New Results
The complete sequence of a human Y chromosome
View ORCID ProfileArang Rhie, Sergey Nurk, View ORCID ProfileMonika Cechova, View ORCID ProfileSavannah J. Hoyt, View ORCID ProfileDylan J. Taylor, View ORCID ProfileNicolas Altemose, View ORCID ProfilePaul W. Hook, View ORCID ProfileSergey Koren, View ORCID ProfileMikko Rautiainen, View ORCID ProfileIvan A. Alexandrov, View ORCID ProfileJamie Allen, View ORCID ProfileMobin Asri, Andrey V. Bzikadze, View ORCID ProfileNae-Chyun Chen, View ORCID ProfileChen-Shan Chin, View ORCID ProfileMark Diekhans, View ORCID ProfilePaul Flicek, View ORCID ProfileGiulio Formenti, View ORCID ProfileArkarachai Fungtammasan, View ORCID ProfileCarlos Garcia Giron, View ORCID ProfileErik Garrison, View ORCID ProfileAriel Gershman, View ORCID ProfileJennifer L. Gerton, View ORCID ProfilePatrick G.S. Grady, View ORCID ProfileAndrea Guarracino, View ORCID ProfileLeanne Haggerty, View ORCID ProfileReza Halabian, View ORCID ProfileNancy F. Hansen, View ORCID ProfileRobert Harris, View ORCID ProfileGabrielle A. Hartley, View ORCID ProfileWilliam T. Harvey, View ORCID ProfileMarina Haukness, View ORCID ProfileJakob Heinz, View ORCID ProfileThibaut Hourlier, View ORCID ProfileRobert M. Hubley, View ORCID ProfileSarah E. Hunt, View ORCID ProfileStephen Hwang, View ORCID ProfileMiten Jain, View ORCID ProfileRupesh K. Kesharwani, View ORCID ProfileAlexandra P. Lewis, View ORCID ProfileHeng Li, View ORCID ProfileGlennis A. Logsdon, View ORCID ProfileJulian K. Lucas, View ORCID ProfileWojciech Makalowski, Christopher Markovic, View ORCID ProfileFergal J. Martin, View ORCID ProfileAnn M. Mc Cartney, View ORCID ProfileRajiv C. McCoy, View ORCID ProfileJennifer McDaniel, Brandy M. McNulty, View ORCID ProfilePaul Medvedev, View ORCID ProfileAlla Mikheenko, View ORCID ProfileKatherine M. Munson, View ORCID ProfileTerence D. Murphy, Hugh E. Olsen, View ORCID ProfileNathan D. Olson, View ORCID ProfileLuis F. Paulin, View ORCID ProfileDavid Porubsky, View ORCID ProfileTamara Potapova, View ORCID ProfileFedor Ryabov, View ORCID ProfileSteven L. Salzberg, View ORCID ProfileMichael E.G. Sauria, View ORCID ProfileFritz J. Sedlazeck, View ORCID ProfileKishwar Shafin, Valery A. Shepelev, View ORCID ProfileAlaina Shumate, View ORCID ProfileJessica M. Storer, View ORCID ProfileLikhitha Surapaneni, View ORCID ProfileAngela M. Taravella Oill, View ORCID ProfileFrançoise Thibaud-Nissen, View ORCID ProfileWinston Timp, View ORCID ProfileMarta Tomaszkiewicz, View ORCID ProfileMitchell R. Vollger, Brian P. Walenz, View ORCID ProfileAllison C. Watwood, View ORCID ProfileMatthias H. Weissensteiner, View ORCID ProfileAaron M. Wenger, View ORCID ProfileMelissa A. Wilson, View ORCID ProfileSamantha Zarate, Yiming Zhu, View ORCID ProfileJustin M. Zook, View ORCID ProfileEvan E. Eichler, View ORCID ProfileRachel J. O’Neill, View ORCID ProfileMichael C. Schatz, View ORCID ProfileKaren H. Miga, View ORCID ProfileKateryna D. Makova, View ORCID ProfileAdam M. Phillippy
doi: https://doi.org/10.1101/2022.12.01.518724
Arang Rhie
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Sergey Nurk
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Monika Cechova
3Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA
Savannah J. Hoyt
4Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Dylan J. Taylor
5Department of Biology, Johns Hopkins University, Baltimore, MD, USA
Nicolas Altemose
6Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA
Paul W. Hook
7Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Sergey Koren
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
Ivan A. Alexandrov
8Federal Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia
9Center for Algorithmic Biotechnology, Saint Petersburg State University, Russia
Jamie Allen
10European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
Mobin Asri
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Andrey V. Bzikadze
12Graduate Program in Bioinformatics and Systems Biology, University of California, San Diego, CA, USA
Nae-Chyun Chen
13Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
Chen-Shan Chin
14GeneDX Holdings Corp, Stamford, CT, USA
15Foundation of Biological Data Science, Belmont, CA, USA
