Giáo trình Essentials of genetics 9e global edition by klug

Brief Contents 1    2    3    4    5    6    7    8    9  10  11  12  13  14  15  16  17  18  19  20  21  22    Introduction to Genetics  17 Mitosis and Meiosis  28 Mendelian Genetics  47 Modification of Mendelian Ratios  69 Sex Determination and Sex Chromosomes  100 Chromosome Mutations: Variation in Number and Arrangement  115 Linkage and Chromosome Mapping in Eukaryotes  136 Genetic Analysis and Mapping in Bacteria and Bacteriophages  159 DNA Structure and Analysis  176 DNA Replication  196 Chromosome Structure and DNA Sequence Organization  215 The Genetic Code and Transcription  231 Translation and Proteins  254 Gene Mutation, DNA Repair, and Transposition  273 Regulation of Gene Expression  296 The Genetics of Cancer  323 Recombinant DNA Technology  338 Genomics, Bioinformatics, and Proteomics  361 Applications and Ethics of Genetic Engineering and Biotechnology  394 Developmental Genetics  419 Quantitative Genetics and Multifactorial Traits  438 Population and Evolutionary Genetics  457 Special Topics in modern Genetics Epigenetics  480 1  2  Emerging Roles of RNA  490 DNA Forensics  503 3  Genomics and Personalized Medicine  513 4  Genetically Modified Foods  523 5  Gene Therapy  535 6  Appendix  Solutions to Selected Problems and Discussion Questions  A-1 Glossary G-1 Credits C-1 Index I-1 ESSENTIALS of GENETICS Ninth Edition Global Edition William S Klug The College of New Jersey Michael R Cummings Illinois Institute of Technology Charlotte A Spencer University of Alberta Michael A Palladino Monmouth University with contributions by Darrell Killian Colorado College www.ebookslides.com Senior Acquisitions Editor: Michael Gillespie Project Manager: Margaret Young Program Manager: Anna Amato Development Editor: Dusty Friedman Assistant Editor: Chloé Veylit Executive Editorial Manager: Ginnie Simione Jutson Program Management Team Lead: Mike Early Project Management Team Lead: David Zielonka Assistant Acquisitions Editor, Global Edition: Murchana Borthakur Project Editor, Global Edition: Amrita Naskar Manager, Media Production, Global Edition: Vikram Kumar Senior Manufacturing Controller, Production, Global Edition: Trudy Kimber Production Management: Rose Kernan, Cenveo® Publisher Services Design Manager: Mark Ong Interior Designer: Tani Hasegawa Cover Designer: Lumina Datamatics Ltd Illustrators: Imagineering Rights & Permissions Project Manager: Donna Kalal Rights & Permissions Management: Rachel Youdelman Photo Researcher: QBS Learning Senior Procurement Specialist: Stacey Weinberger Project Manager–Instructor Media: Chelsea Logan Executive Marketing Manager: Lauren Harp Cover Photo Credit: irin-k /Shutterstock Acknowledgements of third party content appear on page C-1, which constitutes an extension of this ­copyright page Pearson Education Limited Edinburgh Gate Harlow Essex CM20 2JE England and Associated Companies throughout the world Visit us on the World Wide Web at: www.pearsonglobaleditions.com © William S Klug and Michael R Cummings 2017 The rights of  William S Klug, Michael R Cummings, Charlotte A Spencer, and Michael A Palladino to be identified as the authors of this work have been asserted by them in accordance with the Copyright, Designs and Patents Act 1988 Authorized adaptation from the United States edition, entitled Essentials of Genetics, 9th edition, ISBN 978-0-134-04779-9, by William S Klug, Michael R Cummings, Charlotte A Spencer, and Michael A Palladino, published by Pearson Education © 2016 All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without either the prior written permission of the publisher or a license permitting restricted copying in the United Kingdom issued by the Copyright Licensing Agency Ltd, Saffron House, 6–10 Kirby Street, London EC 1N 8TS All trademarks used herein are the property of their respective owners The use of any trademark in this text does not vest in the author or publisher any trademark ownership rights in such trademarks, nor does the use of such trademarks imply any affiliation with or endorsement of this book by such owners MasteringGenetics is a trademark in the U.S and/or other countries, owned by Pearson Education, Inc or its affiliates Unless otherwise indicated herein, any third-party trademarks that may appear in this work are the property of their respective owners and any references to third-party trademarks, logos or other trade dress are for demonstrative or descriptive purposes only Such references are not intended to imply any sponsorship, endorsement, authorization, or promotion of Pearson’s products by the owners of such marks, or any relationship between the owner and Pearson Education, Inc or its affiliates, authors, licensees or distributors ISBN 10: 1-292-10886-X ISBN 13: 978-1-292-10886-5 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library 10 Typeset by Cenveo Publisher Services Printed and bound by Vivar in Malaysia About the Authors William S Klug  is an Emeritus Professor of Biology at The College of New Jersey (formerly Trenton State College) in Ewing, New Jersey, where he served as Chair of the Biology Department for 17 years He received his B.A degree in Biology from Wabash College in Crawfordsville, Indiana, and his Ph.D from Northwestern University in Evanston, Illinois Prior to coming to The College of New Jersey, he was on the faculty of Wabash College as an Assistant Professor, where he first taught genetics, as well as general biology and electron microscopy His research interests have involved ultrastructural and molecular genetic studies of development, utilizing oogenesis in Drosophila as a model system He has taught the genetics course as well as the senior capstone seminar course in Human and Molecular Genetics to undergraduate biology majors for over four decades He was the recipient in 2001 of the first annual teaching award given at The College of New Jersey, granted to the faculty member who “most challenges students to achieve high standards.” He also received the 2004 Outstanding Professor Award from Sigma Pi International, and in the same year, he was nominated as the Educator of the Year, an award given by the Research and Development Council of New Jersey Michael R Cummings   is Research Professor in the Department of Biological, Chemical, and Physical Sciences at Illinois Institute of Technology, Chicago, Illinois For more than 25 years, he was a faculty member in the Department of Biological Sciences and in the Department of Molecular Genetics at the University of Illinois at Chicago He has also served on the faculties of Northwestern University and Florida State University He received his B.A from St Mary’s College in Winona, Minnesota, and his M.S and Ph.D from Northwestern University in Evanston, Illinois In addition to this text and its companion volumes, he has also written textbooks in human genetics and general biology for nonmajors His research interests center on the molecular organization and physical mapping of the heterochromatic regions of human acrocentric chromosomes At the undergraduate level, he teaches courses in Mendelian and molecular genetics, human genetics, and general biology, and has received numerous awards for teaching excellence given by university faculty, student organizations, and graduating seniors Charlotte A Spencer   is a retired Associate Professor from the Department of Oncology at the University of Alberta in Edmonton, Alberta, Canada She has also served as a faculty member in the Department of Biochemistry at the University of Alberta She received her B.Sc in Microbiology from the University of British Columbia and her Ph.D in Genetics from the University of Alberta, followed by postdoctoral training at the Fred Hutchinson Cancer Research Center in Seattle, Washington Her research interests involve the regulation of RNA polymerase II transcription in cancer cells, cells infected with DNA viruses, and cells traversing the mitotic phase of the cell cycle She has taught courses in biochemistry, genetics, molecular biology, and oncology, at both undergraduate and graduate levels In addition, she has written booklets in the Prentice Hall Exploring Biology series, which are aimed at the undergraduate nonmajor level Michael A Palladino    is Dean of the School of Science and Professor of Biology at Monmouth University in West Long Branch, New Jersey He received his B.S degree in Biology from Trenton State College (now known as The College of New Jersey) and his Ph.D in Anatomy and Cell Biology from the University of Virginia He directs an active laboratory of undergraduate student researchers studying molecular mechanisms involved in innate immunity of mammalian male reproductive organs and genes involved in oxygen homeostasis and ischemic injury of the testis He has taught a wide range of courses for both majors and nonmajors and currently teaches genetics, biotechnology, endocrinology, and laboratory in cell and molecular biology He has received several awards for research and teaching, including the 2009 Young Investigator Award of the American Society of Andrology, the 2005 Distinguished Teacher Award from Monmouth University, and the 2005 Caring Heart Award from the New Jersey Association for Biomedical Research He is co-author of the undergraduate textbook Introduction to Biotechnology, Series Editor for the Benjamin Cummings Special Topics in Biology booklet series, and author of the first booklet in the series, Understanding the Human Genome Project www.ebookslides.com This page intentionally left blank Contents Introduction to Genetics 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 17 Genetics Has a Rich and Interesting History 18 Genetics Progressed from Mendel to DNA in Less Than a Century 19 Discovery of the Double Helix Launched the Era of Molecular Genetics 21 Development of Recombinant DNA Technology Began the Era of DNA Cloning 23 The Impact of Biotechnology Is Continually Expanding 23 Genomics, Proteomics, and Bioinformatics Are New and Expanding Fields 24 Genetic Studies Rely on the Use of Model Organisms 25 We Live in the Age of Genetics  26 Problems and Discussion Questions 27 Mitosis and Meiosis 28 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Cell Structure Is Closely Tied to Genetic Function 29 Chromosomes Exist in Homologous Pairs in Diploid Organisms 31 Mitosis Partitions Chromosomes into Dividing Cells 33 Meiosis Creates Haploid Gametes and Spores and Enhances Genetic Variation in Species 37 The Development of Gametes Varies in Spermatogenesis Compared to Oogenesis 40 Meiosis Is Critical to Sexual Reproduction in All Diploid Organisms 42 Electron Microscopy Has Revealed the Physical Structure of Mitotic and Meiotic Chromosomes 42 EXPLORING GENOMICS PubMed: Exploring and Retrieving Biomedical Literature 43 CASE STUDY:Triggering meiotic maturation of oocytes 44 Insights and Solutions 44 3.7 3.8 3.9 3.10 EXPLORING GENOMICS Online Mendelian Inheritance in Man 64 CASE STUDY:To test or not to test 65 Insights and Solutions 65 Problems and Discussion Questions 67 Modification of Mendelian Ratios 4.1 4.2 4.3 4.4 4.5 4.6 3.1 Mendel Used a Model Experimental Approach to Study Patterns of Inheritance 48 3.2 The Monohybrid Cross Reveals How One Trait Is Transmitted from Generation to Generation 48 3.3 Mendel’s Dihybrid Cross Generated a Unique F2 Ratio 52 3.4 The Trihybrid Cross Demonstrates That Mendel’s Principles Apply to Inheritance of Multiple Traits 55 3.5 Mendel’s Work Was Rediscovered in the Early Twentieth Century 57 Evolving Concept of the Gene  58 3.6 Independent Assortment Leads to Extensive Genetic Variation 58 69 Alleles Alter Phenotypes in Different Ways 70 Geneticists Use a Variety of Symbols for Alleles 70 Neither Allele Is Dominant in Incomplete, or Partial, Dominance 71 In Codominance, the Influence of Both Alleles in a Heterozygote Is Clearly Evident 72 Multiple Alleles of a Gene May Exist in a Population 72 Lethal Alleles Represent Essential Genes 74 Evolving Concept of the Gene  74 4.7 4.8 4.9 4.10 4.11 4.12 4.13 Problems and Discussion Questions 45 Mendelian Genetics 47 Laws of Probability Help to Explain Genetic Events 58 Chi-Square Analysis Evaluates the Influence of Chance on Genetic Data 59 Pedigrees Reveal Patterns of Inheritance of Human Traits 62 Tay–Sachs Disease: The Molecular Basis of a Recessive Disorder in Humans 64 4.14 4.15 Combinations of Two Gene Pairs with Two Modes of Inheritance Modify the 9:3:3:1 Ratio 75 Phenotypes Are Often Affected by More Than One Gene 76 Complementation Analysis Can Determine If Two Mutations Causing a Similar Phenotype Are Alleles of the Same Gene 80 Expression of a Single Gene May Have Multiple Effects 82 X-Linkage Describes Genes on the X Chromosome 82 In Sex-Limited and Sex-Influenced Inheritance, an Individual’s Sex Influences the Phenotype 84 Genetic Background and the Environment Affect Phenotypic Expression 86 Genomic (Parental) Imprinting and Gene Silencing 88 Extranuclear Inheritance Modifies Mendelian Patterns 89 GENETICS, TECHNOLOGY, AND SOCIET Y Improving the Genetic Fate of Purebred Dogs 92 CASE STUDY: Sudden blindness 93 Insights and Solutions 94 Problems and Discussion Questions 95 Sex Determination and Sex Chromosomes 5.1 5.2 100 X and Y Chromosomes Were First