KEY BENEFIT: Discovering Genomics is the first genomics text that combines web activities and case studies with a problem-solving approach to teach upper-level undergraduates and first-year graduate students the fundamentals of genomic analysis. More of a workbook than a traditional text, Discovering Genomics, Second Edition allows students to work with real genomic data in solving problems and provides the user with an active learning experience. KEY TOPICS: Genomic Medicine Case Study: What’s wrong with my child? Genome Sequence Acquisition and Analysis, Comparative Genomics in Evolution and Medicine, Genome Variations, Genomic Medicine Case Study: Why Can’t I Just Take a Pill to Lose Weight? Basic Research with DNA Microarrays, Applied Research with DNA Microarrays, Proteomics, Genomic Medicine Case Study: Why Can’t We Cure More Diseases? Genomic Circuits in Single Genes, Integrated Genomic Circuits, Modeling Whole-Genome Circuits. MARKET: For all readers interested in genomics.

Foreword ix
Preface xi
Acknowledgments xiv
Unit One Genome Sequences 1(216)
What's Wrong with My Child? 2(31)
First Patients 3(6)
Phase I: Clinical Presentation 3(1)
Phase II: Family Pedigree 4(1)
Phase III: Karyotyping and Linkage Analysis 5(1)
Phase IV: DNA Sequence Analysis 5(2)
Summary 1.1 7(1)
Math Minute 1.1 What Is an E-Value? 7(2)
The Next Steps in Understanding the Disease 9(24)
The Need for an Animal Model System 9(1)
What Was the Other Protein that Gave Lots of BLASTp Hits? 9(1)
Does Utrophin Play a Role in Muscular Dystrophy, Too? 10(1)
What Does Dystrophin Do? 10(2)
Math Minute 1.2 What's Special about This Graph? 12(1)
Why Do DMD Patients' Muscles Deteriorate after the First Three Years? 13(1)
Is It Possible to Have DMD and Be Wild-Type for Dystrophin? 13(1)
How Can They Have Muscular Dystrophy if Their Dystrophin Genes Are Normal? 14(1)
Math Minute 1.3 What Do You Mean by Highly Unlikely? 15(5)
Where Is the Muscular Dystrophy Field Now? 20(1)
Sixth International Conference on Molecular Causes of Muscular Dystrophies 20(1)
The Meeting Begins 20(1)
Structural Weaknesses 20(2)
Nonfunctional Mutations 22(1)
New Paradigms: Nonstructural Causes for Muscular Dystrophies 23(4)
Final Presentation 27(1)
Math Minute 1.4 Is cGMP Production Elevated? 28(1)
Summary 1.2 29(1)
Conclusions 29(1)
References 29(4)
Genome Sequence Acquisition 33(80)
How Are Genomes Sequenced? 34(25)
What Is Genomics? 34(1)
How Are Whole Genomes Sequenced? 34(2)
How Are Organisms Picked for Genome Sequencing? 36(4)
Math Minute 2.1 What Can You Learn from a Dot Plot? 40(2)
Math Minute 2.2 How Do You Find Motifs? 42(3)
Can We Predict Protein Functions from DNA Sequence? 45(1)
Math Minute 2.3 What Are ``Positives'' and What Do They Have to Do with E-values? 46(2)
What Shapes Are the Proteins? 48(1)
Does Structure Reveal Function? 49(1)
Why Do the Databases Contain So Many Partial Sequences? 49(2)
Which Sequencing Method Worked Better? 51(3)
Annotated Genomes Online 54(1)
How Many Proteins Can One Gene Make? 54(1)
Can the Genome Alter Gene Expression Without Changing the DNA Sequence? 55(2)
What Is the Fifth Base in DNA? Methyl-Cytosine 57(1)
Imprinting, Methylation, and Cancer 58(1)
Summary 2.1 59(1)
What Have We Learned from Unicellular Genomes? 59(54)
Why Do I Get So Many Pimples? 59(1)
Which Genes Cause Pimples? 60(2)
Are All Bacteria Living in Us Bad for Us? 62(2)
Can Microbial Genomes Become Dependent upon Human Genes? 64(1)
What Is the Minimum Number of Genes Possible? 65(1)
Are All Viral Genomes Smaller than All Bacterial Genomes? 66(1)
Is Mimivirus Alive? 67(1)
Do Genomes Reflect an Organism's Ecological Niche? 68(2)
Math Minute 2.4 Can You Estimate the Number of Inversions in a Dot Plot? 70(2)
Why Is MED4's Genome So Small? 72(1)
How Many Genome Changes Are Required Before a New Species Is Created? 73(1)
What Kind of Organism Causes Malaria? 74(1)
