Generation and annotation of the DNA sequences of human chromosomes 2 and 4

La Deana W. Hillier; Tina A. Graves; Robert S. Fulton; Lucinda A. Fulton; Kymberlie H. Pepin; Patrick Minx; Caryn Wagner-McPherson; Dan Layman; Kristine Wylie; Mandeep Sekhon; Michael C. Becker; Ginger A. Fewell; Kimberly D. Delehaunty; Tracie L. Miner; William E. Nash; Colin Kremitzki; Lachlan Oddy; Hui Du; Hui Sun; Holland Bradshaw-Cordum; Johar Ali; Jason Carter; Matt Cordes; Anthony Harris; Amber Isak; Andrew Van Brunt; Christine Nguyen; Feiyu Du; Laura Courtney; Joelle Kalicki; Philip Ozersky; Scott Abbott; Jon Armstrong; Edward A. Belter; Lauren Caruso; Maria Cedroni; Marc Cotton; Teresa Davidson; Anu Desai; Glendoria Elliott; Thomas Erb; Catrina Fronick; Tony Gaige; William Haakenson; Krista Haglund; Andrea Holmes; Richard Harkins; Kyung Kim; Scott S. Kruchowski; Cynthia Madsen Strong; Neenu Grewal; Ernest Goyea; Shunfang Hou; Andrew Levy; Scott Martinka; Kelly Mead; Michael D. McLellan; Rick Meyer; Jennifer Randall-Maher; Chad Tomlinson; Sara Dauphin-Kohlberg; Amy Kozlowicz-Reilly; Neha Shah; Sharhonda Swearengen-Shahid; Jacqueline Snider; Joseph T. Strong; Johanna Thompson; Martin Yoakum; Shawn Leonard; Charlene Pearman; Lee Trani; Maxim Radionenko; Jason E. Waligorski; Chunyan Wang; Susan M. Rock; Aye Mon Tin-Wollam; Rachel Maupin; Phil Latreille; Michael C. Wendl; Shiaw Pyng Yang; Craig Pohl; John W. Wallis; John Spieth; Tamberlyn A. Bieri; Nicolas Berkowicz; Joanne O. Nelson; John Osborne; Li Ding; Rekha Meyer; Aniko Sabo; Yoram Shotland; Prashant Sinha; Patricia E. Wohldmann; Lisa L. Cook; Matthew T. Hickenbotham; James Eldred; Donald Williams; Thomas A. Jones; Xinwei She; Francesca D. Ciccarelli; Elisa Izaurralde; James Taylor; Jeremy Schmutz; Richard M. Myers; David R. Cox; Xiaoqiu Huang; John D. McPherson; Elaine R. Mardis; Sandra W. Clifton; Wesley C. Warren; Asif T. Chinwalla; Sean R. Eddy; Marco A. Marra; Ivan Ovcharenko; Terrence S. Furey; Webb Miller; Evan E. Eichler; Peer Bork; Mikita Suyama; David Torrents; Robert H. Waterston; Richard K. Wilson

