Genetics from genes to genomes, 2003 (3rd edition) leland hartwell, leroy hood, michael l goldberg, ann e reynolds

Dr. Leland Hartwell is President and Director of Seattle’s Fred Hutchinson Cancer Research Center and Professor of Genome Sciences at the University of Washington. Dr. Hartwell’s primary research contributions were in identifying genes that control cell division in yeast including those necessary for the division process as well as those necessary for the fidelity of genome reproduction. Subsequently many of these same genes have been found to control cell division in humans and often to be the site of alteration in cancer cells. Dr. Hartwell is a member of the National Academy of Sciences and has received the Albert Lasker Basic Medical Research Award, the Gairdner Foundation International Award, the Alfred P. Sloan Award in Cancer Research, and the 2001 Nobel Prize in Physiology or Medicine.Genetics research tends to proceed down highly specialized paths. A number of experts in specific areas generously provided information in their areas of expertise. We thank them for their contributions to this edition of our text

Tools to Help You Master Genetics Study Guide/Solutions Manual By Debra Nero, Cornell University ISBN 978-0-07-299587-9 MHID 0-07-299587-4 Written to support the concepts presented in Genetics: From Genes to Genomes, Third Edition, this manual includes solutions to the end-of-chapter problems Solutions are given with step-by-step logic to help strengthen your problem-solving skills McGraw-Hill’s ARIS (Assessment Review and Instruction System) Makes homework meaningful—and manageable—for instructors and students Hartwell Hood Goldberg Reynolds Silver Veres From Genes to Genomes Explore this dynamic site for a variety of study tools • Self-quizzes • Flash cards • Animations with quizzing • Interactive Web Exercises Go to aris.mhhe.com to learn more or go directly to this book’s ARIS site at www.mhhe.com/hartwell3 From Genes to Genomes Animations with Quizzing More than 40 animations are available at www.mhhe.com/hartwell3 These animations set genetics processes in motion, and make great study and review tools since you control the action Third Edition Third Edition Leland H Hartwell Leroy Hood Michael L Goldberg Ann E Reynolds Lee M Silver Ruth C Veres har48464_fm_i-xxiv 8/29/06 5:03 AM Page i GENETICS From Genes to Genomes Third Edition Leland H Hartwell Fred Hutchinson Cancer Research Center Leroy Hood The Institute for Systems Biology Michael L Goldberg Cornell University Ann E Reynolds Fred Hutchinson Cancer Research Center Lee M Silver Princeton University Ruth C Veres CONFIRMING PAGES har48464_fm_i-xxiv 8/29/06 5:42 AM Page ii CONFIRMING PAGES GENETICS: FROM GENES TO GENOMES, THIRD EDITION Published by McGraw-Hill, a business unit of The McGraw-Hill Companies, Inc., 1221 Avenue of the Americas, New York, NY 10020 Copyright © 2008 by The McGraw-Hill Companies, Inc All rights reserved No part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written consent of The McGraw-Hill Companies, Inc., including, but not limited to, in any network or other electronic storage or transmission, or broadcast for distance learning Some ancillaries, including electronic and print components, may not be available to customers outside the United States This book is printed on acid-free paper DOW/DOW ISBN 978–0–07–284846–5 MHID 0–07–284846–4 Publisher: Janice Roerig-Blong Executive Editor: Patrick E Reidy Developmental Editor: Rose M Koos Executive Marketing Manager: Chad E Grall Lead Project Manager: Joyce M Berendes Senior Production Supervisor: Laura Fuller Senior Media Project Manager: Jodi K Banowetz Senior Media Producer: Eric A Weber Senior Designer: David W Hash Cover/Interior Designer: Rokusek Design (USE) Cover Image: DNA, A Pasieka/Photo Researchers, Inc Lead Photo Research Coordinator: Carrie K Burger Photo Research: Jerry Marshall Supplement Producer: Melissa M Leick Compositor: Techbooks Typeface: 10.5/12 Times Roman Printer: R R Donnelley Willard, OH The credits section for this book begins on page C-1 and is considered an extension of the copyright page Library of Congress Cataloging-in-Publication Data Genetics : from genes to genomes / Leland H Hartwell [et al.] — 3rd ed p ; cm Includes bibliographical references and index ISBN 978–0–07–284846–5 — ISBN 0–07–284846–4 (hard copy : alk paper) Genetics I Hartwell, Leland [DNLM: Genetics QU 450 G3287 2008] QH430.G458 576.5—dc22 www.mhhe.com 2008 2006022898 CIP har48464_fm_i-xxiv 8/30/06 10:52 PM Page iii CONFIRMING PAGES About the Authors Dr Leland Hartwell is President and Director of Seattle’s Fred Hutchinson Cancer Research Center and Professor of Genome Sciences at the University of Washington Dr Hartwell’s primary research contributions were in identifying genes that control cell division in yeast including those necessary for the division process as well as those necessary for the fidelity of genome reproduction Subsequently many of these same genes have been found to control cell division in humans and often to be the site of alteration in cancer cells Dr Hartwell is a member of the National Academy of Sciences and has received the Albert Lasker Basic Medical Research Award, the Gairdner Foundation International Award, the Alfred P Sloan Award in Cancer Research, and the 2001 Nobel Prize in Physiology or Medicine Dr Lee Hood received an M.D from the Johns Hopkins Medical School and a Ph.D in biochemistry from the California Institute of Technology His research interests include immunology, cancer biology, development, and the development of biological instrumentation (for example, the protein sequencer and the automated fluorescent DNA sequencer) His early research played a key role in unraveling the mysteries of antibody diversity More recently he has pioneered systems approaches to biology and medicine Dr Hood has taught molecular evolution, immunology, molecular biology, genomics and biochemistry and has co-authored textbooks in biochemistry, molecular biology, and immunology, as well as The Code of Codes—a monograph about the Human Genome Project He was one of the first advocates for the Human Genome Project and directed one of the federal genome centers that sequenced the human genome Dr Hood is currently the president (and co-founder) of the cross-disciplinary Institute for Systems Biology in Seattle, Washington Dr Hood has received a variety of awards, including the Albert Lasker Award for Medical Research (1987), the Distinguished Service Award from the National Association of Teachers (1998) and the Lemelson/MIT Award for Invention (2003) He is the 2002 recipient of the Kyoto Prize in Advanced Biotechnology—an award recognizing his pioneering work in developing the protein and DNA synthesizers and sequencers that provide the technical foundation of modern biology He is deeply involved in K-12 science education His hobbies include running, mountain climbing, and reading Dr Michael Goldberg is a professor at Cornell University, where he teaches introductory genetics He was an undergraduate at Yale University and received his Ph.D in biochemistry from Stanford University Dr Goldberg performed postdoctoral research at the Biozentrum of the University of Basel (Switzerland) and at Harvard University, and he received an NIH Fogarty Senior International Fellowship for study at Imperial College (England) and at the University of Rome (Italy) His current research uses the tools of Drosophila genetics to investigate the mechanisms that ensure proper chromosome segregation during mitosis and meiosis Dr Ann Reynolds is an educator and author She began teaching genetics and biology in 1990, and her research has included studies of gene regulation in E coli, chromosome structure and DNA replication in yeast, and chloroplast gene expression in marine algae She is a graduate of Mount Holyoke College and received her Ph.D from Tufts University Dr Reynolds was a postdoctoral fellow in the Harvard University Department of Molecular Biology and Genome Sciences at the University of Washington She was also an author and producer of the laserdisc and CD-ROM Genetics: Fundamentals to Frontiers iii har48464_fm_i-xxiv iv 8/29/06 5:03 AM Page iv CONFIRMING PAGES About the Authors Dr Lee M Silver received B.A and M.S degrees in physics from the University of Pennsylvania, and a Ph.D in biophysics from Harvard University He obtained further training at New York’s Memorial Sloan-Kettering Cancer Center, Cold Spring Harbor Laboratory, and the Pasteur Institute in Paris, France Since 1984, he has been a professor at Princeton University, currently in the Department of Molecular Biology and the Woodrow Wilson School of Public and International Affairs He also has joint appointments in the Program in Science, Technology, and Environmental Policy, the Center for Health and Wellbeing, the Office of Population Research, and the Princeton Environmental Institute, all at Princeton University Dr Silver has published over 200 articles in the fields of mammalian genetics, evolution, reproduction, embryology, computer modeling, and behavioral science, and other scholarly papers on topics at the interfaces among biotechnology, law, politics, and religion He has been elected to the governing boards of the Genetics Society of America and the International Mammalian Genome Society, and was a member of the New Jersey Bioethics Commission Task Force formed to recommend reproductive policy for the New Jersey State Legislature Silver has been elected a lifetime fellow of the American Association for the Advancement of Science (AAAS) and he received Contributors Genetics research tends to proceed down highly specialized paths A number of experts in specific areas generously provided information in their areas of expertise We thank them for their contributions to this edition of our text Ian Duncan, Washington University, St Louis Sylvia Fromherz, University of Colorado at Boulder a prestigious MERIT Award for outstanding research in genetics from the National Institutes of Health Dr Silver’s other books include Remaking Eden: How Genetic Engineering and Cloning will Transform the American Family, published in 16 languages, Mouse Genetics, and Challenging Nature: The Clash of Science and Spirituality at the New Frontiers of Life He has also written popular articles for The New York Times, Washington Post, Time Magazine, and Newsweek International Further information about Dr Silver is available at www.leemsilver.net Ruth C Veres is a science writer and editor with 35 years of experience in textbook publishing She received her B.A from Swarthmore College, obtained M.A degrees from Columbia University and Tufts University, and taught writing and languages at the University of California at Berkeley In addition to developing and editing more than 30 texts in the fields of political science, economics, psychology, nutrition, chemistry, and biology, Veres has coauthored a book on the immune system and an introductory biology text She is currently working on a book with Dr Lee Hood that looks at biological information and the emergence of systems biology Gail E Gasparich, Towson University Bernadette Holdener, State University of New York, Stony Brook Nancy M Hollingsworth, State University of New York, Stony Brook Kari Beth Krieger, University of Wisconsin, Green Bay Debra Nero, Cornell University Eric Richards, Washington University, St Louis Kenneth Shull, Appalachian State University har48464_fm_i-xxiv 08/21/2006 04:42 PM Page v CONFIRMING PAGES Brief Contents Chapter Chapter Genetics: The Study of Biological Information Gene Expression: The Flow of Genetic Information from DNA to RNA to Protein 255 PART I Basic Principles: How Traits Are Transmitted 13 Chapter Mendel’s Breakthrough: Patterns, Particles, and Principles of Heredity 13 Chapter Extensions to Mendel: Complexities in Relating Genotype to Phenotype 45 Chapter The Chromosome Theory of Inheritance 81 Chapter Linkage, Recombination, and the Mapping of Genes on Chromosomes 123 PART III Genomes 301 Chapter Deconstructing the Genome: DNA at High Resolution 301 Chapter 10 Reconstructing the Genome Through Genetic and Molecular Analysis 351 Chapter 11 The Direct Detection of Genotype Distinguishes Individual Genomes 391 Chapter 12 Systems Biology and Proteomics 437 PART IV How Genes Travel on Chromosomes 465 PART II What Genes Are and What They Do 167 Chapter DNA: How the Molecule of Heredity Carries, Replicates, and Recombines Information 167 Chapter Anatomy and Function of a Gene: Dissection Through Mutation 207 Chapter 13 The Eukaryotic Chromosome: An Organelle for Packaging and Managing DNA 465 Chapter 14 Chromosomal Rearrangements and Changes in Chromosome Number Reshape Eukaryotic Genomes 489 v har48464_fm_i-xxiv vi 08/21/2006 04:42 PM Page vi CONFIRMING PAGES Brief Contents Chapter 15 Chapter 19 The Prokaryotic Chromosome: Genetic Analysis in Bacteria 539 Chapter 16 Cell-Cycle Regulation and the Genetics of Cancer 685 Chapter 20 The Chromosomes of Organelles Outside the Nucleus Exhibit Non-Mendelian Patterns of Inheritance 581 Using Genetics to Study Development 717 PART VI How Genes Change 757 PART V How Genes Are Regulated 609 Chapter 21 Chapter 17 Gene Regulation in Prokaryotes 609 Chapter 18 Gene Regulation in Eukaryotes 643 The Genetic Analysis of Populations and How They Evolve 757 Chapter 22 Evolution at the Molecular Level 791 har48464_fm_i-xxiv 3/14/08 5:24 PM Page vii ppg 108:MHDQ043:har3fm: Contents About the Authors iii Preface xi Acknowledgements xxi Chapter 1.2 1.3 1.4 1.5 1.6 1.7 Extensions to Mendel: Complexities in Relating Genotype to Phenotype 45 3.1 Genetics: The Study of Biological Information 1.1 Chapter The Biological Information Fundamental to Life is Encoded in the DNA Molecule Biological Function Emerges Primarily from Protein Molecules Complex Systems Arise from DNA-Protein and Protein-Protein Interactions All Living Things Are Closely Related at the Molecular Level The Modular Construction of Genomes Has Allowed the Rapid Evolution of Complexity Genetic Techniques Permit the Dissection of Complexity Our Focus Is on Human Genetics 10 3.2 Fast Forward 57 Genetics and Society 68 Chapter The Chromosome Theory of Inheritance 81 4.1 4.2 4.3 4.4 PART I Basic Principles: How Traits Are Transmitted 13 Chapter Mendel’s Breakthrough: Patterns, Particles, and Principles of Heredity 13 2.1 2.2 2.3 Background: The Historical Puzzle of Inheritance 15 Genetic Analysis According to Mendel 19 Mendelian Inheritance in Humans: Two Comprehensive Examples 30 Extensions to Mendel for Single-Gene Inheritance 46 Extensions to Mendel for Multifactorial Inheritance 56 4.5 Chromosomes Contain the Genetic Material 82 Mitosis Ensures That Every Cell in an Organism Carries the Same Chromosomes 88 Meiosis Produces Haploid Germ Cells, the Gametes 93 Gametogenesis Requires Both Mitotic and Meiotic Divisions 103 Validation of the Chromosome Theory 105 Genetics and Society 87 Fast Forward 95 Chapter Linkage, Recombination, and the Mapping of Genes on Chromosomes 123 5.1 5.2 5.3 Gene Linkage and Recombination 124 Mapping: Locating Genes Along a Chromosome 135 Mitotic Recombination Can Produce Genetic Mosaics 152 Tools of Genetics 128 Fast Forward 142 Genetics and Society 154 Fast Forward 22 Tools of Genetics 28 Genetics and Society 34 vii har48464_fm_i-xxiv viii 08/21/2006 04:42 PM Page viii CONFIRMING PAGES Contents PART II What Genes Are and What They Do 167 Chapter 8.3 8.4 8.5 Translation: Base Pairing Between mRNA and tRNAs Directs Assembly of a Polypeptide on the Ribosome 275 There Are Significant Differences in Gene Expression Between Prokaryotes and Eukaryotes 282 Comprehensive Example: A Computerized Analysis of Gene Expression in C elegans 284 How Mutations Affect Gene Expression and Gene Function 285 DNA: How the Molecule of Heredity Carries, Replicates, and Recombines Information 167 8.6 6.1 Genetics and Society 270 6.2 6.3 6.4 6.5 Experiments Designate DNA as the Genetic Material 168 The Watson-Crick Model: DNA Is a Double Helix 173 DNA Stores Information in the Sequence of Its Bases 180 DNA Replication: Copying Genetic Information for Transmission to the Next Generation 184 Recombination Reshuffles the Information Content of DNA 191 Tools of Genetics 182 Chapter Anatomy and Function of a Gene: Dissection Through Mutation 207 7.1 7.2 7.3 7.4 Mutations: Primary Tools of Genetic Analysis 208 What Mutations Tell Us About Gene Structure 224 What Mutations Tell Us About Gene Function 232 How Gene Mutations Affect Light-Receiving Proteins and Vision: A Comprehensive Example 239 Genetics and Society 216 Fast Forward 240 PART III Genomes 301 Chapter Deconstructing the Genome: DNA at High Resolution 301 9.1 9.2 9.3 9.4 9.5 9.6 Fragmenting Complex Genomes into BiteSize Pieces for Analysis 303 Cloning Fragments of DNA 310 Hybridization Is Used to Identify Similar DNA Sequences 319 The Polymerase Chain Reaction Provides a Rapid Method for Isolating DNA Fragments 327 DNA Sequence Analysis 330 Understanding the Genes for Hemoglobin: A Comprehensive Example 335 Tools of Genetics 306 Genetics and Society 320 Chapter 10 Chapter Gene Expression: The Flow of Genetic Information from DNA to RNA to Protein 255 8.1 8.2 The Genetic Code: How Precise Groupings of the Four Nucleotides Specify 20 Amino Acids 257 Transcription: RNA Polymerase Synthesizes a Single-Stranded RNA Copy of a Gene 265 Reconstructing the Genome Through Genetic and Molecular Analysis 351 10.1 10.2 10.3 Analyses of Genomes 354 Major Insights from the Human and Model Organism Genome Sequences 366 High-Throughput Genomic Platforms Permit the Global Analysis of Genes and Their mRNAs 375 Genetics and Society 381 har48464_fm_i-xxiv 08/21/2006 04:42 PM Page ix CONFIRMING PAGES Contents Chapter 11 13.3 The Direct Detection of Genotype Distinguishes Individual Genomes 391 11.1 11.2 11.3 11.4 11.5 DNA Variation Is Multifaceted and Widespread 394 Detecting DNA Genotypes of Different Types of Polymorphisms 399 Positional Cloning: From DNA Markers to Gene Clones 408 Genetic Dissection of Complex Traits 419 Haplotype Association Studies for HighResolution Mapping in Humans 423 Genetics and Society 394 Tools of Genetics 416 13.4 12.1 12.2 12.3 12.4 12.5 What Is Systems Biology? 