Linked to Sex Determination Early in the Twentieth Century 101 The Y Chromosome Determines Maleness in Humans 102 www.ebookslides.com CON TEN T S 5.3 5.4 5.5 5.6 The Ratio of Males to Females in Humans Is Not 1.0 105 Dosage Compensation Prevents Excessive Expression of X-Linked Genes in Humans and Other Mammals 106 The Ratio of X Chromosomes to Sets of Autosomes Can Determine Sex 109 Temperature Variation Controls Sex Determination in Reptiles 111 CASE STUDY: Not reaching puberty 112 7.6 EXPLORING GENOMICS Human Chromosome Maps on the Internet 155 CASE STUDY: Links to autism 155 Insights and Solutions 165 Problems and Discussion Questions 156 Genetic Analysis and Mapping Insights and Solutions 113 in Bacteria and Bacteriophages Problems and Discussion Questions 113 8.1 Chromosome Mutations: Variation in Number and Arrangement 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 8.2 8.3 115 Variation in Chromosome Number: Terminology and Origin 116 Monosomy and Trisomy Result in a Variety of Phenotypic Effects 117 Polyploidy, in Which More Than Two Haploid Sets of Chromosomes Are Present, Is Prevalent in Plants 121 Variation Occurs in the Composition and Arrangement of Chromosomes 123 A Deletion Is a Missing Region of a Chromosome 124 A Duplication Is a Repeated Segment of a Chromosome 126 Inversions Rearrange the Linear Gene Sequence 128 Translocations Alter the Location of Chromosomal Segments in the Genome 129 Fragile Sites in Human Chromosomes Are Susceptible to Breakage 131 CASE STUDY: Changing the face of Down syndrome 133 8.4 8.5 8.6 8.7 Problems and Discussion Questions 134 7.1 Problems and Discussion Questions 174 DNA Structure and Analysis 176 9.1 9.2 9.3 9.4 7.2 7.3 7.4 9.6 136 Genes Linked on the Same Chromosome Segregate Together 137 Crossing Over Serves as the Basis of Determining the Distance between Genes during Mapping 140 Determining the Gene Sequence during Mapping Requires the Analysis of Multiple Crossovers 143 As the Distance between Two Genes Increases, Mapping Estimates Become More Inaccurate 149 Bacteria Mutate Spontaneously and Are Easily Cultured 160 Genetic Recombination Occurs in Bacteria 160 Rec Proteins Are Essential to Bacterial Recombination 166 The F Factor Is an Example of a Plasmid 167 Transformation Is Another Process Leading to Genetic Recombination in Bacteria 168 Bacteriophages Are Bacterial Viruses 169 Transduction Is Virus-Mediated Bacterial DNA Transfer 172 Insights and Solutions 174 9.5 Linkage and Chromosome Mapping 159 CASE STUDY: To treat or not to treat 174 Insights and Solutions 133 in Eukaryotes Other Aspects of Genetic Exchange 153 The Genetic Material Must Exhibit Four Characteristics 177 Until 1944, Observations Favored Protein as the Genetic Material 177 Evidence Favoring DNA as the Genetic Material Was First Obtained during the Study of Bacteria and Bacteriophages 178 Indirect and Direct Evidence Supports the Concept that DNA Is the Genetic Material in Eukaryotes 183 RNA Serves as the Genetic Material in Some Viruses 184 The Structure of DNA Holds the Key to Understanding Its Function 184 Evolving Concept of the Gene  190 9.7 9.8 9.9 Alternative Forms of DNA Exist 190 The Structure of RNA Is Chemically Similar to DNA, but Single-Stranded 190 Many Analytical Techniques Have Been Useful during the Investigation of DNA and RNA 191 EXPLORING GENOMICS Introduction to Bioinformatics: BLAST 193 Evolving Concept of the Gene  152 CASE STUDY: Zigs and zags of the smallpox virus 194 7.5 Insights and Solutions 194 Chromosome Mapping Is Now Possible Using DNA Markers and Annotated Computer Databases 152 Problems and Discussion Questions 194 www.ebookslides.com CO N T EN T S 10 DNA Replication and Recombination 196 10.1 DNA Is Reproduced by Semiconservative 10.2 10.3 10.4 10.5 10.6 10.7 Replication 197 DNA Synthesis in Bacteria Involves Five Polymerases, as Well as Other Enzymes 201 Many Complex Issues Must Be Resolved during DNA Replication 204 A Coherent Model Summarizes DNA Replication 207 Replication Is Controlled by a Variety of Genes 208 Eukaryotic DNA Replication Is Similar to Replication in Prokaryotes, but Is More Complex 208 The Ends of Linear Chromosomes Are Problematic during Replication 210 12.4 The Coding Dictionary Reveals the Function of the 64 Triplets 238 The Genetic Code Has Been Confirmed in Studies of Bacteriophage MS2 239 12.6 The Genetic Code Is Nearly Universal 239 12.7 Different Initiation Points Create Overlapping Genes 240 12.8 Transcription Synthesizes RNA on a DNA Template 241 12.9 RNA Polymerase Directs RNA Synthesis 241 12.10 Transcription in Eukaryotes Differs from Prokaryotic Transcription in Several Ways 243 12.11 The Coding Regions of Eukaryotic Genes Are Interrupted by Intervening Sequences Called Introns 246 12.5 Evolving Concept of the Gene  249 12.12 RNA Editing May Modify the Final Transcript 249 GENETICS, TECHNOLOGY, AND SOCIET Y Telomeres: The Key to Immortality? 212 GENETICS, TECHNOLOGY, AND SOCIET Y Fighting Disease with Antisense Therapeutics 250 CASE STUDY: Premature aging and DNA helicases 213 CASE STUDY: Cystic fibrosis 251 Insights and Solutions 213 Insights and Solutions 251 Problems and Discussion Questions 214 Problems and Discussion Questions 252 11 Chromosome Structure and DNA Sequence Organization 215 11.1 Viral and Bacterial Chromosomes Are Relatively Simple DNA Molecules 216 11.2 Mitochondria and Chloroplasts Contain DNA Similar to Bacteria and Viruses 217 11.3 Specialized Chromosomes Reveal Variations in the Organization of DNA 219 11.4 DNA Is Organized into Chromatin in Eukaryotes 221 11.5 Eukaryotic Genomes Demonstrate Complex Sequence Organization Characterized by Repetitive DNA 225 11.6 The Vast Majority of a Eukaryotic Genome Does Not Encode Functional Genes 228 EXPLORING GENOMICS Database of Genomic Variants: Structural Variations in the Human Genome 228 CASE STUDY: Art inspires learning 229 Insights and Solutions 229 Problems and Discussion Questions 230 13 Translation and Proteins 254 13.1 Translation of mRNA Depends on Ribosomes and Transfer RNAs 255 13.2 Translation of mRNA Can Be Divided into Three Steps 258 13.3 High-Resolution Studies Have Revealed Many Details about the Functional Prokaryotic Ribosome 262 13.4 Translation Is More Complex in Eukaryotes 263 13.5 The Initial Insight That Proteins Are Important in Heredity Was Provided by the Study of Inborn Errors of Metabolism 263 13.6 Studies of Neurospora Led to the One-Gene:One-Enzyme Hypothesis 264 13.7 Studies of Human Hemoglobin Established That One Gene Encodes One Polypeptide 266 Evolving Concept of the Gene  267 13.8 Variation in Protein Structure Is the Basis of Biological Diversity 267 13.9 Proteins Function in Many Diverse Roles 270 CASE STUDY: Crippled ribosomes 271 Insights and Solutions 271 12 The Genetic Code and Transcription Problems and Discussion Questions 271 231 12.1 The Genetic Code Exhibits a Number of Characteristics 232 12.2 Early Studies Established the Basic Operational Patterns of the Code 232 12.3 Studies by Nirenberg, Matthaei, and Others Deciphered the Code 233 14 Gene Mutation, DNA Repair, and Transposition 273 14.1 Gene Mutations Are Classified in Various Ways 274 14.2 Spontaneous Mutations Arise from Replication Errors and Base Modifications 277 www.ebookslides.com CON TEN T S 14.3 Induced Mutations Arise from DNA Damage Caused by 14.4 14.5 14.6 14.7 Chemicals and Radiation 279 Single-Gene Mutations Cause a Wide Range of Human Diseases 281 Organisms Use DNA Repair Systems to Detect and Correct Mutations 282 The Ames Test Is Used to Assess the Mutagenicity of Compounds 303 Transposable Elements Move within the Genome and May Create Mutations 288 16.3 Cancer Cells Contain Genetic Defects Affecting CellCycle Regulation 328 16.4 Proto-oncogenes and Tumor-Suppressor Genes Are Altered in Cancer Cells 330 16.5 Cancer Cells Metastasize and Invade Other Tissues 332 16.6 Predisposition to Some Cancers Can Be Inherited 332 16.7 Viruses and Environmental Agents Contribute to Human Cancers 333 GENETICS, TECHNOLOGY, AND SOCIET Y Breast Cancer: The Double-Edged Sword of Genetic Testing 334 CASE STUDY: Genetic dwarfism 292 CASE STUDY: Screening for cancer can save lives 335 Insights and Solutions 293 Insights and Solutions 335 Problems and Discussion Questions 293 Problems and Discussion Questions 336 15 Regulation of Gene Expression 296 15.1 Prokaryotes Regulate Gene Expression in Response to Both External and Internal Conditions 297 15.2 Lactose Metabolism in E coli Is Regulated by an Inducible System 297 15.3 The Catabolite-Activating Protein (CAP) Exerts Positive Control over the lac Operon 302 15.4 The Tryptophan (trp) Operon in E coli Is a Repressible Gene System 304 Evolving Concept of the Gene  304 15.5 Alterations to RNA Secondary Structure Also Contribute to Prokaryotic Gene Regulation 304 15.6 Eukaryotic Gene Regulation Differs from That in Prokaryotes 307 15.7 Eukaryotic Gene Expression Is Influenced by Chromatin Modifications 308 15.8 Eukaryotic Transcription Regulation Requires Specific Cis-Acting Sites 310 15.9 Eukaryotic Transcription Initiation is Regulated by Transcription Factors That Bind to Cis-Acting Sites 312 15.10 Activators and Repressors Interact with General Transcription Factors and Affect Chromatin Structure 313 15.11 Posttranscriptional Gene Regulation Occurs at Many Steps from RNA Processing to Protein Modification 315 15.12 RNA-Induced Gene Silencing Controls Gene Expression in Several Ways 317 GENETICS, TECHNOLOGY, AND SOCIET Y Quorum Sensing: Social Networking in the Bacterial World 318 CASE STUDY: A mysterious muscular dystrophy 319 Insights and Solutions 319 17 Recombinant DNA Technology 17.1 Recombinant DNA Technology Began with 17.2 17.3 17.4 17.5 17.6 CASE STUDY: Should we worry about recombinant DNA technology? 359 Insights and Solutions 359 Problems and Discussion Questions 360 18 Genomics, Bioinformatics, and Proteomics 361 18.1 Whole-Genome Shotgun Sequencing Is a Widely 18.2 18.3 18.4 323 Two Key Tools: Restriction Enzymes and DNA Cloning Vectors 339 DNA Libraries Are Collections of Cloned Sequences 344 The Polymerase Chain Reaction Is a Powerful Technique for Copying DNA 347 Molecular Techniques for Analyzing DNA 349 DNA Sequencing Is the Ultimate Way to Characterize DNA at the Molecular Level 352 Creating Knockout and Transgenic Organisms for Studying Gene Function 354 EXPLORING GENOMICS Manipulating Recombinant DNA: Restriction Mapping and Designing PCR Primers 358 Problems and Discussion Questions 320 16 The Genetics of Cancer 338 18.5 Used Method for Sequencing and Assembling Entire Genomes 362 DNA Sequence Analysis Relies on Bioinformatics Applications and Genome Databases 364 Genomics Attempts to Identify Potential Functions of Genes and Other Elements in a Genome 366 The Human Genome Project Revealed Many Important Aspects of Genome Organization in Humans 367 After the Human Genome Project: What Is Next? 370 Evolving Concept of the Gene  374 16.1 Cancer Is a Genetic Disease at the Level 18.6 Comparative Genomics Analyzes and Compares of Somatic Cells 324 16.2 Cancer Cells Contain Genetic Defects Affecting Genomic Stability, DNA Repair, and Chromatin Modifications 327 18.7 Comparative Genomics Is Useful for Studying the Genomes from Different Organisms 376 Evolution and Function of Multigene Families 381 www.ebookslides.com I-8 IN D EX Gene mapping (Continued) bioinformatics and, 152 DNA markers in, 152 gene distance in, 140–142, 151 of gene sequences, 146–147 interference in, 151 linkage, 140–152 microsatellites in, 152 reciprocal classes in, 146 restriction fragment length polymorphisms in, 152 sequence maps in, 152 single crossovers and, 142–143, 142f, 143f, 146 single-nucleotide polymorphisms in, 152 steps in, 147–149 three-point, in Drosophila melanogaster, 144–147, 145f for genetic diseases, 370, 371f Internet resources for, 152, 155 Gene mutations See Mutation(s), gene Gene pills, 538 Gene pool, 458 Gene prediction programs, 365–366 Gene redundancy, 126 Gene regulation, 296–319 DNA methylation in, 309–310 in eukaryotes, 307–317 activators in, 312, 314 alternative splicing in, 315–316, 315f, 316f See also Splicing chromatin modification in, 308–310, 314 See also Chromatin modification/ remodeling cis-acting sites in, 310–313 enhancers in, 311 histone modification in, 308–309, 309f mRNA stability and, 316–317 overview of, 307–308, 307f posttranscriptional, 315–317 posttranslational, 317 promoters in, 244, 310–311, 310f, 311f repressors in, 312, 314 RNA-induced gene silencing in, 317 silencers in, 244, 312, 314 transcriptional, 307–315 translational, 317 in prokaryotes, 297–303 catabolite repression in, 302–303, 303f corepressors in, 304 inducible, 297, 299, 299f lac operon in, 298–303 See also lac operon mutations in, 299 negative, 297, 299–302 positive, 297, 302–303, 303f repressible, 297, 302–303 riboswitches in, 306–307, 307f RNA secondary structures in, 305–307, 306f structural genes in, 298–299 transcription attenuation in, 304, 305–306 trp operon in, 304, 305f RNA interference in, 317 Gene sequences, mapping of, 146–147 See also DNA sequencing; Gene mapping Gene silencing in dosage compensation, 106–109 in gene therapy, 544–545 genomic imprinting and, 88–89, 108, 483–485 mechanism of, 108–109 nucleic acid-based drugs in, 250–251 RNA-induced, 317, 482, 494, 