nicolas Altemose, Lev Uralsky, Ariel Gershman, Sergey Aganezov, Savannah J. Hoyt, Mark Diekhans, Glennis A. Logsdon, Michael Alonge, Stylianos E. Antonarakis, Matthew Borchers, Gerard G. Bouffard, Shelise Y. Brooks, Gina V. Caldas, Haoyu Cheng, Chen-Shan Chin, William Chow, Leonardo G. de Lima, Philip C. Dishuck, Richard Durbin, Tatiana Dvorkina, Ian T. Fiddes, Giulio Formenti, Robert S. Fulton, Arkarachai Fungtammasan, Erik Garrison, Patrick G.S. Grady, Tina A. Graves-Lindsay, Ira M. Hall, Nancy F. Hansen, Gabrielle A. Hartley, Marina Haukness, Kerstin Howe, Michael W. Hunkapiller, Chirag Jain, Miten Jain, Erich D. Jarvis, Peter Kerpedjiev, Melanie Kirsche, Mikhail Kolmogorov, Jonas Korlach, Milinn Kremitzki, Heng Li, Valerie V. Maduro, Tobias Marschall, Ann M. McCartney, Jennifer McDaniel, Danny E. Miller, James C. Mullikin, Eugene W. Myers, Nathan D. Olson, Benedict Paten, Paul Peluso, Pavel A. Pevzner, David Porubsky, Tamara Potapova, Evgeny I. Rogaev, Jeffrey A. Rosenfeld, Steven L. Salzberg, Valerie A. Schneider, Fritz J. Sedlazeck, Kishwar Shafin, Colin J. Shew, Alaina Shumate, Yumi Sims, Arian F. A. Smit, Daniela C. Soto, Ivan Sović, Jessica M. Storer, Aaron Streets, Beth A. Sullivan, Françoise Thibaud-Nissen, James Torrance, Justin Wagner, Brian P. Walenz, Aaron Wenger, Jonathan M. D. Wood, Chunlin Xiao, Stephanie M. Yan, Alice C. Young, Samantha Zarate, Urvashi Surti, Rajiv C. McCoy, Megan Y. Dennis, Ivan A. Alexandrov, Jennifer L. Gerton, Rachel J. O’Neill, Winston Timp, Justin M. Zook, Michael C. Schatz, Evan E. Eichler, Karen H. Miga, Adam M. Phillippy
doi: https://doi.org/10.1101/2021.05.26.445798
Sergey Nurk
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
Sergey Koren
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
Arang Rhie
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
Mikko Rautiainen
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
Andrey V. Bzikadze
2Graduate Program in Bioinformatics and Systems Biology, University of California San Diego, La Jolla, CA, USA
Alla Mikheenko
3Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia
Mitchell R. Vollger
4Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Nicolas Altemose
5Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA
Lev Uralsky
6Sirius University of Science and Technology, Sochi, Russia
7Vavilov Institute of General Genetics, Moscow, Russia
Ariel Gershman
8Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, MD, USA
Sergey Aganezov
9Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
Savannah J. Hoyt
10Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Mark Diekhans
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Glennis A. Logsdon
4Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Michael Alonge
9Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
Stylianos E. Antonarakis
12University of Geneva Medical School, Geneva, Switzerland
Matthew Borchers
13Stowers Institute for Medical Research, Kansas City, MO, USA
Gerard G. Bouffard
14NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Shelise Y. Brooks
14NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Gina V. Caldas
15Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Haoyu Cheng
16Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA
17Department of Biomedical Informatics, Harvard Medical School, Boston, MA
Chen-Shan Chin
18DNAnexus, Mountain View, CA, USA
William Chow
19Wellcome Sanger Institute, Cambridge, UK
Leonardo G. de Lima
13Stowers Institute for Medical Research, Kansas City, MO, USA
Philip C. Dishuck
4Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Richard Durbin
21Department of Genetics, University of Cambridge, Cambridge, UK
Tatiana Dvorkina
3Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia
Ian T. Fiddes
22Inscripta, Boulder, CO, USA
Giulio Formenti
23Laboratory of Neurogenetics of Language and The Vertebrate Genome Lab, The Rockefeller University, New York, NY, USA