439 Looking at Biology as an Informational Science Is Central to the Practice of Systems Biology 440 Global Proteomics Strategies and HighThroughput Platforms Make It Possible to Gather and Analyze Systemwide Protein Data 444 Putting It All Together: The Practice of Systems Biology 451 A Systems Approach to Disease Leads to Predictive, Preventive, and Personalized Medicine 455 Genetics and Society 457 Specialized Chromosomal Elements Ensure Accurate Replication and Segregation of Chromosomes 474 How Chromosomal Packaging Influences Gene Activity 479 Chapter 14 Chromosomal Rearrangements and Changes in Chromosome Number Reshape Eukaryotic Genomes 489 14.1 14.2 14.3 Chapter 12 Systems Biology and Proteomics 437 ix Rearrangements of DNA Sequences Within Chromosomes 491 Changes in Chromosome Number 516 A Glimpse of the Future: Emergent Technologies in the Analysis of Chromosomal Rearrangements and Changes in Chromosome Number 524 Fast Forward 492 Chapter 15 The Prokaryotic Chromosome: Genetic Analysis in Bacteria 539 15.1 15.2 15.3 15.4 15.5 A General Overview of Prokaryotes 540 The Bacterial Genome 543 Gene Transfer in Bacteria 550 Comprehensive Example: Genetic Dissection Helps Explain How Bacteria Move 566 Genome Analysis Provides Powerful New Tools for Understanding Bacteria 570 Genetics and Society 544 Chapter 16 PART IV How Genes Travel on Chromosomes 465 The Chromosomes of Organelles Outside the Nucleus Exhibit Non-Mendelian Patterns of Inheritance 581 16.1 16.2 Chapter 13 The Eukaryotic Chromosome: An Organelle for Packaging and Managing DNA 465 13.1 13.2 The Components of Eukaryotic Chromosomes: DNA, Histones, and Nonhistone Proteins 466 Chromosome Structure: Variable DNAProtein Interactions Create Reversible Levels of Compaction 469 16.3 The Structure and Function of Mitochondrial and Chloroplast Genomes 583 Genetic Studies of Organelle Genomes Clarify Key Elements of Non-Mendelian Inheritance 592 Comprehensive Example: How Mutations in mtDNA Affect Human Health 599 Fast Forward 594 Genetics and Society 600 har48564_ndx_I1-I22 9/6/06 01:54 AM Page I-9 Index Garrod, Archibald, 232 Gastrulation, 733, 733f GATC sequence, 221, 222f, 223 G-banding, 472, 473f GCN4 protein, 180f Gel electrophoresis, 307–9, 308f, 309f, 314 to detect locus length-changing alleles, 404, 405f with hybridization to map DNA fragments, 234, 325f–326f in Northern blot, 412, 414f in PCR analysis, 400, 400f in proteome analysis, 445–46, 446f in Sanger sequencing, 333, 333f simple sequence repeats assay, 358, 358f Gene(s), bacterial, nomenclature for, 547 big genes, 372 cancer, 703 candidate See Candidate genes class I, 647, 647f class II, 647, 647f class III, 647, 647f, 648 colinearity of gene and protein, 244, 258, 281 complementary gene action, 59, 59t, 62t definition of, 13, 207, 225, 291t, 393 and development, 717, 745–48 discovery of, 19–21 evidence that genes reside in chromosomes, 81–88 evidence that genes reside in nucleus, 82–83 evolution and, 718–21, 748 finding, in sequenced genome, 364–65 finding in genomic library, 319–24, 322f function of, mutation studies, 232–39 and heritable traits, 13 homologous, 358 and human development, 13 interaction to determine single trait, 56–63, 64f as linear set of nucleotide pairs, 226–32 locus of See Locus monomorphic, 51 mutations in See Mutation(s) new, production of, 804 nomenclature for, 20–21, 21f, 106, 125, 145, 547, 827 number of base pairs in, 226, 292 organization within genome, 370–72 orthologous, 358, 821 paralogous, 358, 365, 368, 370 polymorphic, 51 protein-encoding, 22–23, 234–39, 235f, 367–69, 368f, 647f, 648 mutation in, 285–86, 286f, 290–91, 291f transcription of, 647f, 648 recombination within, 226–27, 227f reporter See Reporter gene sequence of, 268 structure of, 224–32, 806, 806f subunits of, 230 Gene amplification, 692, 697f–699f Gene catalogues, Gene conversion, 193f, 194, 194f, 195f, 807, 808f, 809f intergenic, 806–7, 808f, 809, 809f in yeast, 193f, 194, 194f Gene desert, 372 Gene dosage, 495 dosage compensation, 481–82, 669–70, 674 Gene expression, 3, 255, 256f attenuation of, 282, 626–28, 626f, 627f, 644t in Caenorhabditis elegans, 284–85, 285f cellular components of, 290, 291t chromosome compaction and, 478–82, 479f, 480f in development, 745–47, 746f ectopic, 288f, 289, 728–29, 729f in eukaryotes, 282–84, 283t excessive, 728, 728f mutations and, 285–91, 286f, 287f, 288f, 290t mutations in gene-encoding machinery for, 290–91, 291f in prokaryotes, 282–84, 283t regulation by nonhistone proteins, 468 Gene expression patterns, positional cloning and, 411–15 Gene family, 370, 370f See also Gene superfamilies; Multigene family most populous, 369t origin of, 515 Gene gun, 589 Gene linkage See also Linkage analysis recombination frequency and, 123–35, 134t Gene mapping, 135–51 See also Genetic map; Human Genome Project applications, 140–43 in bacteria, 566 correspondence to physical reality, 140–41 in cystic fibrosis, 142–43, 143f definition of, 134–35 of DNA fragments, with gel electrophoresis and hybridization, 234, 325f–326f fine structure mapping, 227–32, 228f–229f, 231f in fungi, 142–51 See also Tetrad analysis gene-centromere distance, 150–51, 151f, 151t haplotype association studies, 393, 423–25, 425f with hfr X F– mating, 556–60, 558f, 560f, 566 of human X chromosome, 154–55, 155f interference in, 138–39 interrupted mating experiment, 558–59, 558f mapping functions in, 140 multiple-factor crosses in, 141–42 recombination frequency and, 124, 132–34, 133f, 135–51 relative gene order in, 135–40 with three-point crosses, 136–40, 136f, 137f, 139f, 560–61, 560f with two-point crosses, 135–36, 135f using deletions, 230–32, 231f, 259, 260f, 496–98, 497f, 498f using generalized transduction, 563, 564f using translocations, 507–8, 508f of X chromosome of Drosophila melanogaster, 136–37, 136f, 139, 139f Gene pool, 758 Generalized transduction, 563, 563f, 564 mapping genes by, 563, 564f Gene regulation and development, 717, 745–48 in eukaryotes, 632–34, 643–76 fine-tuning of, 658 post-transcription controls, 664–69, 746 vs prokaryotes, 644–45, 644t sex determination in Drosophila melanogaster, 669–76, 673f, 673t transcription initiation controls, 646–64 evolution and, 798–801 in prokaryotes, 609–34 vs eukaryotes, 644–45, 644t expression attenuation, 626–28 global mechanisms, 628–32 overview of, 611–12 regulation of virulence genes in V cholerae, 609, 632–34, 633f transcription regulation, 612–26 Gene regulatory networks, 441–44, 442f, 443f Gene-rich regions, 372, 372f Gene silencing See also Transcriptional silencing by miRNAs, 668 Gene superfamilies, 7–8, 805, 809–10, 810f, 811f Hox gene superfamily, 744–45, 744f immunoglobulin gene superfamily, 813–21, 814t, 816f Gene therapy in cystic fibrosis, 23, 33, 142, 419 germ-line, 382 for sickle-cell disease, 57 somatic, 382 Genetically-modified (GM) crops, 28–29, 320–21, 320f, 321f Genetic code, 5–7, 6f, 255–65 in ciliates, 265 codon-amino acid correspondences, 261–63, 262f, 263f degeneracy of, 261, 264 evolution of, 265 in mitochondria, 265, 588, 588t nonoverlapping codons of, 259–61, 264–65 triplet nature of, 5, 6f, 257–61, 260f, 261f, 264 universality of, 265, 588, 588t, 795 verification using genetics, 264–65, 264f Genetic conservation, in evolution, 718–20, 748 Genetic counseling, 217, 245, 395, 474 Genetic discrimination, 11, 34–35, 87, 427 Genetic disease See also specific diseases banding pattern differences and, 474 haplotype association studies, 393, 423–25, 425f incidence of, 525 linking to causative gene with linkage analysis See Linkage analysis without linkage analysis, 408, 409f I-9 recessive, evolutionary equilibrium and, 767–68 single-gene traits, 30–36, 31t time of onset of, 31–32, 768 Genetic dissection of complex trait, 8–9, 419–23 bacterial chemotaxis, 566–69 difficulties of, 419t, 420–22 methods, 422–23, 422f of development, 721–29 Genetic diversity See Genetic variation Genetic drift, 768–69, 768f, 799, 803–4 Genetic engineering, 11–12, 28–29, 307, 380–81 See also Transgenic technology of chloroplast genome, 589–90 lateral gene transfer and, 373 of plasmids, 549 Genetic heterogeneity, linkage mapping and, 419t, 421 Genetic imbalance, 495 Genetic map of Drosophila melanogaster, 142f of Escherichia coli, 559, 559f of humans, 491–92, 492f of mice, 491–92, 492f Genetic markers, 131 genomewide identification of, 358 genomewide typing of, 358–59, 358f locating with FISH protocol, 361, 362f Genetic mosaic See Mosaic, genetic Genetic privacy, 34–35, 37, 353, 395, 528, 604 Genetic relatedness definition of, 775 of living organisms, 719–20 Genetics, applied, history of, 15–16, 15f coining of term, 46 definition of, 13 history of, 15–19, 15f, 16f importance of, 10 population, 757–81 definition of, 33, 758 reverse, 566, 566f Genetic screening, 546–47 accuracy of, 34 ethical guidelines for, 34–35, 37, 380 identification of development genes, 721, 726 Genetic testing, for predicting and treating cancer, 708–9 Genetic variance, 773–81, 774f definition of, 775 Genetic variation, 192, 394–99, 757f, 758 See also DNA polymorphisms causes of, 13–14 crossing-over and, 101f, 103, 192 in dogs, 15 evolution and, 14 independent assortment and, 101–3, 101f, 192 meiosis and, 101–3, 101f mutation and, 223 sexual reproduction and, 103 Gene transfer in bacteria, 550–66 lateral, 373, 540, 550, 570–71 between organelle and nucleus, 591–92 Genome See also DNA analysis of, 354–66 bacterial, 543–49, 546f, 570 comparative analysis of, 570–72 deconstruction of, 301–39 definition of, 351 of E coli, 8, 9f, 310, 353, 355t, 540, 547, 557–58, 570–71 remnants of bacteriophage genome in, 547–48 fragmenting into bite-size pieces, 303–10 gene deserts, 372 gene organization within, 370–72 gene-rich regions, 372, 372f modular construction of, 7–8, 7f organization of, 805–13 reconstruction of, 351–83 size of in different organisms, 354, 355t increase in, 801–3, 801f, 804f sources of data on, 374t stability of, cell-cycle checkpoints and, 349 Genome, mitochondrial See Mitochondrial genome Genome map high-density linkage maps, 357–59, 357f, 358f integrating linkage, physical, and sequence maps, 364 large-scale maps, 357 long-range physical map, 359–61, 359f har48564_ndx_I1-I22 I-10 9/6/06 01:54 AM Page I-10 Index Genome map—Cont sequence map, 357, 362–64 finding genes in sequenced genome, 364–65 hierarchical shotgun sequencing strategy, 335, 362–63, 363f whole-genome shotgun sequencing strategy, 363–64, 364f techniques for genome mapping, 356–57 Genome sequence See also DNA sequencing accuracy needed, 355 of Arabidopsis thaliana, 353, 355t of Caenorhabditis elegans, 255, 284, 353, 355t of Drosophila melanogaster, 353, 355t of Escherichia coli, 353, 355t of humans, 353, 355t, 364f of Methanococcus jannaschii, 540 of mouse, 353, 355t, 358 of pufferfish, 353, 355t, 366 repeated DNA in, 355 of rice, 353, 355t unclonable DNA, 355–56, 364 unique nongene sequences in, 813 variation in members of same species, 394–96, 394f of yeast, 353, 355t Genome sequencing See DNA sequencing Genome-wide localization, 450, 451f Genomic equivalent, 316 Genomic evolution, 799–805 DNA alterations as basis of, 799 gene regulatory networks as source of, 798–801 increase in genome size, 801–3, 801f, 804f phylogenetic trees, 805, 805f pseudogenes, 803–4 Genomic imprinting, 660–64, 662f–663f biological role of, 664 evolution of, 664 in humans, 661, 663f Genomic instability, in cancer, 697f–699f Genomic library, 311, 314–18, 356 vs CDNA library, 316–17, 317f, 318, 318f compiling of, 315–16 complete, 315–16 long-range physical mapping, 359–61, 359f screening with DNA probe, 319–24, 322f vectors for, 311t Genomics, 351, 375 See also Linkage map; Physical map; Sequence map comparative genome analysis, 570–72 finding gene in sequenced genome, 364–65 global genomic strategies, 378–79 high-throughput technology and, 352, 364, 375–78, 376f, 377f, 378f and systems biology, 438 Genotype definition of, 24 determination by testcross, 24, 24f direct analysis of, 357, 391–425 prediction of, 27 relationship to phenotype, 17, 45–71, 87 in bacteria, 543 in fungi, 142–43 Genotype frequency definition of, 759 effect of natural selection on, 763–66, 764f, 765f Hardy-Weinberg Law, 760–62, 760f, 761f Genotyper, Genotypic classes, 58 Genotypic ratio, 47, 62, 62t Genotyping, 391–92, 392f See also DNA polymorphisms, detection of genetic dissection of complex traits, 8–9, 419–23 difficulties of, 419t, 420–22 methods, 422–23, 422f positional cloning, 408–19 Geospiza fotis, bill depth in, 775–76, 776f Geranium chloroplast genome of, 598, 598f variegation in, 598, 598f Germ cells, 94, 102t, 103 Germ line, 11–12, 103 Germ-line diversity, 818 Germ-line gene therapy, 382 GFP See Green fluorescent protein Ghost, viral, 172f, 173 giant (gt) gene, of Drosophila melanogaster, 738f Giemsa stain, 360, 360f, 472, 473f, 489 Gilbert, Walter, 331, 620–23 Giraffe, neck length in, 763, 763f Glaucoma, juvenile, 68–69, 68f Gleevec, 505 Gliomas, 707 Global genomic strategies, 378–79 Global molecular techniques, 351 Global proteomic strategies, 444–50 Global regulatory mechanisms, 628–32 heat shock response, 628–29, 629f microarrays to study, 629–32 nitrogen fixation, 630–31, 631f sigma factors in, 631 ␣-Globin, 55, 301–2, 302f, 323–24, 805f ␤-Globin, 55, 301–2, 302f, 312, 316–18, 317f, 319–20, 323–24, 805f Globin genes, 335–39, 336f, 338f, 339f evolution of, 7, 337–39, 339f, 804, 805f locus control region of, 336, 336f, 337, 339f mutations in, 337, 338f, 339f sequence of expression, 336–37 ␣-Globin genes, 335–39, 336f, 338f, 339f, 809–10, 810f locus control region of, 337, 339f mutations in, 421 ␤-Globin genes, 34, 335–39, 336f, 338f, 339f, 804, 806, 809–10, 810f See also Sickle-cell disease cloning of, 312 detecting mutations in, 328f–329f DNase hypersensitive sites in, 658 evolution of, 804, 805f locus control region of, 657–58, 657f mutations in, 11, 55–56, 55f, 57, 421 ␣-Globin locus, 336, 336f, 337–39, 339f ␤-Globin locus, 336, 336f, 337–39, 339f detecting mutations in, 400, 400f Globin-related disease, 337, 338f, 339f gluA gene, of Escherichia coli, 632 Golden rice, 29 Goldfish, number of chromosomes in, 85 Golgi bodies, 92 Gonorrhea, 539, 544 Gram-positive bacteria, 541t grande phenotype, in yeast, 581–82 Grandmothers of the Plaza de Mayo, 600–601 Granum, of chloroplast, 584, 584f Graphical integration of data, in systems biology, 452 Great lubber grasshopper, sex determination in, 85, 85f Green fluorescent protein (GFP), 646, 730, 731f Green nonsulfur bacteria, 541t Green-receiving protein, 242, 242f Green sulfur bacteria, 541t Griffith, Frederick, 169–70, 170f, 551 Growth factors, 695, 696f Guanine (G), 1, 2f, 5, 6f, 174f, 175, 177, 178f, 180f, 181f Guide RNA, 587, 587f Gut development, in sea urchins, 443, 443f Gynandromorph, 518, 519f H H2K gene, of mice, 