doi:10.1038/nature03466

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

La Deana W. Hillier, Tina A. Graves, Robert S. Fulton, Lucinda A. Fulton, Kymberlie H. Pepin, Patrick Minx, Caryn Wagner-McPherson, Dan Layman, Kristine Wylie, Mandeep Sekhon, Michael C. Becker, Ginger A. Fewell, Kimberly D. Delehaunty, Tracie L. Miner, William E. Nash, Colin Kremitzki, Lachlan Oddy, Hui Du, Hui Sun, Holland Bradshaw-CordumJohar Ali, Jason Carter, Matt Cordes, Anthony Harris, Amber Isak, Andrew Van Brunt, Christine Nguyen, Feiyu Du, Laura Courtney, Joelle Kalicki, Philip Ozersky, Scott Abbott, Jon Armstrong, Edward A. Belter, Lauren Caruso, Maria Cedroni, Marc Cotton, Teresa Davidson, Anu Desai, Glendoria Elliott, Thomas Erb, Catrina Fronick, Tony Gaige, William Haakenson, Krista Haglund, Andrea Holmes, Richard Harkins, Kyung Kim, Scott S. Kruchowski, Cynthia Madsen Strong, Neenu Grewal, Ernest Goyea, Shunfang Hou, Andrew Levy, Scott Martinka, Kelly Mead, Michael D. McLellan, Rick Meyer, Jennifer Randall-Maher, Chad Tomlinson, Sara Dauphin-Kohlberg, Amy Kozlowicz-Reilly, Neha Shah, Sharhonda Swearengen-Shahid, Jacqueline Snider, Joseph T. Strong, Johanna Thompson, Martin Yoakum, Shawn Leonard, Charlene Pearman, Lee Trani, Maxim Radionenko, Jason E. Waligorski, Chunyan Wang, Susan M. Rock, Aye Mon Tin-Wollam, Rachel Maupin, Phil Latreille, Michael C. Wendl, Shiaw Pyng Yang, Craig Pohl, John W. Wallis, John Spieth, Tamberlyn A. Bieri, Nicolas Berkowicz, Joanne O. Nelson, John Osborne, Li Ding, Rekha Meyer, Aniko Sabo, Yoram Shotland, Prashant Sinha, Patricia E. Wohldmann, Lisa L. Cook, Matthew T. Hickenbotham, James Eldred, Donald Williams, Thomas A. Jones, Xinwei She, Francesca D. Ciccarelli, Elisa Izaurralde, James Taylor, Jeremy Schmutz, Richard M. Myers, David R. Cox, Xiaoqiu Huang, John D. McPherson, Elaine R. Mardis, Sandra W. Clifton, Wesley C. Warren, Asif T. Chinwalla, Sean R. Eddy, Marco A. Marra, Ivan Ovcharenko, Terrence S. Furey, Webb Miller, Evan E. Eichler, Peer Bork, Mikita Suyama, David Torrents, Robert H. Waterston, Richard K. Wilson

Research output: Contribution to journal › Article › peer-review

79 Scopus citations

Abstract

Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.

Original language	English
Pages (from-to)	724-731
Number of pages	8
Journal	Nature
Volume	434
Issue number	7034
DOIs	https://doi.org/10.1038/nature03466
State	Published - Apr 7 2005

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Hillier, L. D. W., Graves, T. A., Fulton, R. S., Fulton, L. A., Pepin, K. H., Minx, P., Wagner-McPherson, C., Layman, D., Wylie, K., Sekhon, M., Becker, M. C., Fewell, G. A., Delehaunty, K. D., Miner, T. L., Nash, W. E., Kremitzki, C., Oddy, L., Du, H., Sun, H., ... Wilson, R. K. (2005). Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature, 434(7034), 724-731. https://doi.org/10.1038/nature03466

@article{fa65bf7317544634ae5a8178e9629de3,

title = "Generation and annotation of the DNA sequences of human chromosomes 2 and 4",

