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Initial sequencing and analysis of the human genome - Vitagenes

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articles443. Roth, F. P., Hughes, J. D., Estep, P. W. & Church, G. M. Finding DNA regulatory motifs withinunaligned noncoding sequences clustered by whole-<strong>genome</strong> mRNA quantitation. Nature Biotechnol.16, 939±945 (1998).444. Cheng, Y. & Church, G. M. Biclustering <strong>of</strong> expression data. ISMB 8, 93±103 (2000).445. Cohen, B. A., Mitra, R. D., Hughes, J. D. & Church, G. M. A computational <strong>analysis</strong> <strong>of</strong> whole<strong>genome</strong>expression data reveals chromosomal domains <strong>of</strong> gene expression. Nature Genet. 26, 183±186 (2000).446. Feil, R. & Khosla, S. Genomic imprinting in mammals: an interplay between chromatin <strong>and</strong> DNAmethylation? Trends Genet. 15, 431±434 (1999).447. Robertson, K. D. & Wolffe, A. P. DNA methylation in health <strong>and</strong> disease. Nature Rev. Genet. 1, 11±19(2000).448. Beck, S., Olek, A. & Walter, J. From genomics to epigenomics: a l<strong>of</strong>tier view <strong>of</strong> life. Nature Biotechnol.17, 1144±1144 (1999).449. Hagmann, M. Mapping a subtext in our genetic book. Science 288, 945±946 (2000).450. Eliot, T. S. in T. S. Eliot. Collected Poems 1909±1962 (Harcourt Brace, New York, 1963).451. Soderl<strong>and</strong>, C., Longden, I. & Mott, R. FPC: a system for building contigs from restriction®ngerprinted clones. Comput. Appl. Biosci. 13, 523±535 (1997).452. Mott, R. & Tribe, R. Approximate statistics <strong>of</strong> gapped alignments. J. Comp. Biol. 6, 91±112 (1999).Supplementary Information is available on Nature's World-Wide Web site(http://www.nature.com) or as paper copy from <strong>the</strong> London editorial <strong>of</strong>®ce <strong>of</strong> Nature.AcknowledgementsBeyond <strong>the</strong> authors, many people contributed to <strong>the</strong> success <strong>of</strong> this work. E. Jordanprovided helpful advice throughout <strong>the</strong> <strong>sequencing</strong> effort. We thank D. Leja <strong>and</strong>J. Shehadeh for <strong>the</strong>ir expert assistance on <strong>the</strong> artwork in this paper, especially <strong>the</strong> foldout®gure; K. Jegalian for editorial assistance; J. Schloss, E. Green <strong>and</strong> M. Seldin for commentson an earlier version <strong>of</strong> <strong>the</strong> manuscript; P. Green <strong>and</strong> F. Ouelette for critiques <strong>of</strong> <strong>the</strong>submitted version; C. Caulcott, A. Iglesias, S. Renfrey, B. Skene <strong>and</strong> J. Stewart <strong>of</strong> <strong>the</strong>Wellcome Trust, P. Whittington <strong>and</strong> T. Dougans <strong>of</strong> NHGRI <strong>and</strong> M. Meugnier <strong>of</strong>Genoscope for staff support for meetings <strong>of</strong> <strong>the</strong> international consortium; <strong>and</strong> <strong>the</strong>University <strong>of</strong> Pennsylvania for facilities for a meeting <strong>of</strong> <strong>the</strong> <strong>genome</strong> <strong>analysis</strong> group.We thank Compaq Computer Corporations's High Performance Technical ComputingGroup for providing a Compaq Biocluster (a 27 node con®guration <strong>of</strong> AlphaServer ES40s,containing 108 CPUs, serving as compute nodes <strong>and</strong> a ®le server with one terabyte <strong>of</strong>secondary storage) to assist in <strong>the</strong> annotation <strong>and</strong> <strong>analysis</strong>. Compaq provided <strong>the</strong> systems<strong>and</strong> implementation services to set up <strong>and</strong> manage <strong>the</strong> cluster for continuous use bymembers <strong>of</strong> <strong>the</strong> <strong>sequencing</strong> consortium. Platform Computing Ltd. provided its LSFscheduling <strong>and</strong> loadsharing s<strong>of</strong>tware without license fee.In addition to <strong>the</strong> data produced by <strong>the</strong> members <strong>of</strong> <strong>the</strong> International Human GenomeSequencing Consortium, <strong>the</strong> draft <strong>genome</strong> sequence includes published <strong>and</strong> unpublished<strong>human</strong> genomic sequence data from many o<strong>the</strong>r groups, all <strong>of</strong> whom gave permission toinclude <strong>the</strong>ir unpublished data. Four <strong>of</strong> <strong>the</strong> groups that contributed particularly signi®cantamounts <strong>of</strong> data were: M. Adams et al. <strong>of</strong> <strong>the</strong> Institute for Genomic Research;E. Chen et al. <strong>of</strong> <strong>the</strong> Center for Genetic Medicine <strong>and</strong> Applied Biosystems; S.-F. Tsai <strong>of</strong>National Yang-Ming University, Institute <strong>of</strong> Genetics, Taipei, Taiwan, Republic <strong>of</strong> China; <strong>and</strong>Y. Nakamura, K. Koyama et al. <strong>of</strong> <strong>the</strong> Institute <strong>of</strong> Medical Science, University <strong>of</strong> Tokyo,Human Genome Center, Laboratory <strong>of</strong> Molecular Medicine, Minato-ku, Tokyo, Japan.Many o<strong>the</strong>r groups provided smaller numbers <strong>of</strong> database entries. We thank <strong>the</strong>m all; a fulllist <strong>of</strong> <strong>the</strong> contributors <strong>of</strong> unpublished sequence is available as Supplementary Information.This work was supported in part by <strong>the</strong> National Human Genome Research Institute <strong>of</strong><strong>the</strong> US NIH; The Wellcome Trust; <strong>the</strong> US Department <strong>of</strong> Energy, Of®ce <strong>of</strong> Biological <strong>and</strong>Environmental Research, Human Genome Program; <strong>the</strong> UK MRC; <strong>the</strong> Human GenomeSequencing Project from <strong>the</strong> Science <strong>and</strong> Technology Agency (STA) Japan; <strong>the</strong> Ministry <strong>of</strong>Education, Science, Sport <strong>and</strong> Culture, Japan; <strong>the</strong> French Ministry <strong>of</strong> Research; <strong>the</strong> FederalGerman Ministry <strong>of</strong> Education, Research <strong>and</strong> Technology (BMBF) through ProjekttraÈgerDLR, in <strong>the</strong> framework <strong>of</strong> <strong>the</strong> German Human Genome Project; BEO, ProjekttraÈgerBiologie, Energie, Umwelt des BMBF und BMWT; <strong>the</strong> Max-Planck-Society; DFGÐDeutsche Forschungsgemeinschaft; TMWFK, ThuÈringer Ministerium fuÈr Wissenschaft,Forschung und Kunst; EC BIOMED2ÐEuropean Commission, Directorate Science,Research <strong>and</strong> Development; Chinese Academy <strong>of</strong> Sciences (CAS), Ministry <strong>of</strong> Science <strong>and</strong>Technology (MOST), National Natural Science Foundation <strong>of</strong> China (NSFC); US NationalScience Foundation EPSCoR <strong>and</strong> The SNP Consortium Ltd. Additional support formembers <strong>of</strong> <strong>the</strong> Genome Analysis group came, in part, from an ARCS FoundationScholarship to T.S.F., a Burroughs Wellcome Foundation grant to C.B.B. <strong>and</strong> P.A.S., a