234, 325f–326f H4 protein, 720 H19 gene, of mice, 661 Haemophilus influenzae, 539, 551 Haig, David, 664 Haig hypothesis, 664 Hairpin loop, 266f–267f Hallucigenia, 797f Halobacterium, genome sequence of, 355t Haltere, 8, 8f, 741, 742f Hansenula, mitochondrial DNA of, 585 Haploid (n) cells, 83–84, 83f, 94, 100, 103 Haploinsufficiency, 289, 289f, 723 Haplospores See Ascospores Haplotype, 423–24, 424f Haplotype association studies, 393, 423–25, 425f Ha-ras gene, 705t Hardy, G H., 760 Hardy-Weinberg equilibrium, 760 Hardy-Weinberg Law, 760–62, 760f, 761f and evolutionary equilibrium, 766–69 natural selection and, 763–66, 764f, 765f Hartsoeker, Nicolaas, 17 Harvey murine sarcoma, 705t Hays, William, 556 HD gene, 32, 32f detection of microsatellites in, 404–6, 405f mapping by positional cloning, 411, 412f Heart disease, penetrance of, 420 Heart rate, epinephrine sensitization and, 668–69, 669f Heat shock response in Escherichia coli, 628–29, 629f sigma factor in, 628–29, 629f Heavy chain, 807f, 817 Heavy-chain gene, 818, 818f, 819f alternative splicing, 274, 274f hedgehog (hh) gene, of Drosophila melanogaster, 738–39, 740f Height, human, 68, 70f, 778 Helix-loop-helix (HLH) motif, 650f, 651, 654, 654f Helix-turn-helix (HTH) motif, 620–21, 621f, 650, 651f Hemizygous, definition of, 108 Hemochromatosis, genetic screening and, 35 Hemoglobin, 4f, 301–2, 302f See also Globin genes adult, 301, 302f, 336 disorders of, 301–2 embryonic, 301, 302f, 336 fetal, 301, 302f, 336–37 functions of, 301 ␤-Globin gene and, 34 structure of, 236–37, 236f, 238, 238f Hemoglobin C, 338f Hemoglobin genes, evolution of, 805f Hemoglobin Hammersmith, 338f Hemoglobin H disease, 338f Hemoglobin S, 338f Hemolytic anemias, 337, 338f Hemophilia, 111, 111f, 123, 123f, 154–55, 155f linkage analysis, 408, 410f, 513 Hepatitis A, 270 Her2/neu protooncogene, 709 Herbicide-resistant plants, 590 Herceptin, 709 Heridity, definition of, 13 Heritability definition of, 775 evolution and, 776–78, 777f measurement of, 775–78, 776f of polygenic traits, in humans, 776–78, 777f Heritable traits, 13 Hershey, Alfred, 172–73, 172f, 822 Hershey-Chase Waring blender experiment, 172–73, 172f Heterochromatic DNA, 353–54 Heterochromatin, 95, 364, 479–82, 479f, 501–2 constitutive, 479 facultative, 480–81, 480f Heterodimers, 651–52 Heteroduplex regions, 193–94, 193f Heterogeneous traits, 62–63, 63f Heteromers, 651, 652f Heteroplasmic cells, 593–96 Heterozygote coining of term, 46 definition of, 24 Heterozygous, definition of, 24 Heterozygous advantage, 765–66, 799 Hexosaminidase A, 53–54 Hfr bacteria, 555–56, 556f, 557f Hfr X F– mating, 556–58, 557f and circular nature of bacterial chromosome, 559, 559f and gene mapping, 556–60, 558f, 560f, 566 HGH See Human growth hormone Hierarchical shotgun sequencing, 335, 362–63, 363f Higher-order processes, understanding of, High-throughput technology, 375–78, 376f, 377f, 378f in academic settings, 457 and global genomic strategies, 378–79 Human Genome Project and, 352, 364 impact of, 379–82 in proteomics, 444–50 HindIII, 182–83, 182f, 304t HIS4 gene, of yeast, 143–45, 146f hisB2 gene, of B subtilis, 551, 552f Histidine, 145 Histidine revertants, 224, 224f Histocompatibility antigens, 50, 695, 695f Histones, 467, 467t, 470f in centromeric heterochromatin, 482 core, 467 DNA interactions, 374–75 evolution of, 467, 720 molecular characteristics of, 467t in nucleosomes, 375, 467, 469, 470f synthesis and incorporation of, 467, 477 HIV/AIDS capacity for mutation, 271, 793 and gene therapy for sickle-cell disease, 57 human immune response and, 792–93 life cycle of, 270, 270f, 330 har48564_ndx_I1-I22 9/6/06 01:54 AM Page I-11 Index PCR assay for, 330 provirus, 327 reverse transcription in, 270–71, 270f structure of, 270, 270f and TB resurgence, 757 treatment of, 271, 382, 438, 670, 793–94 virus responsible for, 181 HLA genes, 50 HLA typing, 600 HMG-CoA reductase, 678 hmLH2 gene, 708t HML locus, of yeast, 659, 659f HMR locus, of yeast, 659, 659f hMSH2 gene, 708t Holliday, Robin, 197f Holliday intermediate, 198f–199f Holliday junction, 197f Homeobox, 744 Homeodomain, 729, 730f, 744 Homeostasis, 439 Homeotic genes, of Drosophila melanogaster, 732–33, 741–45, 742f, 743f Homeotic mutation, 741–42, 742f Homogeneously staining region (HSR), 692, 693f Homogentisic acid, 232, 232f Homologous chromosomes, 84, 84f, 99–100, 102t, 107t, 367 See also Meiosis recombination between See Recombination Homologous genes, 358 Homologs See Homologous chromosomes Homology-dependent repair, 220 Homomers, 651, 652f Homoplasmic cells, 593–94 Homo sapiens, 167 Homozygosity of mutant alleles, 62–63, 63f Homozygote coining of term, 46 definition of, 24 Homozygous, definition of, 24 Homunculus, 16, 17f Honeybee, base composition of DNA of, 176t Hopkins, Samuel, 381 Horizontal gene transfer See Lateral gene transfer Horizontal pattern of inheritance, 32–33, 33f, 33t, 64, 66f Hormones, 695, 695f, 696f in development, 747 Hot spots, 140, 231f, 232 Housekeeping genes, 9, 479 House mouse See Mouse Hox genes, 744–45, 744f of Drosophila melanogaster, 811f of mice, 744–45, 744f, 810, 811f Hox gene superfamily, 744–45, 744f HpaI, 182–83, 182f HpaII, 659 HPV See Human papillomavirus H-ras gene, 705f, 705t HSR See Homogeneously staining region hst gene, 705t HTH See Helix-turn-helix (HTH) motif Human(s) albinism in, 64, 66f aneuploidy in, 525–26, 526t bacteria in, 541 base composition of DNA of, 176t color perception in, 239–42, 242f cellular and molecular basis of, 241–42, 242f mutations affecting, 242f, 243–44 comparative genome analysis and, 571 continuous traits in, 68–69, 70f early species of, 167 eye development in, 720, 730f FGFR3 gene in, 728 gamete nuclei, size of, 83 gene nomenclature for, 827 genomic imprinting in, 661, 663f height of, 68, 70f, 778 heritability of polygenic traits, 776–78, 777f Hox genes in, 744 identification of remains, 408, 780–81 mitochondrial genome of, 585, 585t, 586–87, 586f, 592, 594–95, 595f kinship determination from, 600–601 MERFF and, 599–602, 601f, 602f mutation in, and neurodegenerative disease, 593, 593f natural selection and, 763–64 olfactory multigene family in, 370, 371f oogenesis in, 103–4, 104f Pax-6 gene of, 730f polyploidy in, 519 proteome of, 369t races of, 374 and reproductive cloning, 750 sex determination in, 82, 86–88, 86f, 86t single-gene traits in, 30–36, 31t skin color in, 68–69, 70f spermatogenesis in, 104–5, 105f transcription factor domain and architecture, 366f trypsinogen genes of, 820f, 821 X- and Y-linked traits in, 110–11, 111f, 115 X chromosome of aneuploidy in, 516–17, 517f, 525–26, 526t colorblindness gene, 473, 473f genetic map of, 154–55, 155f number of genes on, 124 Human brain as biological system, 4–5 evolution of, 798 Human chromosomes, 83–85, 85f, 207, 208f, 468f, 473–74, 473f base pairs in, 465 base sequences in, 180 Human development, 13, 717–18, 718f, 720–21 Human evolution, 7–8, 592, 594–95, 595f, 798–99, 798f Human genetics complexity of, 30, 45–46 similarities and differences of appearance, 13, 14f single gene traits, 30–36, 31t Human genome, 351, 351f vs chimpanzee genome, 798 DNA polymorphisms in, 357, 365, 383 genetic markers in, 358 vs mouse genome, 365–66, 367f, 489–90, 490f, 514 number of base pairs in, 302–3 number of genes in, 8, 9f, 366–67 vs pufferfish genome, 366 repeat sequences in, 369–70 sequencing of, 353, 355t, 364 size of, 354 transposable elements in, 509–10, 510f, 513 Human Genome Project, 8, 9f, 10–11, 351–65, 351f, 352f, 383, 524, 820 ELSI arm of, 353 error rate of, 355 and genetic testing for cancer, 708–9 impact of, 365–66, 379–82, 457 insights from, 366–72 objectives of, 352, 362 proteomics and, 445 scientific merits of, 352–54 sources of data on, 374t systems biology and, 439–40 Human growth hormone (HGH), 678 synthesis of, 626 Human immunodeficiency virus See HIV/AIDS Human lymphocyte antigens (HLA), kinship determination from, 600 Human papillomavirus (HPV), 705 hunchback (hb) gene, of Drosophila melanogaster, 736, 736f, 737, 738f Hunter syndrome, 155f Huntington disease, 30, 31t See also HD gene detection of alleles for, 404–6, 405f genetic screening for, 34 pedigree analysis in, 31–32, 32f RNA interference therapy for, 670 trinucleotide repeats in, 217, 405–6, 405f Hybrid(s), 18, 18f Hybrid dysgenesis, 511–13 Hybridization, 302, 319–24, 322f, 498, 498f allele-specific oligonucleotide (ASO) detection of BRCA1 mutations, 402–3, 402f detection of CFTR genotypes, 419 detection of SNPs, 400–403, 401f, 402f chromosome painting, 504f, 694f, 697f–699f degree of complimentarity needed for, 324 DNA chips and, 9, 10f of DNA from deletion heterozygote, 498f fluorescence in situ (FISH), 361, 362f, 499f, 508 with gel electrophoresis to map DNA fragments, 324, 325f–326f in genome mapping and sequencing, 356 PCR and, 327 RNA in situ, 729–30, 730f, 746 in silico, 411, 413f SKY chromosomal, 361, 361f SNP analysis, 379, 401–3, 401f, 402f I-11 Hydrogen bonds, in DNA, 175, 176f, 177 Hydrolysis, mutations caused by, 212, 213f Hydroxylamine, 218f–219f Hydroxylating agent, 218f–219f Hydroxyurea, 57 Hypercholesterolemia, 31t RNA interference therapy for, 670 Hypermorphic mutation, 289, 290t Hypomorphic mutation, 287, 290t, 723 Hypophosphatemia, 111, 111f Hypothesis-driven query, in systems biology, 452 I ICAT See Isotope-coded affinity tag ID See Intelligent design Idiogram, 360f I gene, 48, 48f, 49, 49f, 60–61, 60f Igf2 (insulin-like growth factor) gene, of mice, 660–61, 662f–663f Illegitimate recombination, 195–200, 200f, 565f See also Unequal crossing-over Immortality of cancer cells, 699f Immune-cell receptors, 815–20, 817f, 818f gene rearrangements in, 818–20, 819f Immune response, 792–93, 793f adaptivity of, 818 control of, 437 evolution of, 813–21, 814t, 816f in vertebrates, 820 memory of, 818 specificity of, 818 Immune system cancer evasion of immune response, 697f–699f and cell-to-cell contact, 695, 695f defense against bacteria, 545 histocompatibility antigens, 50 immune-cell receptors, 815–20, 817f, 818f immunoglobulin supergene family, 813–21, 814t, 816f programmed DNA rearrangements and, 492–94, 492f, 493f, 494f sickle-cell disease and, 57 state of knowledge about, 437 T-cell receptors, 489–90 Immunity, state of knowledge about, 437 Immunoglobulin fold, 813 Immunoglobulin gene superfamily, 813–21, 814t, 816f Immunoglobulin homology unit, 813 evolution of, 813–15, 816f Immunoglobulins, 492, 818 bacterial pathogens and, 545 Inborn error of metabolism, 232, 232f Incompatibility genes, in plants, 51–52, 52f Incomplete dominance, 46–48, 47f, 54t in dihybrid cross, 63, 64f mutation and, 287–88, 287f Incomplete penetrance, 65, 419t, 420, 420f Independent assortment and genetic diversity, 101–3, 101f, 192 law of, 25–27, 25f, 26f, 106, 107t, 134, 145 departures from Mendelian phenotype ratios and, 63 Inducer, 612–13, 614f, 615f, 616, 616f, 620 Induction, 612–13 Informational science, biology as, 440–44 infra-abdominal (iab) genes, of Drosophila melanogaster, 742 Ingram, Vernon, 236 Inheritance blended, 17–20 chromosome theory of, 81–112 criss-cross, 108, 108f horizontal pattern of, 32–33, 33f, 33t, 64, 66f uniparental, 592–97 in Chlamydomonas reinhardtii, 596, 597f units of, 20 vertical pattern of, 31–32, 32f, 33t Initiation codon, 264, 279f, 281 Initiation factors, 279f Initiation phase of transcription, 611, 611f of translation, 278–81, 279f, 612 in prokaryotes vs eukaryotes, 282, 283t Initiation site, 648 Initiation stage of replication, 188f, 190 Initiator protein, 188f Initiator tRNA, 279f, 283, 283t har48564_ndx_I1-I22 I-12 9/6/06 01:54 AM Page I-12 Index Inner membrane of chloroplast, 584, 584f of mitochondria, 583, 583f Insecticide resistance See Pesticide resistance Insects pesticide resistance in, 770–71, 771f sex determination in, 88, 88t Insertion, 208–9, 209f, 259, 264 direct detection of, 404 as DNA polymorphism class, 398–99, 398f Insertional inactivation, 313f Insertion sequence (IS) in bacterial chromosome, 548, 548f in F plasmid, 555–56, 556f In silico hybridization, 411, 413f Insulator, 661, 662f–663f Insulin, synthesis of, with recombinant DNA technology, 183f, 307, 318, 319f, 626 Insurance, genetic screening and, 34–35, 87, 427 Integration of data, in systems biology, 452 Intelligent design (ID), vs evolution, 802–3 Interactome, 449 Intercalating agent, 218f–219f, 220 Interferon-gamma, 307 Intergenic gene conversion, 806–7, 808f, 809, 809f Intergenic mutation, 232 Interkinesis, 97f, 100, 102t Interleukin (IL) receptors, 238, 239f Intermembrane space of chloroplast, 584, 584f of mitochondria, 583, 583f Interphase, 89, 89f, 93f, 187 Interrupted mating experiment gene mapping by, 558–59, 558f proof that bacterial chromosome is circular, 559, 559f Intersex (ix) gene, of Drosophila melanogaster, 675 Intragenic mutation, 232 Intragenic suppression, 259–61, 261f Intrinsic terminator, 267f Intron, 7, 7f, 272–73, 274f, 467, 547 evolution and, 795 identification of, 324 in organelle genomes, 587 RNA splicing, 271–73, 273f, 274f, 283t, 284 Inversion, 209, 209f, 216, 491t, 501–3, 501f, 508, 515 effect on phenotype, 501, 501f evolution and, 515 paracentric, 501, 501f, 502, 503f pericentric, 501, 501f, 502, 503f Inversion heterozygote, 502–3, 502f, 508 Inversion loop, 502, 502f, 503f In vitro fertilization, 391–92, 392f, 395, 750 Ion trap tandem spectrometer, 445 IS See Insertion sequence IS10, 548, 548f Isogamous species, 596 Isoniazid resistance, 769–70 Isotope analysis, 446–47 Isotope-coded affinity tag (ICAT), 446–47, 447f, 454 Iterative perturbations, in systems biology, 452 J Jacob, Franỗois, 557, 61318 Janssens, Frans, 131 Jefferson, Thomas, 381 Jeffreys, Alec, 406 Jenner, Edward, 437, 438f Joining segments, 818, 818f Jones, John E., 803 Junctional diversity, 819f jun gene, 705t Junk DNA, 370 Jun polypeptide, 651, 652f Juxtacrine signaling, in development, 747 K KADAP See WTC Kinship and Data Analysis Panel Kanamycin resistance, 550f Kappa (␬) light-chain genes, 818, 818f Karyotype, 84–85, 85f, 472–74, 473f, 492 in cancer, 697f–699f constancy with species, 490 of human female, 473f of human male, 84, 85f of humans, 360f in long-range physical mapping, 360–61 revealing causes of genetic diseases, 474 Karyotyping, 87 ethical issues in, 527–28 limitations of, 524 Kernel mottling, in corn, 510, 510f Khorana, Har Gobind, 262 Killer T cells, 697f–699f Kinetochore, 90f, 91, 99–100, 477–78, 478f Kinetochore microtubules, 90f, 91 Kinetoplast, 585, 585f, 587 King, Mary Claire, 600 Kinky allele, in mice, 288f, 289 Klebsiella, 630 Klinefelter syndrome, 86, 86t, 100, 516, 516f, 526t Knirps (kni) gene, of Drosophila melanogaster, 738f Knockout mice, 419, 721–23, 722f Knockout mutations in development research, 721–23, 722f in gene mapping, 565, 566f Kornberg, Arthur, 187 KpnI, 304f, 304t K-ras gene, 705t Krebs cycle, 583–84, 583f Krüppel (kr) gene, of Drosophila melanogaster, 737, 738f, 741f, 746 L Labial (lab) gene, of Drosophila melanogaster, 742f, 743 Labile-toxin (LT) gene, of Escherichia coli, 590 Labrador retriever, coat color in, 14, 14f, 60, 60f, 62t lacA gene, 613–15, 614f, 615f, 618 lac gene fusions controlling gene expression using, 624–26 identifying regulatory sites using, 624 measuring gene expression using, 624, 625f lacI gene, 614f lacI– mutants, 615–17, 617f, 631 lacIs mutants, 616–17, 617f, 618f Lacl repressor family, 621 lac operators, 614f, 616, 621–22 lac– mutants, 615 lacOc mutants, 617–18, 618f, 620, 620f repressor binding in, 620, 620f lac operon, in Escherichia coli, 609f, 613–26, 614f, 629–32 analysis of mutants in, 615–18 complementation testing of lactose-utilization genes, 615, 615f negative control of See lac repressor operon theory, 613–15, 614f positive regulation of, 618–19, 619f trans- and cis-acting regulatory elements, 614f, 617–18, 618f, 624 Lac permease, 612–15, 612f lac promoter, 614f lac repressor, 609f, 614f, 615f, 617–18, 622, 622f binding to DNA, 622, 622f binding to operator DNA, 620, 620f DNA-binding domains of, 616–17, 616f, 620 experimental evidence for, 615–16, 615f helix-turn-helix motif in, 620–21, 621f inducer-binding domain of, 616–17, 616f, 620 interaction with RNA polymerase, 623, 624f structure of, 622, 622f Lactate dehydrogenase, 4f Lactic acid bacteria, 541t Lactose, 612 lacY gene, 613–15, 614f, 615f, 617–18 lacZ gene, of E coli, 313–14, 313f, 546–48, 548f, 613–15, 614f, 615f, 617–18, 623–26, 625f, 633 Lagging strand, in replication, 189f, 190 Lambda (␭) light-chain genes, 818, 818f Lariat structure, 273, 273f Late-onset genetic condition, 32, 35, 54, 768 Late promoter, 665, 665f Lateral gene transfer, 373, 