Edited by Jan A. Witkowski, Cold Spring Harbor Laboratory, Alexander Gann, Cold Spring Harbor Laboratory, and Joseph F. Sambrook, Peter MacCallum Cancer Institute his book is the second volume of an intellectual history of the T science done at CSHL (the first volume, Illuminating Life, showed that genetics became the dominant theme of research at CSH by as early as 1904). The appointment of as Director of the Laboratory in 1968 set off the explosive research development at CSH, as he recruited widely and wisely teams of investigators with diverse scientific interests. From this collection of papers, presented in full on the accompanying CD, several themes emerge: the characterization and exploitation of mobile genetic elements; the mechanics of DNA replication and regulation of the cell cycle; the behavior and internal architecture of cells; how viruses induce tumors; the discovery of cancer genes; the characteristics of neurons; and the invention of techniques that make possible further progress. Each theme is introduced in the context of the science of the time, and each paper has a commentary by, in most cases, one of its authors. Life Illuminated is a story of scientific innovation and achievement, told in the words of the investigators themselves. 2008, 242 pp., illustrations from original articles, indexes, CD Hardcover $39 ISBN 978-087969804-1

CONTENTS Preface NEUROSCIENCE Acknowledgments Eric Kandel, Ron McKay, Birgit Zipser, Tim Tully GENETICS CANCER Gerald R. Fink, Rasika Harshey, Bukhari Memoriam, Arnold J. Levine, Mitchell Goldfarb, Earl Ruley, James B. Hicks, Robert Martienssen, David Beach Scott Powers, Douglas Hanahan, B. Robert Franza, Jr., Ed Harlow DNA Bruce Alberts, Joseph F. Sambrook, Bruce Stillman, TECHNIQUES Richard J. Roberts Angela N.H. Creager, Richard J. Roberts, James I. Garrels, Joseph F. Sambrook, Tom Maniatis CELL David L. Spector, Klaus Weber, Guenter Albrecht-Buehler, Author Index Dafna Bar-Sagi and James R. Feramisco, Carol W. Greider Index TUMOR VIRUSES Joseph F. Sambrook, Terri Grodzicker, Louise T. Chow, Michael Botchan, Robert Tjian, Carl S. Thummel, Winship Herr

To order or request additional information, please visit our website or: Call: 1-800-843-4388 (Continental US and Canada) 516-422-4100 (All other locations) FAX: 516-422-4097 E-mail: [email protected] Write: Cold Spring Harbor Laboratory Press, 500 Sunnyside Blvd., Woodbury, NY 11797-2924 Thank you for sharing in the celebration

HudsonAlpha Institute for Grand Opening April 24-25, 2008

Now, share in the adventure

Applying genome-scale technology to human diversity and disease

Huntsville, Alabama

genomic research • educational outreach • economic development • hudsonalpha.org LongAmp Taq now available New England for larger PCR products Biolabs

yield of dreams.

T a q DNA Polymerase from New England Biolabs HIGH YIELD, Robust and Reliable PCR Reactions in Convenient Formats Amplicon Size (kb) 0.5 0.6 2 3 4 8 12 20 30 M Looking for the right solution for your high yield PCR? Choose recombinant Taq DNA Polymerase kb from New England Biolabs. As the leader in enzyme technology, New England Biolabs provides — 10.0 — 5.0 the highest quality recombinant Taq at exceptional value. Our expanded selection of Taq based ;; — 3.0 products includes kits, master mixes, and a choice of reaction buffers. Choose Taq DNA polymerase from NEB for guaranteed Performance, Convenience and Results. — 1.5

n Taq with Standard Buffer r ...... M0273S/L/X n Taq with Standard (Mg-free) Buffer r ...... M0320S/L

n r Taq with ThermoPol Buffer ...... M0267S/L/X — 0.5 n Taq with ThermoPol II (Mg-free) Buffer r ...... M0321S/L ­ n Taq 2X Master Mix r ...... M0270S/L Amplification of specific sequences from human genomic DNA using

n Taq 5X Master Mix r ...... M0285S/L LongAmp Taq DNA Polymerase. Amplicon sizes are indicated above gel. n Quick-Load ™ Taq 2X Master Mix r ...... M0271S/L Marker M is the 1 kb DNA Ladder (NEB #3232). n Taq PCR Kits r ...... E5000S/E5100S n LongAmp Taq DNA Polymerase r ...... M0323S/L n LongAmp Taq PCR Kit r ...... E5200S n LongAmp Taq 2X Master Mix r ...... M0287S/L

r = Recombinant

For more information and international distribution network, please visit www.neb.com

New England Biolabs Inc. 240 County Road, Ipswich, MA 01938 USA 1-800-NEB-LABS Tel. (978) 927-5054 Fax (978) 921-1350 [email protected] Canada Tel. (800) 387-1095 [email protected] • China Tel. 010-82378266 [email protected] • Tel. 0800/246 5227 [email protected] Japan Tel. +81 (0)3 5669 6191 [email protected] • UK Tel. (0800) 318486 [email protected] the leader in enzyme technology www.roche-applied-science.com

Genome Sequencer FLX System

Longer sequencing reads mean more applications.