Mark Diekhans
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Paul Flicek
10European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
16Department of Genetics, University of Cambridge, Cambridge, United Kingdom
Giulio Formenti
17The Rockefeller University, New York, NY, USA
Arkarachai Fungtammasan
18DNAnexus, Inc., Mountain View, CA, USA
Carlos Garcia Giron
10European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
Erik Garrison
19Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, USA
Ariel Gershman
7Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Jennifer L. Gerton
20Stowers Institute for Medical Research, Kansas City, MO, USA
21University of Kansas Medical Center, Kansas City, MO, USA
Patrick G.S. Grady
4Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
Andrea Guarracino
22Genomics Research Centre, Human Technopole, Viale Rita Levi-Montalcini 1, Milan, Italy
19Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee, USA
Leanne Haggerty
10European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
Reza Halabian
23Institute of Bioinformatics, Faculty of Medicine, University of Münster, Münster, Germany
Nancy F. Hansen
24Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Robert Harris
25Department of Biology, Pennsylvania State University, University Park, PA, USA
Gabrielle A. Hartley
4Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
William T. Harvey
26Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Marina Haukness
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Jakob Heinz
7Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Thibaut Hourlier
10European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
Robert M. Hubley
27Institute for Systems Biology, Seattle, WA, USA
Sarah E. Hunt
10European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
Stephen Hwang
28XDBio Program, Johns Hopkins University, Baltimore, MD, USA
Miten Jain
29Department of Bioengineering, Department of Physics, Northeastern University, Boston, MA, USA
Rupesh K. Kesharwani
30Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA
Alexandra P. Lewis
26Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Heng Li
31Department of data sciences, Dana-Farber Cancer Institute, Boston, MA, USA
32Department of biomedical informatics, Harvard Medical School, Boston, MA, USA
Glennis A. Logsdon
26Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Julian K. Lucas
3Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Wojciech Makalowski
23Institute of Bioinformatics, Faculty of Medicine, University of Münster, Münster, Germany
Christopher Markovic
33Genome Technology Access Center at the McDonnell Genome Institute (GTAC@MGI) Washington University, St. Louis, MO, USA
Fergal J. Martin
10European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
Ann M. Mc Cartney
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Rajiv C. McCoy
5Department of Biology, Johns Hopkins University, Baltimore, MD, USA
Jennifer McDaniel
34Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
Brandy M. McNulty
3Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Paul Medvedev
35Department of Computer Science and Engineering, Pennsylvania State University, University Park, PA, USA
36Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA
37Center for Computational Biology and Bioinformatics, Pennsylvania State University, University Park, PA, USA
Alla Mikheenko
9Center for Algorithmic Biotechnology, Saint Petersburg State University, Russia
38UCL Queen Square Institute of Neurology, UCL, London, UK
Katherine M. Munson
26Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Terence D. Murphy
39National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
Hugh E. Olsen
3Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Nathan D. Olson
34Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
Luis F. Paulin
30Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA
David Porubsky
26Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Tamara Potapova
20Stowers Institute for Medical Research, Kansas City, MO, USA
Fedor Ryabov
40Masters Program in National Research University Higher School of Economics, Moscow, Russia
Steven L. Salzberg