497–498 Gene targeting See Gene editing Gene therapy, 411, 535–546 approval for, 542b conditions used for, 535 CRISPR/Cas technology in, 543–544 definition of, 535 enhancement, 545–546 ethical concerns in, 545–546 future of, 545–546 gene delivery methods in, 535–538 gene pills, 538 nonviral, 538 viral vectors, 536–538, 540–541 gene editing in, 357, 541–544 gene silencing in, 544–545 for hemophilia, 541 for HIV infection, 542–543 for lipoprotein lipase deficiency, 542b for metachromatic leukodystrophy, 541–542 for retinal blindness, 540–541 setbacks in, 539–541 for severe combined immunodeficiency, 538–539, 540 somatic, 545 successful trials of initial, 538–539 recent, 541–542 targeted approaches for, 542–545 transcription activator–like effector nucleases in, 357, 542 translational medicine and, 535 for Wiskott-Aldrich syndrome, 541–542 zinc-finger nucleases in, 357, 541–542 Gene transfer horizontal, 161 vertical, 161 Gene-expression analysis DNA microarrays in, 383–384, 384f transcriptome, 383 Gene-expression databases, 383 Gene-expression microarrays, 405–407, 406f, 408f Genentech, 395 GenePeeks, 415 Gene-protein correlation, 384–385 General transcription factors, 245, 313–315, 314f Gene-regulatory networks, 429–430, 429f Genetic anticipation, 88, 132 Genetic background, phenotypic expression and, 86 Genetic bottlenecks, 469 Genetic code, 22, 232–240 amino acid assignment in, 236–239, 236t, 237f, 237t, 238f coding dictionary for, 238–239, 238f confirmation of, 239 deciphering of by Grunberg-Manago and Ochoa, 233 by Nirenberg and Matthaei, 233 polynucleotide phosphorylase in, 233, 233f repeating RNA copolymers in, 236–237 RNA heteropolymers in, 234, 235f RNA homopolymers in, 234 triplet binding assay in, 234–236, 236f, 236t in vitro protein-synthesizing system in, 233 degeneracy of, 232, 236, 238 early studies of, 232–233 exceptions to, 239–240, 240t frameshift mutations and, 233, 233f general features of, 232 nonoverlapping, 232 ordered, 239 triplet nature of, 232–233, 233f unambiguous nature of, 232, 236 universality of, 232, 239–240 wobble hypothesis and, 238 Genetic counseling, 119–120 Genetic disorders achondroplasia, 282t, 292, 468 age at onset of, 87–88 albinism, 62–63, 469–470, 470f alkaptonuria, 264 Angelman syndrome, 88, 485 arginosuccinate aciduria, 477 arrhythmogenic right ventricular cardiomyopathy, 409 Beckwith-Wiedemann syndrome, 450, 484 bioengineered therapeutics for, 395–398, 396t Bloom syndrome, 154 cancer, 324–326 See also Cancer carriers of, 84 testing for, 518 cleidocranial dysplasia, 425–426, 426f copy number variants and, 128 cri du chat syndrome, 125, 125f cystic fibrosis, 152, 282t, 464 diagnosis of, 24, 402–408 See also Genetic testing personalized medicine and, 517–520 Diamond-Blackfan syndrome, 271 Down Syndrome 117-104, 130-115 Edwards syndrome, 120 epidermolysis bullosa, 543 epigenetics and, 484–485 expression quantitative trait loci and, 452–453 familial hypercholesterolemia, 63–64, 282t fragile-X syndrome, 132, 132f G6PD deficiency, 107–108 gene mapping for, 152, 370, 371f See also Gene mapping gene therapy for, 411 genetic anticipation in, 88 genetic engineering and, 402–408 See also Medical applications, of genetic engineering and genomics genome sequencing for, 370, 408–409 genomic imprinting in, 88–89, 108, 484–485, 484f, 484t hemophilia, 291, 541 Huntington disease, 63, 74–75, 88, 282t inborn errors of metabolism, 263–264 interrelationships of, 388–389, 390f Klinefelter syndrome, 102–103, 102f, 107 Leber congenital amaurosis, 540–541 Lesch-Nyhan syndrome, 87 lipoprotein lipase deficiency, 542b Marfan syndrome, 82, 275, 282t metachromatic leukodystrophy, 541 microbiome and, 391 model organisms for, 25–26, 26t muscular dystrophy, 84, 87, 88, 250–251, 291, 319 myoclonic epilepsy and ragged-red fiber disease, 91 myotonic dystrophy, 88, 316 newborn screening for, 414 Noonan syndrome, 412 ornithine transcarbamylase deficiency, 539–540 Patau syndrome, 120, 120f paternal age effect and, 105 pattern baldness, 85 porphyria variegata, 82 Prader-Willi syndrome, 88, 485 preconception testing for, 415 Proteus syndrome, 409 Rubenstein-Taybi syndrome, 486 severe combined immunodeficiency, 538–539, 540 sickle-cell anemia, 22, 266–267, 266f, 270, 404 single-gene, 281–282, 282t systems biology model of, 388–389, 390f Tay-Sachs disease, 69, 71, 87 Turner syndrome, 102–103, 102f, 107 in vitro fertilization and, 484–485 Wiskott-Aldrich syndrome, 541 xeroderma pigmentosum, 286, 286f, 327 Genetic diversity See Variation www.ebookslides.com I N D EX I-9 Genetic drift, 469–470, 470f Genetic engineering, 394–416 See also Biotechnology; Recombinant DNA technology definition of, 394 ethical aspects of, 412–415 genetically modified organisms and, 395–400, 522–533 See also under Transgenic medical applications of, 402–408 Genetic information flow, 177, 232, 232f, 241 Genetic Information Nondiscrimination Act, 413 Genetic linkage See Linkage Genetic material definition of, 176 DNA as, 178–184 essential characteristics of, 177 protein as, 177–178 RNA as, 184 Genetic recombination See Recombination Genetic testing, 24, 402–408, 518 allele-specific oligonucleotides in, 404–405, 405f carrier, 518 direct-to-consumer, 413 DNA microarrays in, 405–407 ethical aspects of, 367–368, 412–413, 415–416 gene-expression microarrays in, 405–407, 406f, 408f preconception, 415 predictive, 518 preimplantation, 404–405, 412, 518 prenatal, 119–120, 402–403, 402f, 518 privacy issues and, 412–413, 415–416 RFLP analysis in, 403–404, 404f Genetic Testing Registry, 413 Genetic variation See Variation Genetically modified crops, 23, 398–399, 399f, 400, 451–452, 453, 523–534 approved, 524t controversial aspects of, 531–533 creation of, 528–531 Agrobacterium tumefaciens–mediated transformation in, 528 biolistic method of, 528 selectable markers in, 528–529 definition of, 523 development of, 523 environmental effects of, 531–533 future of, 533–534 gene flow from, 533 herbicide-resistant, 23, 399, 523–524 insect-resistant, 525–526 outcrossing from, 533 overview of, 523–524 papaya, 526b quantitative trait loci in, 451–452, 452f rice, 453, 526–527, 527–528, 528–529 safety of, 531 soybeans, 529 tomatoes, 523, 524 types of, 524t Genetically modified organisms (GMOs), 395–400, 396t, 523 animals, 399–400, 400f, 524 definition of, 394 overview of, 394–395 plants, 23, 398–399, 399f, 400f, 451–452, 453 See also Genetically modified crops Genetically modified plants Bt, 525–526 creation of, 528–531 crop See Genetically modified crops quantitative trait loci in, 451–452 vaccines from, 398 Genetics classical (forward), 24 definition of, 19 developmental, 419–436 evolutionary, 457–458 historical perspective on, 26–27, 26f Mendelian, 47–65 Nobel Prizes for, 27 population, 457–464 reverse, 24 societal impact of, 27 terminology of, 50 timeline for, 26f transmission, 47 Genic balance theory, 110 Genital ridges, 104 Genome(s) copy number variations in, 228–229, 370 definition of, 23, 31, 361 duplication of, 127 epigenetic alterations to, 480–483 eukaryotic, 93, 225–229 gene density in, 377, 378t introns in, 377–378 repetitive sequences in, 378 vs prokaryotic, 377–378, 378t gene density in, 369, 377, 378t haploid, 373 human functional categories for, 369, 369f major features of, 368–369, 368t sequencing of See Human Genome Project interspecies similarities in, 369, 376–383 See also Comparative genomics of model organisms, 378, 378t noncoding regions of, 228, 490 physical maps of, 152 prokaryotic basic features of, 377 gene density in, 377 vs eukaryotic, 377–378, 378t reference, 368 sequencing of See Genome sequencing synthetic, 401, 401f Genome 10K plan, 376 Genome editing, CRISPR/Cas, 357, 493–494, 495b, 542–543 Genome, protein set of, 384–387 See also Proteomics Genome scanning, 407 Genome sequencing, 24, 152, 367–370, 369f See also DNA sequencing for dogs, 93 ethical issues in, 367–368, 412, 414–416 exome, 409 high throughput, 364 for humans See Human Genome Project individual, 408–409 medical applications of, 408–409 for nonhuman organisms, 374–376, 378–381 See also Comparative genomics personalized, 372–373, 518–520, 519b privacy issues and, 412–413, 415–416 single-cell, 409 whole-genome (shotgun), 362–363, 363f whole-genome amplification and, 409 Genome-wide association studies, 409–411 Genomic imprinting, 88–89, 108, 483–485 epigenetics and, 483–485, 484f genetic disorders and, 88–89, 484–485 Genomic libraries, 344 Genomic variation, 370, 459 Genomics, 24, 347 bioinformatics in, 363, 364–366 comparative, 376–383, 378t definition of, 361 DNA sequencing in See DNA sequencing environmental, 381–383 functional, 366–367 Genome 10K plan and, 376 genome sequencing in See Genome sequencing Human Genome Project and See Human Genome Project Human Microbiome Project and, 374–375 medical applications of, 24, 370, 402–408, 513–521 metagenomics, 381–383 overview of, 361–362 paleogenomics, 475–476 personalized medicine and, 372–373, 411, 513–521 See also Personalized medicine privacy issues and, 412–413, 415–416 Stone Age, 376, 380–381, 475–476 structural, 362 techniques in, 361–362 transcriptome analysis and, 383–384 Genomics era, 347 Genotype(s), 20 definition of, 50 expressivity of, 86 penetrance of, 86 phenotypes and, 22, 438–439 See also Heritability Genotype frequency, Hardy-Weinberg law and, 459–464 Genotype-by-environment interaction variance, 445 Genotypic ratios, 71 Genotypic sex determination, 111–112 Genotypic variation, 445 Genotyping microarrays, 407–408 George III (King of England), 82 Germ cells, mutations in, 276 German, James, 154 Germ-line therapy, 545 Germ-line transformation, 291 Germ-line transpositions, 292 Gilbert, Walter, 302, 491 Gleevec (imatinib), 411, 516t Global analysis of gene expression, 383–384 Global Ocean Sampling Expedition, 382, 382f Globin genes, 366–367, 381, 381f GloFish, 400 Glucose-22-pyruvate dehydrogenase (G6PD) deficiency, Lyon hypothesis and, 107–108 Glutamate receptor channels (GluR), 249 Glycocalyx, 29f, 30 Glycomics, 372 Glyphosphate (Roundup), 524–525, 529, 533 GMOs See Genetically modified organisms (GMOs) Goldberg-Hogness box, 244 Golden Rice, 453, 526–527, 529–530 Gonadal ridges, 104 Gonads, bipotential, 104 Gossypium, 123, 123f G-quartets, 210 Gratuitous inducers, 299 Greece, Ancient, 18 Green Revolution, 453 Greider, Carol, 211 Griffith, Frederick, 178–179 gRNA (guide RNA), 249 Growth hormone, genetically engineered, 396 Grunberg-Manago, Marianne, 233 GTP (guanine triphosphate), 187 GTP-dependent release factors, 261 Guanine, 21, 185, 185f, 187 Guanine triphosphate (GTP), 187 Guide RNA (gRNA), 249 Gurdon, John, 27 Gut microbiome, inflammatory bowel disease and, 391 Guthrie, Arlo, 74 Guthrie, Woody, 74 www.ebookslides.com I-10 IN D EX H H substance, 73 Haemophilus influenzae, whole-genome sequencing of, 363, 368 Hairpins, 243 terminator/antiterminator, 306 Half-life, of mRNA, 316–317 Haploid genome, 373 Haploid number, 20, 31, 32t Haploinsufficiency, 117, 275 Haplotypes, 403 Hardy-Weinberg equilibrium, testing for, 462–463 Hardy-Weinberg law, 459–464 in allele frequency calculation, 462–464, 462t, 464t application to humans, 461–464, 462f, 462t calculating allele frequencies and, 460 calculating genotype frequencies and, 459–460 fitness and, 465–466 genetic drift and, 470–471 in heterozygote frequency calculation, 464 migration and, 468 mutation and, 467–468 natural selection and, 464–465, 465–467, 466f predictions of, 460–461 speciation and, 473 underlying assumptions for, 460–461 Harlequin chromosomes, 154, 154f Hartwell, Lee, 37 Harvey, William, 18 Hayes, William, 162–163 HbA, 266 HbS, 266 Heat-shock proteins, 269 Helicases, 204, 207, 207f Helix alpha, 268, 269f double, 21, 21f, 188–189, 188f antiparallel strands in, 205–206 left-handed, 189 unwinding of, 204 Hemizygosity, 83 Hemoglobin, 270, 381, 381f globin genes and, 366–367, 381, 381f one-gene:one-polypeptide hypothesis and, 264–265 sickle-cell, 22, 23f, 266–267, 266f Hemophilia, 291 gene therapy for, 541 Henking, H., 101 Hepatitis B vaccine, 397 HER-18, in breast cancer, 514–515, 515f Herbicide-resistant crops, 23, 399, 523–524 Herceptin (trastuzumab), 514–515, 515f, 516t Hereditary deafness, 76 Hereditary nonpolyposis colorectal cancer, 327 Heredity See also Inheritance organelle, 89 Heritability, 444–448 broad-sense, 446 definition of, 444 narrow-sense, 446, 448t realized, 447 Heritability estimates, 444–448 twin studies and, 448–450 Heritability studies, limitations of, 448 Hershey, Alfred, 181 Hershey-Chase experiment, 180–181, 182f Heterochromatic regions, of Y chromosome, 104 Heterochromatin, 86, 224 Heterochromosomes, 101 Heteroduplexes, 169, 246, 246f Heterogametic sex, 101 Heterogeneous nuclear ribonucleoprotein particles (hnRNPs), 244 Heterogeneous nuclear RNA (hnRNA), 244, 245 Heterogeneous traits, 76 Heterokaryons, 286 Heteromorphic chromosomes, 100 See also Sex chromosomes Heteroplasmy, 89 Heterozygosity, loss of, in cancer, 333 Heterozygote(s), 50 inversion, 128, 129f Heterozygote frequency, calculation of, 464 Heterozygous, 50 Hexosaminidase A (Hex-A), in Tay-Sachs disease, 69, 71 High-frequency recombination (Hfr) bacteria, 163–165, 164f, 165f, 167f Highly repetitive DNA, 226 High-throughput sequencing, 364 Hippocrates, 18 Histone(s), 221, 270 acetylation of, 224 definition of, 221 methylation of, 224 modification