In 2005, the Genome Sequencer 20 System was launched ■ Read length: 100 bases ■ 20 million bases in less than 5 hours

In 2007, the Genome Sequencer FLX System was launched ■ Read length: 250 to 300 bases ■ 100 million bases in less than 8 hours

Available in 2008, the Genome Sequencer FLX with improved chemistries ■ Read length: >400 bases ■ 1 billion bases in less than 24 hours

More applications lead to more publications.

Sequencing-by-Synthesis: Using an enzymatically Proven performance with an expanding list of applications and coupled reaction, light is generated when individual more than 130 peer-reviewed publications. nucleotides are incorporated. Hundreds of thousands of Visit www.genome-sequencing.com to learn more. individual DNA fragments are sequenced in parallel.

Roche Diagnostics Roche Applied Science For life science research only. Not for use in diagnostic procedures. Indianapolis, Indiana 454 and 454 SEQUENCING are trademarks of 454 Life Sciences Corporation, Branford, CT, USA. © 2008 Roche Diagnostics. All rights reserved.

Edited by C. David O’Connor, Centre for Proteomic Research, University of Southampton, Southampton, UK and B. David Hames, University of Leeds, Leeds, UK roteomics: Methods Express identifies the most powerful new technologies and presents P them in a way that allows their robust implementation. The focus is on proteomic methods and strategies that are reliable and of general applicability. Each chapter presents descriptions of what can, and cannot, be achieved with the relevant procedures so that readers can make informed judgments prior to establishing the methods in-house. Every chapter discusses the merits and limitations of various approaches then provides tried-and-tested protocols with hints and tips for success and troubleshooting for when things go wrong. November 2007, 256 pp. Paperback $75.00 ISBN 978-1-904842-132

CONTENTS 1. Sample preparation and subcellular 6. Desorption electrospray ionization: 10. Protein microarray technologies. fractionation approaches: purification of proteomics studies by a method that Chien-Sheng Chen, Sheng-Ce Tao, membranes and their microdomains for bridges ESI and MALDI. and Heng Zhu, Johns Hopkins University mass spectrometry analysis. Zoltán Takáts, Justin M. Wiseman, School of Medicine, Baltimore, MD, USA. Yan Li, Phil Oh, and Jan E. Schnitzer, Demian R. Ifa, and R. Graham Cooks, 11. Intelligent mining of complex data: Sidney Kimmel Cancer Center, San Diego, Purdue University, West Lafayette, IN, USA. challenging the proteomic bottleneck. CA, USA. 7. Analysis of cellular protein complexes Dan Bach Kristensen, Maxygen, 2. An isotope-coding strategy for by affinity purification and mass Hoersholm, Denmark; and Alexandre quantitative proteomics. spectrometry. Podtelejnikov, Proxeon, Odense, Xian Chen, University of North Carolina Tilmann Bürckstümmer and Keiryn L. Denmark. at Chapel Hill, USA. Bennett, Research Center for Molecular 12. Bioinformatic approaches in 3. Gel-based approaches. Medicine of the Austrian Academy of proteomics. Stuart J. Cordwell and Ben Crossett, Sciences (CeMM), Vienna, Austria. Sandra Orchard and Henning both at The University of Sydney, New 8. Clinical proteomic profiling and Hermjakob, European Bioinformatics South Wales, Australia; and Melanie Y. disease signatures. Institute, Wellcome Trust, Cambridge, UK. White, Minomic Pty Ltd., New South Rosamonde E. Banks, David A. Cairns, List of suppliers Wales, Australia. David N. Perkins, and Jennifer H. Index 4. Peptide sorting by reverse-phase Barrett, Cancer Research UK Clinical diagonal chromatography. Centre, St James’ s University Hospital, Kris Gevaert and Joël Vandekerckhove, Leeds, UK. Ghent University and Flanders 9. Characterization of post-translational Methods Express Interuniversity Institute for Biotechnology, modifications: undertaking the • protocols in step-by-step detail Ghent, Belgium. phosphoproteome. • comprehensive troubleshooting 5. Mass spectrometry strategies for protein W. Andy Tao, Purdue University, West Lafayette, IN, USA; Bernd Bodenmiller • example data as benchmarks identification. • key references to further reading David R. Goodlett, University of and Ruedi Aebersold, both at Institute for Washington, Seattle, WA, USA, and Molecular Systems Biology, Federal Institute Series Editor: B. David Hames, University of Leeds Garry L. Corthals, University of Turku of Technology, Zurich, Switzerland. and Abo Akademi, Turku, Finland.