540, 550, 570–71 Lawn of bacteria, 227, 228f, 306 Law of independent assortment, 25–27, 25f, 26f, 106, 107t, 134, 145 departures from Mendelian phenotype ratios and, 63 Law of segregation, 19–24, 20f, 21f, 106, 107f, 107t dominance relations and, 48–49 Mendelian phenotype ratios and, 63 LCR See Locus control region LDL See Low-density lipoprotein Leader sequence, 627–28, 627f Leading strand, in replication, 189f, 190 Leber’s hereditary optic neuropathy (LHON), 593–95, 593f Leder, Philip, 262–63, 263f Lederberg, Joshua, 553–54, 553f Leeuwenhoek, Anton van, 82–83 Legal issues, in predictive/preventive medicine, 11–12 Leishmania, mitochondrial DNA of, 585 ␤2 Lens crystallin, 238, 239f Lentils, seed coat color in, 45–46, 45f, 46f, 48, 48f, 50, 50f, 56–58, 58f, 62t Leptotene, 96f, 98, 98f Lethal allele, 53–54, 53f conditional, 66, 240 See also Conditional lethal mutants recessive, 53–54, 54t, 55, 55f Leucine, 262, 547 Leucine zipper motif, 651–52, 652f, 654, 654f leu genes, in Escherichia coli, 547 Leukemia, 697f–699f Ableson, 705t chronic myelogenous, 504–5, 505f molecular markers for, 709 reciprocal translocations and, 504–5, 505f Lewis, Edward B., 735, 742 lexA repressor, 651, 652f LHON See Leber’s hereditary optic neuropathy Library, 356 complementary DNA See Complementary DNA (cDNA) library genomic See Genomic library screening with DNA probe, 319–24, 322f Ligand, 726, 747–48 Light chain, 807f, 817, 819 Light chain gene, 818, 818f, 819f Light repair, 220 LINE (long interspersed element), 369–70, 370f, 509–10, 510f, 513, 821 creation of, 811–12, 812f L1, 509 and selective advantage, 812 Linkage analysis of autosomal traits, 127, 127f chi square test in, 127–31, 129t correlating phenotype to genome area, 410–12, 410f, 412f genetic dissection of complex traits, 8–9, 419–23 difficulties of, 419t, 420–22 methods, 422–23, 422f vs high-density linkage maps, 357 with pedigrees and LOD scores, 416–17, 416f percentages of parental and recombinant classes, 127 in positional cloning, 408–15, 410f preponderance of parental genotypes in F2, 126, 126f recombination frequency and, 124–35 Linkage disequilibrium, 424 Linkage group, 141, 141f Linkage map, 410 high-density integrating with physical and sequence maps, 364 making of, 357–59, 357f, 358f Linked genes, 126 Linker DNA, 469, 470f Link protein, 815 Lip cancer, 701t Literature, biological, in systems biology, 451 Liver cancer, 701t Liverwort chloroplast DNA of, 588, 588t, 589f mitochondrial DNA of, 585t, 586f, 587 Living organisms characteristics of, common origin of, 5–7, 6f evolution of, 7, 8t, 374, 490 See also Evolution first cell, 794–96 multicellular organisms, 7–8, 8t, 796–99, 796f, 797f family tree of, 540, 540f genetic relatedness of, 719–20 origin of, 794–99 Lizards, sex determination in, 88, 88t Locus, 134–35, 336 anonymous, 395 definition of, 393 polymorphic, 395–96 Locus control region (LCR), 336, 336f of ␣-globin gene, 337, 339f of ␤-globin gene, 657–58, 657f har48564_ndx_I1-I22 9/6/06 01:54 AM Page I-13 Index LOD score, 416–17, 417f Logarithmic growth stage, 551 Long interspersed element See LINE Long terminal repeat(s) (LTR), 510, 511f Long terminal repeat retroposon, 370, 370f Loss-of-function mutations, 287–89 development research and, 721–26 Lou Gehrig’s disease See Amyotrophic lateral sclerosis Low-density lipoprotein (LDL), 670, 678 LTR See Long terminal repeat(s) Lung cancer, 701–2, 702f penetrance and expressivity of, 67 Luria, Salvador, 211, 211f Luria-Delbrück fluctuation experiment, 211, 211f Lymphocytes, 492, 792–93, 793f, 818 See also B cell(s); T cell(s) Lymphoma, 697f–699f Burkitt’s, 494, 494f Lynx Therapeutics multiple parallel signature sequencing strategy (MPSS), 379f lysA gene, of E coli, 563, 564f Lysate, 563 Lysogenic cycle of bacteriophage, 564, 564f, 565f of bacteriophage lambda, 565f Lysozyme, 545 Lytic cycle of bacteriophage, 562–64, 564f of bacteriophage T4, 228f M Macaroni wheat, 29, 85 McCarty, MacIyn, 171 McClintock, Barbara, 131, 509, 509f, 510 Macleod, Colin, 171 McLeod’s blood type, 474 Macroarray, 376 Macroevolution, 762 Macrophages, 545, 695, 745f, 817f Macrosatellites, 812–13 Madeira, speciation on, 515, 515f Major groove, of DNA, 177, 178f, 181, 621f Major histocompatibility complex (MHC) class I molecules, 817, 817f class II molecules, 817, 817f evolution of, 815 human, class III region of, 372, 372f in mice, 324 Major histocompatibility complex (MHC) genes class I genes, 807, 808f in mice, 808f Major histocompatibility complex (MHC) receptors, 817, 818f, 819–20 Malaria, sickle-cell disease and, 55–56, 55f, 57, 765–66, 767f Male(s), mutation rate in, 373–74 Male bacteria, 544f–545f Male pattern baldness, 112, 112f Mammal(s) evolution of, 798 genome of, 354, 473–74, 805–13 sex determination in, 82, 86–88, 86f, 86t Mammalian expression vectors, 318–19 Maori people (New Zealand), 53 Mapping See Gene mapping; Genetic map; Restriction mapping Mapping functions, 140 Map unit (m.u.), 133–34, 140 Marchantia polymorpha See Liverwort Margulis, Lynn, 591 Marker fragments, 308f, 309 Masking of allele effects, 60–62, 60f, 61f Mass Fatality Identification System (M-FISys) software, 781 Massively parallel signature sequence (MPSS) technique, 378–79, 379f Mass spectrometry, 445–46, 445f affinity capture/mass spectrometry, 448, 448f time-of-flight, 403f, 404 in typing of SNPs, 358, 379 Master plate, 212f Maternal age, meiotic segregational errors and, 104, 518 Maternal-effect genes, of Drosophila melanogaster, 734–37, 740, 741f Maternal-effect mutations, 734 in Drosophila melanogaster, 734–35 Maternal inheritance of chloroplast genome, 592–93, 596 of mitochondrial genome, 592–93, 593f, 596 in tobacco, 593 in Xenopus, 592, 593f Maternally supplied components, 734 Mathematical integration of data, in systems biology, 452 Mating, consanguineous, 30, 33 Mating type in Chlamydomonas reinhardtii, 596, 597f in fungi, 144f in yeast, 598, 599f, 653, 653f, 659–60, 719 MAT locus, of yeast, 659–60 Matrix, of mitochondria, 583, 583f, 584 Matthaei, Heinrich, 262 Maxam, Alan, 331 max gene, 654–55, 654f Maxicircle DNA, 585 Mean, 773, 774f Media, genetic education and, 11 Medicine, future of, 455–56 Meiosis, 81–83, 93–101, 94f, 96f–97f chromosomes in, 81–82 chromosome theory of inheritance and, 105–6, 107t comparison to mitosis, 102t, 103 contribution to genetic diversity, 101–3, 101f errors in, 100–101, 101f, 109–10, 109f maternal age and, 104, 518 oogenesis and, 103–4, 104f recombination and, 132, 133f resetting of genomic imprints during, 661, 662f spermatogenesis and, 104–5, 105f summary of, 100–101 in translocation heterozygote, 506–7 Meiosis I, 94–100, 94f, 96f–97f, 102t chromosomal interference and, 138 nondisjunction in, 517–18, 517f recombination frequency and, 134 Meiosis II, 94, 94f, 96f–97f, 100, 102t nondisjunction in, 517–18, 517f Meiotic arrest, 97f Meiotic nondisjunction, 517–18 Meiotic spindle, 96f, 99–100, 102t Melanin, 66, 67f, 70 Melanoma, 701t, 707 molecular markers for, 709 Memory, in immune response, 818 Memory cells, 492, 793, 793f Mendel, Gregor, 14f, 30f, 821 biographical information about, 13–14, 16, 16f, 792, 821 experimental method of, 17–19, 17f, 18f, 46, 71 experiments with garden peas, 12, 14, 17–29, 17f, 18f, 19f–21f, 24f–27f, 47, 351, 513 rediscovery of his work in early 1900s, 29, 30f Mendel’s laws applicability of, 14, 27 correlations with chromosome theory of inheritance, 105–6, 107t discovery of, 14 modern extensions to for multifactorial traits, 56–71, 62t for single-gene inheritance, 46–56, 54t multifactorial traits and, 45 reception by scientific community, 27–29, 30f, 68 Menopause, 103 Menstrual cycle, 103, 104f Mercury resistance, 550f Merodiploids, 561f, 562, 562t MERRF (myoclonic epilepsy with ragged red fiber disease), 599–602, 601f, 602f Meselson, Matthew, 185–87, 186f, 192f Mesosome, 542 Messenger RNA (mRNA), 256, 256f See also Primary transcript big genes and, 372 cDNA libraries, 316–17, 317f development and, 746–47 discovery of, 261–62 formation of, in eukaryotes, 611, 611f methylated cap of, 269–70, 269f, 279f, 283t, 284 mutations in, 287 polarity of, 263, 268 poly-A tail of, 269–70, 269f, 284 polycistronic, 282, 285, 611, 614f, 618 processing of primary transcript, 269–75, 269f, 272f, 273f, 274f, 282–84, 282f, 283t, 291t quantitative analysis of, 378–79 RNA interference and, 668 synthesis of See Transcription I-13 synthetic, in vitro transplantation of, 262–63, 262f, 263f in translation See Translation 5'-untranslated region of, 282–84 Metabolic diversity, among bacteria, 541t, 542 Metabolism, Metacentric chromosome, 84, 84f, 478 Metaphase chromosomes shape and, 84, 472 of meiosis I, 96f, 99–100 of meiosis II, 96f, 100, 102t of mitosis, 90f, 91, 93f Metaphase chromosome, 84, 84f Metaphase plate, 90f, 91, 96f, 99, 138 Metastasis, 697f–699f Metazoan explosion, 797–98 Metazoans, evolution of, 797–98 See also Multicellular organisms Methanococcus jannaschii, genome of, 540 Methionine, 283, 283t, 546 Methylases, 182–83, 661, 662f Methylated cap, of mRNA, 269–70, 269f, 279f, 283t, 284 Methylation, of DNA, 182–83, 306, 659–60, 660f, 661, 664 Methyl-directed mismatch repair, 213, 221, 222f Methyl transferase, 269 MHC See Major histocompatibility complex Microarray, 376–77, 377f, 379, 452, 629–32 Microbial ecology, 571 Microevolution, 758, 762 Microfluidics, 455 Micro-RNAs (MiRNAs), 665–68, 666f generation of, 667–68, 667f and RNA interference, 668 Microsatellite See Simple sequence repeat Microsort, 394 Microtubule(s), 238, 239f in Drosophila melanogaster egg chamber, 747 meiosis and, 100 mitosis and, 89, 90f, 91 Midparent value, 775 Miescher, Friedrich, 168, 467 Minicircle DNA, 585 Minimal media, 543, 546–47 Minimal tiling path, 362, 363f Minisatellites, 396t, 397–98, 398f, 812–13 DNA fingerprinting and, 406–8, 406f, 407f Minor groove of DNA, 177, 178f, 181 Minute genes, of Drosophila melanogaster, 290 Minutes, 692, 693f Minutes of chromosome transfer, 559, 559f MiRNAs See Micro-RNAs Mismatch repair, 193f, 194, 707 methyl-directed, 213, 221, 222f Missense mutation, 237, 264, 286, 286f, 415 conservative, 286 nonconservative, 286 Mitochondria division of, 585 DNA of, 584 See also Mitochondrial genome evolution of, 572, 582, 587, 591–92 functions of, 583–84, 583f organization and structure of, 583, 583f translation in, 588, 588t Mitochondrial DNA tests, 600–601 Mitochondrial Eve, 592, 594 Mitochondrial genome, 584–88 biparental inheritance of, 598–99, 599f cooperation with nuclear genome, 590–91, 590f of Drosophila melanogaster, 585t functions of, 585, 585t gene content, 585, 585t genetic code in, 265, 588, 588t gene transfer between mitochondria and nucleus, 591–92 heteroplasmic, 593–96 homoplasmic, 593–94 of humans, 585, 585t, 586–87, 586f, 592, 594–95, 595f kinship determination from, 600–601 MERFF and, 599–602, 601f, 602f mutation in, and neurodegenerative disease, 593, 593f inheritance in identical twins, 602 of liverwort, 585t, 586f, 587 maternal inheritance of, 592–93, 593f, 596 mitotic segregation of, 585, 594–96, 601–2 mutation in, 581–82, 592–93, 593f, 599–602, 601f, 602f and aging, 602–3 mutation rate in, 592, 602 of pea, 585t of Plasmodium, 585, 585t of protozoan parasites, 585, 585f replication of, 585 har48564_ndx_I1-I22 I-14 9/6/06 01:54 AM Page I-14 Index Mitochondrial genome—Cont RNA editing of mitochondrial transcripts, 587–88, 587f shape of, 585 size of, 584–85, 585t uniparental inheritance of, 592–97 of yeast, 585, 585t, 587, 598–99, 599f Mitochondrial nucleoid, 584–85 Mitochondrial tRNA genes, 585t, 588, 591, 601 Mitosis, 81–83, 89–92, 89f, 90f, 686–87, 687f cell-cycle checkpoints and, 92–93, 93f chromosomes in, 81–82 comparison to meiosis, 102t, 103 decision to separate, 92–93 dissolution of nuclear membrane, 690 errors in, 93, 95, 95f Myc-Max system and, 655 nondisjunction in, 518, 519f oogenesis and, 103, 104f segregation of mitochondrial genome during, 585, 594–96, 601–2 segregation of organelle genome during, 594–96 spermatogenesis and, 104, 105f Mitotic nondisjunction, 518, 519f Mitotic recombination, 124, 152–53, 152f, 153f, 195 cancer formation and, 154, 154f in Drosophila melanogaster, 152–53, 152f in yeast, 153, 153f Mitotic spindle, 91, 102t, 238, 239f, 693f, 694 Model(s), in systems biology, 451–52 Model organisms, 6–7, 351 advantages of, 719 for developmental studies, 718–21 genome sequencing, 351, 353, 355t Modification, 306 Modification enzymes, 306 Modifier genes, 65–66, 69 Molecular archaeology, 804–5 Molecular clock, 804 Molecular cloning, 310–14 amplification of vector-insert recombinants, 313–14 biotechnology and, 318–19, 319f in genome mapping and sequencing, 356, 359 hybridization See Hybridization identification of transformed host cells, 312, 313f, 314 ligation of fragments to cloning vector, 311–12, 312f purification of cloned DNA, 310, 314, 315f transformation step in, 313–14 unclonable DNA, 355–56, 364 Molecular imaging techniques, and future of medicine, 455 Molecular machines, 440–43, 441f Molecular systems biology, 10–11, 438–44, 439f, 449f in academic setting, 457 algorithm for using, 451–52 biology as informational science, 440–44 example of approach, 452–55, 452f, 453f, 454f and future of medicine, 455–56 overview of, 455, 455f Moloney murine sarcoma, 705t Monamine oxidase gene, 73 “Monkey Trial,” 802 Monocytes, 745f Monod, Jacques, 613–14, 613f, 615–18 Monohybrid, 20 Monohybrid cross, 19–21, 19f Monomorphic gene, 51 Monoploidy, 491t, 519–21, 522f Monosomy, 491t, 516, 518, 526 Monozygotic twins heritability studies, 777–78, 777f mitochondrial inheritance in, 602 Moore, John, 710–11 Moore v Regents of California, 711 Morgan, Thomas Hunt, 106–9, 108f, 112, 131, 133–34, 215, 225, 351, 511, 513, 822 Morphogen, 734–37, 735f, 736f, 747 Morphogen gradient, 734–37, 735f, 736f Mosaic, genetic, 124, 518 aneuploid, 518–19, 519f in caenorhabditis elegans, 731 in Drosophila melanogaster, 731 sex chromosomes and, 518, 519f in tracing tissue effect, 731, 732f Mosaic determination, 721 Mosquito, DDT resistance in, 770–71, 771f mot genes, in bacteria, 568, 570f Moths, sex determination in, 88, 88t Motor mutant, 568 Mouse achondroplasia in, 728, 728f agouti gene of, 51, 51f, 53, 53f, 63, 70, 722f albinism in, 63–64, 65f, 70 base composition of DNA of, 176t chimeric, 731 chromosomes of, 465f coat color in, 51, 51f, 53, 53f, 63–64, 65f, 70–71, 209–10, 210f, 357 eye development in, 5, 720 fibroblast growth factor receptor (FGFR) gene of, 726, 726f, 728 gene nomenclature for, 827 gene therapy for sickle-cell disease in, 57 genetic mosaics in, 731 genome of, 8, 9f, 365–66, 367f, 489–90, 490f, 514 genome sequence of, 353, 355t, 358 globin genes of, 7, 809–10, 810f H2K gene of, 234, 325f–326f H19 gene of, 661 Hox genes of, 744–45, 744f, 810, 811f human tumor DNA in, 704f, 705 Igf2 (insulin-like growth factor) gene of, 660–61, 662f–663f immune system of, 7–8 Kinky allele in, 288f, 289 knockout, 419, 721–23, 722f linkage map of, 491–92, 492f major histocampatibility complex (MHC) genes in, 808f major histocompatibility complex (MHC) in, 324 model of amyotrophic lateral sclerosis, 672 model of cholera, 634 model of cystic fibrosis, 324, 417–19, 418f model of hypercholesterolemia, 670 as model organism, 351, 353, 718 P53 gene of, 700, 700f Pax-6 gene of, 720, 720f, 729 protein tracking in, 730, 731f tail length in, 65–66 targeted mutagenesis in, 419 T-cell receptor genes of, 820f, 821 T locus in, 288–89, 288f trypsinogen genes of, 820f, 821 MPF protein, in Xenopus, 690 M phase, 89–92, 89f, 90f, 686–87, 687f, 692 G2-to-M checkpoint, 692, 693f G2-to-M transition, 691, 691f spindle checkpoint in, 693f, 694–95 MPSS technique See Massively parallel signature sequence technique mRNA See Messenger RNA MspI, 659 m.u See Map unit Mucosal membranes, bacterial pathogens and, 544–45 Mule, sterility in, 101, 101f Muller, Herman J., 215–16 Mullis, Kary, 330 Multicellular organisms, evolution of, 7–8, 8t, 796–99, 796f, 797f Multifactorial trait analyzing quantitative variation in, 773–81 definition of, 773 vs polygenic trait, 70 definition of, 45 modern extensions to Mendelian analysis, 56–71, 62t multiple homozygosity and, 62–63, 63f Multigene family, 7, 515, 805–10, 808f concerted evolution of, 808–9, 809f creation of, 808f evolution and, 805–10 paralogous genes as, 358 Multihybrid crosses, 27 Multilocus minisatellite, 396–98, 396t Multimer, 238, 239f Multiple alleles, 49–50, 49f, 50f, 54t Multiple-factor cross, 141–42 Multipotent cells, 724 Muscular dystrophy, Duchenne, 474 See also Duchenne muscular dystrophy (DMD) gene Mus musculus See Mouse Mustard weed, proteome