What Sort of Genome Does Plasmodium Possess? 75(1)
Is the Predicted Proteome Equally Bizarre? 76(2)
Is There a Model Eukaryote Genome? 78(3)
What Did the Investigators Predict for the Future of Genomics? 81(1)
Epilog for the Yeast Genome 81(2)
Summary 2.2 83(1)
What Have We Learned from Metazoan Genomes? 83(1)
Are Animal Genomes Harder to Finish? 83(1)
What Are Polythene Chromosomes? 83(4)
What Makes a Fly Different from Other Eukaryotes? 87(1)
Is the Fly Still a Good Model Organism? 88(1)
Fly Genome Epilog 89(1)
Do We Need Two Plant Genome Sequences? 90(1)
Plants Seem Simpler than Animals, but Are Their Genomes? 91(1)
Can We Draw Any Conclusions from Draft Sequences? 91(3)
What Lessons Have We Learned? 94(1)
Rice Epilog 95(1)
What Can We Possibly Learn from a Puffer Fish Genome? 96(1)
Did the Genome Reveal Any Surprises? 97(1)
Are There More Big Lessons from Tetraodon? 98(1)
What Makes Humans Different? 99(2)
Math Minute 2.5 How Do You Fit a Line to Data? 101(1)
Whose DNA Did We Sequence? 102(1)
Can We Describe a Typical Human Gene? 103(3)
Human Genome Epilog 106(2)
What Is the Next Goal in Human Genomics? 108(1)
Summary 2.3 109(1)
Conclusions 109(1)
References 109(4)
Comparative Genomics in Evolution and Medicine 113(64)
Comparative Genomics 114(12)
How Can E. coli Be Lethal and in Our Intestines at the Same Time? 114(1)
Math Minute 3.1 How Can You Tell if Base Compositions Are Different? 115(1)
Two Hundred Genomes: What Can Comparative Genomics Tell Us about Prokaryotes? 116(1)
Do All Prokaryotes Have One Circular Chromosome? 116(1)
Are the Genomes Still Changing? 117(1)
How Many Genomes Are There? 118(3)
What Can We Learn by Comparing Many Whole Genomes? 121(2)
What Can We See at the Chromosomal Perspective? 123(22)
Summary 3.1 145
Evolution of Genomes 126(19)
What Organism Is the Root of the Tree of Life? 126(3)
What Are the Origins of our Nuclear Genes? 129(3)
Math Minute 3.2 Are the Hit Numbers Significantly Different 132(1)
Is There Evidence of Intermediate Stages in Genomic Evolution? 132(1)
Are You Going to Eat That? 133(3)
A Missing Link of Biblical Proportions 136(1)
Could Nuclei Evolve without Symbiosis? 137(1)
Are We Related to Rats? 138(1)
What Is the Origin of Our Species? 139(2)
Are We All of African Descent? 141(2)
Math Minute 3.3 How Do You Know if the Tree Is Correct? 143(1)
Have We Stopped Evolving? 143(2)
Summary 3.2 145(1)
Genomic Identifications 145(17)
How Can We Identify Biological Weapons? 145(4)
How Long Can DNA Survive? 149(3)
How Did Tuberculosis Reach North America? 152(3)
How Are Newly Emerging Diseases Identified? 155(4)
What Other Outbreaks Are Coming? 159(2)
Summary 3.3 161(1)
Biomedical Genome Research 162(15)
Can We Use Genomic Sequences to Make New Vaccines? 162(2)
Can We Make New Types of Antibiotics? 164(2)
Can We Invent a New Class of Medication? 166(3)
Is There an Alternative Way to Inhibit RNAs? 169(1)
Are There More Stable RNA Genomes We Can Target? 170(2)
Summary 3.4 172(1)
Conclusions 172(1)
References 172(5)
Genomic Variations 177(40)
Environmental Case Study 178(8)
Can Genomic Diversity Affect Global Warming? 178(2)
Math Minute 4.1 How Do You Measure Genetic Diversity? 180(4)
Math Minute 4.2 How Do You Model Population Diversity? 184(2)
Summary 4.1 186(1)
Human Genomic Variation 186(12)
How Much Variation Is in the Human Genome? 186(1)
What's the Difference Between a Mutation and an Allele? 187(1)
Why Should We Care about NSPs? 188(1)
Math Minute 4.3 Are All SNPs Really SNPs? 188(4)
Do Any SNPs Produce Common Phenotypes? 192(2)
Are There Vital SNPs That Can Surprise Me? 194(1)
Patent Law and Genomics 195(1)
Why the SNP Frenzy? Pharmacogenomics! 196(2)
Summary 4.2 198(1)
The Ultimate Genomic Phenotype---Death? 198(5)
Why Do We Age? 199(1)
Are There Hidden Costs for a Prolonged Life? 200(1)
Do Bacteria Experience Genomic Tradeoffs Too? 201(1)
Summary 4.3 202(1)
Ethical Consequences of Genomic Variations 203(14)