41Departments of Biomedical Engineering, Computer Science, and Biostatistics, Johns Hopkins University, Baltimore, MD
Michael E.G. Sauria
5Department of Biology, Johns Hopkins University, Baltimore, MD, USA
Fritz J. Sedlazeck
30Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA
42Department of Computer Science, Rice University, Houston, TX, USA
Kishwar Shafin
43Google Inc, 1600 Amphitheatre Pkwy, Mountain View, CA, USA
Valery A. Shepelev
44Institute of Molecular Genetics, Moscow, Russia
Alaina Shumate
7Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Jessica M. Storer
27Institute for Systems Biology, Seattle, WA, USA
Likhitha Surapaneni
10European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom
Angela M. Taravella Oill
45Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, AZ, USA
Françoise Thibaud-Nissen
39National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
Winston Timp
7Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
Marta Tomaszkiewicz
25Department of Biology, Pennsylvania State University, University Park, PA, USA
46Department of Biomedical Engineering, Pennsylvania State University, State College, PA, USA
Mitchell R. Vollger
26Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
Brian P. Walenz
1Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Allison C. Watwood
25Department of Biology, Pennsylvania State University, University Park, PA, USA
Matthias H. Weissensteiner
25Department of Biology, Pennsylvania State University, University Park, PA, USA
Aaron M. Wenger
47Pacific Biosciences, Menlo Park, CA, USA
Melissa A. Wilson
45Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, AZ, USA
Samantha Zarate
13Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
Yiming Zhu
30Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA
Justin M. Zook
34Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
Evan E. Eichler
26Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA
48Investigator, Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA
Rachel J. O’Neill
4Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA
49Institute for Systems Genomics, University of Connecticut, Storrs, CT, USA
50Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, USA
Michael C. Schatz
13Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
5Department of Biology, Johns Hopkins University, Baltimore, MD, USA
Karen H. Miga
3Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA
11UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA
Kateryna D. Makova
25Department of Biology, Pennsylvania State University, University Park, PA, 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
The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure including long palindromes, tandem repeats, and segmental duplications1–3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished4, 5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029 base pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, revealing the complete ampliconic structures of TSPY, DAZ, and RBMY gene families; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a prior assembly of the CHM13 genome4 and mapped available population variation, clinical variants, and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.
Competing Interest Statement
S.N. is now an employee of Oxford Nanopore Technologies; S.K. has received travel funds to speak at events hosted by Oxford Nanopore Technologies; A.F. is an employee of DNAnexus; C.-S.C. is an employee of GeneDX Holdings Corp.; N.-C.C. is an employee of Exai Bio; L.F.P. receives research support from Genetech; F.J.S. receives research support from Pacific Biosciences, Oxford Nanopore Technologies, Illumina, and Genetech; K.S. is an employee of Google LLC and owns Alphabet stock as part of the standard compensation package; W.T. has two patents (8,748,091 and 8,394,584) licensed to Oxford Nanopore Technologies; E.E.E. is a scientific advisory board member of Variant Bio, Inc. All other authors declare no competing interests.
Footnotes
↵# Retired
The manuscript has been updated to reflect updates in gene annotations and to make the manuscript more succinct.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.
Posted July 11, 2023.