24Howard Hughes Medical Institute, Chevy Chase, MD, USA
Robert S. Fulton
25Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA
Arkarachai Fungtammasan
18DNAnexus, Mountain View, CA, USA
Erik Garrison
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
26University of Tennessee Health Science Center, Memphis, TN, USA
Patrick G.S. Grady
10Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Tina A. Graves-Lindsay
27McDonnell Genome Institute, Washington University in St. Louis, MO, USA
Ira M. Hall
28Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
Nancy F. Hansen
29Comparative Genomics Analysis Unit, Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Gabrielle A. Hartley
10Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Marina Haukness
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Kerstin Howe
19Wellcome Sanger Institute, Cambridge, UK
Michael W. Hunkapiller
30Pacific Biosciences, Menlo Park, CA, USA
Chirag Jain
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
31Department of Computational and Data Sciences, Indian Institute of Science, Bangalore KA, India
Miten Jain
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Erich D. Jarvis
23Laboratory of Neurogenetics of Language and The Vertebrate Genome Lab, The Rockefeller University, New York, NY, USA
24Howard Hughes Medical Institute, Chevy Chase, MD, USA
Peter Kerpedjiev
32Reservoir Genomics LLC, Oakland, CA
Melanie Kirsche
9Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
Mikhail Kolmogorov
33Department of Computer Science and Engineering, UC San Diego, CA, USA
Jonas Korlach
30Pacific Biosciences, Menlo Park, CA, USA
Milinn Kremitzki
27McDonnell Genome Institute, Washington University in St. Louis, MO, USA
Heng Li
16Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA
17Department of Biomedical Informatics, Harvard Medical School, Boston, MA
Valerie V. Maduro
34Undiagnosed Diseases Program, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Tobias Marschall
35Heinrich Heine University Düsseldorf, Medical Faculty, Institute for Medical Biometry and Bioinformatics, Düsseldorf, Germany
Ann M. McCartney
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
Jennifer McDaniel
36Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
Danny E. Miller
4Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
37Department of Pediatrics, Division of Genetic Medicine, University of Washington and Seattle Children’s Hospital, Seattle, WA, USA
James C. Mullikin
14NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
29Comparative Genomics Analysis Unit, Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Eugene W. Myers
38Max-Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Nathan D. Olson
36Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
Benedict Paten
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Paul Peluso
30Pacific Biosciences, Menlo Park, CA, USA
Pavel A. Pevzner
33Department of Computer Science and Engineering, UC San Diego, CA, USA
David Porubsky
4Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Tamara Potapova
13Stowers Institute for Medical Research, Kansas City, MO, USA
Evgeny I. Rogaev
6Sirius University of Science and Technology, Sochi, Russia
7Vavilov Institute of General Genetics, Moscow, Russia
39Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, USA
40Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
Jeffrey A. Rosenfeld
41Cancer Institute of New Jersey, New Brunswick, NJ, USA
Steven L. Salzberg
9Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
42Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Valerie A. Schneider
43National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD, USA
Fritz J. Sedlazeck
44Human Genome Sequencing Center, Baylor College of Medicine, Houston TX, USA
Kishwar Shafin
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Colin J. Shew
20Genome Center, MIND Institute, Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA
Alaina Shumate
42Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Yumi Sims
19Wellcome Sanger Institute, Cambridge, UK
Arian F. A. Smit
45Institute for Systems Biology, Seattle, WA, USA
Daniela C. Soto
20Genome Center, MIND Institute, Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA
Ivan Sović
30Pacific Biosciences, Menlo Park, CA, USA
46Digital BioLogic d.o.o., Ivanić-Grad, Croatia
Jessica M. Storer
45Institute for Systems Biology, Seattle, WA, USA
Aaron Streets
5Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA
47Chan Zuckerberg Biohub, San Francisco, CA, USA
Beth A. Sullivan
48Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA
Françoise Thibaud-Nissen
43National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD, USA
James Torrance
19Wellcome Sanger Institute, Cambridge, UK
Justin Wagner
36Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
Brian P. Walenz
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
Aaron Wenger
30Pacific Biosciences, Menlo Park, CA, USA
Jonathan M. D. Wood
19Wellcome Sanger Institute, Cambridge, UK
Chunlin Xiao
43National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD, USA
Stephanie M. Yan
49Department of Biology, Johns Hopkins University, Baltimore, MD, USA
Alice C. Young
14NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Samantha Zarate
9Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
Urvashi Surti
50Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
Rajiv C. McCoy
49Department of Biology, Johns Hopkins University, Baltimore, MD, USA
Megan Y. Dennis
20Genome Center, MIND Institute, Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA
Ivan A. Alexandrov
3Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg, Russia
7Vavilov Institute of General Genetics, Moscow, Russia
51Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia
Jennifer L. Gerton
13Stowers Institute for Medical Research, Kansas City, MO, USA
Rachel J. O’Neill
10Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Winston Timp
8Department of Molecular Biology and Genetics, Johns Hopkins University, Baltimore, MD, USA
42Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Justin M. Zook
36Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
Michael C. Schatz
9Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
49Department of Biology, Johns Hopkins University, Baltimore, MD, USA
Evan E. Eichler
4Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
24Howard Hughes Medical Institute, Chevy Chase, MD, USA
Karen H. Miga
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Adam M. Phillippy
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD USA
Abstract
In 2001, Celera Genomics and the International Human Genome Sequencing Consortium published their initial drafts of the human genome, which revolutionized the field of genomics. While these drafts and the updates that followed effectively covered the euchromatic fraction of the genome, the heterochromatin and many other complex regions were left unfinished or erroneous. Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release. The new T2T-CHM13 reference includes gapless assemblies for all 22 autosomes plus Chromosome X, corrects numerous errors, and introduces nearly 200 million bp of novel sequence containing 2,226 paralogous gene copies, 115 of which are predicted to be protein coding. The newly completed regions include all centromeric satellite arrays and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies for the first time.
Competing Interest Statement
AF and CSC are employees of DNAnexus; IS, JK, MWH, PP, and AW are employees of Pacific Biosciences; FJS has received travel funds to speak at events hosted by Pacific Biosciences; SK and FJS have received travel funds to speak at events hosted by Oxford Nanopore Technologies. WT has licensed two patents to Oxford Nanopore Technologies (US 8748091 and 8394584).
Footnotes