of in cancer, 328, 486 in chromatin remodeling, 308–309, 309f, 328 epigenetic changes and, 481–482 See also Epigenetics in nucleosomes, 221–223, 222f phosphorylation of, 224 Histone acetyltransferase (HAT), 224, 309 Histone code, 482 Histone deacetylase inhibitors, for cancer, 486 Histone methyltransferase, 497 Histone tails, 223 Histone-like nucleoid structuring proteins, 216 HIV infection gene therapy for, 542–543 resistance to, 461–462, 462f, 462t vaccine for, 398 hMTIIA gene, 312–313, 313f hnRNA (heterogeneous nuclear RNA), 244, 245 hnRNPs (heterogeneous nuclear ribonucleoprotein particles), 244 H-NS proteins, 216 Hogness, David, 290 Holley, Robert, 256 Holliday, Robin, 481b Holoenzymes in DNA replication, 203–204, 206 in transcription, 241, 243f Homeobox, 426–427 Homeodomains, 427 Homeotic mutations, 426–428, 426f Homeotic selector genes See Hox genes Homo erectus, 476 Homo heidelbergensis, 476–477 Homo neanderthalis divergence from modern humans, 475–476 genome of, 376, 380–381 Homo sapiens See also under Human evolution of, 475–476 Homogametic sex, 101, 276 Homologous chromosomes, 20, 31, 31f, 32f, 32t, 42, 57–58 Homologous genes, identification of, 366–367 Homologous recombination repair, 287, 287f Homozygote, 50 Homozygous, 50 Homunculus, 18, 19f Honeybees, colony collapse order and, 382–383 Horizontal gene transfer, 161 Howard-Flanders, Paul, 285 Howeler, C.J., 88 Hox genes, 423 in Drosophila melanogaster, 426–427, 426f, 427t, 428f, 431–432 in humans, 427–428, 429f in plants, 430–432, 431f, 432f HU proteins, 216 Huebner, Kay, 132–133 Hughes, Walter, 199 Human Epigenome Project, 372, 489 Human evolution, 475–476 Human genome functional categories for, 369 major features of, 368–369, 368t, 369f sequencing of See Human Genome Project Human Genome Nomenclature Committee, 364 Human Genome Project, 24, 152, 367–370 applications of, 370–376, 518–520 ELSI Program and, 367–368, 412, 414–415 future directions for, 370–376 mapping and, 152 “omics” era and, 370–372 origins of, 367–368 sequencing of nonhuman organisms in, 374–376, 378–381 Human immunodeficiency virus infection gene therapy for, 542–543 resistance to, 461–462, 462f, 462t vaccine for, 398 Human metallothionein IIA gene, 312–313, 313f Human Microbiome Project, 374–375, 382–383 Human migration, out-of-Africa hypothesis and, 476–477 Human papillomavirus vaccine, 398 Human Proteome Project, 385 Humulin, 395 Hunchback gene, 424 Hunt, Tim, 37 Huntington disease, 88, 270, 282t pedigree for, 63 Hybrid dysgenesis, 291 Hybridization molecular, 191, 226, 246 in polymerase chain reaction, 347 in probe processing, 345 Hydrogen bonds, in DNA, 189 Hydrophilic bases, 189 Hydrophobic bases, 189 Hypercholesterolemia, familial, 282t pedigree for, 63–64 Hyperchromic shift, 191 Hyperlipidemia, drug therapy for, 17–18 Hypervariable segment I and II, in mtDNA profiling, 507 Hypoallergenic milk, 400 Hypostatic alleles, 76 I Identical twins, 448 See also Twin studies copy number variations in, 449 in pedigrees, 62, 62f Identity values, 364 Ideograms, 370, 371f Imatinib (Gleevec), 411, 516t Immunity adaptive, 493 innate, 492–493 RNA-guided, 492–494 Immunization See Vaccines Immunoglobulins, 270 Imprinting, genomic, 88–89, 108, 483–485 epigenetics and, 483–485, 484f genetic disorders and, 88–89, 484–485 In situ hybridization fluorescent, 192 molecular, 192, 226 In vitro evolution, 491 www.ebookslides.com I N D EX I-11 In vitro fertilization ethical aspects of, 415 genetic testing and, 402–403, 415 imprinting and, 484–485 In vitro protein-synthesizing system, in genetic code cracking, 233 Inactivated vaccines, 397 Inborn errors of metabolism, 263–264 See also Genetic disorders Inbreeding, 470–471 Incomplete dominance, 71, 72f Indels, 379 Independent assortment, 53–55, 57, 58, 137, 137f Induced mutations, 276 Induced pluripotent stem cells, 435 Inducers, 297 gratuitous, 299, 299f Inducible enzymes, 297 Inflammatory bowel disease, gut microbiome and, 391 Information flow, cellular, 177, 177f, 231, 232f, 241 See also Transcription; Translation Information technology See Bioinformatics Ingram, Vernon, 266 Inheritance biparental, 32 chromosomal theory of, 19, 20, 57, 84, 142 codominant, 72 crisscross pattern of, 83–84 dominant, 62–64, 63f, 71, 72f extranuclear, 89–92 heritability and, 444–448 quantitative, 438 recessive, 49–50, 62–499, 63f sex-influenced, 84–85 sex-limited, 84–85 Initiation complex, 259 Initiation factors, in bacterial translation, 259 Initiator codons, 239 Innate immunity, 492–493 Inr element, 311 Insect-resistant crops, 525–526 Insertion sequences, 289, 289f Insertion/deletion editing, 249 Insulin, recombinant human, 395–396 Intellectual property, 413–414, 415 Interactive variance, 446 Interactomes, 389 Intercalary deletions, 124, 125f Intercalating agents, mutagenic, 279, 280f Interchromosomal domains, 308 Interference crossing over and, 150–151 See also Gene editing in gene editing, 493–494 RNA See RNA interference (RNAi) International Cancer Genome Consortium, 489 International HapMap Project, 372 International Human Epigenome Consortium, 489 Internet resources databases See Databases for gene mapping, 155 PubMed, 43 Webcutter, 358 Interphase, 33–35, 33f, 34f electron microscopy of, 42–43, 42f Interrupted mating technique, 163–165, 164f Intersex, 102, 110 Intervening sequences, 246, 246f, 247 Introns, 218, 246f, 247, 247t, 377–378 genomic number and size of, 377–378 splicing of, 247–248, 248f See also Splicing Inversion(s), 124f, 128–129 definition of, 128 evolutionary advantages of, 129 during gamete formation, 128 paracentric, 128, 128f pericentric, 128 Inversion heterozygotes, 128, 129f Inversion loops, 128, 129f Inverted terminal repeats, 289 Ionizing radiation cancer and, 334 as mutagen, 281 IS elements, 289 Isoaccepting tRNA, 259 Isoagglutinogens, 73 Isoelectric focusing, 385 Isopropylthiogalactoside, 299, 299f J J Craig Venter Institute (JCVI), 382, 401, 415 Jackson, Christine, 510b Jacob, Franỗois, 163165, 232, 241, 297, 299–302 Jacobs, Patricia, 103 Janssens, F.A., 140 Jeffreys, Alec, 503, 504b Johnson, Justin Albert, 510b Johnson, Rebecca, 508b Jumping genes, 288–292 See also Transposable elements K Karyokinesis, 33 Karyotypes, 20, 20f, 31 in Klinefelter syndrome, 102–103, 102f spectral, 351–352 in Turner syndrome, 102–103, 102f Kazazian, Haig, 291 Keratin, 270 Khorana, Gobind, 236–237 Kinases, 37 in cancer, 327 in chromatin remodeling, 224 cyclin-dependent, 329 Kinetochore, 35–36, 35f, 226 Kinetochore microtubules, 36 Klinefelter syndrome, 102–103, 102f, 116 Barr bodies in, 107, 107f Klug, Aaron, 222, 257 knirps gene, 424 Knockout, 24, 354–357 conditional, 357 Kornberg, Arthur, 201 Kornberg, Roger, 222 Kozak sequences, 263 Kras gene, 326 Kreitman, Martin, 458 Krüppel gene, 424 Kumra, Raveesh, 511b Kynamro (mipomersen), 250 L L1 family, 227 La Apoyo (Nicaragua), 472, 473f lac genes, constitutive mutants and, 299 lac operon, 298–303 components of, 299, 300f genetic proof of, 299–301 as inducible system, 297–302 operator region of, 299 operon model and, 299–302 regulation of negative, 299–302 positive, 302–303 structural genes in, 298–299, 298f lac repressor, 299 isolation of, 302 Lactose metabolism, 297–303 regulation of, 297–303 See also lac operon lacZ gene, in recombinant human insulin production, 396 Lagging strands, 205f, 206, 206f, 207, 207f Lambda (l) phage, 216, 216f, 217t as cloning vector, 342 Lampbrush chromosomes, 220, 220f Landsteiner, Karl, 72 Lariats, 248f, 249 Laws of probability, 58–59 Leader sequence, in trp operon, 304 Leading strands, 205f, 206, 206f, 207, 207f Leaf variegation, chloroplast-based inheritance in, 89–90, 90f Leber congenital amaurosis, gene therapy for, 540–541 Leder, Philip, 234, 246 Lederberg, Joshua, 161–162, 172, 297, 298 Lederberg-Tatum experiment, 161–162, 161f Lederberg-Zinder experiment, 172–173 Legal issues DNA profiling, 503–512 genetic testing, 412–415 intellectual property and patents, 413–414, 415 LeJeune, Jérôme, 125 Lentivirus vectors, in gene therapy, 537 Lesch-Nyhan syndrome, 87 Lethal alleles dominant, 74–75 recessive, 74, 74f Lethal mutations, 275 Leukemia acute lymphoblastic, 519b chronic myelogenous, 327 Levan, Albert, 102 Levene, Phoebus, 178, 187 Lewis, Edward B., 81, 92, 422 Ley, Timothy, 519b Libraries, DNA, 344–347, 345f, 346f Light, ultraviolet absorption spectrum of, 183, 183f, 281f action spectrum of, 183, 183f, 281f mutations from, 183, 280, 281f, 284, 284f Lincoln, Abraham, 82 LINEs (long interspersed elements), 227, 291 Linkage, 75–76, 136–138 in bacteria, 169 complete, 137, 139f with crossing over, 137–138, 137f transformation and, 169 without crossing over, 137, 137f Linkage groups, 138, 179 Linkage maps, 140–152 See also Maps/mapping Linkage ratio, 138, 139f Lipid-lowering agents, development of, 17–18 Lipoprotein lipase deficiency, gene therapy for, 542b Livestock, transgenic, 23–24, 23f Locus, 32, 57 Long interspersed elements (LINEs), 227, 291 Long noncoding RNA, 482–483, 498–499 Loss of heterozygosity, in cancer, 333 Loss-of-function mutations, 70, 208, 274 Lung cancer, 334, 514b copy number variants and, 128 fragile sites in, 132–133 Lwoff, André, 297 Lygaeus turcicus sex chromosomes in, 101 sex determination in, 101 Lymphoma, Burkitt, 325 Lyon hypothesis, 107–108, 108f Lyon, Mary, 107 Lysogeny, 171–172 Lytic phages, 171–172 M M checkpoint, 328–329 Macaque monkeys, genome of, 378t, 380 www.ebookslides.com I-12 IN D EX MacLeod, Colin, 21, 178, 179–180 Macroevolution, 458 Mad cow disease, 270 MADS-box proteins, 431 Maize selective breeding of, 398–399, 399f transposable elements in, 289–290, 290f Male pattern baldness, 85 Males See under Sex Male-specific region of the Y, 104, 104f Malignant transformation, 326 Mammoths, genome of, 376 Mann, Lynda, 504b Map unit (mu), 141–142 Map Viewer, 370 Maps/mapping bioinformatics and, 152 gene See Gene mapping Internet resources for, 152, 155 network, 389, 390f physical, 152 quantitative trait loci, 450–453, 451f, 452t restriction, 349–350, 358–359 sequence, 152 Marfan syndrome, 82, 175, 282t Marker genes, 529 Mass spectrometry, 386–387, 388f, 389f Mass-to-charge (m/z) ratio, 386 Mastitis-resistant cows, 400 MaTCH database, 449 Maternal effect, 92 Drosophila melanogaster embryonic development and, 92 Maternal parent, 57 Maternal-effect genes, 422–423, 423f MaterniT21 test, 403 Mating negative assortive, 470 nonrandom, allele frequency and, 470–471 positive assortive, 470 Matthaei, J Heinrich, 233 McCarty, Maclyn, 21, 178, 179–180 McClintock, Barbara, 153, 289–290 McClung, Clarence, 101 Mdm2, 317 Mean, 442 Mean value, calculation of, 443–444 Medical applications of genetic engineering and genomics, 24, 370, 402–408, 513–521 See also Personalized medicine allele-specific oligonucleotides, 404–405, 405f microarrays, 407–408 prenatal diagnosis, 402–403 RFLP analysis, 403–404, 404f of genome-wide association studies, 409–411 of Human Genome Project, 370 of model organisms, 25–26, 26t Medicine See also Genetic disorders personalized, 513–521 translational, 17–18, 534 Meiosis, 20, 37–40 chromosome behavior in, 37–40, 38f, 42–43, 42f, 57–58 crossing over in, 37, 38f, 40, 42 electron microscopy of, 42–43, 42f first division in, 37–40, 38f in fungi, 42 gametogenesis in, 40–42 in males vs females, 40–42, 41f oogenesis in, 40, 41f in plants, 42 second division in, 38f–39f, 40 in sexual reproduction, 42 spermatogenesis in, 40–42, 41f vs mitosis, 28 Mello, Craig, 494 Melting profile, 191, 191f Melting temperature, 191 Mendel, Gregor, 19, 20, 26, 47f, 48, 457 experiments of, 48, 49f Mendelian genetics, 47–65 chromosomal theory of inheritance and, 57 crosses in, 48–56 See also Crosses experimental basis of, 48–50, 49f independent assortment in, 53–55, 55–56 notation in, 50 postulates of, 49–50, 53–55, 57 Punnett squares and, 50–51, 51f rediscovery of, 57–58, 457 terminology of, 50 trihybrid crosses in, 55–56, 55f, 57f vs extranuclear inheritance, 89–92 Mendelian ratios 25:19:19:17 dihybrid, 55, 75–76, 75f genotypic, 71 modification of, 69–93 dihybrid, 75–76, 75f phenotypic, 71 Mendel’s Principles of Heredity (Bateson), 264 Merozygotes, 166, 167f, 300 Meselson, Matthew, 198–199 Meselson-Stahl experiment, 198–199, 198f, 199f Messenger RNA See mRNA (messenger RNA) Meta-analysis of Twin Correlations and Heritability (MaTCH), 449 Metabolomics, 372 Metachromatic leukodystrophy, gene therapy for, 541–542 Metafemales, 110 Metagenomics, 372, 381–383 Metalloproteinases, 332 Metamales, 110 Metaphase in meiosis, 38f, 39, 39f, 40 in mitosis, 33f, 34f, 35 Metastasis, 325, 332 Methionine, in transcription, 239 Methylation cytosine, 224 DNA in cancer, 485–486, 485f, 485t epigenetic, 481, 483f in gene regulation, 309–310 in genomic imprinting, 89, 483 in mismatch repair, 283 epigenetic changes and, 481, 481f See also Epigenetics histone, 224 23-Methylguanosine, 245, 263 Methyltransferases, in chromatin remodeling, 224 Mice coat color in, 74, 74f, 78–80 epigenetics and, 487–488, 487f genome of, 378, 378t knockout, 24, 354–357 as model organisms, 25 recessive lethal alleles in, 74, 74f segmentation genes in, 425–426, 426f transgenic, 105 Microarrays DNA, 383–384, 384f, 405–407, 406f gene-expression, 405–408, 406f, 408f genotyping, 405–408 for pathogens, 407–408 protein, 387 Microbial communities, DNA sequencing for, 381–383 Microbiome, inflammatory bowel