Generation and annotation of the DNA sequences of human chromosomes 2 and 4 : Abstract : Nature

Nature 434, 724-731 (7 April 2005) | doi:10.1038/nature03466; Received 25 October 2004; Accepted 11 February 2005

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

LaDeana W. Hillier¹, Tina A. Graves¹, Robert S. Fulton¹, Lucinda A. Fulton¹, Kymberlie H. Pepin¹, Patrick Minx¹, Caryn Wagner-McPherson¹, Dan Layman¹, Kristine Wylie¹, Mandeep Sekhon¹, Michael C. Becker¹, Ginger A. Fewell¹, Kimberly D. Delehaunty¹, Tracie L. Miner¹, William E. Nash¹, Colin Kremitzki¹, Lachlan Oddy¹, Hui Du¹, Hui Sun¹, Holland Bradshaw-Cordum¹, Johar Ali¹, Jason Carter¹, Matt Cordes¹, Anthony Harris¹, Amber Isak¹, Andrew van Brunt¹, Christine Nguyen¹, Feiyu Du¹, Laura Courtney¹, Joelle Kalicki¹, Philip Ozersky¹, Scott Abbott¹, Jon Armstrong¹, Edward A. Belter¹, Lauren Caruso¹, Maria Cedroni¹, Marc Cotton¹, Teresa Davidson¹, Anu Desai¹, Glendoria Elliott¹, Thomas Erb¹, Catrina Fronick¹, Tony Gaige¹, William Haakenson¹, Krista Haglund¹, Andrea Holmes¹, Richard Harkins¹, Kyung Kim¹, Scott S. Kruchowski¹, Cynthia Madsen Strong¹, Neenu Grewal¹, Ernest Goyea¹, Shunfang Hou¹, Andrew Levy¹, Scott Martinka¹, Kelly Mead¹, Michael D. McLellan¹, Rick Meyer¹, Jennifer Randall-Maher¹, Chad Tomlinson¹, Sara Dauphin-Kohlberg¹, Amy Kozlowicz-Reilly¹, Neha Shah¹, Sharhonda Swearengen-Shahid¹, Jacqueline Snider¹, Joseph T. Strong¹, Johanna Thompson¹, Martin Yoakum¹, Shawn Leonard¹, Charlene Pearman¹, Lee Trani¹, Maxim Radionenko¹, Jason E. Waligorski¹, Chunyan Wang¹, Susan M. Rock¹, Aye-Mon Tin-Wollam¹, Rachel Maupin¹, Phil Latreille¹, Michael C. Wendl¹, Shiaw-Pyng Yang¹, Craig Pohl¹, John W. Wallis¹, John Spieth¹, Tamberlyn A. Bieri¹, Nicolas Berkowicz¹, Joanne O. Nelson¹, John Osborne¹, Li Ding¹, Rekha Meyer¹, Aniko Sabo¹, Yoram Shotland¹, Prashant Sinha¹, Patricia E. Wohldmann¹, Lisa L. Cook¹, Matthew T. Hickenbotham¹, James Eldred¹, Donald Williams¹, Thomas A. Jones², Xinwei She³, Francesca D. Ciccarelli⁴, Elisa Izaurralde⁴, James Taylor⁵, Jeremy Schmutz⁶, Richard M. Myers⁶, David R. Cox^6,¹⁰, Xiaoqiu Huang⁷, John D. McPherson^1,¹⁰, Elaine R. Mardis¹, Sandra W. Clifton¹, Wesley C. Warren¹, Asif T. Chinwalla¹, Sean R. Eddy², Marco A. Marra^1,¹⁰, Ivan Ovcharenko⁸, Terrence S. Furey⁹, Webb Miller⁵, Evan E. Eichler³, Peer Bork⁴, Mikita Suyama⁴, David Torrents⁴, Robert H. Waterston^1,¹⁰ and Richard K. Wilson¹

Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St. Louis, Missouri 63108, USA
Howard Hughes Medical Institute and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA
Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA
EMBL, Meyerhofstrasse 1, Heidelberg 69117, Germany
Center for Comparative Genomics and Bioinformatics, Departments of Biology and Computer Science, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Stanford Human Genome Center, Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
Department of Computer Science, Iowa State University, Ames, Iowa 50011-1040, USA
EEBI Division and Genome Biology Division, Lawrence Livermore National Laboratory, Livermore, California 94550, USA
Center for Biomolecular Science and Engineering, University of California, Santa Cruz, California 95064, USA
Present addresses: Perlegen Sciences Inc., 2021 Stierlin Court, Mountain View, California 94943, USA (D.R.C); Baylor College of Medicine, 1 Baylor Plaza, Human Genome Sequencing Center, N1519, Houston, Texas 77030, USA (J.D.M.); Genome Sciences Centre, British Columbia Cancer Agency, 600 West 10th Avenue, Room 3427, Vancouver, British Columbia V5Z 4E6, Canada (M.A.M.); Department of Genome Sciences, Box 357730, University of Washington, 1705 NE Pacific Street, Seattle, Washington 98195-7730, USA (R.H.W.).

Correspondence to: Richard K. Wilson¹ Correspondence and requests for materials should be addressed to R.K.W. (Email: rwilson@watson.wustl.edu).
All reported DNA sequences have been deposited in GenBank or EMBL. Accession numbers for the chromosome sequence analysed for this paper can be found in Supplementary Table 1. The updated chromosome 2 and 4 sequences can be accessed through GenBank accession numbers NC_000002 (chromosome 2) and NC_000004 (chromosome 4). Primate resequencing data can be accessed using GenBank accession numbers CZ179368–CZ179565. The mRNA resequencing data can be accessed via GenBank/dbSNP identifiers ss35032449–ss35032461, ss35033273–ss35033317.

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.

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