To order or request additional information: Call: 1-866-854-3301 (Continental US and Canada) Fax: 516-422-4097 Email: [email protected] WWW Site: www.scionpublishing.com Write: Scion Publishing Ltd., 500 Sunnyside Blvd., Woodbury, NY 11797-2924 By Stewart Scherer How many genes are in the human genome? Which genes are commonly associated with genetic diseases? How many mobile elements, simple sequence repeats, or protein kinases are encoded in the genome? What are the largest genes and proteins? How similar are human proteins to those of mouse, yeast, or bacteria? Although the human genome has been sequenced, it often can be surprisingly difficult to find answers to seemingly simple questions about its characteristics. This convenient handbook, written in question-and-answer format, allows researchers and teachers alike access to basic facts about the human genome. Using a recent assembly of the human genome sequence, Stewart Scherer has compiled answers to a broad range of questions about the structure and function of the human genome. Answers to each question are presented in a direct, straightforward style. Numerous figures and tables are included to illustrate and summarize the information. 2008, 173 pp., illus., index Paperback $29 ISBN 978-087969791-4

CONTENTS 1. Introduction Which Genes Host Small Nuclear RNAs How Are the Histone Gene Families Polymorphisms in the Genome? 2. DNA and Chromosomes and Small Nucleolar RNAs? Organized? Which ABO Allele Is in the Reference What Is the Size of Each Chromosome? How Are microRNA Genes Distributed in How Are the Keratin Genes Organized? Genome? What Is the Base Composition of the the Genome? How Many Protein Kinases Are Encoded in How Variable Are the HLA Proteins? Nuclear Genome? What Is the Size Distribution of snRNA the Genome? Which Genes Have Common What Is the Base Composition of the Genes and Related Sequences in the Which Types of Proteases Are Found in the Polymorphisms? Mitochondrial Genome? Genome? Human Genome? Which Genes and Alleles Are Associated What Is the Frequency of Each What Are the Sequences at Splice Junctions? How Many Genes Are in the Major with Common Genetic Diseases? Dinucleotide? Which Genes Use RNA Editing? Factor Families? Which Genes Function as Tumor Does Base Composition Vary Among the 5. Proteins Which Are the Important Residues in the Suppressors? Chromosomes? What Is the Size of a Typical Protein? Homeobox? 10. Comparative Genomics What Are the Frequencies and Sizes of What Is the Amino Acid Composition of a How Are the HOX Genes Organized? What Are the Major Differences Between Simple Sequence Repeats? Typical Protein? Which Sequences Are Shared in Helix-loop- the Human and Mouse Genomes? Which Sequences Are Present at the How Do Mitochondrial Proteins Differ in helix Transcription Factors? How Do the Mitochondrial Genomes Vary Centromeres? Composition from Typical Proteins? Which Residues Define the DEXD Among Species? What Are the Sequences at the Telomeres? Which Amino Acids Are Commonly Helicases? How Does Codon Usage Differ in the 3. Genes Located in the Amino-terminal Region of a Which Are the Conserved Features of the Eukaryotes? How Many Protein-coding Genes Are Protein? WD Domain? How Similar Are Human Proteins to Those Present in the Genome? Which Amino Acids Are Commonly How Are the Olfactory Receptor Genes and in Other Species? Is Gene Density Uniform Across the Located in the Carboxy-terminal Region of Pseudogenes Distributed in the Genome? How Similar Are Human Genes to Those in Chromosomes? a Protein? How Are the Taste Receptor Genes and Other Species at the Nucleotide Level? How Common Are Pseudogenes? What Are the Largest Proteins? Pseudogenes Distributed in the Genome? How Are Human and Bacterial Ribosomes What Is the Size of a Typical Gene? Which Proteins Have Large Homopolymer 8. Mobile Elements and Rearranging Related? Tracts? Genes What Are the Largest Genes? Are Human DNA Replication Proteins What Proteins Are Rich in Particular Amino How Much of the Genome Is Composed of Related to Those of Bacteria? Which Genes Have the Most Exons? Acids? Mobile Elements? Are Human Proteins for mRNA Processing Does Exon Number Correlate with Gene For Proteins That Are Rich in a Specific What Types of L1 Elements Are Present in Functions Conserved in Eukaryotes? Size or Protein Size? Amino Acid, How Are the Residues the Genome? How Does Protein Sequence Conservation What Is the Size of a Typical Exon? Distributed Across the Polypeptide Chains? What Is the Number and Size Distribution Differ Among the Histone Types? What Is the Size of a Typical Intron? Which Proteins Lack Specific Amino Acids? of Alu Family Sequences in the Genome? How Conserved Are the Branches of the Which Genes Have the Largest Introns? Which Proteins Are Post-translationally What Are the Common DNA Transposons Ras Superfamily? Do Gene-rich Chromosomes Have Smaller Cleaved into Multiple Hormones and in the Genome? How Do the Sizes of Gene Families for Genes? Related Peptides Which Endogenous Retroviral Genomes Are Structural Proteins Vary Among the How Are CpG Islands Associated with 6. Translation and Protein Modification Largely Intact? Eukaryotes? Genes? How Does Codon Usage Vary Among Are the Immunoglobulin and T-cell How Large Are Gene Families for Do Large mRNAs Have Large UTRs? Human Genes? Receptor Loci Very Large? Developmental Signaling in Animals? Which Genes Are Located in the Introns of Which Proteins Contain Selenocysteine? How Are the Immunoglobulin Genes Which Species Have Genes Related to Other Genes? Which Amino Acids Are Introduced into Organized? Those with Functions in Human Host Which Genes Are Present in the Proteins by Post-translational Modifications? How Are the T-cell Receptor Loci Defense? Mitochondrial Genome? Which Sequences Are Associated with the Organized? Which Human Proteins Are Related to How Are Genes Organized in the Formylglycine Modification? What Sequences Direct DNA Joining at the Retroviral Proteins? Mitochondrial Genome? Which Proteins Contain Á- Immunoglobulin and T-cell Receptor Loci? Human Gene Index 4. RNA Carboxyglutamate? 9. Polymorphism How Are the Ribosomal RNA Genes 7. Gene Families What Is the Frequency of Single Nucleotide Organized in the Genome? How Are DNA Polymerases Related to Each Which Transfer RNAs Are Present in the Other? Genome? www.nimblegen.com Seize the Genome NimbleGen Sequence Capture Service Maximize the power of next-generation sequencing by capturing and enriching specific regions of interest for targeted resequencing.