abstract = "Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.",

author = "Hillier, {La Deana W.} and Graves, {Tina A.} and Fulton, {Robert S.} and Fulton, {Lucinda A.} and Pepin, {Kymberlie H.} and Patrick Minx and Caryn Wagner-McPherson and Dan Layman and Kristine Wylie and Mandeep Sekhon and Becker, {Michael C.} and Fewell, {Ginger A.} and Delehaunty, {Kimberly D.} and Miner, {Tracie L.} and Nash, {William E.} and Colin Kremitzki and Lachlan Oddy and Hui Du and Hui Sun and Holland Bradshaw-Cordum and Johar Ali and Jason Carter and Matt Cordes and Anthony Harris and Amber Isak and {Van Brunt}, Andrew and Christine Nguyen and Feiyu Du and Laura Courtney and Joelle Kalicki and Philip Ozersky and Scott Abbott and Jon Armstrong and Belter, {Edward A.} and Lauren Caruso and Maria Cedroni and Marc Cotton and Teresa Davidson and Anu Desai and Glendoria Elliott and Thomas Erb and Catrina Fronick and Tony Gaige and William Haakenson and Krista Haglund and Andrea Holmes and Richard Harkins and Kyung Kim and Kruchowski, {Scott S.} and Strong, {Cynthia Madsen} and Neenu Grewal and Ernest Goyea and Shunfang Hou and Andrew Levy and Scott Martinka and Kelly Mead and McLellan, {Michael D.} and Rick Meyer and Jennifer Randall-Maher and Chad Tomlinson and Sara Dauphin-Kohlberg and Amy Kozlowicz-Reilly and Neha Shah and Sharhonda Swearengen-Shahid and Jacqueline Snider and Strong, {Joseph T.} and Johanna Thompson and Martin Yoakum and Shawn Leonard and Charlene Pearman and Lee Trani and Maxim Radionenko and Waligorski, {Jason E.} and Chunyan Wang and Rock, {Susan M.} and Tin-Wollam, {Aye Mon} and Rachel Maupin and Phil Latreille and Wendl, {Michael C.} and Yang, {Shiaw Pyng} and Craig Pohl and Wallis, {John W.} and John Spieth and Bieri, {Tamberlyn A.} and Nicolas Berkowicz and Nelson, {Joanne O.} and John Osborne and Li Ding and Rekha Meyer and Aniko Sabo and Yoram Shotland and Prashant Sinha and Wohldmann, {Patricia E.} and Cook, {Lisa L.} and Hickenbotham, {Matthew T.} and James Eldred and Donald Williams and Jones, {Thomas A.} and Xinwei She and Ciccarelli, {Francesca D.} and Elisa Izaurralde and James Taylor and Jeremy Schmutz and Myers, {Richard M.} and Cox, {David R.} and Xiaoqiu Huang and McPherson, {John D.} and Mardis, {Elaine R.} and Clifton, {Sandra W.} and Warren, {Wesley C.} and Chinwalla, {Asif T.} and Eddy, {Sean R.} and Marra, {Marco A.} and Ivan Ovcharenko and Furey, {Terrence S.} and Webb Miller and Eichler, {Evan E.} and Peer Bork and Mikita Suyama and David Torrents and Waterston, {Robert H.} and Wilson, {Richard K.}",

note = "Funding Information: Acknowledgements The authors would like to thank the staff, past and present, of the Washington University Genome Sequencing Center as well as the following laboratories that contributed sequence segments to the final chromosome 2 and 4 sequence: the Broad Institute of MIT; Stanford DNA Sequencing and Technology Development Center; the Sanger Centre; National Yang-Ming University in Taipei; Genoscope; Baylor College of Medicine; the Joint Genome Institute; University of Washington Multimegabase Sequencing Center; DOE Joint Genome Institute; and Roswell Park Cancer Institute. We thank T. Hubbard, J. Ashurst, J. Gilbert and S. Keenan for Ensembl pipeline assistance. We thank the Broad Institute of MIT, Harvard and Agencourt Bioscience for making a preliminary assembly of dog genome sequence available to us. We thank the Zebrafish Sequencing Group at the Sanger Centre for the Danio rerio preliminary protein set. We thank the International HapMap Consortium and their sponsors for use of their data and J. Mullikin for help with alignment of their data to the human genome. We thank the Chimpanzee Genome Sequencing Consortium for use of the chimpanzee sequence data. The authors would also like to acknowledge the efforts of the HUGO Gene Nomenclature Committee. Finally, the authors acknowledge the National Human Genome Research Institute for funding this work.",