of, 369t Mutagen(s), 212, 213f, 215–20, 218f–219f Ames test for, 223–24, 224f, 245 definition of, 216–17 treatment of bacteria with, 546 Mutagenesis dissecting biological processes with, 240–41 transposon, 566 Mutant alleles, 51–52, 51f Mutant tumor-suppressor genes, 703–4, 703f, 706–7, 708t genetic tests for, 708–9 Mutation(s) See also Chromosomal rearrangement; specific types of mutations analysis of gene function with, 232–39 analysis of gene structure with, 224–32 antimorphic, 289, 290t auxotrophic, 543 bacterial finding, 543–47 in flagella, 568–69, 568f, 569f isolation of, 565 cancer-associated, 696–703 in chloroplast genome, 581–82, 592, 595–96 cis configuration of, 230 complementation testing of See Complementation testing conditional, 723, 723f conditional lethal, 66, 67f, 240, 546, 628–29, 723, 723f isolation of, 688, 688f in yeast, 687–88, 688f definition of, 207–9 deleterious, 799 DNA repair and, 220–23, 220f, 221f, 222f effect on allele frequency, 762–73 evolution and, 223–24 and evolutionary equilibrium, 766–69 favorable, 799 forward, 208, 210 frequency of, 51 and gene expression, 285–91, 286f, 287f, 288f, 290t in gene expression components, 290–91, 291f in gene outside coding sequence, 286–87 and genetic dissection of development, 721–29 and genetic variation, 223 and genomic evolution, 799–805 in globin genes, 55–56, 55f, 57, 337, 338f, 339f hot spots within genes, 231f, 232 human health and, 223 hypermorphic, 289, 290t hypomorphic, 287, 290t, 723 induced, 215–20, 218f–219f loss-of-function, 287–89 development research and, 721–26 in mitochondrial genome, 581–82, 592–93, 593f, 599–602, 601f, 602f and aging, 602–3 mitotic errors and, 95, 95f mutagens and See Mutagen(s) neomorphic, 289, 290t neutral, 799 null (amorphic), 287, 287f, 290t predicting effect of, 289–90, 290t in protein-encoding mechanism, 285–86, 286f, 290–91, 291f random causes of, 210–14, 213f, 215f recombination errors, 213–14 replication errors and, 212–13 reverse See Reversion in rhodopsin gene, 243–44, 243f, 289 as source of new alleles, 50–52, 51f, 52f spontaneous, 209–14 substitution, 208, 209f, 799 survival and, 223–24 temperature-sensitive, 66, 67f, 240, 546, 628–29, 723, 723f isolation of, 688, 688f in yeast, 687–88, 688f trans configuration of, 230 transposable elements and, 214, 215f, 513, 513f trinucleotide repeats and, 214 in tRNA genes, 290–91, 291f types of, 208–9, 208f, 218f–219f unequal crossing-over and See Unequal crossing-over in yeast and mold, 143–45 Mutation rate, 209–10, 210f, 706, 766 in bacteria, 210, 546 in Drosophila melanogaster, 215f, 216–17 forward vs reverse mutations, 210 in males vs females, 373–74 in mitochondrial genome, 592, 602 in polygenic traits, 779–80, 779f in pseudogenes, 803–4 variation from gene to gene, 209–10 MutH, 221, 222f MutL, 221, 222f, 223 MutS, 221, 222f, 223 myc gene, 705t myc gene, 654–55, 654f, 705f, 705t Myc-Max system, 654–55, 654f Mycobacterium tuberculosis, 544, 544f, 570, 757f See also Tuberculosis myc oncogene, 700f har48564_ndx_I1-I22 9/6/06 01:54 AM Page I-15 Index Mycoplasma capricolum, tRNAs of, 277 Mycoplasmas, 541t Myocilin gene, 69 Myoclonic epilepsy with ragged red fiber disease See MERRF Myoglobin gene, 804, 805f Myoglobin genes, 809–10, 810f Myxobacteria, 541t N nanos (nos) gene, of Drosophila melanogaster, 736–37, 736f, 746–47 Nanotechnology, 455–56 Napp, Cyril, 16–17, 28 Nash, Adam, 394 Nasopharynx, cancer of, 701t Native configuration, of protein, 237 Natural, as term, 341 Natural selection age of disease onset and, 768 Darwin on, 791–92 effect on allele frequency, 763–76, 763f, 764f, 765f and evolutionary equilibrium, 766–69 Natural transformation, 551–52, 552f Nature, vs nurture, 444f Nature magazine, 352f NDase I, 475 Neanderthals, 167, 168f, 327, 595 Neck length, in giraffes, 763, 763f Nectocaris, 797f Negative selection, 799 Neisseria gonorrhoeae, 539, 544, 551 penicillin-resistant, 539, 545, 552 Nematode See Caenorhabditis elegans Neomorphic mutation, 289, 290t Nested array, of DNA fragments, 331 Neurexin genes, 373, 373f Neurons, big genes and, 372 Neurospora crassa, 143 ARG genes of, 150–51, 151f, 233f, 234 Beadle and Tatum experiment with, 232–34, 233f, 238 finding gene-centromere distance in, 150–51, 151f, 151t life cycle of, 144f ordered-tetrad analysis in, 149–51, 150f See also Tetrad analysis reproduction in, 143, 144f thr gene of, 150–51, 151f white-spore gene of, 149–50, 150f Neutral mutation, 799 Nicholas II (Czar of Russia), 408 Nicotiana tabacum See Tobacco nif genes, 631 Night blindness, 207, 243, 243f, 289 Nirenberg, Marshall, 262–63, 263f Nitrifying bacteria, 542 Nitrogen cycle, 542 Nitrogen fertilizers, inorganic, 630 Nitrogen fixation, 630–31, 631f Nitrogen-fixing bacteria, 541t, 542 Nitrogen limitation response of B subtilis to, 629 response of E coli to, 632 Nitrogenous base, 169f, 173, 174f base analogs, 217, 218f–219f o-Nitrophenyl-galactoside (ONPG), 613 Nitrous acid, 218f–219f Node, of phylogenetic tree, 805 Nod factors, 630–31, 631f nod genes, 630–31, 631f Nomenclature for genes, 20–21, 21f, 106, 125, 145, 547, 827 Nonautonomous elements, 513 Nonautonomous transposable elements, 513 Nonautonomous transposon-derived repeats, 370 Noncoding DNA regions, 7, 7f, 263, 395 Noncoding RNA genes, 367 Noncoding strand, 263 Nondisjunction, 100, 109–10, 109f meiotic, 517–18, 517f mitotic, 518, 519f Nonhistone proteins, 467–69, 468f, 470–71 synthesis and incorporation of, 477 Nonhomologous chromosomes, 84, 84f, 101, 101f Nonhomologous end-joining, 222f, 223 Nonhomologous unequal crossing-over, 802 Non-Mendelian inheritance, 581–82, 599 Nonparental ditype tetrad (NPD), 145–48, 146f–147f Nonreciprocal translocation, 491t Nonsense codon, 263–65, 281, 281f, 284, 287, 588, 588t Nonsense mutation, 264, 286, 286f Nonsense suppressor tRNAs, 290–91, 291f Nonsulfur purple bacteria, 591 Nonsynonymous substitutions, 799 Nontandem duplication, 498, 499f Northern blot, 412–13, 414f Notch gene, of Drosophila melanogaster, 495, 495f, 499, 500f NotI, 303t, 304, 307 NPD See Nonparental ditype tetrad N terminus, of protein, 235f, 236 ntrC gene, of Escherichia coli, 632 Nuclear envelope, 88, 90f, 96f, 97f, 100 Nuclear lamins, 690, 690f Nuclear membrane, dissolution of, 282, 283t, 690 Nuclear pores, 440–41, 441f Nuclein, 168, 467 Nucleoid, mitochondrial, 584–85 Nucleoid body, bacterial, 542 Nucleolus, 88, 91 Nucleosome, 467, 469–70, 469t, 470f, 658, 659f X-ray diffraction analysis of, 469, 470f Nucleotide(s), 1, 2f, 168, 169f, 169t, 173–75, 174f complementarity in, 175–76 DNA replication and, 188f–189f in RNA, 181f, 184 Nucleotide excision repair, 221, 221f Nucleus, evidence that genes reside in, 82–83 Null allele, 721 Null hypothesis, 129–30, 129t Null mutation, 287, 287f, 290t in development, 721–23 Numerator elements, 673–74, 674f Nurse cells, 747, 747f Nurture, vs nature, 444f Nüsslein-Volhard, Christiane, 734–35, 737, 742, 747 I-15 Operon theory, 613–15, 614f Ordered tetrads formation of, 149, 149f tetrad analysis in, 145, 149–51, 149f, 150f, 151t ORF See Open reading frame Organelle, chromosomes as, 81 Organelle, extranuclear See also Chloroplast; Mitochondria DNA of, 584 evolution of, 572, 582, 797 oriC region, 548, 549f Original replicator, 795 Origin of life, 794–99 Origin of replication, 188f, 190–91, 474–75, 475f in bacteria, 549, 549f chromosome function and, 465–66 in Drosophila melanogaster, 475, 475f in yeast, 475, 475f Origin of transfer, 556, 557f Orrego, C., 600 Orthologous genes, 358, 821 Oryza sativa See Rice Outer membrane of chloroplast, 584, 584f of mitochondria, 583, 583f Ovarian cancer, 701t, 710 Ovarian ligament, 104f Ovary fetal, 103, 104f of garden pea, 17f Ovules, in garden pea, 17f Ovum, 103, 104f Oxidation, mutations caused by, 212, 213f Oxidative phosphorylation, 583–84, 583f, 585t, 586, 591, 602 Oxidative phosphorylation genes, 590, 590f, 592 Oxygen, inhibition of nitrogen fixation, 631, 631f P O OCA See Ocular-cutaneous albinism Ocean microbes, 571, 572f Ocher codon, 263 Octad, 149 Octaploids, 521, 521f, 523 Ocular-cutaneous albinism (OCA), 64, 66f Office for Human Research Protections (OHRP), 37 Of Pandas and People, 802–3 OGH See Comparative genomic hybridization OHRP See Office for Human Research Protections Okazaki fragments, 189f, 190 Olfactory receptor gene families, 370, 371f Oligonucleotide, 323, 323f, 377 allele-specific, 401–2 See also Allele-specific oligonucleotide (ASO) hybridization Oligonucleotide array, 358, 377–78, 378f, 379 optic fiber technology, 378, 378f Oligonucleotide primer, 327, 328f–329f, 331–33, 331f Oligonucleotide synthesizer, antisense therapy with, 670, 671f Oligopeptide, 236 Oligo (dT) primer, 317, 317f Oncogenes, 504, 703–6, 705t associated retroviruses, 705t and cell proliferation, 704–6, 704f genetic tests for, 708–9 isolation of, 704–5, 704f and signal transduction system, 705, 705t types of, 703–4, 703f One cell, one antibody phenomenon, 493–94 One gene, one enzyme hypothesis, 232–34, 233f, 238 ONPG, 613 On the Origin of Species (Darwin), 14, 16, 791, 821 Oocyte primary, 103, 104f secondary, 103, 104f Oogenesis, in humans, 103–4, 104f Oogonia, 103, 104f Opal codon, 263 Open promoter complex, 267f Open reading frame (ORF), 284, 547 in chloroplast genome, 589–99 Operator site, 616, 616f Operon, 613 identification of, 632 P11 protein, 456 p16 gene, 689t, 706–7 p21 gene, 689t p21 protein, 692, 693f p53 gene, 692, 693f, 705–6, 708t, 709 of mice, 700, 700f p53 pathway, 692, 693f Pachytene, 96f, 98, 98f Paired-box structure, Pair-rule genes, of Drosophila melanogaster, 737, 739f, 740, 741f, 746 Pairs, antagonistic, 18, 18f PaJaMo experiment, 615–16, 615f Pancreatic cancer, 701t, 708 Papovaviruses, 179, 179f par-1 gene, of Caenorhabditis elegans, 727, 727f Paracentric inversion, 501, 501f, 502, 503f Paracrine factors, in development, 747 Paradigm, 380 Paralogous genes, 358, 365, 368, 370 Paramecium, 585 Pardee, Arthur, 615–17 Parentage determination ABO blood groups in, 49–50 from mitochondrial DNA, 600–601 Parental class, 126–27, 134 Parental ditype tetrad (PD), 145–48, 146f, 147f Parental (P) generation, 19, 19f Parental types, 25, 25f, 125–26, 125f, 126f, 132f Paroxonase, 142–43 Parthenogenesis, 519 Partial digest, 305 Parvovirus, 179f Patau syndrome See Trisomy 13 Patentability of DNA, 381–82, 384 Paternity test See Parentage determination Pathogenic bacteria, 544–45, 544f damage caused by, 544–45 drug resistance in, 539, 545–46, 549–50, 550f, 571, 769–70, 770f evasion of immune response by, 545 human defenses against, 545 lateral gene transfer and, 570–71 plasmids and, 549–50 steps of bacterial pathogenesis, 544–45, 544f virulence of, 544–45 Pathogenicity island, 570–71 Pathogens, 544 har48564_ndx_I1-I22 I-16 9/6/06 01:54 AM Page I-16 Index Patinez, Maria, 527 Pattern baldness, 112, 112f Pauling, Linus, 804 Pax-6 gene, 5–6, 746 of humans, 730f of mice, 720, 720f, 729 PCD (programmed cell death) See Apoptosis PCR See Polymerase chain reaction PD See Parental ditype tetrad Pea, mitochondrial DNA of, 585t Peanut, 521 Pear trees, Bartlett, 521 peas See Garden pea Pedigree analysis of, 30–31, 31f, 64, 66f, 110–11, 111f, 123, 124f Chi-square test and, 130 gene mapping and, 154–55, 155f linkage analysis, 408, 410–11, 410f, 412f, 416–17, 416f and privacy, 37, 68–69 of breast cancer, 420, 420f definition of, 30 of dominant trait, 32, 32f, 33t of fragile X syndrome, 217f of genomic imprinting, 661, 663f of juvenile glaucoma, 68–69, 68f of maternal inheritance, 593, 593f, 601, 601f of MERRF, 600, 601f of mitochondrial disease, 593, 593f of polydactyly, 717 of recessive trait, 32–33, 33f, 33t symbols used in, 30, 31f of X-linked trait, 110–11, 111f, 123, 124f P element, in Drosophila melanogaster, 510–13, 512f Penetrance, 65 chance and, 67–69 complete, 65 environment and, 66–67, 69 incomplete, 65, 419t, 420, 420f of juvenile glaucoma, 391 modifier genes and, 65–66, 69 Penicillin, enrichment for auxotrophic mutants with, 546, 547f Penicillinase, 539 Penicillin resistance, 545 in Neisseria gonorrhoeae, 539, 545, 552 Peptide bonds, protein structure and, 234–36, 235f Peptidyl (P) site, on ribosome, 278, 278f, 280f Peptidyl transferase, 278, 280f Pericentric inversion, 501, 501f, 502, 503f Permissive temperature, 66, 688, 688f, 723 Personalized medicine, 380, 455–56, 459 Pesticide resistance biological costs of, 771–72 ecological considerations in, 772–73, 772f evolution of, 770–71, 771f in insects, 757 petite phenotype, in yeast, 581–82, 592 Petunia, incompatibility gene in, 51–52 PGD See Preimplantation genetic diagnosis Phage See Bacteriophage Phagocytes, 544–45, 692 Phase of linkage, 416–17 Phenocopy, 67 linkage mapping and, 419t, 420–21 Phenotype in bacteria, 543 definition of, 24, 24f deletion and, 500–501 duplication and, 499–501, 500f environment and, 66–67, 67f, 69, 773–81 expressivity and, 64–68 from interaction of two alleles, 56–73, 64f linking to causative gene with linkage analysis See Linkage analysis without linkage analysis, 408, 409f mutant mtDNAs and, 601, 602f penetrance and, 64–68 prediction of, 27 relationship to genotype, 17, 45–71, 87 in bacteria, 543 in fungi, 142–43 transgenic modification of, 415, 415f translocation and, 504 visible mutant, testing for, 546–47 Phenotype frequency definition of, 759 Hardy-Weinberg Law, 760–62, 760f, 761f Phenotypic ratio, 47, 54t, 62, 62t, 63 and mode of inheritance, 47–48 Phenylalanine (Phe), 262 Phenylalanine hydroxylase, 67 Phenylketonuria (PKU), 31t, 67, 762 Pheromones, 643 Phipps, James, 437, 438f Phocomelia, 67 Phosphate group in DNA, 2f, 173, 174f in RNA, 181f Phosphodiester bond, 168, 169f, 173, 174f, 175, 182f, 184, 187, 187f, 267f, 306 Phosphorylation, of proteins, 668–69, 669f, 690, 690f, 691–92, 726 Photolyase, 220 Photoreceptor proteins, in humans, 241–42, 242f Photorepair, 220 Photosynthesis, 584, 588, 589f, 591–92, 595–96 Phylogenetic tree, 805, 805f Physical associations, in biological system, 439–40, 439f Physical map, 359 long-range, 359–61, 359f integrating with linkage and sequence maps, 364 short-range, 310f Physical markers, 131 Phytase, 342 Pikaia, 797f Pilus, 554, 554f–555f, 609 Pisum sativum See Garden pea PKU See Phenylketonuria Plant(s) germ cells in, 94 herbicide-resistant, 590 incompatibility genes in, 51–52, 52f monoploid, 519–21, 520f polyploid, 518–19, 521–22, 521f, 523–24, 524f Plant breeding genetic engineering, 28–29 history of, 15, 15f Plant cells, cytokinesis in, 92, 92f Plant height, in pole beans, 69, 71f Plaque, viral, 227, 228f Plasma cells, 492, 793f Plasmid, 549–50, 550f carrying resistance genes, 770 as cloning vector, 311–14, 311t, 313f, 315f, 316, 335 in conjugation See Conjugation conjugative, 553 expression vectors, 318 F plasmid See F plasmid recombinant, 312 separation from host DNA, 314, 315f recombinant DNA technology and, 183–84, 183f Plasmodium, mitochondrial DNA of, 585, 585t Platform, 375 Plating efficiency, 306 Pleiotropy, 53–54, 53f, 54t in ␤-globin gene, 55 Ploidy See also Aneuploidy; Monoploidy; Polyploidy; Tetraploidy; Triploidy changes in, 694–95, 694f Pluripotent cells, 724 Pod traits, in garden pea, 18f Point mutation, 230, 231f, 258 Polar body first, 103, 104f second, 103, 104f Polarity of DNA, 175, 263, 268 of messenger RNA, 263, 268 of protein, 263 Polar microtubules, 90f, 91 Pole bean, plant height in, 69, 71f Pole cells, 733, 733f, 734f Polio, 181 Pollination, artificial, 15, 15f Poly-A binding protein, 270 Polyacrylamide gel electrophoresis, 309, 309f, 333 Poly-A polymerase, 269f, 270 Poly-A tail of mRNA, 269–70, 269f, 284 of retroposons, 510, 511f Poly-C, 262, 262f Polycistronic mRNA, 282, 285, 611f, 614f, 618 Polydactyly, 717, 717f Poly-G, 262, 262f Polygenic traits, 70, 773 gene mapping and, 419t, 421–22 heritability of, in humans, 776–78, 777f mutation rate in, 779–80, 779f number of loci determining, 780–81 twin studies in humans, 776–78, 777f Polymer, in DNA, 168, 169f Polymerase See DNA polymerase; RNA polymerase Polymerase chain reaction (PCR), 310, 327–30, 328f–329f amplification in preimplantation genetic diagnosis, 391, 392f applications of, 327–30 assay for leukemic cells, 504–5, 505f detection of deletions, 494, 495f detection of locus length-changing alleles, 404–5, 405f, 406 detection of SNPs, 400, 400f diagnosis of myelogenous leukemia, 504–5, 505f in gene mapping of bacteria, 566 in genome analysis, 571–72 in genome mapping and sequencing, 356, 359–60 PCR machine, 358 Polymerization, 189f Polymorphic gene, 51 Polymorphic locus, 395–96 Polymorphisms See DNA polymorphisms Polypeptides, 235f, 236 See also Protein(s) crystalline (CRY), 