DFGgrant to P.B., DOE grants to D.H., E.E.E. <strong>and</strong> T.S.F., an EU grant to P.B., a Marie-CurieFellowship to L.C., an NIH-NHGRI grant to S.R.E., an NIH grant to E.E.E., an NIH SBIR toD.K., an NSF grant to D.H., a Swiss National Science Foundation grant to L.C., <strong>the</strong> David<strong>and</strong> Lucille Packard Foundation, <strong>the</strong> Howard Hughes Medical Institute, <strong>the</strong> University <strong>of</strong>California at Santa Cruz <strong>and</strong> <strong>the</strong> W. M. Keck Foundation.Correspondence <strong>and</strong> requests for materials should be addressed to E. S. L<strong>and</strong>er (e-mail:l<strong>and</strong>er@<strong>genome</strong>.wi.mit.edu), R. H. Waterston (e-mail: bwaterst@watson.wustl.edu),J. Sulston (e-mail: jes@sanger.ac.uk) or F. S. Collins (e-mail: fc23a@nih.gov).Af®liations for authors: 1, Whitehead Institute for Biomedical Research, Center forGenome Research, Nine Cambridge Center, Cambridge, Massachusetts 02142,USA; 2, The Sanger Centre, The Wellcome Trust Genome Campus, Hinxton,Cambridgeshire CB10 1RQ, United Kingdom; 3, Washington University GenomeSequencing Center, Box 8501, 4444 Forest Park Avenue, St. Louis, Missouri 63108,USA; 4, US DOE Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek,California 94598, USA; 5, Baylor College <strong>of</strong> Medicine Human GenomeSequencing Center, Department <strong>of</strong> Molecular <strong>and</strong> Human Genetics, One BaylorPlaza, Houston, Texas 77030, USA; 6, Department <strong>of</strong> Cellular <strong>and</strong> StructuralBiology, The University <strong>of</strong> Texas Health Science Center at San Antonio, 7703 FloydCurl Drive, San Antonio, Texas 78229-3900, USA; 7, Department <strong>of</strong> MolecularGenetics, Albert Einstein College <strong>of</strong> Medicine, 1635 Poplar Street, Bronx, New York10461, USA; 8, Baylor College <strong>of</strong> Medicine Human Genome Sequencing Center<strong>and</strong> <strong>the</strong> Department <strong>of</strong> Microbiology & Molecular Genetics, University <strong>of</strong> TexasMedical School, PO Box 20708, Houston, Texas 77225, USA; 9, RIKEN GenomicSciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku Yokohama-city, Kanagawa230-0045, Japan; 10, Genoscope <strong>and</strong> CNRS UMR-8030, 2 Rue Gaston Cremieux,CP 5706, 91057 Evry Cedex, France; 11, GTC Sequencing Center, GenomeTherapeutics Corporation, 100 Beaver Street, Waltham, Massachusetts02453-8443, USA; 12, Department <strong>of</strong> Genome Analysis, Institute <strong>of</strong> MolecularBiotechnology, Beutenbergstrasse 11, D-07745 Jena, Germany; 13, BeijingGenomics Institute/Human Genome Center, Institute <strong>of</strong> Genetics, ChineseAcademy <strong>of</strong> Sciences, Beijing 100101, China; 14, Sou<strong>the</strong>rn China NationalHuman Genome Research Center, Shanghai 201203, China; 15, Nor<strong>the</strong>rn ChinaNational Human Genome Research Center, Beijing 100176, China; 16,Multimegabase Sequencing Center, The Institute for Systems Biology,4225 Roosevelt Way, NE Suite 200, Seattle, Washington 98105, USA; 17, StanfordGenome Technology Center, 855 California Avenue, Palo Alto, California 94304,USA; 18, Stanford Human Genome Center <strong>and</strong> Department <strong>of</strong> Genetics, StanfordUniversity School <strong>of</strong> Medicine, Stanford, California 94305-5120, USA;19, University <strong>of</strong> Washington Genome Center, 225 Fluke Hall on Mason Road,Seattle, Washington 98195, USA; 20, Department <strong>of</strong> Molecular Biology,Keio University School <strong>of</strong> Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo160-8582, Japan; 21, University <strong>of</strong> Texas Southwestern Medical Center at Dallas,6000 Harry Hines Blvd., Dallas, Texas 75235-8591, USA; 22, University <strong>of</strong>Oklahoma's Advanced Center for Genome Technology, Dept. <strong>of</strong> Chemistry <strong>and</strong>Biochemistry, University <strong>of</strong> Oklahoma, 620 Parrington Oval, Rm 311, Norman,Oklahoma 73019, USA; 23, Max Planck Institute for Molecular Genetics,Ihnestrasse 73, 14195 Berlin, Germany; 24, Cold Spring Harbor Laboratory, LitaAnnenberg Hazen Genome Center, 1 Bungtown Road, Cold Spring Harbor, NewYork 11724, USA; 25, GBF - German Research Centre for Biotechnology,Mascheroder Weg 1, D-38124 Braunschweig, Germany; 26, National Center forBiotechnology Information, National Library <strong>of</strong> Medicine, National Institutes <strong>of</strong>Health, Bldg. 38A, 8600 Rockville Pike, Be<strong>the</strong>sda, Maryl<strong>and</strong> 20894, USA; 27,Department <strong>of</strong> Genetics, Case Western Reserve School <strong>of</strong> Medicine <strong>and</strong> UniversityHospitals <strong>of</strong> Clevel<strong>and</strong>, BRB 720, 10900 Euclid Ave., Clevel<strong>and</strong>, Ohio 44106, USA;28, EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus,Hinxton, Cambridge CB10 1SD, United Kingdom; 29, Max DelbruÈck Center forMolecular Medicine, Robert-Rossle-Strasse 10, 13125 Berlin-Buch, Germany;30, EMBL, Meyerh<strong>of</strong>strasse 1, 69012 Heidelberg, Germany; 31, Dept. <strong>of</strong> Biology,Massachusetts Institute <strong>of</strong> Technology, 77 Massachusetts Ave., Cambridge,Massachusetts 02139-4307, USA; 32, Howard Hughes Medical Institute,Dept. <strong>of</strong> Genetics, Washington University School <strong>of</strong> Medicine, Saint Louis,Missouri 63110, USA; 33, Dept. <strong>of</strong> Computer Science, University <strong>of</strong> California atSanta Cruz, Santa Cruz, California 95064, USA; 34, Affymetrix, Inc., 2612 8th St,Berkeley, California 94710, USA; 35, Genome Exploration Research Group,Genomic Sciences Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho,Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; 36, Howard HughesMedical Institute, Department <strong>of</strong> Computer Science, University <strong>of</strong> California atSanta Cruz, California 95064, USA; 37, University <strong>of</strong> Dublin, Trinity College,Department <strong>of</strong> Genetics, Smur®t Institute, Dublin 2, Irel<strong>and</strong>; 38, CambridgeResearch Laboratory, Compaq Computer Corporation <strong>and</strong> MIT Genome Center,1 Cambridge Center, Cambridge, Massachusetts 02142, USA; 39, Dept. <strong>of</strong>Ma<strong>the</strong>matics, University <strong>of</strong> California at Santa Cruz, Santa Cruz, California95064, USA; 40, Dept. <strong>of</strong> Biology, University <strong>of</strong> California at Santa Cruz, SantaCruz, California 95064, USA; 41, Crown Human Genetics Center <strong>and</strong>Department <strong>of</strong> Molecular Genetics, The Weizmann Institute <strong>of</strong> Science, Rehovot71600, Israel; 42, Dept. <strong>of</strong> Genetics, Stanford University School <strong>of</strong> Medicine,Stanford, California 94305, USA; 43, The University <strong>of</strong> Michigan Medical School,Departments <strong>of</strong> Human Genetics <strong>and</strong> Internal Medicine, Ann Arbor, Michigan920 © 2001 Macmillan Magazines Ltd NATURE | VOL 409 | 15 FEBRUARY 2001 | www.nature.com

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