disease and, 391 Microevolution, 458 MicroRNA (miRNA), 191, 494, 496–497 epigenetic modifications and, 482, 488 primary, 496 Microsatellites, 152, 227 in DNA fingerprinting, 503–504, 505f–507f, 509t Microscopy, electron of chromosomes, 42–43 time-resolved single particle, 262 for transcription, 250 Microtubules, 36 Midas cichlid, speciation and, 472–473, 473f Middle lamella, 36 Middle repetitive DNA, 227–228 Miescher, Friedrich, 177 Migration early human, 476–477 variation from, 468, 469f Milk, hypoallergenic, 400 Minimal medium, 160, 161f Minisatellites, 227 Mintz, Beatrice, 184 Mipomersen (Kynamro), 250 miRNA (microRNA), 191, 494, 496–497 epigenetic modifications and, 482, 488 primary, 496 Mismatch repair, 283 Missense mutations, 274 disease-causing, 282 Mitchell, Hershel, 90 Mitchell, Mary B., 90 Mitochondria, 29f, 30 chromosomes of, 217–218, 218f Mitochondrial DNA (mtDNA), 217–218, 218f, 240 hypervariable segments I and II in, 507 Mitochondrial DNA (mtDNA) profiling, 507, 508b Mitochondrial mutations, 90–92 aging and, 91–92 in human disease, 91–92 in myoclonic epilepsy and ragged-red fiber disease, 91 in yeast, 90 Mitosis, 20, 33–37, 328–329 in anaphase, 33f, 34f, 36 chromosome behavior in, 33–37, 34f, 42–43, 42f electron microscopy of, 42–43, 42f interphase and, 33–35, 33f, 34f metaphase, 33f, 34f, 35 prometaphase, 33f, 34f, 35 prophase, 33f, 34f, 35–36 telophase, 33f, 34f, 36 vs meiosis, 28 MN blood group, 72 Mobile controlling elements, 290 Model organisms, 25–26 See also specific organisms in developmental genetics, 421 genomes of, 378, 378t medical applications of, 25–26, 26t types of, 25 Moderately repetitive DNA, 227 Molecular chaperones, 270 Molecular clocks, 474–475, 475f Molecular hybridization, 191, 226, 246 Monod, Jacques, 232, 241, 297, 299–302 Monogenic diseases, 281–282, 282t Monohybrid crosses, 48–52, 49f, 51f, 52f Monosomes, 255 Monosomy, 116, 116f, 116t, 117 partial, 125 Monozygotic twins, 448 See also Twin studies copy number variations in, 449 in pedigrees, 62, 62f Moore, Keith, 106 Morgan, Thomas H., 27, 74, 82, 126, 140 www.ebookslides.com I N D EX I-13 Mosaics, 103, 107, 108f, 373–374, 449 Motifs, 367 Mouse See Mice mRNA (messenger RNA), 22, 190–191, 232, 499–502 See also RNA comparative size of, 247t half-life of, 316–317 monocistronic, 243 polycistronic, 243 posttranscriptional regulation of, 499–502 pre-mRNA, 244, 248f, 249 splicing of See Splicing stability of, regulation of, 316–317 steady-state level of, 316 translation of See Translation MSH genes, 327 mtDNA (mitochondrial DNA), 217–218, 218f, 240 hypervariable segments I and II in, 507 mtDNA (mitochondrial DNA) profiling, 507, 508b MTE sequence motif, 311 Muller, Herman J., 126, 276 Müller-Hill, Benno, 302 Mullis, Kary, 347 Multifactorial traits, 439 heritability of, 444–448 See also Heritability Multigene families, 381 evolution and function of, 381, 381f Multiple alleles, 72–74 Multiple cloning site, 341 Multiple-gene hypothesis, 439, 439f Multiple-strand exchanges, 150, 151f Mus musculus See Mice Muscular dystrophy, 291, 319 Duchenne, 84, 87 myotonic, 88 Mut genes, in mismatch repair, 283 Mutagens, 279–281 Ames test for, 288, 288f chemical, 279–280, 280f definition of, 279 radiation, 281, 281f Mutants, constitutive, 299 Mutation(s), 22 apoptosis and, 329 in bacteria, 160 behavioral, 275 biochemical, 275 in cancer, 325–326, 485–486 in cell cycle, 37 chloroplast, 89–90, 90f chromosome, 115–133 aneuploidy, 116, 116t, 117 copy number variants and, 127–128 definition of, 115 deletions, 124–125, 124f–126f duplications, 126–128, 127f euploidy, 116, 116t inversions, 128–129 monosomy, 116f, 116t, 117 nondisjunction, 39, 103, 116–117, 116f polyploidy, 116, 117t, 120–123 translocations, 124f, 130–131, 130f trisomy, 116, 117–120, 117t, 118f–120f variations in composition and arrangement, 123–131, 124f variations in number, 116–123, 117t complementation analysis of, 80–82 conditional, 87, 87f, 208, 275 definition of, 20 disease-causing, 281–282 See also Genetic disorders dominant gain-of-function, 275 dominant negative, 275 driver, in cancer, 326 drug metabolism and, 516–517 expressivity of, 86 gene, 273–292 autosomal, 276 base substitution, 274, 274f from chemicals, 279–280, 280f classification of, 274–276, 274f from deamination, 278, 278f definition of, 273 from depurination, 278 frameshift, 233, 233f, 274, 274f gain-of-function, 70, 275 induced, 276, 279–281 from ionizing radiation, 281 loss-of-function, 70, 208, 274 missense, 274, 282 neutral, 70, 275 nonsense, 239, 274, 282 null, 274 nutritional, 275 from oxidative damage, 278–279 point, 274, 274f from replication errors and slippage, 277 silent, 274 somatic, 275–276 spontaneous, 276, 277–279 from tautomeric shifts, 277–278, 277f, 278f from UV light, 183, 280, 281f, 284, 284f visible, 275 X-linked, 276 Y-linked, 276 homeotic, 426–428 lethal, 74–75, 74f, 275 mitochondrial, 90–92 aging and, 91–92 in human disease, 91–92 in myoclonic epilepsy and ragged-red fiber disease, 91 in yeast, 90 ordered genetic code and, 239 passenger, in cancer, 326 paternal age effect, 105 penetrance of, 86 reduction of, 329 regulatory, 275, 299 repair of, 277–289 See also DNA repair temperature-sensitive, 87, 87f, 208, 275 transposable elements and, 291–292 Mutation hot spots, 276 Mutation rate, 276, 325, 467–468 Mutator phenotype, 327 Mycoplasma genitalium genome, synthetic, 401, 401f Myoclonic epilepsy and ragged-red fiber disease, 91 Myoglobin, 269f, 270, 381, 381f Myosin, 270 Myotonia, 316 Myotonic dystrophy, 88, 316 m/z ratio, 386 N Naked DNA, in gene therapy, 538 Narrow-sense heritability, 446, 448t Nathans, Daniel, 338 National Center for Biotechnology Information (NCBI), 154, 364, 412 National Institute of General Medical Sciences (NIGMS), 385 National Institutes of Health (NIH), 385, 412, 489 Natural selection, 19, 457 allele frequency and, 465–467, 466f definition of, 465 detection of, 464–465 directional, 466, 466f disruptive, 467, 467f fitness and, 465–466 principles of, 464–465 stabilizing, 467, 467f types of, 467 Navajo, albinism in, 469–470, 470f Neanderthals divergence from modern humans, 475–476 genome of, 376, 380–381 Neel, James, 266 Negative assortive mating, 470 Negative mutations, dominant, 70, 275 Neisseria meningitidis, gene expression profile for, 408, 408f Nematode worm See Caenorhabditis elegans Neo-Darwinism, 457 Neonatal screening, 414 NER pathway, 285, 285f Network maps, 389, 390f Neurospora crassa one-gene:one-enzyme hypothesis and, 264–265 poky mutations in, 90 Neutral mutations, 70, 275 Newborn screening, 414 Next-generation sequencing technologies, 354, 459 25:19:19:17 dihybrid ratio, 55 modification of, 75–76, 75f 9mers, 204 Nirenberg, Marshall, 233–235 Nisson-Ehle, Hermann, 439–440 Nitrogenous bases See Base(s) Nitrosamines, as carcinogens, 334 Nobel Prizes, 27 Noller, Harry, 262 Nonadditive alleles, 440 Noncoding RNA, 228, 490 long, 482–483, 498–499 small, 317, 492, 494–498 Noncrossover gametes, 137 Nondisjunction, 39, 103, 116–117, 116f Nonhomologous end joining, 287 Noninvasive prenatal genetic diagnosis, 119–120 Nonrandom mating, 470–471 Nonrecombining region of the the Y, 104 Nonsense codons, 261 Nonsense mutations, 239, 274 disease-causing, 282 Nonsister chromatids, 39 Noonan syndrome, 412 Normal distribution, 442, 442f Northern blotting, 350 Notation, for genes, 50 Notch signal system, 432–433, 432t, 433f Nuclear relocation model, 314 Nucleic acid(s), 21 See also DNA; RNA denaturing/renaturing of, 191 Nucleic acid–based drugs, gene silencing by, 250 Nuclein, 177 Nucleoids, 30, 216, 218f Nucleolar organizer region, 126 Nucleolus, 29f, 30 Nucleolus organizer region, 30 Nucleoside diphosphates, 186, 186f Nucleoside monophosphates, 186, 186f Nucleoside triphosphates, 186–187, 186f Nucleosides, structure of, 185f, 186–187, 186f Nucleosomal chromatin, 221–223, 221f, 222f modification of, 221–223, 221f, 222f, 308–309, 309f Nucleosome(s) definition of, 221 structure of, 221–223, 221f, 222f Nucleosome core particles, 222, 222f Nucleotide(s), 21 bonds in, 186, 186f, 187, 187f early studies of, 177–178 structure of, 185f, 186, 186f www.ebookslides.com I-14 IN D EX Nucleotide excision repair, 284–286, 285f in xeroderma pigmentosum, 286, 286f Nucleus, cell, 30 Null alleles, 70 Null hypothesis (H0), 59, 61f Null mutations, 274 Nurse, Paul, 37 Nüsslein-Volhard, Christiane, 92, 422 Nutrigenomics, 372, 407 Nutrition cancer and, 334 epigenetics and, 488 Nutritional mutations, 275 Nutritionally enhanced foods, 399 O Ochoa, Severo, 233 Ohno, Susumo, 106, 127 Okazaki, Reiji, 206 Okazaki, Tuneko, 206 Okazaki fragments, 206, 207, 207f, 209 Oligonucleotides, 187 allele-specific, 404–405, 405f antisense, 250–251 Olins, Ada, 221 Olins, Donald, 221 O’Malley, Bert, 247 Omics era, 370–372 Omics profiling, 521b On the Origin of Species (Darwin), 457 Oncogenes, 330, 330t Oncotype DX, 515–516 One-factor (monohybrid) crosses, 48–52, 49f, 51f, 52f One-gene:one-enzyme hypothesis, 264–265 One-gene:one-polypeptide chain hypothesis, 264–265 One-gene:one-protein hypothesis, 264–265 Online Mendelian Inheritance in Man database, 64–65, 282 Online resources See Internet resources Oocytes, 40, 41f Oogenesis, 40, 41f Oogonium, 40 Ootids, 41, 41f Open reading frames, 366 Operator region, 299 Operon(s), 299–302, 377 lac, 298–303 transcription attenuation in, 305–306 trp, 304 Ordered genetic code, 239 ORFX gene, 452 Organelle heredity, 89 Organelles, 29f, 30 Orgel, Leslie, 490 OriC, 204 Origin of replication, 200 Ornithine transcarbamylase deficiency, 539–540 Orthologs, 366 Outcrossing, from genetically modified crops, 533 Out-of-Africa hypothesis, 476–477 Ova, formation of, 40, 41f Ovalbumin gene, 246f, 247 Ovaries, development of, 104 Overlapping genes, 240 Oxidants, reactive, mutations from, 278–279 P p (proband), 62 p arm, 30 P elements, 291, 291f P (peptidyl) site, 259–260, 262 P1 generation, 48 p53 protein, 317, 331 in cancer, 331 p53 tumor suppressor gene, 331 Paăaăbo, Svante, 380 Pace, Norman, 184 Pair-rule genes, 424, 424t, 425f Paleogenomics, 475–476 Palindromes, 339 Panitumab (Vectibix), 515 Papaya, genetically modified, 526b Paracentric inversions, 128, 128f Paralogs, 367 Pardue, Lou, 226 Parental gametes, 137, 140 Parental (P1) generation, 48 Parental (genomic) imprinting, 88–89, 108, 483–485 epigenetics and, 483–485, 484f genetic disorders and, 88–89, 484–485 Parkinson disease, 270 Partial digests, 362–363 Partial dominance, 71, 72f Partial monosomy, 125 Passenger mutations, in cancer, 326 Pasteur, Louis, 19 Patau syndrome, 120 Patents, 413–414, 415 Paternal age effects, 105 Paternal parent, 57 Pathogens, microarrays for, 407–408 Pattern baldness, 85 Pauling, Linus, 187, 190, 266, 268 PCGEM1, 499 PCR machines, 347 See also Polymerase chain reaction (PCR) PCSK9, cholesterol-lowering drugs and, 17–18 P-DNA, 190 Pedigrees, 62–64 analysis of, 62–64, 63f construction of, 62, 62f Penetrance, 86 Penny, Graeme, 109 Penta-X syndrome, 103 Pentose sugar, in nucleotide, 185 Peptide bonds, 267–268 Peptidyl (P) site, 259–260, 262 Peptidyl transferase, 259–260 Pericentric inversions, 128 Permease, in lac operon, 298, 298f Personal Genome Project, 373 Personal genomics, 372–374 exome sequencing and, 373–374 genome sequencing and, 373 Personalized medicine, 373, 513–521 diagnosis and, 517–520 ethical aspects of, 520–521 genome sequencing and, 518–520, 519b genomics and, 411 omics profiling and, 521b pharmacogenomics and, 513–518 social impact of, 520–521 technical issues in, 520–521 Pest-resistant crops, 23, 399 petite mutations, 90 Phages See Bacteriophage(s) Pharmaceuticals See also under Drug bioreactors for, 396, 400 Pharmacogenomics, 372, 411, 513–518 See also Drug development adverse drug reactions and, 516–517 database for, 517b definition of, 513 rational drug design and, 411 Pharmacogenomics Knowledge Base (PharmGKB), 517b PharmGKB database, 517b Phenotypes, 20 definition of, 50 disease, 22 expression of, 86–88 See also Gene expression gene interaction and, 76–78 genotypes and, 22, 438–439 See also Heritability novel, 80 reciprocal classes of, 146 wild-type, 144 Phenotypic ratios, 71 Phenotypic variation, 444–446 See also Variation components of, 445–446 epigenetics and, 480, 481f genotype-by-environment interaction variance and, 445 heritability and, 444–448 Phenylketonuria (PKU), 380 fX174 bacteriophage, 216, 217t, 240 Philadelphia chromosome, 327, 327f Phosphate group, in nucleotides, 185 Phosphodiester bond, 187, 187f Phosphomannose isomerase, marker, 529 Phosphorylation, histone, 224 Photoreactivation DNA repair, 284, 284f Photoreactivation enzyme, 284, 284f Phylogenetic trees, 473–474, 473f Phylogeny, evolutionary history and, 473–474 Physical maps, 152 Pieau, Claude, 112 Pitchfork, Colin, 504b Piwi-interacting RNA (piRNA), 494 Plants chloroplast-based inheritance in, 89–90, 90f development in, 430–432 extracellular RNA in, 500 genetically modified See Genetically modified crops as model organisms See Arabidopsis thaliana Plaque assays, 170–171, 171f Plasma membrane, 29, 29f Plasmid(s), 162, 167–168 in cloning, 340–342, 341f Col, 168 definition of, 167 F factor, 162, 167–168 R, 166–167, 168f, 289 Ti, 343–344 genetically modified plants and, 528 structure of, 528, 528f Pleiotropy, 82 Pluripotent stem cells, 435 Point mutations, 274, 274f poky mutations, in Neurospora crassa, 90 