year = "2005",

month = apr,

day = "7",

doi = "10.1038/nature03466",

language = "English",

volume = "434",

pages = "724--731",

journal = "Nature",

issn = "0028-0836",

number = "7034",

}

Hillier, LDW, Graves, TA , Fulton, RS , Fulton, LA, Pepin, KH, Minx, P, Wagner-McPherson, C, Layman, D, Wylie, K, Sekhon, M, Becker, MC, Fewell, GA, Delehaunty, KD, Miner, TL, Nash, WE, Kremitzki, C, Oddy, L, Du, H, Sun, H, Bradshaw-Cordum, H, Ali, J, Carter, J, Cordes, M, Harris, A, Isak, A, Van Brunt, A, Nguyen, C, Du, F, Courtney, L, Kalicki, J, Ozersky, P, Abbott, S, Armstrong, J, Belter, EA, Caruso, L, Cedroni, M, Cotton, M, Davidson, T, Desai, A, Elliott, G, Erb, T, Fronick, C, Gaige, T, Haakenson, W, Haglund, K, Holmes, A, Harkins, R, Kim, K, Kruchowski, SS, Strong, CM, Grewal, N, Goyea, E, Hou, S, Levy, A, Martinka, S, Mead, K, McLellan, MD, Meyer, R, Randall-Maher, J, Tomlinson, C, Dauphin-Kohlberg, S, Kozlowicz-Reilly, A, Shah, N, Swearengen-Shahid, S, Snider, J, Strong, JT, Thompson, J, Yoakum, M, Leonard, S, Pearman, C, Trani, L, Radionenko, M, Waligorski, JE, Wang, C, Rock, SM, Tin-Wollam, AM, Maupin, R, Latreille, P, Wendl, MC, Yang, SP, Pohl, C, Wallis, JW, Spieth, J, Bieri, TA, Berkowicz, N, Nelson, JO, Osborne, J, Ding, L, Meyer, R, Sabo, A, Shotland, Y, Sinha, P, Wohldmann, PE, Cook, LL, Hickenbotham, MT, Eldred, J, Williams, D, Jones, TA, She, X, Ciccarelli, FD, Izaurralde, E, Taylor, J, Schmutz, J, Myers, RM, Cox, DR, Huang, X, McPherson, JD, Mardis, ER, Clifton, SW, Warren, WC, Chinwalla, AT, Eddy, SR, Marra, MA, Ovcharenko, I, Furey, TS, Miller, W, Eichler, EE, Bork, P, Suyama, M, Torrents, D, Waterston, RH & Wilson, RK 2005, 'Generation and annotation of the DNA sequences of human chromosomes 2 and 4', Nature, vol. 434, no. 7034, pp. 724-731. https://doi.org/10.1038/nature03466

TY - JOUR

T1 - Generation and annotation of the DNA sequences of human chromosomes 2 and 4

AU - Hillier, La Deana W.

AU - Graves, Tina A.

AU - Fulton, Robert S.

AU - Fulton, Lucinda A.

AU - Pepin, Kymberlie H.

AU - Minx, Patrick

AU - Wagner-McPherson, Caryn

AU - Layman, Dan

AU - Wylie, Kristine

AU - Sekhon, Mandeep

AU - Becker, Michael C.

AU - Fewell, Ginger A.

AU - Delehaunty, Kimberly D.

AU - Miner, Tracie L.

AU - Nash, William E.

AU - Kremitzki, Colin

AU - Oddy, Lachlan

AU - Du, Hui

AU - Sun, Hui

AU - Bradshaw-Cordum, Holland

AU - Ali, Johar

AU - Carter, Jason

AU - Cordes, Matt

AU - Harris, Anthony

AU - Isak, Amber

AU - Van Brunt, Andrew

AU - Nguyen, Christine

AU - Du, Feiyu

AU - Courtney, Laura

AU - Kalicki, Joelle

AU - Ozersky, Philip

AU - Abbott, Scott

AU - Armstrong, Jon

AU - Belter, Edward A.

AU - Caruso, Lauren

AU - Cedroni, Maria

AU - Cotton, Marc

AU - Davidson, Teresa

AU - Desai, Anu

AU - Elliott, Glendoria

AU - Erb, Thomas

AU - Fronick, Catrina

AU - Gaige, Tony

AU - Haakenson, William

AU - Haglund, Krista

AU - Holmes, Andrea

AU - Harkins, Richard

AU - Kim, Kyung

AU - Kruchowski, Scott S.

AU - Strong, Cynthia Madsen

AU - Grewal, Neenu

AU - Goyea, Ernest

AU - Hou, Shunfang

AU - Levy, Andrew

AU - Martinka, Scott

AU - Mead, Kelly

AU - McLellan, Michael D.