http://genome.ucsc.edu/cgi-bin/hgTracks?genome=t2t-chm13-v1.0&hubUrl=http://t2t.gi.ucsc.edu/chm13/hub/hub.txt
https://resgen.io/paper-data/T2T-Nurk-et-al-2021/views/t2t-identity
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Posted May 27, 2021.
The complete sequence of a human genome
Sergey Nurk, Sergey Koren, Arang Rhie, Mikko Rautiainen, Andrey V. Bzikadze, Alla Mikheenko, Mitchell R. Vollger, Nicolas Altemose, Lev Uralsky, Ariel Gershman, Sergey Aganezov, Savannah J. Hoyt, Mark Diekhans, Glennis A. Logsdon, Michael Alonge, Stylianos E. Antonarakis, Matthew Borchers, Gerard G. Bouffard, Shelise Y. Brooks, Gina V. Caldas, Haoyu Cheng, Chen-Shan Chin, William Chow, Leonardo G. de Lima, Philip C. Dishuck, Richard Durbin, Tatiana Dvorkina, Ian T. Fiddes, Giulio Formenti, Robert S. Fulton, Arkarachai Fungtammasan, Erik Garrison, Patrick G.S. Grady, Tina A. Graves-Lindsay, Ira M. Hall, Nancy F. Hansen, Gabrielle A. Hartley, Marina Haukness, Kerstin Howe, Michael W. Hunkapiller, Chirag Jain, Miten Jain, Erich D. Jarvis, Peter Kerpedjiev, Melanie Kirsche, Mikhail Kolmogorov, Jonas Korlach, Milinn Kremitzki, Heng Li, Valerie V. Maduro, Tobias Marschall, Ann M. McCartney, Jennifer McDaniel, Danny E. Miller, James C. Mullikin, Eugene W. Myers, Nathan D. Olson, Benedict Paten, Paul Peluso, Pavel A. Pevzner, David Porubsky, Tamara Potapova, Evgeny I. Rogaev, Jeffrey A. Rosenfeld, Steven L. Salzberg, Valerie A. Schneider, Fritz J. Sedlazeck, Kishwar Shafin, Colin J. Shew, Alaina Shumate, Yumi Sims, Arian F. A. Smit, Daniela C. Soto, Ivan Sović, Jessica M. Storer, Aaron Streets, Beth A. Sullivan, Françoise Thibaud-Nissen, James Torrance, Justin Wagner, Brian P. Walenz, Aaron Wenger, Jonathan M. D. Wood, Chunlin Xiao, Stephanie M. Yan, Alice C. Young, Samantha Zarate, Urvashi Surti, Rajiv C. McCoy, Megan Y. Dennis, Ivan A. Alexandrov, Jennifer L. Gerton, Rachel J. O’Neill, Winston Timp, Justin M. Zook, Michael C. Schatz, Evan E. Eichler, Karen H. Miga, Adam M. Phillippy
bioRxiv 2021.05.26.445798; doi: https://doi.org/10.1101/2021.05.26.445798
The complete sequence of a human genome
Sergey Nurk, Sergey Koren, Arang Rhie, Mikko Rautiainen, Andrey V. Bzikadze, Alla Mikheenko, Mitchell R. Vollger, Nicolas Altemose, Lev Uralsky, Ariel Gershman, Sergey Aganezov, Savannah J. Hoyt, Mark Diekhans, Glennis A. Logsdon, Michael Alonge, Stylianos E. Antonarakis, Matthew Borchers, Gerard G. Bouffard, Shelise Y. Brooks, Gina V. Caldas, Haoyu Cheng, Chen-Shan Chin, William Chow, Leonardo G. de Lima, Philip C. Dishuck, Richard Durbin, Tatiana Dvorkina, Ian T. Fiddes, Giulio Formenti, Robert S. Fulton, Arkarachai Fungtammasan, Erik Garrison, Patrick G.S. Grady, Tina A. Graves-Lindsay, Ira M. Hall, Nancy F. Hansen, Gabrielle A. Hartley, Marina Haukness, Kerstin Howe, Michael W. Hunkapiller, Chirag Jain, Miten Jain, Erich D. Jarvis, Peter Kerpedjiev, Melanie Kirsche, Mikhail Kolmogorov, Jonas Korlach, Milinn Kremitzki, Heng Li, Valerie V. Maduro, Tobias Marschall, Ann M. McCartney, Jennifer McDaniel, Danny E. Miller, James C. Mullikin, Eugene W. Myers, Nathan D. Olson, Benedict Paten, Paul Peluso, Pavel A. Pevzner, David Porubsky, Tamara Potapova, Evgeny I. Rogaev, Jeffrey A. Rosenfeld, Steven L. Salzberg, Valerie A. Schneider, Fritz J. Sedlazeck, Kishwar Shafin, Colin J. Shew, Alaina Shumate, Yumi Sims, Arian F. A. Smit, Daniela C. Soto, Ivan Sović, Jessica M. Storer, Aaron Streets, Beth A. Sullivan, Françoise Thibaud-Nissen, James Torrance, Justin Wagner, Brian P. Walenz, Aaron Wenger, Jonathan M. D. Wood, Chunlin Xiao, Stephanie M. Yan, Alice C. Young, Samantha Zarate, Urvashi Surti, Rajiv C. McCoy, Megan Y. Dennis, Ivan A. Alexandrov, Jennifer L. Gerton, Rachel J. O’Neill, Winston Timp, Justin M. Zook, Michael C. Schatz, Evan E. Eichler, Karen H. Miga, Adam M. Phillippy
bioRxiv 2021.05.26.445798; doi: https://doi.org/10.1101/2021.05.26.445798
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