Pol a, 209 Pol d, 209 Pol e, 209 Pol g, 209 polA 17 mutation, 202, 208 Polar bodies, 40–41, 41f Poly-A tail, 245, 245f, 263 Polyacrylamide gel, in electrophoresis, 192, 192f Polyadenylation, in translation, 263 Polycomb gene, 431 Polygenes, 438 calculation of, 441 Polygenic diseases, 281 Polygenic traits See Quantitative trait(s) Polymerase chain reaction (PCR), 347–349, 348f applications of, 349 in DNA profiling, 505–506, 505f–507f limitations of, 348–349 quantitative real-time, 349 reverse transcription, 349 Polymerase switching, 209 Polynucleotide phosphorylase, in genetic code cracking, 233, 233f www.ebookslides.com I N D EX I-15 Polynucleotides, 187 Polyoma virus, 216 Polypeptides, definition of, 267 Polyploidy, 116, 117t, 120–123 Polyps, colonic, 326, 326f, 333 Polyribosomes (polysomes), 261–262, 261f Polytene chromosomes, 219–220, 219f Population, definition of, 458 Population genetics, 457–464 artificial selection and, 458 genetic drift and, 469–470, 470f Hardy-Weinberg law and, 459–464 inbreeding and, 470–471 migration and, 468, 469f mutation and, 467–468 natural selection and, 465–467, 466f–467f nonrandom mating and, 470–471 overview of, 457–458 speciation and, 457–458, 471–473 Population size, small, inbreeding and, 470–471 Porphyria variegata, 82 Position effects, 86, 224 Positive assortive mating, 470 Postreplication repair, 283, 284f Posttranscriptional modification, 244, 249, 256, 315–317 Posttranslational gene regulation, 317 Postzygotic isolating mechanisms, 472 Prader-Willi syndrome, 94, 485 Preconception testing, 415 Preformation, 18 Preimplantation genetic diagnosis, 404–405, 518 ethical aspects of, 412 Preinitiation complex, 313 formation of, 245, 314f Pre-miRNA, 496 Pre-mRNA, 244 splicing of, 248f, 249 Prenatal diagnosis of genetic disorders, 119–120, 402–403, 518 ethical issues in, 412–413, 415 of sickle-cell anemia, 404 Prezygotic isolating mechanisms, 472 Pribnow box, 242 Primary miRNA, 496 Primary oocytes, 40, 41f Primary sex ratio, 105–106 Primary spermatocytes, 40, 41f Primary structures, 268, 269f Primase, 205, 211 Primates, nonhuman, genomes of, 378t, 379–380 Primer(s) in polymerase chain reaction, 347 in replication, 203, 204, 205, 205f, 207, 207f Prion diseases, 270 Privacy issues, genomics and, 412–413, 415–416 PRNCR1, 499 Probability laws, 53, 58–59 Probability values, 60–66, 61f Proband, 62 Probes, 191 allele-specific oligonucleotides, 404–405, 405f in library screening, 345–347, 346f microarray, 405–407 Processivity, 204, 206, 209 Product law, 53, 58, 144 Product rule, 509 Profile probability, 509, 509t Progressive retinal atrophy, 92–93 Project Jim, 373 Prokaryotes See also Bacteria cell division in, 30, 30f gene regulation in, 297–303 genome of, 377 RNA-guided viral defenses in, 492–494 Prometaphase, 33f, 34f, 35 Promoter(s) core, 244, 310, 311f transcription factors and, 313–315 eukaryotic, 244, 310–311, 310f, 311f prokaryotic, 242, 243f Promoter elements, 310, 310f, 311f proximal, 244, 310 Proofreading, 207, 283 Prophages, 171–172 Prophase in meiosis, 37–39, 38f, 39, 40 in mitosis, 33f, 34f, 35–36 Prosecutor’s fallacy, 510 Proteasomes, 270 Protein(s), 22 amino acids in, 22 See also Amino acid(s) cellular complement of, 384–387 See also Proteomics chaperone, 270 contractile, 270 definition of, 267 enzyme, 22 functions of, 22, 270–271 prediction by sequence analysis, 366–367 fusion, 396 as genetic material, 177–178 heat-shock, 269 misfolded, 269–270 phenotypes and, 22 ribosomal, 255–256 structural, 270 structure of, 22, 267–270, 269f primary, 268, 269f quaternary, 268 secondary, 268, 269f tertiary, 268, 269f, 270 synthesis of, 21–22, 22 See also Translation transport, 270 types of, 22 vs polypeptides, 267 Protein domains, 270–271 structural analysis of, 367 Protein folding, 269–270 Protein kinases See Kinases Protein microarrays, 387 Protein quantitative trait loci, 452 Protein Structure Initiative, 385 Protein-coding genes, number in genome, 369 Protein-gene correlation, 384–385 Protenor, sex determination in, 101 Proteome, 316 definition of, 385 size of, 385 Proteomics, 24, 372, 384–387 definition of, 385 gene-protein correlation and, 384–385 isoelectric focusing in, 385 mass spectrometry in, 386–387, 389f, 398f two-dimensional gel electrophoresis in, 385–386, 386f Proteus syndrome, 409 Proto-oncogenes, 70, 330–332, 330t ras, 330 Protoplasts, 181 Prototrophs, 160, 161f Proximal-promoter elements, 244, 310 Pseudoagouti coat color, 487, 487f Pseudoautosomal regions, 104, 104f Pseudogenes, 228, 379 PubMed, 43 Puffs, 219 Punnett, Reginald, 50, 79 Punnett squares, 50–51, 51f Purines, 185, 185f Pyrimidine dimers, in UV-induced mutagenesis, 280 Pyrimidines, 185, 185f Q q arm, 30 QTL mapping, 450–453, 451f, 452t Quantitative inheritance, 438 multifactorial, 439 multiple-gene hypothesis for, 439, 439f Quantitative real-time polymerase chain reaction, 349 Quantitative trait(s) analysis of, 443–444 heritability of, 444–448 See also Heritability inheritance of See Quantitative inheritance polygenes of, 441 statistical analysis of, 441–444 Quantitative trait loci, 450–453 expression, 452 mapping of, 451–453, 451f, 452t protein, 452 Quaternary structures, 268, 269f Quorum sensing, 318 R R group, in amino acids, 267 R plasmids (factors), 168, 168f, 289 Radiation cancer and, 286, 334 ionizing as carcinogen, 334 as mutagen, 281, 281f ultraviolet absorption spectrum of, 183, 183f, 281f action spectrum of, 183, 183f, 281f mutations from, 183, 280, 281f, 284, 284f Radical group, in amino acids, 267 Ramakrishnan, Venkatraman, 262 Random match probability, 509, 509t ras gene family, in cancer, 330 ras proto-oncogene, 330 Rational drug design, 411 RB1 tumor suppressor gene, 331–332, 331f R-determinants, 168 rDNA (ribosomal DNA), 126, 256 Reactive oxidants, mutations from, 278–279 Reading frames, 233 open, 366 Realized heritability, 447 REBASE, 359 Rec proteins, 166–167 Receptors, 29f, 30 Recessive dystrophic epidermolysis bullosa, gene therapy for, 543 Recessive epistasis, 79 Recessive lethal alleles, 74, 74f Recessive mutations, 275 Recessiveness, 49–50 pedigrees and, 62–64, 63f Reciprocal classes, 146 Reciprocal crosses, 49 Reciprocal translocations, 129–130, 130f Recognition sequences, 339, 339f Recombinant DNA technology, 23–24, 338–359 See also Biotechnology bioinformatics and, 24 cloning in, 340–344 concerns about, 359 DNA as genetic material and, 183–184 DNA libraries in, 344–347, 345f, 346f DNA sequencing in, 192, 192f, 352–354 fluorescent in situ hybridization in, 192, 192f, 350–352 www.ebookslides.com I-16 IN D EX Recombinant DNA technology Continued gene editing in, 357 gene knockout in, 24, 354–357 gene-targeting methods in, 355 genetic engineering and, 394–416 See also Genetic engineering historical perspective on, 23–24 next-generation sequencing technology and, 459 nucleic acid blotting in, 350–352 polymerase chain reaction in, 347–349 proteomics and, 24 restriction enzymes in, 339–340 restriction mapping in, 349–350 transgenic organisms in, 354–358 variation and, 458–459 Recombinant gametes, 137, 140 Recombinant human antithrombin, 396 Recombinant human insulin, 395–396 Recombinase, 292 Recombination, 136, 160–174 in bacteria, 160–174 conjugation in, 161–166 F factor in, 162–166, 163f, 164f, 167–168 high-frequency, 163–165, 164f, 165f, 167f Rec proteins in, 166–167 single-strand displacement in, 167 transduction in, 172–173 transformation in, 168–169 crossing over in, 140 See also Crosses; Crossing over definition of, 160 in eukaryotes, 160 Recruitment model, 314 Red-green color blindness, 108 Reference genomes, 368 Regulatory mutations, 275 Repetitive DNA, 225–228, 225f categories of, 225, 225f genome size and, 378 highly repetitive, 226 middle, 227 satellite DNA and, 225–226 Repetitive transposable sequences, 227 Replication, 196–213 accuracy of, 202, 207 autoradiographic analysis of, 199–200, 200f in bacteria, 201–207, 201f, 208t chain elongation in, 201, 202f chromatin in, 209 coherent model of, 207–208, 207f concurrent, 206–207, 206f conservative, 197 continuous, 205–206 direction of, 191f, 200–201, 202, 202f discontinuous, 205–206 dispersive, 197–198 DNA gyrase in, 204–205, 207, 207f DNA polymerases in See also DNA polymerase(s) in bacteria, 201–207, 202f, 203t, 206f, 207f in eukaryotes, 209 errors in correction of, 207 mutations from, 277–279 in eukaryotes, 199–200, 208–212 helicases in, 204, 207, 207f helix unwinding in, 204–205 initiation of in bacteria, 205 in eukaryotes, 208–209 during interphase, 33–35, 33f leading and lagging strands in, 205f, 206, 206f, 207, 207f Meselson-Stahl experiment and, 198–199, 198f, 199f Okazaki fragments in in bacteria, 206, 207, 207f in eukaryotes, 209 polymerase switching in, 209 primers in, 203, 204, 205, 205f, 207, 207f processivity in, 206 proofreading in, 207, 283 regulation of in bacteria, 207 in eukaryotes, 208–209 semiconservative, 189, 197–201, 197f semidiscontinuous, 206n single-stranded binding proteins in, 204, 207, 207f sliding DNA clamp in, 203, 206–207, 206f, 207f, 208 steps in, 204, 207–208, 207f Taylor-Woods-Hughes experiment and, 199–200, 200f at telomeres, 210–213, 210f, 211f units of, 200–201 Replication bubbles, 208–209 Replication forks in bacteria, 200, 204, 205 in eukaryotes, 208–209, 209f from replication bubbles, 208–209 Replication origins, 200 in bacteria, 204 in eukaryotes, 208–209 Replication slippage, 277 Replicon, 200 Replisomes, 205 Repression, catabolite, 302–303 Repressor(s), 245, 312, 313–314, 314 allosteric, 299 corepressors and, 299 lac, 299–302, 300f, 303f trp, 304, 305f Repressor genes, 299 Repressor molecules, 299 Reproduction, sexual, meiosis in, 42 Reproductive isolation, 472 Reptiles, sex determination in, 111–112, 112f Resistance transfer factor, 168 Restriction endonucleases, 23 Restriction Enzyme Database, 359 Restriction enzymes, 339–340 Restriction fragment length polymorphisms (RFLPs), 152, 403–404, 404f Restriction mapping, 152, 349–350, 358–359 Restriction sites, 339, 339f Retinal blindness, gene therapy for, 540–541 Retinoblastoma, 331–332 Retrotransposons, 227 Retroviral vectors, in gene therapy, 536 Retroviruses, 184 cancer and, 333t Reverse genetics, 24 Reverse transcriptase, 184, 227 in cDNA library construction, 345f Reverse transcription, 184, 211 Reverse transcription polymerase chain reaction, 349 RFLP analysis, 403–404, 404f Rhesus monkeys, genome of, 378t, 380 Rhizobium radiobacter, 343 r (rho) termination factor, 243 Ribonuclease, 180 Ribonucleic acid See RNA Ribonucleoprotein, 211, 502 Ribose, 185f Ribosomal DNA (rDNA), 126, 256 Ribosomal proteins, 255–256 Ribosomal RNA (rRNA), 126, 190, 255–256, 255f Ribosomes, 22, 29f, 30, 190 A site on, 259, 262 E site on, 259, 262 P site on, 259–260, 262 prokaryotic, 261–262, 261f structure of, 261–262, 261f vs eukaryotic, 255–256, 255f structure of, 255–2406 in translation, 255–256, 255f Riboswitches, 306–307, 307f Ribozymes, 247, 260, 491–492 genetic engineering of, 491–492, 491f origin of life and, 490–491 structure of, 491f Rice genetically modified, 453, 526–527, 529–530 selective breeding of, 453, 527–528 Rich, Alexander, 190, 257 Richmond, Timothy, 223 Rituximab, 516t RNA, 21–22 analytic techniques for, 191–192 antisense, 191 catalytic activity of, 490–492 CRISPR-derived, 357, 493–494, 495b, 542–543 denaturing/renaturing of, 191 diversity of, 490 electrophoresis of, 192 emerging roles of, 490–502 extracellular, in signaling, 500 as genetic material, 184 heterogeneous nuclear, 244, 245 messenger See mRNA (messenger RNA) micro, 191, 494, 496–497 epigenetic modifications and, 482, 488 primary, 496 noncoding, 490 long, 482–483, 498–499 small, 317, 492, 494–498 origins of life and, 490–491 posttranscriptional modification of, 244, 249, 256 posttranslational modification of, 317 ribosomal, 126, 190, 255–256, 255f sense, 250 small interfering, 191, 494–496, 543 small nuclear, 191, 490 splicing of See Splicing structure of, 185, 185f, 190, 490 synthesis of See Transcription telomerase, 191 transfer See tRNA (transfer RNA) RNA editing, 249 RNA heteropolymers, in genetic code cracking, 234, 235f RNA homopolymers, in genetic code cracking, 234 RNA interference (RNAi) in gene regulation, 317 siRNA and, 494–496 therapeutic applications of, 250, 317, 543–544 RNA polymerase, 241–243 RNA-directed, 497 vs DNA polymerase, 241 RNA polymerase II, 244 transcription factors and, 313–315 RNA primers, in replication, 204, 205, 205f, 207, 207f RNA sequencing, 383 RNA transcripts, posttranscriptional modification of, 245–246, 249, 256 RNA World hypothesis, 491 RNA-binding proteins, 501 RNA-directed RNA polymerase, 497 RNA-guided viral defenses, in prokaryotes, 492–494 RNAi See RNA interference (RNAi) RNA-induced gene silencing, 317, 482, 494, 497–498 RNA-induced silencing complex (RISC), 482, 543 www.ebookslides.com I N D EX I-17 RNA-induced transcriptional silencing (RITS) complex, 482, 497–498 Roadmap Epigenomics Project, 489 Roberts, J., 257 Roberts, Richard, 246 Robertsonian translocation, 130–131 Rough colonies, 178 Rough endoplasmic reticulum, 29f, 30 Roundup, 524–525, 529, 533 RPE65 gene, 541 rRNA (ribosomal RNA), 126, 190, 255–256, 255f Rubenstein-Taybi syndrome, 486 Rubin, Gerald, 290 runt gene, 425–426 Russell, Liane, 107 S S phase, 33–35, 33f Saccharomyces cerevisiae, 25, 25f, 26t genome of, 378, 378t petite mutations in, 90 