320 quenching, 652–53, 653f Polyploidy, 491t, 518–19 in animals, 519 doubling in, 523 in plants, 518–19, 521–22, 521f, 523–24, 524f Polyprotein, 282, 282f Polyribosome, 280f Polytene chromosomes, 497–98, 497f, 499 deletion mapping with, 497–98, 497f duplication loops in, 499 Poly-U, 262, 262f PON gene, 142–43, 143f Population, definition of, 758 Population genetics, 757–81 definition of, 33, 758 Positional cloning, 393, 408–19 correlating phenotypic transmission with area of genome, 410–12, 410f, 412f of cystic fibrosis gene, 415–19, 418f finding gene responsible for phenotype, 413–15 identification of candidate genes, 411–13, 413f Position-effect variegation, in Drosophila melanogaster, 480–81, 480f, 501–2, 664 Positive control, of lac operon, 618–19, 619f Positive selection, 799 postbithorax (pbx) gene, of Drosophila melanogaster, 741, 742f Posttranscriptional control, 612 Posttranslational modification of proteins, 282, 282f, 668–69, 669f Prader-Willi syndrome, 661–62 Predator species, pesticide use and, 772–73, 772f Prediction of phenotype and genotype, 27 Predictive/preventive medicine, 380 early instances of, 437 social, ethical, and legal issues in, 11–12, 380–82, 459 systems approach and, 455–56, 459 Preimplantation genetic diagnosis (PGD), 391–92, 392f, 394–95 Premutation allele, 216–17, 217f Prenatal diagnosis, 32, 34, 400, 400f See also Amniocentesis; Preimplantation genetic diagnosis ethics and, 113–14 Preventive medicine See Predictive/preventive medicine Primary oocyte, 103, 104f Primary spermatocyte, 104, 105f Primary structure of proteins, 234–38, 237f of tRNA, 275, 275f Primary transcript, 266f–267f, 268, 268f processing of, 269–75, 269f, 272f, 273f, 274f, 282–84, 283t, 291t RNA splicing, 271–73, 273f, 274f, 283–84 Primase, 188f–189f, 190 Primates, evolution of, 798, 798f Primer extension, single nucleotide DNApolymerase-assisted, detection of SNPs with, 403–4 Primer walking, 335 Privacy See also Genetic privacy disease prevention and, 68–69 genetic screening and, 34–35, 37 har48564_ndx_I1-I22 9/6/06 01:54 AM Page I-17 Index Probability, rules of, 21–22 and prediction of phenotype and genotype, 27 uses of, 27 Proboscipedia (Pb) gene, of Drosophila melanogaster, 742f, 743 Processed pseudogene, 369 Product rule, 21, 25–27 Proflavin, 218f–219f, 259–60, 260f Programmed cell death (PCD) See Apoptosis Programmed DNA rearrangements, immune system and, 492–94, 492f, 493f, 494f Prokaryotes See also Bacteria characteristics of, 169 chromosome of, 179, 539–72 evolution of, 7, 8t, 540, 540f, 572–73 in family tree of organisms, 540, 540f gene expression in, 282–84, 283t gene regulation in, 609–34 vs eukaryotes, 644–45, 644t expression attenuation, 626–28 global mechanisms, 628–32 overview of, 611–12 regulation of virulence genes in V cholerae, 609, 632–34, 633f transcription regulation, 612–26 gene relocation in, 514 overview of, 540–43 transcription in, 268, 282, 283t, 611–26, 611f, 626–28, 626f, 627f translation in, 282–84, 283t, 611 Prometaphase, of mitosis, 90f, 91 Promoter, 266f–267f, 268, 268f, 611, 611f, 614f, 616, 645, 646f class II, 648–57 eukaryotic, 659f expression vectors and, 318, 319f mutations in, 286 excessive gene activity, 728 oncogenes and, 704 of Sxl gene of Drosophila melanogaster, 665, 665f Promoter complex closed, 267f open, 267f Prophage, 564, 565f Prophase of meiosis I, 96f–97f, 98–99, 98f, 102t, 133f of meiosis II, 96f, 100 of mitosis, 90f, 91, 93f Proposition 71, 724 Prostate cancer, 455, 701t molecular markers for, 709 Prostate-specific antigen (PSA), 455 Protease, 445 Protease inhibitors, 271 Protein(s) See also DNA-binding proteins; Regulatory proteins allosteric, 616 biological function and, chaperone, 628 chemical modification of, 369 colinearity of gene and protein, 244, 258, 281 C terminus of, 235f, 236 degradation of, 668, 669f, 692 denaturation of, 238 dephosphorylation of, 669, 669f, 691, 691f DNA protein-encoding regions, 7, 7f, 547 DNA-protein interactions, 469–74 measurement of, 450 in eukaryotic chromosomes, 467–69 evolution of function, 5, 804–5 function of, 238–39, 256 identification of protein-protein interactions, 448–50, 448f identifying in mixtures, 445–46, 446f interaction with chromosomes, 374–75 native configuration of, 237 nonfunctional, 243 nonhistone, 467–69, 468f, 470–71 synthesis and incorporation of, 477 N terminus of, 235f, 236 phosphorylation of, 668–69, 669f, 690, 690f, 691–92, 726 polarity of, 263 posttranslational modification of, 282, 282f, 668–69, 669f primary structure of, 234–38, 237f processing, cellular components of, 290, 291t quaternary structure of, 238, 239f reading of DNA base sequences, 180–81, 180f secondary structure of, 237–38, 237f, 620 structure of, 3, 4f subunits of, 238, 239f synthesis of, 22–23, 234–39, 235f See also Translation tertiary structure of, 237–38, 237f truncated, 286 types of, 234 ubiquitination of, 668–69, 669f, 692 Protein arrays, 449–50, 449f Protein chips, 449, 449f Protein concentration, quantifying changes in, 446–47 Protein domain, 365 domain architecture, 365, 367–68, 368f Protein-encoding genes, 22–23, 234–39, 235f, 367–69, 368f, 647f, 648 mutation in, 285–86, 286f, 290–91, 291f transcription of, 647f, 648 Protein fingerprints, 455–56 Protein kinases, 449f, 690 Protein machines, 441 Protein networks, 441, 441f, 443 Protein translation factors, 281 Protein tyrosine kinase, 505 Proteome, 366f, 367–68, 438 Proteomics challenges of, 444–45 global proteomic strategies, 444–50 high-throughput technology, 444–50 and systems biology, 438 Proteosome, 668, 669f, 692 Protooncogene, 504, 704, 704f, 708 Prototroph, 233, 543, 546–47, 547f Provirus, 330 Prozac, 456 PSA See Prostate-specific antigen Pseudodominance, 496, 496f Pseudogene, 336f, 339, 339f, 370, 803–4, 805f orphons, 810 processed, 369 as reservoir of genetic information, 807 Pseudolinkage, 507–8 Pseudomonas, 541t, 550 Pseudomonas aeruginosa, 571–72 P site, on ribosome, 278, 278f, 280f Psychophysics, 240 Ptashne, Mark, 620 Puberty, female, 103 Pufferfish (Fugu rubripes), genome sequence of, 353, 355t, 366 Pulp content, of tomatoes, 422–23, 422f Punctuated equilibrium, 797 Punnett, Reginald, 21 Punnett square, 21 for codominant traits, 48f for dihybrid cross, 25, 25f for incomplete dominance, 47f for lethal trait, 53, 53f for monohybrid cross, 21f for multihybrid crosses, 27 rules of probability and, 21 of testcross, 24, 24f uses of, 27 Pure-breeding lines, 18, 24 Purines, 173–77, 174f, 178f, 180f Purple bacteria, 541t p value, 128–30, 129t Pyrimidines, 173–77, 174f, 178f, 180f Pyrophosphate (PPi), 187f Q QTL See Quantitative trait loci Quagga, 167, 168f Quantitative trait loci (QTL), 421, 780–81 Quantitative variance definition of, 17, 773 Mendelian analysis and, 68–71, 70f multifactorial, analysis of, 773–81 Quaternary structure, of protein, 238, 239f Quenching polypeptides, 652–53, 653f R Rabies, 270 Races, human, 374 Rad9 gene, 692 I-17 Rad9 protein, 689t Radial loop-scaffold model of chromosome compaction, 470–72, 471f, 472f Radiation, mutations caused by, 212, 213f raf gene, 705t RagI enzyme, 494, 494f, 820 RagII enzyme, 494, 494f, 820 Ralph, G Scott, 672 Random walk, 567–68, 567f biased, 567 Raphanobrassica, 523 RAS gene, 695–96, 696f, 700f, 704f, 705 RAS protein, 695, 696f Rat, warfarin resistance in, 772 RB gene, 154, 154f, 691, 702, 702f, 703f, 705–7, 706f, 708t RB protein, 689t Read (sequencing unit), 354 Reading frame, 259–60, 261f, 264, 272 open (ORF), 284, 547, 589–99 Rearrangement See Chromosomal rearrangement RecA protein, 196f Receptor(s), 695, 696f ␤-adrenergic, 668–69, 669f antigen, evolution of, 815 in bacteria, mutations in, 568–69, 569f immune-cell, 815–20, 817f, 818f gene rearrangements in, 818–20, 819f interleukin (IL), 238, 239f major histocompatibility complex (MHC), 817, 818f, 819–20 olfactory receptor gene families, 370, 371f photoreceptor proteins in humans, 241–42, 242f steroid hormone, 650f, 651 Receptor genes, T-cell, 372–73, 372f, 491–92 evolution of, 815, 820–21, 820f of humans, 820f, 821 of mice, 820f, 821 Recessive alleles decrease in frequency over time, 765, 765f definition of, 46, 47f designation of, 20–21, 21f pedigree of, 32–33, 33f, 33t relative nature of, 49, 53–54, 56 Recessive epistasis, 60, 60f, 62t Recessive lethal allele, 53–54, 53f, 54t, 55 Recessive trait discovery of, 19–20 X-linked, 111, 111f, 111t Recipient, 55 universal, 49 Reciprocal cross, 18 Reciprocal recombination, 131, 132f, 148–49, 153 Reciprocal translocation, 209, 209f, 491t, 503–4, 504f, 505f, 508 in leukemia, 504–5, 505f Recognition sites, 303–5, 305f, 330 Recombinant, definition of, 192 Recombinant class, 126–27, 134 Recombinant DNA molecule, 183, 183f, 311–12 Recombinant DNA technology, 183–84, 183f, 302, 543, 729–30, 731f See also Restriction enzymes; Restriction fragment cloning fragment of DNA, 310–19 fragmenting complex genomes, 303–10 and genetically modified (GM) crops, 28–29, 320–21, 320f, 321f hybridization See Hybridization molecular cloning and, 318–19, 319f patentability of DNA, 381–82, 384 Recombinant plasmid, 312 separation from host DNA, 314, 315f Recombinant progeny, 123 Recombinant type, 25, 25f, 125–26, 125f, 126f Recombination, 98–99, 99f, 123–35, 192–95 branch migration step of, 197f breaking and rejoining of DNA, 192–93, 192f chiasmata in, 132–33, 133f crossing-over and, 131–34 definition of, 192 double Holliday junction formation in, 197f double-strand-break model of, 194–95, 195f–199f errors in, 213–14 within genes, 226–27, 227f heteroduplex regions in, 193–94, 193f Holliday intermediate in, 198f–199f hot spots for, 140 illegitimate, 195–200, 200f, 565f See also Unequal crossing-over in inversion heterozygote, 501–2, 502f har48564_ndx_I1-I22 I-18 9/6/06 01:54 AM Page I-18 Index Recombination—Cont mismatch repair, 193f, 194, 707 methyl-directed, 213, 221, 222f mitotic See Mitotic recombination molecular model of crossing-over, 194–95, 196f–199f between mutations in same gene, 229f occurrence at four-strand stage, 148, 148f reciprocal nature of, 131, 132f, 148–49, 153 recombination deserts, 140 resolution of Holliday junctions in, 199f strand invasion steps in, 196f Recombination frequency (RF) distance between genes and, 132–34, 133f, 134t gene linkage and, 123–35, 134t gene mapping and, 124, 132–34, 133f, 135–51 relating to physical distance, 140–41 in tetrad analysis, 148 upper limit on, 134, 140, 148 variations by species and sex, 140–41 Recombination nodule, 98, 98f, 99 Red blood cells, 745, 745f I gene and, 48, 48f Red colorblindness, 243, 243f Red-green colorblindness, 110, 110f, 123, 123f, 154–55, 155f, 214, 215f, 243–44, 243f Red-receiving protein, 242, 242f Reduction division, 100 Regional continuity theory, of human evolution, 595, 595f Regulative determination, 721 Regulatory proteins computer analysis of, 632 evolution and, 80f, 798, 804 interaction with DNA, 612, 615, 621–22, 622f interaction with RDA polymerase, 623, 623f Regulons, 628 Release factors, 281f Repetitive DNA, 355, 476, 477f, 811–13 Replacement theory of human evolution, 595, 595f Replica plating, 211, 212f, 546, 558f Replication, 184–91, 185f, 186f accuracy of, 191, 212–13, 220 in bacteria, 544–45, 548–49, 549f bidirectional, 190, 190f, 474 biotechnology and, 302 in cancer cells, 697f–699f at chromosomal level, 190–91, 190f of circular chromosome, 190, 190f complementary base pairing in, 184–87, 185f, 188f–189f conservative, 185, 185f direction of, 187, 187f, 188f–189f dispersive, 185, 185f elongation stage of, 188f–189f, 190 errors in, 212–13 initiation of, 188f, 190 lagging strand in, 189f, 190 leading strand in, 189f, 190 Meselson-Stahl experiment, 185–87, 186f microsatellites and, 397, 397f of mitochondrial DNA, 585 molecular mechanism of, 187–90, 187f, 188f, 189f original replicator molecules, 795 origin of See Origin of replication RNA primer for, 188f–189f, 190 semiconservative, 184–87, 185f of telomeres, 475–76, 477f template strand, 184, 185f, 188, 263, 263f, 266f–267f, 268 termination region, 190f, 191 unwinding of DNA, 180, 180f, 184, 185f, 188f–189f, 190, 190f, 191, 611 Replication bubble, 188f, 474 Replication fork, 188f–189f, 190, 190f, 474–75, 549, 549f Replication unit See Replicon Replicon, 474–75, 475f Reporter construct, 645–46 Reporter gene, 623 green fluorescent protein (GFP), 646, 730, 731f LacZ gene, 623–26, 625f, 633 Repressor corepressor, 626, 626f, 653, 655, 658 eukaryotic, 652–53, 653f, 658, 675, 675f experimental evidence for, 615–16, 615f lac See lac repressor prokaryotic, 613, 614f, 615–17, 617f, 620–21, 626 structure of, 616–17, 616f quenching by, 652–53, 653f superrepressor, 616–18, 618f Reproduction, asexual, 521 Reproductive cloning, 724, 725f, 750 Research funding equity in, 307 ethical issues in, 483–84 government regulation and, 11 Resistance See Antibiotic resistance; Drug resistance; Pesticide resistance Response to selection, 778 (R) Restriction, 306 Restriction enzymes, 182–84, 182f, 183f, 302–7 commonly-used, 303, 304t complete digestion with, 305 discovery of, 306–7 lengths of fragments produced by, 304–5, 305f number of fragments per genome, 305–7 partial digest with, 305 recognition site of, 303–5, 305f, 330 Restriction fragment, 303 See also DNA fingerprinting with blunt ends, 303, 304f cloning of, 310–19 determining length of, 307–9, 308f–309f gel electrophoresis of, 307–9, 308f–309f lengths of, 304–5, 305f number of fragments per genome, 305–7 with sticky ends, 303–4, 304f, 311 Restriction fragment length polymorphism (RFLP), 400, 594 Restriction mapping, 309–10, 310f Restrictive conditions, 240 Restrictive temperature, 66, 688, 688f, 723 Retina, 241, 242f Retinal, 242 Retinitis pigmentosa, 243, 243f, 474 Retinoblastoma, 154, 154f, 496, 702, 703f, 706–7, 706f penetrance and expressivity of, 67–68 Retinoblastoma (RB) gene See RB gene Retroposon, 509–10, 511f long terminal repeats in, 510, 511f poly-A tail of, 510, 511f structure and movement of, 510, 511f Retrovirus, 270, 316, 793, 811 cancer-causing, 704–5, 704f, 705t endogenous, 330 evolution of, 811 expression vectors, 672 Reverse genetics, 566, 566f Reverse mutation See Reversion Reverse phase column, 445 Reverse transcriptase, 270–71, 270f, 316–17, 330, 335, 513, 793, 811–12 Reverse transcriptase inhibitors, 793 Reverse transcription, 256, 268, 270–71, 270f error rate, 271, 793 Reverse translation, 323, 323f Reversion, 208, 210 RF See Recombination frequency RFLP See Restriction fragment length polymorphism R group, 234, 235f, 237 Rhizobial bacteria, nitrogen fixation by, 630–31, 631f Rhizobium, 542, 630 Rhizobium meliloti, 630–31, 631f Rhoades, Marcus, 509 Rho-dependent termination, 611, 611f Rhodopsin, 238, 242, 242f Rhodopsin gene, 207–8, 242, 242f mutations in, 243–44, 243f, 289 Rho factor, 267f, 581–82, 611, 611f Rho-independent termination, 611, 611f Ribonuclease, in miRNA generation, 667–68, 667f Ribonucleic acid See RNA Ribonucleoprotein, 476 Ribonucleotide triphosphates, 268 Ribose, 181f, 184 Ribosomal gene family, 807 Ribosomal RNA (rRNA), 256, 277–78, 278f Ribosomal RNA (rRNA) genes, 284, 367, 591, 808 chloroplast, 588 transcription of, 647–48, 647f Ribosome, 256 A site on, 278, 278f, 280f E site on, 278, 278f, 280f manufacture of, 88 P site on, 278, 278f, 280f structure of, 278, 278f subunits of, 278, 278f, 279f, 283t in translation, 277–78, 278f Ribosome binding site, 279f Ribozyme, 273 Ribulose biphosphate carboxylase (Rubisco), 593 Rice (Oryza sativa) chloroplast genome of, 588t genome sequence of, 353, 355t Rice, golden, 29 Rickets, vitamin D-resistant, 111, 111f Rickettsias, 541t Rifampicin resistance, 769–70 rII region, of phage T4, 227–30, 228f–229f complementation testing in, 227–30, 229f deletion mapping of, 230–32, 231f, 259, 260f fine structure mapping of, 227–32, 228f–229f, 231f frameshift mutations in, 259–60, 260f phenotypic properties of mutants, 228f recombination between mutants in same gene, 229f RISC See RNA-induced silencing complex RNA chemical constituents of, 181–84, 181f in chromatin, 467 double-stranded, 181f, 185, 727, 727f evolution and, functions of, 5, 6f guide, 587f messenger See Messenger RNA mutations in encoding mechanism, 290 as original replicator molecule, 795 ribosomal See Ribosomal RNA small nuclear, 273, 274f, 367 transcription of, 648 small nucleolar, 367 structure of, 5, 181–84, 181f synthesis of See Transcription transfer See Transfer RNA transport from nucleus to cytoplasm, 644t Xist, 481–82 RNA-dependent DNA polymerase See Reverse transcriptase RNA editing of mitochondrial transcripts, 587–88, 587f in trypanosomes, 285, 587, 587f RNA genes, noncoding, 367 