The complete sequence of a human Y chromosome
Arang Rhie, Sergey Nurk, Monika Cechova, Savannah J. Hoyt, Dylan J. Taylor, Nicolas Altemose, Paul W. Hook, Sergey Koren, Mikko Rautiainen, Ivan A. Alexandrov, Jamie Allen, Mobin Asri, Andrey V. Bzikadze, Nae-Chyun Chen, Chen-Shan Chin, Mark Diekhans, Paul Flicek, Giulio Formenti, Arkarachai Fungtammasan, Carlos Garcia Giron, Erik Garrison, Ariel Gershman, Jennifer L. Gerton, Patrick G.S. Grady, Andrea Guarracino, Leanne Haggerty, Reza Halabian, Nancy F. Hansen, Robert Harris, Gabrielle A. Hartley, William T. Harvey, Marina Haukness, Jakob Heinz, Thibaut Hourlier, Robert M. Hubley, Sarah E. Hunt, Stephen Hwang, Miten Jain, Rupesh K. Kesharwani, Alexandra P. Lewis, Heng Li, Glennis A. Logsdon, Julian K. Lucas, Wojciech Makalowski, Christopher Markovic, Fergal J. Martin, Ann M. Mc Cartney, Rajiv C. McCoy, Jennifer McDaniel, Brandy M. McNulty, Paul Medvedev, Alla Mikheenko, Katherine M. Munson, Terence D. Murphy, Hugh E. Olsen, Nathan D. Olson, Luis F. Paulin, David Porubsky, Tamara Potapova, Fedor Ryabov, Steven L. Salzberg, Michael E.G. Sauria, Fritz J. Sedlazeck, Kishwar Shafin, Valery A. Shepelev, Alaina Shumate, Jessica M. Storer, Likhitha Surapaneni, Angela M. Taravella Oill, Françoise Thibaud-Nissen, Winston Timp, Marta Tomaszkiewicz, Mitchell R. Vollger, Brian P. Walenz, Allison C. Watwood, Matthias H. Weissensteiner, Aaron M. Wenger, Melissa A. Wilson, Samantha Zarate, Yiming Zhu, Justin M. Zook, Evan E. Eichler, Rachel J. O’Neill, Michael C. Schatz, Karen H. Miga, Kateryna D. Makova, Adam M. Phillippy
bioRxiv 2022.12.01.518724; doi: https://doi.org/10.1101/2022.12.01.518724
The complete sequence of a human Y chromosome
Arang Rhie, Sergey Nurk, Monika Cechova, Savannah J. Hoyt, Dylan J. Taylor, Nicolas Altemose, Paul W. Hook, Sergey Koren, Mikko Rautiainen, Ivan A. Alexandrov, Jamie Allen, Mobin Asri, Andrey V. Bzikadze, Nae-Chyun Chen, Chen-Shan Chin, Mark Diekhans, Paul Flicek, Giulio Formenti, Arkarachai Fungtammasan, Carlos Garcia Giron, Erik Garrison, Ariel Gershman, Jennifer L. Gerton, Patrick G.S. Grady, Andrea Guarracino, Leanne Haggerty, Reza Halabian, Nancy F. Hansen, Robert Harris, Gabrielle A. Hartley, William T. Harvey, Marina Haukness, Jakob Heinz, Thibaut Hourlier, Robert M. Hubley, Sarah E. Hunt, Stephen Hwang, Miten Jain, Rupesh K. Kesharwani, Alexandra P. Lewis, Heng Li, Glennis A. Logsdon, Julian K. Lucas, Wojciech Makalowski, Christopher Markovic, Fergal J. Martin, Ann M. Mc Cartney, Rajiv C. McCoy, Jennifer McDaniel, Brandy M. McNulty, Paul Medvedev, Alla Mikheenko, Katherine M. Munson, Terence D. Murphy, Hugh E. Olsen, Nathan D. Olson, Luis F. Paulin, David Porubsky, Tamara Potapova, Fedor Ryabov, Steven L. Salzberg, Michael E.G. Sauria, Fritz J. Sedlazeck, Kishwar Shafin, Valery A. Shepelev, Alaina Shumate, Jessica M. Storer, Likhitha Surapaneni, Angela M. Taravella Oill, Françoise Thibaud-Nissen, Winston Timp, Marta Tomaszkiewicz, Mitchell R. Vollger, Brian P. Walenz, Allison C. Watwood, Matthias H. Weissensteiner, Aaron M. Wenger, Melissa A. Wilson, Samantha Zarate, Yiming Zhu, Justin M. Zook, Evan E. Eichler, Rachel J. O’Neill, Michael C. Schatz, Karen H. Miga, Kateryna D. Makova, Adam M. Phillippy
bioRxiv 2022.12.01.518724; doi: https://doi.org/10.1101/2022.12.01.518724
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