Salmon, genetically modified, 525b, 533–534 Sanger sequencing, 352–354, 373f SARS (severe combined acute respiratory syndrome), genotyping of, 407, 408f Satellite DNA, 225–226, 225f Schleiden, Matthias, 18 Schwann, Theodor, 18 Scrapie, 270 Screening blue-white, 341, 343f for breast cancer, 334–335 neonatal, 414 SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis), 385–386 Sea urchin, genome of, 378–379, 378t Second filial (F2) generation, 48 Second polar body, 41, 41f Secondary oocytes, 41, 41f Secondary sex ratio, 105–106 Secondary spermatocytes, 40, 41f Secondary structures, 268, 269f Sedimentation equilibrium centrifugation, 198 Segment polarity genes, 424–425, 424f, 424t, 425f, 425t, 426f Segmental deletions, 125 Segmentation genes, 423–428, 424t in Drosophila melanogaster, 424–425, 424t, 425f in humans, 425–426 in mice, 425–426, 426f Segregation, 50, 57 Selectable marker genes, 340 Selection differential, 447 Selection response, 447 Selective breeding, 92–93, 398–399, 399f, 446–448, 453, 458 Selfing, 48 Self-splicing, 247–248, 248f Semiconservative replication, 189, 197–201, 197f Semidiscontinuous replication, 206n Semisterility, 130 Sense RNA, 250 Separase, 35 Sequence maps, 152 Sequencing methods DNA See DNA sequencing RNA, 383 Serial dilution technique, 160, 160f Serotypes, 178 Severe combined acute respiratory syndrome (SARS), genotyping of, 407, 408f Severe combined immunodeficiency, gene therapy for, 538–539, 540 Sex chromatin bodies, 106–107, 107f Sex chromosomes, 32, 100, 101–111 early studies of, 101 sex determination and, 101–105 Sex determination, 100–112 See also Sexual differentiation in Caenorhabditis elegans, 110–111 chromosomal, 111–112 in Drosophila melanogaster, 109–110, 110f genotypic, 111–112 overview of, 100–101 in reptiles, 111–112, 112f sex chromosomes and, 101–105 steroids in, 112 temperature-dependent, 111–112, 112f XX/XO (Protenor) mode of, 101 XX/XY (Lygaeus) mode of, 101 ZZ/ZW mode of, 101 Sex differentiation, steroids in, 112 Sex pilus, 162 Sex ratios, 105–106 Sex selection, 415 Sex-determining chromosomes, 32 See also X chromosome; Y chromosome Sex-determining region Y, 104, 104f, 105 Sex-influenced inheritance, 84–85 Sex-lethal gene, 110 Sex-limited inheritance, 84–85 Sexual differentiation, 100 See also Sex determination in Caenorhabditis elegans, 110–111, 111f in humans, 103–104 Sexual reproduction, meiosis in, 42 Sharp, Philip, 246 Sheep, cloned, 23–24, 23f Shine-Dalgarno sequences, 259, 263 Short (small) interfering RNA (siRNA), 191, 494–496, 543 Short interspersed elements (SINEs), 227, 291–292 Short tandem repeats (STRs), 227 in DNA profiling, 505–506, 505f–507f, 509t Shotgun sequencing, 362–363, 363f medical applications of, 408–409 Shugoshin, 35, 35f Sibs, in pedigrees, 62 Sibship line, 62 Sickle-cell anemia, 22, 22f, 23f, 266–267, 266f, 270 prenatal diagnosis of, 404 RFLP analysis of, 404, 404f Sickle-cell trait, 266 s (sigma) subunit, in transcription, 241–242, 243f Signal transduction in Caenorhabditis elegans development, 432–433, 432t, 433f, 434f in cell cycle, 328 extracellular RNA in, 500b Silencers, 244–245, 311, 314 Silent mutations, 274 Similarity scores, 364 SINEs (short interspersed elements), 227, 291–292 Single crossovers, 142–143, 142f, 143f, 146 Single crystal X-ray analysis, 190 Single-cell genome sequencing, 409 Single-gene disorders, 281–282, 282t Single-nucleotide polymorphisms (SNPs), 367, 370 detection of, 404 in DNA profiling, 507–508, 508f in mapping, 152 Single-strand displacement, 167 Single-stranded binding proteins, 204, 207, 207f siRNA (small interfering RNA), 191, 494–496, 543 Sister chromatids, 31 in meiosis, 37–40, 38f–39f in mitosis, 35, 35f, 154, 154f Sliding DNA clamp, 203, 204f, 206–207, 206f, 207, 207f Sliding DNA clamp loader, 203, 204f Small (short) interfering RNA (siRNA), 191, 494–496, 544 Small noncoding RNA (sncRNA), 317 in eukaryotes, 494–498 in prokaryotes, 492 Small nuclear RNA (snRNA), 191, 490 Smith, Courtney, 510b Smith, Hamilton, 338 Smithies, Mario, 355 Smoking, cancer and, 334 Smooth colonies, 178 Smooth endoplasmic reticulum, 29f, 30 Snapping shrimp, speciation and, 472, 472f sncRNA (small noncoding RNA), 317, 492, 494–498 snRNA (small nuclear RNA), 191, 490 Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), 385–386 Solenoids, 222f, 223 Somatic cell hybridization, 286 Somatic gene therapy, 545 Somatic mosaicism, 449 Somatic mutations, 275–276 Sorcerer II Global Ocean Sampling Expedition, 382, 382f SOS repair system, 284 Sotir, Beverly, 514b Southern blotting, 350, 351f Soybeans, genetically modified, 529 Speciation, 457–458, 471–473 barriers to, 472 changes leading to, 472, 472f phylogenetic trees and, 473–474 rate of, 472–473 Species, definition of, 471 Specification, in development, 419, 426–428 Spectral karyotypes, 351–352 Sperm, 40, 41f Spermatids, 40, 41f Spermatocytes, 40, 41f Spermatogenesis, 40–42, 41f Spermatogonium, 40, 41f Spermatozoa, 40, 41f Spermiogenesis, 40 Spheroplasts, 181 Spiegelman, Sol, 184 Spindle fibers, 30, 35, 35f, 36 Spliceopathies, 316 Spliceosomes, 248–249, 248f Splicing, 247–249 alternative, 249, 369 in gene regulation, 315–316, 315f, 316f mutations affecting, 316 in sex determination, 110 cotranscriptional, 245f definition of, 110 self-splicing in, 247–248, 248f in sex determination, 110 transesterification reactions in, 247, 248f Splicing mutations, disease-causing, 282 Split genes, 244, 246 Spontaneous mutations, 276 Spores, 28 Sporophyte stage, 42 Sports, gene doping in, 546b Stabilizing selection, 467, 467f Stahl, Franklin, 198–199 Standard deviation, 442–443, 442t Standard error of the mean, 443 Statistical analysis, 441–444 Stem cell(s), 435–436 cancer and, 325 in knockout technology, 356–357 www.ebookslides.com I-18 IN D EX Stem cell hypothesis, for cancer, 325 Stern, Curt, 153 Steroids, in sex differentiation, 112 Stone Age genomics, 376, 380–381, 475–476 Stop (termination) codons, 237, 239, 261 STR DNA profiling, 505–506, 509t Streptococcus pneumoniae, transformation in, 178–180, 178t Stress, epigenetic changes and, 488 Structural genes, in lac operon, 298–299, 298f Structural genomics, 362 Sturtevant, Alfred H., 110, 126, 140–142 Substitution editing, 249 Subunit vaccines, 397 Sum law, 58 Sunitinib (Sutent), 519b Supercoiling, 204 Superfamilies, 381 evolution and function of, 381f Sutton, Walter, 20, 57, 136 SV40 virus, 240 Svedberg coefficient, 190, 255 Swanson, Robert, 395 SWI/SNF complex, 309, 309f Sxl gene, 110 Synapsis, 38 translocations and, 129–130 Synpolydactyly, 428, 429f Synthetic biology, 402 legal aspects of, 413–414, 415 Synthetic genomes, 401, 401f Systems biology, 388–389, 390f T t 17/18, of mRNA, 316–317 TAFs (TBP associated factors), 313 TALENS (transcription activator-like effector nucleases), in gene therapy, 543 Tanksley, Steven, 452 Taq polymerase, 347 Tarceva (erlotinib), 516t TATA box, 242, 244, 311, 312f TATA-binding protein, 313 Tatum, Edward, 161–162, 264–265, 385 Tautomer, 277 Tautomeric shifts, 277–278, 277f, 278f Taylor, J Herbert, 199 Taylor-Woods-Hughes experiment, 199–200, 200f Tay-Sachs disease, 69, 71, 87 TBP (TATA-binding protein), 313 TBP associated factors (TAFs), 313 T-DNA (transfer DNA), in genetically modified plants, 528–529 Telomerase, 211–212, 211f Telomerase RNA, 191 Telomere(s) aging and, 212–213 definition of, 210 replication at, 210–212, 210f, 211f structure of, 210 Telophase in meiosis, 38f, 39f, 40 in mitosis, 33f, 34f, 36 Temperate phages, 172 Temperature melting, 191 in phenotypic expression, 87, 87f Temperature-dependent sex determination, 111–112, 112f Temperature-sensitive mutations, 87, 87f, 208, 275 Terminal deletions, 124, 125f Termination codons, 237, 239, 261 Terminator hairpins, 306 Tertiary structures, 268, 269f, 270 Testcrosses, one-character, 52, 52f Testis, development of, 104–105 Testis-determining factor, 105 Tetrads, 38, 38f Tetrahymena, telomerase in, 211, 212 Tetranucleotide hypothesis, 178, 187 Tetraploidy, 116, 117t, 121 Tetra-X syndrome, 103 T-even phages, 169, 170f TFIIA, 245 TFIIB, 245 TFIID, 245 Thalassemia, gene therapy for, 541 Thermocyclers, 347 13mers, 204 19’ poly-A tail, 245, 245f, 263 Three-factor (trihybrid) crosses, 55–56, 55f, 57f Thymine, 185, 185f, 187 Ti plasmid, 343–344 genetically modified plants and, 528 structure of, 528, 528f Tijo, Joe Hin, 102 Time-resolved single particle cryo-electron microscopy (cryo-EM), 262 Tissue inhibitors of metalloproteinases (TIMPs), 332 T-loops, 210 Tn elements, 289 Tobacco mosaic virus, 184 Tomatoes genetically modified, 523, 524 selective breeding of, 451–452 Topoisomerases, DNA, 204–205 Totipotent stem cells, 435 Toxicogenomics, 372 Traits complex, 439 definition of, 48 dominant, 49–50, 62–64, 63f, 71, 72, 72f epigenetic, 480 heterogeneous, 76 in Mendel’s experiments, 48, 49–50, 49f multifactorial, 439 polygenic, 438 recessive, 49–50, 62–64, 63f X-linked, 82–84, 83f, 84f Transacetylase, in lac operon, 298, 298f trans-acting factors, 242, 244 trans-acting molecules, 297 Transcription, 21, 21f, 177, 241–250 alpha subunit in, 242, 243f attenuation of, 304, 305–306 chain elongation in, 242–243 consensus sequences in, 242 definition of, 241 early studies of, 241 electron microscopy in, 250 in eukaryotes, 243–249 activators in, 312, 314 enhancers in, 311 initiation of, 244–245, 313–314, 314f pre-initiation complex in, 313, 314f promoters in, 244, 310–311, 310f, 311f regulation of, 312–317 See also Gene regulation, in eukaryotes repressors in, 312, 314 silencers in, 311 transcription factors in, 312–315 introns in, 246f, 247, 247t nuclear relocation model for, 314 partner strand in, 242, 243f pre-initiation complex in, 313, 314f in prokaryotes, 241–243, 242–243, 243f initiation of, 239, 242 promoters in, 242, 243f regulation of, 297–303 See also Gene regulation, in prokaryotes repressors in, 245, 299–302, 304 recruitment model for, 314 reverse, 184, 211 ribonucleotide addition in, 241, 243f RNA polymerases in in eukaryotes, 244 in prokaryotes, 241–243 sigma subunit in, 241–242, 243f start site in, 242 template binding in, 242, 243f template strand in, 242, 243f termination of, 239, 243, 304–306 attenuation and, 304, 305–306 transcript processing in, 244 Transcription activator-like effector nucleases, in gene therapy, 543 Transcription factors, 105, 244, 245, 270 general, 245, 313–315, 314f p53 as, 317 Transcription factory, 308 Transcriptional activators, 245, 312, 314 Transcriptional repressors, 245, 299–302, 304, 312, 313–314 See also Repressor(s) Transcriptional silencing, RNA-induced, 317, 482, 497–498 Transcriptome analysis, 383–384 of pathogens, 408 Transcriptomics, 372, 383–384 Transduction, 172–173 cotransduction and, 173 in Lederberg-Zinder experiment, 172–173, 172f steps in, 172, 172f Transesterification reactions, in splicing, 247, 248f Transfection, 181–182 Transfer DNA (T-DNA), in genetically modified plants, 528–529 Transfer RNA See tRNA (transfer RNA) Transformation in Alloway’s experiment, 179–180 in Avery-Collins-McCarty experiment, 179–180, 180f in bacteria, 168–169, 178–180, 180f, 341–342 in Dawson’s experiment, 179–180, 180 definition of, 179 in Griffith’s experiment, 178–179 transformer gene, 110 Transforming principle, 179 Transgenic animals, 23–24, 105, 184, 357–358, 399–400, 400f, 522 as bioreactors, 396, 397, 400 creation of, 357–358 examples of, 105 as food, 525, 533–534 mice, 105 as recombinant protein hosts, 396 Transgenic plants, 23, 398–399, 399f, 453, 522–533 See also Genetically modified crops quantitative trait loci in, 451–452, 452f vaccines from, 398 Transitions, 274 Translation, 21f, 22, 177, 254–264 chain elongation in in eukaryotes, 263 in prokaryotes, 258t, 259–260, 260f definition of, 255 in eukaryotes, 263 initiation of, 239 in eukaryotes, 263 in prokaryotes, 258t, 259, 259f mRNA stability and, 316–317 polyribosomes in, 261–262, 261f in prokaryotes, 258–262 www.ebookslides.com I N D EX I-19 vs in eukaryotes, 263 protein factors in, 258t, 259 regulation of, 317 ribosomes in, 255–256, 255f, 261–262, 261f termination of, 239 in eukaryotes, 263 in prokaryotes, 258t, 261 triplet code in, 232–240 See also Genetic code Translational medicine, 17–18, 535 See also Gene therapy Translocation, in translation, 260 Translocations, chromosomal, 124f, 129–131, 130f in familial Down syndrome, 130–131, 130f Robertsonian, 130–131 Transmission genetics, 47 See also Mendelian genetics Transplantation, fecal microbial, 391 Transport proteins, 270 Transposable elements, 288–292 Ac-Ds system, 289–290, 290f bacterial, 289 Copia, 290–291, 291f in Drosophila melanogaster, 290–291, 291f in evolution, 292 in humans, 227, 291–292 IS, 289, 289f long interspersed elements (LINEs), 227, 291 mutations and, 291–292 P, 291, 291f research applications of, 292 short interspersed elements (SINEs), 227, 291–292 Tn, 289 Transposable sequences, repetitive, 227 Transposase, 289 Transpositions See also Transposable elements germ-line, 292 Transposons See Transposable elements Transversions, 274 Trastuzumab (Herceptin), 514–515, 515f, 516t Trihybrid crosses, 55–56, 55f, 57f Trinucleotide repeats, 132 in single-gene disorders, 282 Tripeptides, 268 Triplet binding assay, 234–236, 236f, 236t Triploidy, 116, 117t Triplo-X syndrome, 103 Trisomy, 116, 117–120, 117t, 118f–120f in Edwards syndrome, 120 in Patau syndrome, 120, 120f Trisomy 37 (Down syndrome), 117–120, 118f, 119f familial, 130–131, 130f paternal age effect and, 105 Triticale, 123 Triticum, 123 tRNA (transfer RNA), 22, 190, 255 charging, 257–258, 258f cloverleaf model of, 256, 257f functions of, 255 isoaccepting, 258 splicing of, 247 structure of, 256–257 in translation, 256–257, 257f, 258f trp operon, 304 in attenuation, 304 components of, 304, 305f leader sequence in, 304 True single-molecule sequencing, 519b Tryptophan synthase, 304 Tschermak, Erich, 19, 57 Tubulin, 270 Tumor(s) benign, 325 malignant, 325 See also Cancer Tumor suppressor genes, 330–332, 330t, 331f Tumorigenesis, 325 Turner syndrome, 102–103, 102f, 116 Barr bodies in, 107, 107f 23andMe, 415 Twin(s) concordant, 448 discordant, 448 dizygotic (fraternal), 448, 454 epigenetic changes in, 450 monozygotic (identical), 448 copy number variations in, 449 Twin studies, 448–450 large scale analysis of, 449 limitations of, 449–450 Two-dimensional gel electrophoresis (2DGE), 385–386, 386f, 388f Two-factor (dihybrid) crosses, 52–55, 53f, 54f modified, 75–76 Tyrosine, 21 U Ubiquitin, 270, 317 Ultraviolet light absorption spectrum of, 183, 183f, 281f action spectrum of, 183, 183f, 281f mutations from, 183, 280, 281f repair of, 284, 284f Unidirectional replication, 200–201 Unit factors, 49, 50, 57, 264 U.S Food and Drug Administration (FDA), 395 Unscheduled DNA synthesis, 286 Uracil, 185, 185f V Vaccines attenuated, 397 DNA-based, 398 Ebola, 398 hepatitis B, 397 HIV, 398 human papillomavirus, 398 inactivated, 397 subunit, 397 from transgenic plants, 398 Variable gene activity hypothesis, 420 Variable number tandem repeats, 227 in DNA fingerprinting, 503–504, 505f–507f Variance, 442, 442f additive, 446 dominance, 446 environmental, 445 genotype-by-environment interaction, 445 genotypic, 445 interactive, 446 phenotypic, 444–446 Variation continuous, additive alleles and, 440 copy number, 127–128, 228–229, 370 in twins, 449 detection by artificial selection, 458 discontinuous, 77 environmental, 445 epigenetics and, 480, 481f founder effect and, 469, 470f gene duplication and, 127 genetic drift and, 469–470 genomic, 370, 459 genotypic, 445 Hardy-Weinberg law and, 459–464 heritability and, 444–448 from independent assortment, 58 from meiosis, 42 from migration, 468, 469f from mutation, 467–468 See also Mutation(s) phenotypic, 444–446 from protein structure, 267–270 single-nucleotide polymorphisms and, 370 sources of, 177, 370, 458 Vascular endothelial growth factor, 119 Vectibix (panitumab), 515 Vectors, 23 cloning, 23, 339, 340–344 bacterial artificial chromosome, 343 bacterial plasmid, 340–342, 341f expression, 343 viral, in gene therapy, 536–538, 540–541 Venter, J Craig, 363, 368, 373, 382, 401, 415 Vertical gene transfer, 161 Vicia faba, 199, 200f Vidaza (decitabine), 486 Virulent phages, 172 Virulent strains, 178 Viruses bacterial See Bacteriophage(s) cancer and, 333, 333t chromosomes of, 216, 216f as gene therapy vectors, 536–538, 540–541 RNA as genetic material in, 184 RNA-guided defenses against, in prokaryotes, 492–494 Visible mutations, 275 Vitamin A deficiency, Golden Rice and, 527–528 Vitravene (fomivirsen), 250 VNTR-based DNA fingerprinting, 503–504, 505f–507f Volker, Nicholas, 409 W Waddington, C.H., 481b Wallace, Alfred Russel, 19, 57, 457, 464 Wang, Andrew, 190 Warfarin (Coumadin), 516–517 Wartman, Lukas, 519b Watson, James, 21, 26, 184, 185, 196, 197 genome sequencing for, 373 Human Genome Project and, 367 Watson-Crick model, 188–189, 188f Webcutter, 358 Weiss, Samuel, 241 Western blotting, 350 white locus, 73–74 Whole-genome amplification, 409 Whole-genome sequencing, 362–363, 363f ethical aspects of, 414–415 medical applications of, 408–409 See also Genome sequencing Whole-genome shotgun cloning, 344 Whole-genome transcriptome analysis, of pathogens, 408 Wieschaus, Eric, 92, 422 Wildlife smuggling, 508b Wild-type alleles, 70 Wild-type phenotype, 144 Wilkins, Maurice, 21, 26 Wilson, Edmund B., 101 Wiskott-Aldrich syndrome, gene therapy for, 541–542 Wobble hypothesis, 238, 262 Woese, Carl, 490 Wollman, Ellie, 163–165 Wood, William, 170 Woods, Philip, 199 Woolly mammoths, genome of, 376 Wright, Sewall, 470 www.ebookslides.com I-20 IN D EX X X chromosome, 32 dosage compensation and, 106–109 early studies of, 101 inactivation of, 107–109, 481 in sex determination, 101, 101f in Drosophila melanogaster, 109–110, 110f X inactivation center (Xic), 109 X rays cancer and, 334 as mutagens, 281, 281f Xenopus laevis, rDNA in, 126 Xeroderma pigmentosum, 286, 286f, 327 Xic (X inactivation center), 109 X-inactive specific transcript (XIST), 109 Xist gene, 109 X-linkage, 82–84 definition of, 82 dosage compensation and, 106–109 in Drosophila melanogaster, 82–83, 83f in humans, 84, 84f X-linked inhibitor of apoptosis, 409 X-linked mutations, 276 X-ray diffraction analysis, 186f, 187–188 XX/XO (Protenor) mode, of sex determination, 101 XX/XY (Lygaeus) mode, of sex determination, 101 Y Y chromosome, 32, 101 early studies of, 101 euchromatic regions of, 104 heterochromatic regions of, 104 in Klinefelter syndrome, 102–103, 102f in male development, 104–105 male-specific region of, 104, 104f pseudoautosomal regions of, 104, 104f in sex determination, 101–105, 101f sex-determining region of, 104, 104f, 105 in Turner syndrome, 102–103, 102f Y chromosome STR profiling, 506 Yamanaka, Shinya, 27 Yanofsky, Charles, 305 Yeast See also Saccharomyces cerevisiae autonomously replicating sequences in, 209 mitochondrial mutations in, 90 as recombinant protein host, 396 Yeast artificial chromosomes, 343 Y-linked mutations, 276 Young, Michael, 290 Yule, G Udny, 439 Z Z-DNA, 190 Zea mays selective breeding of, 398–399, 399f transposable elements in, 289–290, 290f Zinc-finger nucleases, in gene therapy, 542–543 Zinder, Norton, 172–173 Zip code, 501 Zip code banding protein 17, 501 ZNF9 gene, 316 Zolinza, 486 Zygote, 33 Zygotic genes, 422–426, 423f, 424t ZZ/ZW mode, of sex determination, 101 www.ebookslides.com EVOLVING CONCEPT OF A GENE The Evolving Concept of the Gene is a new feature, integrated in key chapters, that highlights how scientists’ understanding of the gene has changed over time By underscoring how the conceptualization of the gene has evolved, our goal is to help students appreciate the process of discovery that has led to an ever more sophisticated understanding of hereditary information CHAPTER pg 58 Based on the pioneering work of Gregor Mendel, we can view the gene as a heritable unit factor that determines the expression of an observable trait, or phenotype CHAPTER pg 74 Based on the work of many geneticists following the rediscovery of Mendel’s work in the very early part of the twentieth century, the chromosome theory of inheritance was put forward, which hypothesized that chromosomes are the carriers of genes and that meiosis is the physical basis of Mendel’s postulates In the ensuing 40 years, the concept of a gene evolved to reflect that this hereditary unit can exist in multiple forms, or alleles, each of which can impact on the phenotype in different ways, leading to incomplete dominance, codominance, and even lethality It became clear that the process of mutation was the source of new alleles CHAPTER pg 152 Based on the gene-mapping studies in Drosophila and many other organisms from the 1920s through the mid-1950s, geneticists regarded genes as hereditary units organized in a specific sequence along chromosomes, between which recombination could occur Genes were thus viewed as indivisible “beads on a string.” CHAPTER pg 190 Based on the model of DNA put forward by Watson and Crick in 1953, the gene was viewed for the first time in molecular terms as a sequence of nucleotides in a DNA helix that encodes genetic information CHAPTER 18 pg 374 Based on the work of the ENCODE project, we now know that DNA sequences that have previously been thought of as “junk DNA,” which not encode proteins, are nonetheless often transcribed into what we call noncoding RNA (ncRNA) Since the function of some these RNAs is now being determined, we must consider whether the concept of the gene should be expanded to include DNA sequences that encode ncRNAs At this writing, there is no consensus, but it is important for you to be aware of these current findings CHAPTER 15 pg 304 The groundbreaking work of Jacob, Monod, and Lwoff in the early 1960s, which established the operon model for the regulation of gene expression in bacteria, expanded the concept of the gene to include noncoding regulatory sequences that are present upstream (59) from the coding region In bacterial operons, the transcription of several contiguous structural genes whose products are involved in the same biochemical pathway are regulated by a single set of regulatory sequences CHAPTER 13 pg 267 In the 1940s, a time when the molecular nature of the gene had yet to be defined, groundbreaking work of Beadle and Tatum provided the first experimental evidence concerning the product of genes, their “one-gene:oneenzyme” hypothesis This idea received further support and was later modified to indicate that one gene specifies one polypeptide chain CHAPTER 12 pg 249 The elucidation of the genetic code in the 1960s supported the concept that the gene is composed of a linear series of triplet nucleotides encoding the amino acid sequence of a protein While this is indeed the case in prokaryotes and viruses, in 1977, it became apparent that in eukaryotes, the gene is divided into coding sequences, called exons, which are interrupted by noncoding sequences, called introns (intervening sequences), which must be spliced out during production of the mature mRNA www.ebookslides.com A   Selection of Nobel Prizes Awarded for Research in Genetics or Genetics-Related Areas Year Recipients Nobel Prize* Discovery/Research Topic 2012 J.B Gurdon, S Yamanaka P/M Differentiated cells can be reprogrammed to become pluripotent 2009 E H Blackburn C W Greider J W Szostak P/M The nature and replication of the DNA of telomeres, and   the discovery of the telomere-replenishing ribonucleoprotein   enzyme telomerase 2008 O Shimomura, M Chalfie, R Tsien C Discovery and development of the green fluorescent protein (GFP)   technology as a tool for genetic research 2007 M R Capecchi M J Evans O Smithies P/M Gene-targeting technology essential to the creation   of knockout mice serving as animal models of   human disease 2006 R Kornberg C Molecular basis of eukaryotic transcription 2006 A Z Fire, C C Mello P/M Gene silencing using RNA interference (RNAi) 2002 S Brenner, H R Horvitz, J E Sulston P/M Genetic regulation of organ development and programmed   cell death (apoptosis) 2001 L Hartwell, T Hunt, P Nurse P/M Genes and regulatory molecules controlling the cell cycle 1997 S Prusiner P/M Prions, a new biological principle of infection 1995 E B Lewis, C ­Nusslein-Volhard, P/M E Wieschaus Genetic control of early development in Drosophila 1993 R Roberts, P Sharp P/M RNA processing of split genes 1993 K Mullis M Smith C Development of polymerase chain reaction (PCR) and   site-directed mutagenesis (SDM) 1989 J M Bishop, H E Varmus P/M Role of retroviruses and oncogenes in cancer 1989 T R Cech, S Altman C Catalytic properties of RNA 1987 S Tonegawa P/M Genetic basis of antibody diversity 1983 B McClintock P/M Mobile genetic elements in maize 1982 A Klug C Crystalline structure analysis of significant complexes,   including tRNA and nucleosomes 1980 P Berg, W Gilbert, F Sanger C Development of recombinant DNA and DNA sequencing  technology 1978 W Arber, D Nathans, H O Smith P/M Recombinant DNA technology using restriction endonuclease  technology 1976 B S Blumberg D C Gajdusek P/M Elucidation of the human prion-based diseases, kuru and   Creutzfeldt-Jakob disease 1975 D Baltimore, R Delbecco, H Temin P/M Molecular genetics of tumor viruses 1970 N Borlaug PP Genetic improvement of Mexican wheat 1969 M Delbrück, A D Hershey, S E Luria P/M Replication mechanisms and genetic structure of  bacteriophages 1968 H G Khorana, M W Nirenberg P/M Deciphering the genetic code 1968 R W Holley P/M Structure and nucleotide sequence of transfer RNA 1965 F Jacob, A M Lwoff, J L Monod P/M Genetic regulation of enzyme synthesis in bacteria 1962 F H C Crick, J D Watson, M H F Wilkins P/M Double helical model of DNA 1959 A Kornberg, S Ochoa P/M Biological synthesis of DNA and RNA 1958 G W Beadle, E L Tatum P/M Genetic control of biochemical processes 1958 J Lederberg P/M Genetic recombination in bacteria 1954 L Pauling C Alpha helical structure of proteins 1946 H J Muller P/M X-ray induction of mutations in Drosophila 1933 T H Morgan P/M Chromosomal theory of inheritance *C = Chemistry; P/M = Physiology or Medicine; PP = Peace Prize ... Index I-1 ESSENTIALS of GENETICS Ninth Edition Global Edition William S Klug The College of New Jersey Michael R Cummings Illinois Institute of Technology Charlotte A Spencer University of Alberta... Editor, Global Edition: Murchana Borthakur Project Editor, Global Edition: Amrita Naskar Manager, Media Production, Global Edition: Vikram Kumar Senior Manufacturing Controller, Production, Global Edition: ... management Because Essentials of Genetics is shorter than many other texts, it is also more manageable in one-quarter and trimester courses Goals In this edition of Essentials of Genetics, the two