AU - Meyer, Rick

AU - Randall-Maher, Jennifer

AU - Tomlinson, Chad

AU - Dauphin-Kohlberg, Sara

AU - Kozlowicz-Reilly, Amy

AU - Shah, Neha

AU - Swearengen-Shahid, Sharhonda

AU - Snider, Jacqueline

AU - Strong, Joseph T.

AU - Thompson, Johanna

AU - Yoakum, Martin

AU - Leonard, Shawn

AU - Pearman, Charlene

AU - Trani, Lee

AU - Radionenko, Maxim

AU - Waligorski, Jason E.

AU - Wang, Chunyan

AU - Rock, Susan M.

AU - Tin-Wollam, Aye Mon

AU - Maupin, Rachel

AU - Latreille, Phil

AU - Wendl, Michael C.

AU - Yang, Shiaw Pyng

AU - Pohl, Craig

AU - Wallis, John W.

AU - Spieth, John

AU - Bieri, Tamberlyn A.

AU - Berkowicz, Nicolas

AU - Nelson, Joanne O.

AU - Osborne, John

AU - Ding, Li

AU - Meyer, Rekha

AU - Sabo, Aniko

AU - Shotland, Yoram

AU - Sinha, Prashant

AU - Wohldmann, Patricia E.

AU - Cook, Lisa L.

AU - Hickenbotham, Matthew T.

AU - Eldred, James

AU - Williams, Donald

AU - Jones, Thomas A.

AU - She, Xinwei

AU - Ciccarelli, Francesca D.

AU - Izaurralde, Elisa

AU - Taylor, James

AU - Schmutz, Jeremy

AU - Myers, Richard M.

AU - Cox, David R.

AU - Huang, Xiaoqiu

AU - McPherson, John D.

AU - Mardis, Elaine R.

AU - Clifton, Sandra W.

AU - Warren, Wesley C.

AU - Chinwalla, Asif T.

AU - Eddy, Sean R.

AU - Marra, Marco A.

AU - Ovcharenko, Ivan

AU - Furey, Terrence S.

AU - Miller, Webb

AU - Eichler, Evan E.

AU - Bork, Peer

AU - Suyama, Mikita

AU - Torrents, David

AU - Waterston, Robert H.

AU - Wilson, Richard K.

N1 - Funding Information: Acknowledgements The authors would like to thank the staff, past and present, of the Washington University Genome Sequencing Center as well as the following laboratories that contributed sequence segments to the final chromosome 2 and 4 sequence: the Broad Institute of MIT; Stanford DNA Sequencing and Technology Development Center; the Sanger Centre; National Yang-Ming University in Taipei; Genoscope; Baylor College of Medicine; the Joint Genome Institute; University of Washington Multimegabase Sequencing Center; DOE Joint Genome Institute; and Roswell Park Cancer Institute. We thank T. Hubbard, J. Ashurst, J. Gilbert and S. Keenan for Ensembl pipeline assistance. We thank the Broad Institute of MIT, Harvard and Agencourt Bioscience for making a preliminary assembly of dog genome sequence available to us. We thank the Zebrafish Sequencing Group at the Sanger Centre for the Danio rerio preliminary protein set. We thank the International HapMap Consortium and their sponsors for use of their data and J. Mullikin for help with alignment of their data to the human genome. We thank the Chimpanzee Genome Sequencing Consortium for use of the chimpanzee sequence data. The authors would also like to acknowledge the efforts of the HUGO Gene Nomenclature Committee. Finally, the authors acknowledge the National Human Genome Research Institute for funding this work.

PY - 2005/4/7

Y1 - 2005/4/7

N2 - Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.

AB - Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.

UR - http://www.scopus.com/inward/record.url?scp=20244378058&partnerID=8YFLogxK

U2 - 10.1038/nature03466

DO - 10.1038/nature03466

M3 - Article

C2 - 15815621

AN - SCOPUS:20244378058

SN - 0028-0836

VL - 434

SP - 724

EP - 731

JO - Nature

JF - Nature

IS - 7034

ER -

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

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