Are Genetically Modified Organisms Bad? 203(2)
Is Genetic Testing Good? 205(3)
Math Minute 4.4 What Does a Positive Test Result Really Mean? 208(1)
Genomic Diversity Banks and Small Populations 209(1)
Who Benefits from Genomic Medicine? 210(1)
Are There Simple Applications for Complex Genomes? 210(1)
Should I Get a Genetic Test? 211(1)
Should Humans Be Cloned? 212(2)
Summary 4.4 214(1)
Conclusions 214(1)
References 214(3)
Unit Two Genome Expression 217(112)
Why Can't I Just Take a Pill to Lose Weight? 218(15)
Hungry for Knowledge 219(5)
Saturday, 21 October. 7:30 A.M. 219(1)
Library Opens at 8:30 A.M. on Saturdays 219(1)
Building a Model for Weight Homeostasis 220(1)
Cloning the Leptin Gene 220(3)
Functional Tests for Leptin 223(1)
Time to Visit Grandma 224(9)
Grandma Gives You Homework! 224(7)
Conclusions 231(1)
References 231(2)
Basic Research with DNA Microarrays 233(30)
Introduction to Microarrays 234(20)
What Happened to My Home Brew? 234(1)
Where's the Probe? 235(2)
Microarray Data Look Good, but Are They Real? 237(1)
How Do You Analyze These Data? 238(1)
Math Minute 6.1 Why Should You Log-Transform Microarray Data? 239(1)
Math Minute 6.2 How Do You Measure Similarity between Expression Patterns? 240(1)
Math Minute 6.3 How Do You Cluster Genes? 241(4)
Can Chips Reveal Regulatory Sequences? 245(1)
Can We Formulate Testable Predictions with These Data? 245(3)
Microarrays Seem Too Good to Be True---Are They? 248(1)
Why Did the Beer Blow? 249(1)
What Can We Learn from Stressed-Out Yeast? 250(1)
Do Fungi Feel Stress? 251(1)
What Goes Up? 251(1)
Why Are There So Many Copies of Some Genes but Not Others? 252(1)
How Well Do Promoters Control Gene Expression? 253(1)
Do Promoters Work in Reverse? 254(1)
Summary 6.1 254(1)
Alternative Uses of DNA Microarrays 254(9)
Why Do So Many Unrelated Genes Share the Same Expression Profile? 255(1)
Math Minute 6.4 Is It Useful to Compare the Columns of a Gene Expression Matrix? 256(2)
Can Cells Verify Their Own Genes? 258(1)
Which Predicted Genes Are Real and Which Ones Aren't? 259(1)
Can Microarrays Improve Annotations? 259(1)
Could a Microarray Validate Annotation of an Entire Genome? 259(2)
Summary 6.2 261(1)
Conclusions 261(1)
References 261(2)
Applied Research with DNA Microarrays 263(22)
Cancer and Genomic Microarrays 264(9)
Are There Better Ways to Diagnose Cancer? 264(2)
Math Minute 7.1 What Are Signature Genes, and How Do You Use Them? 266(2)
Can Breast Cancer Be Categorized with Microarrays? 268(2)
What Genomic Changes Occur in Cancer Cells? 270(2)
Summary 7.1 272(1)
Improving Health Care with DNA Microarrays 273(12)
Why Is the Tuberculosis Vaccine Less Effective Now? 273(3)
Can We Choose the Most Effective Medication for Each Cancer? 276(1)
Can We Predict Effectiveness of Chemotherapy? 276(1)
What Happens When You Accumulate Fat? 277(4)
What Effect Does Leptin Have on wt Adipose Tissue? 281(1)
Summary 7.2 282(1)
Conclusions 282(1)
References 282(3)
Proteomics 285(44)
Introduction 285(10)
What Do All These Proteins Do? 286(3)
Where Are These Proteins Located? 289(1)
Which Proteins Are Needed in Different Conditions? 290(2)
Math Minute 8.1 How Do You Know if You Have Sampled Enough Cells? 292(2)
Summary 8.1 294(1)
Protein 3D Structures 295(4)
Does a Protein's Shape Reveal Its Function? 295(2)
Can We Use Structures to Develop Better Drugs? 297(1)
Can One Protein Kill You? 297(2)
Summary 8.2 299(1)
Protein Interaction Networks 299(8)
Which Proteins Interact with Each Other? 299(1)
Can Sequence Analysis Uncover Interactions? 300(1)
Can We Detect Protein Interactions? 300(3)
Math Minute 8.2 Is Sup35 a Central Protein in the Network? 303(1)
Is It Possible to Understand Proteome-Wide Interactions? 304(2)
Summary 8.3 306(1)
Measuring Proteins 307(22)
Which Proteins Are Present? 307(1)
What Are 2D Gels? 307(3)
What Proteins Do Our White Blood Cells Need to Kill a Pathogen? 310(1)