RNA-induced silencing complex (RISC), 667f, 668, 670–72, 671f RNA in situ hybridization, 729–30, 730f, 746 RNA interference, 644–45, 665, 668, 670–72, 671f in development research, 726–28, 727f RNA leader, 627–28, 627f RNA-like strand, 263, 263f RNA-mediated interference (RNAi), in Caenorhabditis elegans, 727, 727f RNA polymerase, 268, 589f core enzyme, 266f–267f of eukaryotes, 646–47, 647f, 658, 659f holoenzyme, 267f interaction with regulatory proteins, 612, 623, 624f in prokaryotes, 611–12, 611f, 618–19 sigma factor See Sigma factor RNA polymerase I, 647–48, 647f RNA polymerase II, 647, 647f, 648–49, 651f RNA polymerase III, 647, 647f, 648 RNA primer, for replication, 188f–189f, 190 RNA processing, 283t, 644t, 647–48, 647f RNase, 667–68, 667f RNA splicing, 271–73, 272f, 273f, 274f, 283t, 284, 291t, 664–65, 665f, 666f, 675, 675f alternative, 273–75, 274f, 284–85, 368, 378, 644t RNA transcript See Transcript RNA viruses, 181–84, 270 RNA world, 795 Robertson, W R B., 504 Robertsonian translocation, 504, 504f, 507, 508f, 515, 515f Rocket immunoelectrophoresis, 287f Rod cells, 241–42, 242f, 243, 289 Roe v Wade (1973), 428 Romanov family, 408 Roslin Institute, 407 Rough bacteria, 169–72, 170f, 171f roughest gene, of Drosophila melanogaster, 480–81, 480f, 498f Roundworm See Caenorhabditis elegans Rous sarcoma, 705t rpoH gene, 628–29, 629f rRNA See Ribosomal RNA RsaI, 304, 304f, 304t, 305, 307 Rubisco See Ribulose biphosphate carboxylase Rye, 523, 524f har48564_ndx_I1-I22 9/6/06 01:54 AM Page I-19 Index S Saccharomyces cerevisiae See Yeast SAD mice, 57 SAGE See Serial analysis of gene expression Salmonella typhimurium, Ames test and, 224, 224f Sample size, and probability, 128 Sander, Klaus, 735 Sanger, Fred, 331 Sanger method, for DNA sequencing, 331–34, 331f–333f, 357, 375, 376f SAR See Scaffold-associated region Sarcoma, 705t ␣-Satellite, 478 Satellite DNA, 477–78, 482 Sau3AI, 304t Sauromatum guttatum, 603 Savior siblings, 394 Scaffold, chromosome, 468, 468f, 470–72, 471f Scaffold-associated region (SAR), 472 SCF protein, 692 Schiff reagent, 168 Schizosaccharomyces pombe See Yeast SCID See Severe combined immune deficiency Science, big vs small, 352, 457 Science magazine, 352f Scopes, John, 802 Scopes Trial, 802 Sea urchins gene regulatory network in, 800–801, 800f gut development in, 443, 443f Secondary oocyte, 103, 104f Secondary spermatocyte, 104, 105f Secondary structure of proteins, 237–38, 237f, 620 of tRNA, 275f, 276 Second-division segregation pattern, 150, 150f Second filial (F2) generation, 19, 19f, 30 Sectors, in yeast, 153, 153f Seed coat color, in lentils, 45–46, 45f, 46f, 48, 48f, 50, 50f, 56–58, 58f, 62t Seedless fruit, 521 Seed traits, in garden pea, 18f, 19–21, 19f, 20f, 21f, 22–27, 23f, 24f, 25f, 26f, 107t Segmental duplication, 369 Segmentation genes, of Drosophila melanogaster, 732–40, 746 Segment-polarity genes, of Drosophila melanogaster, 739–40, 740f, 741f, 746 Segregation, 477–79 alternate segregation pattern, 506f, 507 definition of, 20 errors in, 100–101, 101f maternal age and, 104, 518 law of, 19–24, 20f, 21f, 106, 107f, 107t dominance relations and, 48–49 Mendelian phenotype ratios and, 63 mitotic error and, 95 in tetraploids, 523 Segregation studies, mutation and, 51 Selectable markers, 312, 313f Selection, 546 artificial, 15, 763, 778 at molecular level, 794, 796 natural See Natural selection negative, 799 neutral mutations and, 799 and new gene creation, 804 positive, 799 Selection coefficient, 765 Selection differential, 778 Selective breeding, vs genetic engineering, 28 Selective plateau, 780 Self-fertilization, 17, 21–22 Selfing See Self-fertilization Semen, spermatozoa in, 82–83 Semiautonomous organelles, 590–91 Semiconservative replication, 184–87, 185f cell cycle and, 187 Meselson-Stahl experiment, 185–87, 186f Semisterility, 507–8 in corn, 506f, 507 Sense strand, 263, 670 Sensitization, 668 Septicemia, 545 Sequence, of gene, 268 Sequence errors, distinguishing from DNA polymorphisms, 355–56 Sequence map, 357, 362–64 finding genes in sequenced genome, 364–65 hierarchical shotgun sequencing strategy, 335, 362–63, 363f integrating with linkage and physical maps, 364 whole-genome shotgun sequencing strategy, 363–64, 364f Sequence tagged site (STS) in integrating linkage, physical, and sequence maps, 364 for long-range physical mapping, 359–60, 359f Sequoia trees, number of chromosomes in, 85 Serial analysis of gene expression (SAGE), 378 Serial dilution, 228f, 542 Serotonin, 455–56 Serotonin reuptake inhibitors, 456 Severe combined immune deficiency (XSCID), X-linked, 238, 239f Sex, as binary trait, 82 Sex chromosomes, 84–88, 85f, 86f, 86t, 88t errors in, 86, 86t, 100 illegitimate recombination in, 195–200, 200f mosaicism and, 518, 519f nondisjunction and, 109, 109f spermatogenesis and, 104–5 Sex combs reduced (Scr) gene, of Drosophila melanogaster, 742f, 743 Sex determination, 82, 85–88, 86f, 86t, 88t in Caenorhabditis elegans, 88, 88t in Drosophila melanogaster, 86–88, 86t, 109–10, 109f, 664–65, 665f, 669–76, 673f, 673t in great lubber grasshopper, 85, 85f in humans, 82, 86–88, 86f, 86t Sex-influenced traits, 112, 112f Sex-limited traits, 112 Sex selection, 394 Sex-specific trait, in Drosophila melanogaster, 673f Sexual behavior, in Drosophila melanogaster, 676 Sexual reproduction, 94 genetic diversity and, 103 SF gene, 416–17, 416f Sheep, reproductive cloning of, 724, 725f shibire gene, of Drosophila melanogaster, 66 Shigella dysenteriae, 544, 549–50 Shine-Dalgarno box, 279f, 282 Short interfering RNA (siRNA), 670–72, 671f Short interspersed element See SINE Shotgun sequencing, 335, 335f, 362 hierarchical shotgun sequencing strategy, 362–63, 363f whole-genome shotgun sequencing strategy, 363–64, 364f Siamese cat, coat pattern in, 66, 67f Sibship, 30, 31f Sickle-cell disease, 54–56, 55f, 301–2, 337, 338f See also ␤-Globin genes cause of, 11, 13, 31t, 54–55 detecting mutations in ␤-globin gene, 400, 400f effects of, 31t gene therapy for, 57 incidence of, 31t and malaria, 55–56, 55f, 57, 765–66, 767f molecular basis of, 236–37, 236f, 238 penetrance of, 420 screening program for, 34 Sigma (␴) factor, 268, 611, 611f in heat shock response, 628–29, 629f sigma-24, 629f, 630 sigma-32, 628–29, 629f sigma-54, 631, 631f sigma-70, 628–29, 629f Signal recognition particle, 814 Signal transducers, 695, 696f Signal transduction system, 695–96, 696f in bacteria, mutations in, 568 in development, 726, 739 oncogenes in, 705, 705t Silent mutation, 286, 286f Simian sarcoma, 705t Simple sequence repeat (SSR; microsatellite), 396–97, 397t, 812–13 detection of, 404–6, 405f genomewide identification of, 358 genomewide typing of, 358–59, 358f identification of human remains from, 780–81 in integrating linkage, physical, and sequence maps, 364 in large-scale linkage mapping, 357–59, 357f in long-range physical mapping, 360 two-stage assay for, 358, 358f I-19 SINE (short interspersed element), 370, 370f, 509–11, 513 creation of, 812, 812f and selective advantage, 812 singed bristles mutation, in Drosophila melanogaster, 152f, 153 Single-celled organisms, evolution of, 794–96 Single-gene inheritance, modern extensions to Mendelian analysis, 46–56, 54t Single-gene traits, in humans, 30–36, 31t Single nucleotide polymorphism (SNP), 396, 396t analysis of, 379 direct detection of ASO hybridization, 400–403, 401f, 402f oligonucleotide arrays, 378 PCR method, 400, 400f single neocleotide primer extension, 403–4, 403f Southern blot analysis, 399f, 401–2 formation of, 423 genomewide identification of, 358 genomewide typing of, 358–59, 358f as haplotype marker, 423–24 identification of human remains from, 780–81 in integrating linkage, physical, and sequence maps, 364 in large-scale linkage mapping, 357–59, 357f in long-range physical mapping, 360 Single nucleotide primer extension, DNA-polymeraseassisted, detection of SNPs with, 403–4, 403f SIR genes, of yeast, 660, 660f siRNA See Short interfering RNA sis gene, 705t Sister chromatids, 84, 84f, 88–92, 89f, 90f, 96f, 99–100, 102t, 132, 133f, 187 holding together, 478, 478f separation of, 668, 669f Sisterless-A protein, 673 Sisterless-B protein, 673 Skin bacterial pathogens and, 544–45 color, in humans, 68–69, 70f Skin cancer, DNA repair mechanisms and, 223, 223f SKY chromosomal in situ hybridization, 361, 361f Small nuclear ribonucleoprotein (snRNP), 273, 274f Small nuclear RNA (snRNA), 273, 274f, 367 transcription of, 648 Small nucleolar RNA (snoRNA), 367 Smallpox, 437, 438f Small science vs big science, 352, 457 Smooth bacteria, 169–72, 170f, 171f Snapdragon, flower color in, 47–48, 47f snoRNA See Small nucleolar RNA SNP See Single nucleotide polymorphism SNP Consortium, 396 snRNA See Small nuclear RNA SnRNP See Small nuclear ribonucleoprotein Social issues, in predictive/preventive medicine, 11–12, 380–82 SOD1 gene, 672 Somatic cell nuclear transfer, 724, 725f Somatic cells, 94, 102t, 491f, 493 Somatic gene therapy, 382 Somatic hypermutation, 818–19 sonic hedgehog gene, of chicken, 739 SOS system, 222 Southern, Edward, 324 Southern blot, 324, 325f–326f, 407, 407f detection of SNPs with, 399–400, 401f Spacer DNA, 587 Specialized transducing phage, 564, 565f Specialized transduction, 564, 565f Species chromosome banding differences between, 473–74, 473f new, evolution of, 490, 514–15, 515f, 720–21 Specificity of immune response, 818 Spectinomycin, 539, 545 Sperm, 103–4, 105f discovery of, 82–83 telomeres in, 476 Spermatid, 104, 105f Spermatocyte primary, 104, 105f secondary, 104, 105f Spermatogenesis, in humans, 104–5, 105f Spermatogonia, 104, 105f S phase, 89, 89f, 102t, 185, 474–75, 478, 686, 687f, 692 G1-to-S checkpoint, 692, 693f G1-to-S transition, 690–91, 691f Spindle checkpoint, in M phase, 693f, 694–95 Spirochete, 541t Splice acceptor sites, 272–73, 273f, 287 har48564_ndx_I1-I22 I-20 9/6/06 01:54 AM Page I-20 Index Splice donor sites, 272–73, 273f, 287 Spliceosome, 273, 274f, 367 Spo11 protein, 194–95, 196f Sponge, Hox gene in, 745 Spontaneous abortion, 516, 519, 526, 718 Sporulation, in Bacillus subtilis, 629 src gene, 705t SRY gene, 195–200, 200f, 413, 414f, 415, 415f, 427 SSR See Simple sequence repeat Stage of logarithmic growth, 551 Stahl, Franklin, 185–87, 186f Staphylococcus, 545, 571 Staphylococcus affermentams, base composition of DNA of, 176t Starch-branching enzyme (SBE1), in garden pea, 22–23, 22f Starfish, gene regulatory network in, 800–801, 800f Statins, 678 Stem cells, 724 adult, 724 embryonic, 721, 724, 725f Stem length in dandelions, 773–75, 774f in garden pea, 18f Stem-loop structure, 611, 611f, 627–28, 627f, 666f, 667 Sterility See Fertility Stern, Curt, 131, 153 Steroid hormone receptor, 650f, 651 Sticky (cohesive) ends, 182f, 183 DNA with, 182f, 183, 303–4, 304f restriction fragment with, 303–4, 304f vectors with, 311 Stigma, in garden pea, 17f Stomach cancer, 701t Stop codon See Nonsense codon Straight run, 567, 567f Strawberries, polyploid, 521, 521f Strep throat, 545 Streptococcus, 545, 571 Streptococcus pneumoniae, transformation in, 169–72, 170f, 171f, 551 Streptomycin, 558, 558f organelle function and, 589 Streptomycin resistance, 546 in bacteria, 550f in Chlamydomonas reinhardtii, 596, 597f in Escherichia coli, 543 String gene, of Drosophila melanogaster, 648, 649f Stroma, of chloroplast, 584, 584f STS See Sequence tagged site stuck mutation in Drosophila melanogaster, 112 Sturtevant, Alfred H., 133, 135, 137–38 139–140, 139f Subclone, 315f, 316 Subcloning, 316 Substance H, 60f, 61 Substitution mutation, 208, 209f nonsynonymous, 799 synonymous, 799 Substrate, 690 Subunit, 238, 239f Sulfonamide resistance, 550f Summer squash, fruit color in, 61, 61f, 62t Sum rule, 21 Supercoiling, 190f, 191, 469t, 470, 471f, 543 Superrepressor, 616–18, 618f Suppression, intragenic, 259–61, 261f Survival, mutation and, 223–24 Survival advantage, and new allele perpetuation, 51 “Survival of the fittest” principle, 791 Sutton, Walter, 85, 105–6, 107t SV40 virus, 307, 310 Sweet pea, flower color in, 59, 59f, 62t Sxl (sex lethal) gene, of Drosophila melanogaster, 664–65, 665f, 673–75, 673t, 674f expression in early development, 665, 665f, 674 mutations in, 674 as trigger for cascade of RNA splicing, 675, 675f Synapsis, 96f, 98, 98f Synaptonemal complex, 96f–97f, 98, 98f, 99, 132, 133f, 138 Syncytial blastoderm, 733, 733f, 740 Syncytium, 92, 93f Synonymous substitutions, 799 Synpolydactyly, 745, 745f Syntenic blocks, 366 Syntenic genes, 125 Syntenic segments, 489 Synteny, conserved, 366 Synthetic mRNA, in vitro transplantation of, 262–63, 262f, 263f Systems biology See Molecular systems biology T T See Tetratype tetrad; Thymine TAF See TBP-associated factors Tail length, in mice, 65–66, 288–89, 288f Tandem duplication, 498, 499f Tandem repeat, 806, 808f Taq DNA polymerase, 328f–329f TaqI, 304t Targeted mutagenesis, 419 in mice, 419 Target transcripts, 670 TATA box, 337, 339f, 648 TATA box-binding protein (TBP), 649, 650f Tatum, Edward, 232–34, 233f, 238, 553–54, 553f Taxacarum See Dandelion Taxol, 710 Tay-Sachs disease, 31t, 54 genetic screening and, 33–34 TB See Tuberculosis TBP See TATA box-binding protein TBP-associated factors (TAF), 649, 650f TCA cycle See Krebs cycle T cell(s), 492, 695, 695f, 745f, 817 T-cell receptor, 817, 817f, 818–19 T-cell receptor genes, 372–73, 372f, 491–92 evolution of, 815, 820–21, 820f of humans, 820f, 821 of mice, 820f, 821 tcpP gene, 633, 633f T-cytotoxic cells, 817 TDF See Testes-determining factor Telomerase, 476–77, 477f aging and, 476–77 in cancer cells, 476, 697f–699f RNA portion of, 476, 477f, 479 Telomerase gene, 477 Telomeres, 132, 191, 369, 474–77 chromosome function and, 465–66 in Drosophila melanogaster, 509 repeated DNA sequences in, 476, 477f, 813 replication of, 475–76, 477f shortening with cell division, 477 Telophase of meiosis I, 97f, 100 of meiosis II, 97f, 100 of mitosis, 90f, 92, 93f Temin, Howard, 270 Temperate bacteriophage, 564, 565f Temperature and conditional lethal gene in Drosophila melanogaster, 66 permissive, 66, 688, 688f, 723 restrictive, 66, 688, 688f, 723 Temperature effect, effect on phenotype, 66, 66f Temperature-sensitive enzymes, 66, 67f Temperature-sensitive mutants, 66, 67f, 240, 546, 628–29, 723, 723f isolation of, 688, 688f in yeast, 687–88, 688f Temperature-shift analysis, 723, 723f Template strand, 184, 185f, 188, 263, 263f, 266f–267f, 268 10-fold sequence coverage, 356 terC region, 548, 549f Terminal deoxynucleotide transferase, 819 Terminalization, of chiasmata, 132, 133f Termination codon See Nonsense codon Termination phase of transcription, 266f–267f and attenuation of gene expression, 626–28, 626f, 627f Rho-dependent, 611, 611f Rho-independent, 611, 611f of translation, 278–81, 281f, 612 mutation and, 286–87 Terminator, 268 extrinsic, 267f intrinsic, 267f Tertiary structure of proteins, 237–38, 237f of tRNA, 275–76, 275f TEs See Transposable elements Testcross on dihybrids, 26–27, 26f to establish genotype, 24, 24f Testes-determining factor (TDF), 413, 414f, 415, 415f Tetanus, 544 Tetracycline resistance, 539, 545, 550f Tetrad (ascospores), 143 Tetrad (homologous chromatids), 98 Tetrad (ascospores) analysis calculation of recombination frequency, 148 demonstration of reciprocal recombination, 148–49 demonstration of recombination at four-strand stage, 148, 148f finding gene-centromere distance, 150–51, 151f, 151t in fungi, 142–51 linked genes, 147–48, 147f nonparental ditype tetrads, 145–48, 146f, 147f ordered tetrads, 145, 149–51, 149f, 150f, 151t parental ditype tetrads, 145–48, 146f, 147f rules for, 151t tetratype tetrads, 145, 146f, 147f unlinked genes, 145, 146f unordered tetrads, 145–49, 151t Tetrahymena, 476, 585 Tetraploidy, 491t, 518, 521, 522f, 523 Tetrasomy, 491t, 516 Tetratype tetrad (T), 145, 146f, 147t Thalassemia, 31t, 301–2, 337, 338f, 339f, 765 ␣-thalassemia, 337, 338f, 339f, 421 ␤-thalassemia, 35, 337, 338f, 339f, 421 Thalidomide, 67 T helper cells, 817 The Origin of Species (Darwin), 14, 16, 791, 821 Therapeutic cloning, 724, 725f Thermal cycler, 325f–326f Thermophilic bacteria, 570 Thermotogas, 541t Thomas, Lewis, 223 Three-point cross, gene mapping with, 136–40, 136f, 137f, 139f, 560–61, 560f correction for double crossovers, 136–39, 137f X chromosome of Drosophila melanogaster, 136–37, 136f, 139, 139f Threonine, 150–51, 558, 558f thr gene, of Neurospora crassa, 150–51, 151f thyA gene, of E coli, 563, 564f Thylakoid lumen, of chloroplast, 584, 584f Thylakoid membrane, of chloroplast, 584, 584f Thymine (T), 1, 2f, 174f, 175, 177, 178f, 180f Thymine dimer, 213f Thymine-thymine dimers, 212, 213f, 221–22, 221f, 223 