n Target Specific Regions of Interest Capture up to 5 Mb total sequence on a single array with high coverage and specificity.

n Reduce Cost Significantly reduce time and cost compared to laborious and limiting PCR-based methods.

n Generate Data with Confidence Ensure system performance prior to sequencing with built-in QC probes.

n Customize Each Capture Design Specify the array design to capture contiguous genomic regions or thousands of exons in parallel. Figure 1: NimbleGen Sequence Capture Protocol 1. The genomic DNA sample is fragmented. 2. The sample is hybridized to a custom NimbleGen Sequence Capture array. 3. Unbound fragments are removed. 4. To seize command of your sequencing project, The target-enriched pool is eluted and amplified. 5. The visit www.nimblegen.com/seqcap enriched sample is ready for processing in the GS FLX sample processing workflow. or call (877) NimbleGen / (608) 218-7600

Roche NimbleGen, Inc. 454 and 454 SEQUENCING are trademarks of Madison WI USA 454 Life Sciences Corporation, Branford, CT, USA © 2008 Roche NimbleGen, Inc. All rights reserved.

GORDON RESEARCH CONFERENCES Experience Summer at a 2008 Gordon Research Conference GRC will hold over 120 conferences from June to September of 2008. A sampling of these exciting and unique offerings is listed below. Submit an online application today! http://www.grc.org/application.aspx

The informal atmosphere of a GRC provides unique opportunities to access cutting edge research, engage in informal discussions and build networks for future collaboration.

Auditory System NEW Neurobiology of Brain Disorders NEW June 29-July 4, 2008 August 24-29, 2008 Colby-Sawyer College, New London, NH Magdalen College, Oxford, UK

Biointerface Science Oceans and Human Health NEW September 14-19, 2008 June 29 - July 4, 2008 Centre Paul Langevin, Aussois, France Tilton School, Tilton, NH

Chemistry at Interfaces Plasmonics July 13-18, 2008 July 27 - August 1, 2008 Waterville Valley Resort, Waterville Valley, NH Tilton School, Tilton, NH

Mechanisms of Epilepsy & Neuronal Radiation Chemistry Synchronization July 6-11, 2008 August 3-8, 2008 Waterville Valley Resort, Waterville Valley, NH Colby College, Waterville, ME

Single Molecule Approaches to Biology August 17-22, 2008 Colby-Sawyer College, New London, NH

Visit the frontiers of science... attend a GRC! www.grc.org