Thyroid-stimulating hormone (TSH), 695, 695f Thyroxine, 695f Time-of-Flight mass spectrometry, 403f, 404 Time-of-function analysis, 723, 723f Tissue(s), differentiation in, 732–40, 745–47 Tissue plasminogen activator (TPA), 307 Tissue plasminogen activator (TPA) gene, 806, 807f T locus, in mice, 288–89, 288f Tn10, 548, 548f, 566 Tobacco chloroplast genome of, 588t, 590 continuous variation in, 69 maternal inheritance in, 593 Tolerance, state of knowledge about, 437 Tomato incompatibility gene in, 51–52 pulp content of, 422–23, 422f Top-down mapping approach, 360–61, 362f Topoisomerase II, 470, 471f Tortoises, sex determination in, 88, 88t Total phenotype variance, 774f, 775 Tox proteins, of Vibrio cholerae, 632–34, 633f TPA See Tissue plasminogen activator tra gene, of Drosophila melanogaster, 673t, 675, 675f, 676, 676f Trait(s) continuous See Continuous traits discontinuous, 68 discrete, 17 genes and, 13 heritable, 13 heterogeneous, 62–63, 63f interaction of genes to determine, 56–63, 64f multifactorial See Multifactorial trait sex-influenced, 112, 112f sex-limited, 112 transmission with chromosomes, 106–12 X-linked See X-linked trait har48564_ndx_I1-I22 9/6/06 01:54 AM Page I-21 Index trans-acting factors, 646 trans-acting regulatory element, 646, 646f, 648–57 lac operon, 614f, 617–18, 618f, 624 miRNAs, 668 trans configuration, 230 Transcript, 256, 256f mitochondrial, 587 RNA editing of, 587f Transcription, 256, 256f, 265–75, 266f–267f in bacteria, 265–69, 266f–267f, 268f, 548 cellular components of, 290, 291t control of, 442, 442f coupling to translation, 282 details of process, 265–69, 266f–267f, 268f in development, 746 direction of, 266f–267f, 268 in E coli, 265–69, 266f–267f, 268f, 548 elongation stage of, 266f–267f, 611, 611f in eukaryotes, 268, 282, 283t processing of primary transcripts, 269–75, 269f, 272f, 273f, 274f, 282–84, 283t heterochromatin vs euchromatin, 479–80, 479f identification of proteins regulating, 632 initiation of, 266f–267f, 611, 611f, 619–20 regulation of, 646–64 in prokaryotes, 268, 282, 283t, 611–26, 611f, 626–28, 626f, 627f regulation of, 612–28, 626f, 627f reverse, 256, 268, 270–71, 270f error rate, 271, 793 specificity of transcription factors, 653, 653f termination of, 266f–267f and attenuation of gene expression, 626–28, 626f, 627f Rho-dependent, 611, 611f Rho-independent, 611, 611f Transcriptional silencing, 659–61, 660f Transcription bubble, 266f–267f Transcription factor genes, 442f Transcription factors, 284, 441–42, 442f, 443f, 450, 646, 646f, 658, 695, 696f, 744, 746, 800, 800f See also Activator domains and architecture of, 365, 366f, 367–68, 367f Transcriptome, 378, 379f Transductant, 550 Transduction, 550, 551f, 562–64, 563f, 564f in bacteria, 550, 551f, 562–64, 563f, 564f bacterial virulence and, 571 generalized, 563, 563f, 564 mapping genes by, 563, 564f specialized, 564, 565f Transferase, 655, 656f Transfer RNA (tRNA), 256, 275–77, 275f, 276f, 277f charged, 276, 276f of Escherichia coli, 276–77 function of, 276–77, 276f, 277f of Mycoplasma capricolum, 277 nonsense suppressor, 290–91, 291f structure of, 275–76, 275f transcription of, 648 in translation, 275–82, 275f, 276f, 277f, 278f, 279f–280f wobble, 276–77, 276f, 588t Transfer RNA (tRNA) genes, 284, 367, 808 in chloroplasts, 588 mitochondrial, 585t, 588, 591, 601 mutations in, 290–91, 291f Transformant, 448, 550, 552f Transformation artificial, 551, 553 in Bacillus subtilis, 551–53, 552f in bacteria, 169–72, 170f, 171f, 550–53, 551f, 552f in molecular cloning identification of transformed host cells, 312, 313f, 314 inserting DNA into host cell, 313–14 natural, 551–52, 552f as proof that DNA is genetic material, 169–72, 170f, 171f Transforming principle, 171–72, 171f Transgenes, 28, 342, 416 Transgenic organisms, 342, 415 Transgenic technology, 11–12, 415, 415f in mice, 415, 415f proving equivalence of candidate gene and trait locus, 415 Transition, 208, 209f Translation, 256, 256f, 275–82 cellular components of, 290, 291t coupling to transcription, 282 direction of, 280f elongation phase of, 278–81, 280f in eukaryotes, 279f–281f inhibitors of, 589, 591, 598 initiation phase, 278–81, 279f, 612 in prokaryotes vs eukaryotes, 282, 283t mechanism of, 278–81, 279f–281f in mitochondria, 588, 588t in prokaryotes, 611 in prokaryotes vs eukaryotes, 282–84, 283t reverse, 323, 323f ribosomes as site of polypeptide synthesis, 277–78, 278f termination phase of, 278–81, 281f, 612 in vitro, of synthetic mRNA, 262–63, 262f, 263f Translocation, 503–8, 504f, 515 cancer-related, 504–5, 505f, 697f–699f evolution and, 515 gene mapping and, 507–8, 508f nonreciprocal, 491t reciprocal, 209, 209f, 491t, 503–5, 504f, 505f, 508 Robertsonian, 504, 504f, 507, 508f, 515, 515f Translocation Down syndrome, 507–8, 508f Translocation heterozygote, 506–8, 508f Translocation homozygote, 506 Transposable elements (TEs), 369, 508–14, 509f, 512f, 571–72 autonomous, 513 in bacteria, 548, 548f and chromosomal rearrangements, 513–14, 514f classes of, 509–10 in corn, 510, 510f defective copies of, 513 discovery of, 509, 509f in Drosophila melanogaster, 509 in F plasmid, 555 in humans, 509–10, 510f, 513 length of, 509 mutant screens and, 565 and mutations, 214, 215f, 513, 513f nonautonomous, 513 structure and movement of, 510, 512f Tn10, 548, 548f, 566 Transposase, 510, 512f Transposition, 491t, 508–14, 509f duplication by, 801–2, 801f, 804f, 810 and evolution, 515 relocation of genes by, 514, 514f Transposon See Transposable elements Transposon-derived repeats, 369–70, 370f autonomous, 370 Transposon mutagenesis, 566 Trans-splicing, 274f, 275 in Caenorhabditis elegans, 284–85 Transversion, 208, 209f Tra proteins, 676, 676f T regulatory cells, 817 Tricarboxylic acid (TCA) cycle See Krebs cycle Trilaminar plate, 478f Trinucleotide repeats medical consequences of, 216–17, 216f, 217f mutations and, 214 Triple drug therapy, 382, 794 Triploidy, 491t, 518, 521–23, 521f, 526 Triplolethal (Tpl) gene, of Drosophila melanogaster, 495, 499–500, 500f Trisomy, 100, 104, 491t, 516, 518, 526, 526t Trisomy 13, 516, 526t Trisomy 18, 516, 526t Trisomy 21 See Down syndrome Tritanopia, 243, 243f Triticale, 523–24, 524f trk gene, 705t tRNA See Transfer RNA TRP1 gene, of yeast, 145, 146f trpA gene, of Escherichia coli, 259, 259f, 264–65, 264f trpC2 gene, of B subtilis, 551, 552f trp operator, 62f, 626–28, 627f trp operon attenuation in, 626–28, 626f, 627f of Escherichia coli, 561, 626–28, 626f, 627f trp plasmid, 562 trp promoter, 626–28, 626f trp repressor, 626–28, 626f, 626t, 627f trpR gene, 626–28, 626f, 626t, 627f I-21 Trypanosomes mitochondrial DNA of, 585 RNA editing in, 285, 587, 587f Trypsin, 445–46, 446f, 447 Trypsinogen genes of humans, 820f, 821 of mice, 820f, 821 Tryptic peptides, 445–46 Tryptophan, 145 Tryptophan biosynthesis, 561f, 562 Tryptophan operon, 626–28, 626f, 627f Tryptophan synthetase gene, 290 TSH See Thyroid-stimulating hormone tsr gene, of bacteria, 570f Tuberculosis (TB), 544, 757, 758f drug-resistant, 757, 769–70, 770f Tubulin, 520–21 ␣-tubulin, 238, 239f ␤-tubulin, 238, 239f Tumble, 567, 567f Tumor cells See Cancer cells Tumor-suppressor genes, 154 mutations in, 703–4, 703f, 706–7, 708t genetic tests for, 708–9 Turner syndrome, 86, 86t, 516–18, 526t Turtles, sex determination in, 88, 88t Twin spots, in Drosophila melanogaster, 153, 153f Twin studies, of heritability of polygenic traits, 776–78, 777f Two-point cross, gene mapping with, 135–36, 135f Ty element, of yeast, 510, 511f Tyrosine, 4f, 5, 6f, 66 U UAS See Upstream activation site Ubiquitination, of proteins, 668–69, 669f, 692 Ulcer, 544 Ultrabithorax (Ubx) gene, of Drosophila melanogaster, 742, 744 Ultraviolet light, mutagenicity of, 212, 213f Unequal crossing-over, 213–14, 215f, 243–44, 243f, 397, 398f, 500, 500f duplication from, 802–3, 804f and gene superfamilies, 809, 810f multigene families and, 806–9, 808f, 809f nonhomologous, 802 and repetitive DNA, 813 Uniparental inheritance, 592–97 in Chlamydomonas reinhardtii, 596, 597f Universal donor, 49 Universal recipient, 49 Unordered tetrad, tetrad analysis in, 145–49, 151t 5'-Untranslated region, of mRNA, 282–84 Unvarying expressivity, 65 Upstream activation site (UAS), of yeast, 648 Upstream direction, 267f URA2 gene, of yeast, 147–48, 147f Uracil (U), 5, 6f, 181–84, 181f, 212, 213f, 220–21, 220f, 262 Uracil-DNA glycosylase, 220–21 Uracil editing, 587, 587f Urease, 544 U.S Food and Drug Administration, 223–24 U-tube experiment, 552f, 553–54 V Vaccines for AIDS, 271 genetic engineering and, 28–29 genome analysis and, 571 invention of, 437, 438f Variable domain, of antibody chain, 492, 493f Variable expressivity, 65 linkage mapping and, 420 Variable homology units, 817 Variable segments, 818, 818f Variance, 773, 774f environmental, 773–81, 774f definition of, 773 genetic, 773–81, 774f definition of, 775 har48564_ndx_I1-I22 I-22 9/6/06 01:54 AM Page I-22 Index Variance—Cont quantitative definition of, 17, 773 Mendelian analysis and, 68–71, 70f multifactorial, analysis of, 773–81 total phenotypic, 774f, 775 Variegation in four o’clock, 581–82, 582f, 592, 595 in geranium, 598, 598f position-effect, in Drosophila melanogaster, 480–81, 480f, 501–2, 664 Vector with blunt ends, 311 expression, 318–19, 319f ligation of DNA fragments to, 311–12, 312f plasmids as, 311–14, 311t, 313f, 315f, 316, 318, 335 separating genomic inserts from, 314, 315f with sticky ends, 311 types of, 311–12, 311t Ventral furrow, 733 Vertebrates, evolution of immune response in, 820 Vertical pattern of inheritance, 31–32, 32f, 33t vestigial (vg) gene, of Drosophila melanogaster, 136–39, 136f, 137f Vibrio cholerae, 544, 546, 571, 609–10, 610f ctx genes of, 632–34, 633f Tox proteins of, 632–34, 633f virulence genes in, 570, 609, 632–34, 633f Victoria (Queen of England), 111f, 409f Viral plaque, 227, 228f Viral shell (ghost), 172f, 173 Virulence, of pathogenic bacteria, 544–45 Virulence genes, in Vibrio cholerae, 570, 609, 632–34, 633f Virus cancer-causing, 701, 704–5, 704f chromosomes of, 179, 179f genome mapping in, 309–10, 310f RNA, 181–84 structure and life-cycle of, 172, 172f Visible mutant phenotypes, 546–47 Vision See also Colorblindness cellular and molecular basis of, 241–42, 242f color perception in humans, 239–42, 242f cellular and molecular basis of, 241–42, 242f mutations affecting, 243–44, 243f Vitamin A, 29 Vitamin D-resistant rickets, 111, 111f von Tschermak, Eric, 29, 30f Voodoo lily, 603 Vornlocher, Hans-Peter, 670 vulva development, in Caenorhabditis elegans, 727, 727f W Warfarin resistance, in rats, 772 Wasps, sex determination in, 88, 88t Watermelon, 521 Watson, James, 173, 175, 177, 177f, 184, 185f, 257, 351, 353, 792, 822 W chromosome, 88 Weigle, Jean, 192f Weinberg, W., 760 Wheat, 29, 85, 354, 518–19, 523, 524f white gene, of Drosophila melanogaster, 106–10, 108f, 109f, 125–27, 125f, 126f, 225, 480, 480f, 495, 509, 513, 513f white-spore gene, of Neurospora crassa, 149–50, 150f Wieschaus, Eric, 734–35, 737, 742, 747 Wild-type allele, 51–52, 52f, 208, 227, 227f Wilkins, Maurice, 173f, 175 Wilson, A C., 600 Wilson, Allan C., 594 Wilson, E B., 106, 110–11 Wing(s), of fly, 8, 8f wingless (wg) gene, of Drosophila melanogaster, 723, 738–39, 740f Wing morphology, in Drosophila melanogaster, 127, 127f, 133, 133f, 136–39, 136f, 139f, 495, 495f, 498, 498f, 745, 746f Wobble, 276–77, 276f, 588t Wollman, Elie, 557 World Health Organization, 29 WTC Kinship and Data Analysis Panel (KADAP), 780 X Xanthine dehydrogenase, 287f X chromosome, 85–88, 86f, 86t, 88t of Drosophila melanogaster, 95, 95f, 106–10, 108f, 109f, 112–13, 124–27, 125f, 126f, 131, 132f, 135, 135f, 139, 139f, 152f, 153, 215–16, 215f, 224–26, 225f, 226f, 481, 509 of humans aneuploidy in, 516–17, 517f, 525–26, 526t colorblindness gene, 473, 473f genetic map of, 154–55, 155f number of genes on, 124 inactivation of, 481–82, 516–17, 517f, 664, 700, 700f ratio to autosomes, and gene regulation, 669–75, 674t, 675f reactivation of, 517 Xenopus maternal inheritance in, 592, 593f MPF protein in, 690 Xeroderma pigmentosum, 223, 223f, 697f–699f X-gal, 313f, 314, 547, 613, 646 Xist gene, 481–82 Xist RNA, 481–82 X-linked severe combined immune deficiency (XSCID), 238, 239f X-linked trait, 108–9, 108f, 123, 124f, 474 dominant, 111, 111f, 111t in humans, 110–11, 111f, 111t recessive, 111, 111f, 111t XO females, 516 XP gene, 708t X-ray(s), mutagenicity of, 213f, 215–16, 215f, 223 X-ray diffraction analysis of DNA, 173, 173f, 175 of nucleosome cores, 469, 470f XX males, 195–200, 200f XXY males, 516, 516f XY females, 198 XYY karyotype, 114, 526t Y YAC See Yeast artificial chromosome Yanofsky, Charles, 258, 264–65, 264f, 627 Y chromosome, 85–88, 86f, 86t, 88t aneuploidy in humans, 526t of Drosophila melanogaster, 95, 95f Yeast, 143 ADE2 gene of, 152, 152f ARG3 gene of, 147–48, 147f autonomously replicating sequence in, 475, 475f base composition of DNA of, 176t budding in, 687, 687f, 688f, 689f CDC2 gene of, 689–90 CDC7 gene of, 688, 689f, 689t CDC28 gene of, 688–89, 689f, 689t, 690 cell-cycle mutants in, 687–92, 687f–691f centromeres of, 478f, 479 chloramphenicol resistance in, 598 chromosomes of, 465 colony, size of, 581–82 expression vectors, 318–19 galactose-utilization system of, 452–55, 452f, 453f, 454f, 655–57, 656f gene conversion in, 193f, 194, 194f gene nomenclature for, 145, 827 genome of, 8, 9f genome sequence of, 353, 355t HIS4 gene of, 143–45, 146f HML locus of, 659, 659f HMR locus of, 659, 659f life cycle of, 144f, 599f long terminal repeats in, 510 mating type in, 598, 599f, 653, 653f, 659–60, 719 MAT locus of, 659–60 meiosis in, 99 mitochondrial genome of, 585, 585t, 587, 598–99, 599f mitotic recombination in, 153, 153f as model organism, 353, 718–19 origin of replication in, 475, 475f petite phenotype in, 581–82, 592 protein-protein interactions in, 453 proteome of, 367, 369t reproduction in, 143, 144f sectors in, 153, 153f SIR genes of, 660, 660f Spo11 protein in, 194–95 sterility in, 659–60 temperature-sensitive mutants in, 687–88, 688f tetrad analysis in See Tetrad analysis TRP1 gene of, 145, 146f Ty element of, 510, 511f upstream activation site (UAS) of, 648 URA2 gene of, 147–48, 147f Yeast artificial chromosome (YAC), 311t, 312, 315, 465–66 Yeast two-hybrid interactions, 448–49, 449f Yersinia pestis, 544 Y-linked traits, 111, 111t Yogyakarta, Sultan of, 391f YP1 gene, of Drosophila melanogaster, 675–76, 675f Z Z chromosome, 88, 88t zerknullt (zen) gene, of Drosophila melanogaster, 743 Z-form DNA, 178, 179f, 469 Zinc-finger motif, 643, 650f, 651 Zuckerkandl, Emile, 804 zw10 mutation, in Drosophila melanogaster, 95, 95f zyg-9 gene, of Caenorhabditis elegans, 723, 723f Zygote formation of, 81–83, 83f, 103 law of segregation and, 20–21, 20f Zygotene, 96f, 98, 98f Zygotic genes, in Drosophila melanogaster development, 737, 747 Tools to Help You Master Genetics Study Guide/Solutions Manual By Debra Nero, Cornell University ISBN 978-0-07-299587-9 MHID 0-07-299587-4 Written to support the concepts presented in Genetics: From Genes to Genomes, Third Edition, this manual includes solutions to the end-of-chapter problems Solutions are given with step-by-step logic to help strengthen your problem-solving skills McGraw-Hill’s ARIS (Assessment Review and Instruction System) Makes homework meaningful—and manageable—for instructors and students Hartwell Hood Goldberg Reynolds Silver Veres From Genes to Genomes Explore this dynamic site for a variety of study tools • Self-quizzes • Flash cards • Animations with quizzing • Interactive Web Exercises Go to aris.mhhe.com to learn more or go directly to this book’s ARIS site at www.mhhe.com/hartwell3 From Genes to Genomes Animations with Quizzing More than 40 animations are available at www.mhhe.com/hartwell3 These animations set genetics processes in motion, and make great study and review tools since you control the action Third Edition Third Edition Leland H Hartwell Leroy Hood Michael L Goldberg Ann E Reynolds Lee M Silver Ruth C Veres ... deamination i X-ray irradiation j intercalator k unequal crossing-over the gene map in a chromosome is changed from bog-rad-fox1-fox2-try-duf to bog-rad-fox2fox1-try-duf Suppose you wanted to study genes. .. the gene map in a given chromosome is changed from bog-rad-fox1-fox2-try-duf to bog-rad-fox1-mel-qui-txu-sqm Section 7.1 The DNA sequence of a gene from three independently isolated mutants is... changed to AACGTCACATCG the gene map in a given chromosome arm is changed from bog-rad-fox1-fox2-try-duf (where fox1 and fox2 are highly homologous, recently diverged genes) to bog-rad-fox1-fox3-fox2-tryduf