Math Minute 8.3 How Do You Identify Proteins on 2D Gels? 311(3)
How Much of Each Protein Is Present? 314(1)
Can We Quantify Proteomes in Cultured Cells? 314(2)
Can We Quantify Proteins in Any Cell? 316(1)
Nice Idea, But Does ICAT Work? 316(3)
Is the Last Unexplored Ecosystem on Earth Inside the Cell? 319(1)
Can We Make Protein Microarrays? 320(1)
Can Microarrays Detect Proteome Interactions? 320(1)
Can Protein Microarrays Measure Kinase Activity? 321(2)
Are All Cells Equal? 323(2)
What Does a Proteome Produce? 325(2)
Summary 8.4 327(1)
Conclusions 327(1)
References 327(2)
Unit Three Whole Genome Perspective 329(92)
Why Can't We Cure More Diseases? 330(11)
How Are New Medications Developed? 331(10)
Focus 1: Location, Location, Location 331(1)
Focus 2: Delivery Vehicles 331(2)
Focus 3: Specificity 333(2)
Math Minute 9.1 What's the Right Dose? 335(1)
How Many Drugs Does It Take to Cure a Disease? 336(1)
What Type of Drug Works Best? 336(1)
Can Medication Do More than Simply Mask Symptoms? 337(1)
Do We Know the Answers? 338(1)
Conclusions 339(1)
References 340(1)
Genomic Circuits in Single Genes 341(28)
Dissecting a Gene's Circuitry 342(24)
How Are Genes Regulated? 342(1)
Molecular Dissection of Development 343(1)
Expression of Endo16 343(1)
How Does a Gene Control Location, Timing, and Quantity of Transcription? 344(1)
Which Modules Control Location? 344(1)
Why Do Modules F, E, and DC Promote Expression in the Wrong Cells? 345(3)
How Does Lithium Affect Transcription? 348(2)
What Controls the Timing of Endo16 Transcription? 350(1)
Does Module G Have a Function? 351(1)
Can We Draw a Transcription Circuit for Endo16? 352(3)
What Makes Module A So Special? 355(1)
How Do Module A-Binding Proteins Work? 355(4)
Which Module A Sites Respond to Repression by Modules DC, E, and F? 359(1)
How Does Module A Interact with the Basic Promoter? 360(1)
Are Genes Hard-Wired? 361(2)
Do Genes Contain Miniature Computer Programs? 363(1)
Math Minute 10.1 How Do You Make a Computer Understand Gene Regulation? 364(2)
Summary 10.1 366(1)
Integrating Single-Gene Circuits 366(3)
How Can We Describe to Others What We Know About a Genome Circuit? 366(1)
Does Interactivity Enhance Understanding? 366(1)
Technical Hints 366(1)
Summary 10.2 367(1)
Conclusions 367(1)
References 368(1)
Integrated Genomic Circuits 369(40)
Natural Gene Circuits 370(24)
Can Genes Form Toggle Switches and Make Choices? 370(1)
How Do Toggle Switches Work? 370(1)
What Effect Do Noise and Stochastic Behavior Have on a Cell? 371(1)
Math Minute 11.1 How Are Stochastic Models Applied to Cellular Processes? 371(3)
Theory Is Nice, but Do Toggle Switches Really Exist? 374(2)
How Can Multicellular Organisms Develop with Noisy Circuits? 376(1)
Redundancy: Does Gene Duplication Really Increase Genome Reliability? 377(1)
Does Memory Formation Require Toggle Switches? 378(2)
Are Simple Models of Complex Circuits Worthwhile? 380(1)
How Much Math Is Required to Model Memory? 380(1)
How Do You Build Complex Models? 381(1)
Can a Transient Stimulus Produce Persistent Kinase Activation? 381(1)
Why Does 100 Minutes of 5 nM EGF Achieve Long-Term Activation? 382(2)
Math Minute 11.2 Is It Possible to Predict Steady-State Behavior? 384(1)
Can the Modeled Circuit Accommodate Learning and Forgetting? 385(1)
What Roles Do Other Integrated Circuits Play in LTP? 386(1)
Do They Need a More Complex Model to Match Reality? 387(3)
Are LTP and Long-Term Memory Related? 390(1)
What Have We Learned (How Much LTP Have We Generated)? 391(1)
Can We Understand Cancer Better by Visualizing Its Circuitry? 391(2)
Summary 11.1 393(1)
Synthetic Biology 394(15)
Can Humans Engineer a Genetic Toggle Switch? 394(1)
How to Build a Toggle Switch 394(2)
Can We Build a Synthetic Oscillating Clock? 396(1)
Math Minute 11.3 How Can You Visualize Gene Regulation Logic? 397(3)
Can Synthetic Devices Alter Gene Expression? 400(2)
If Circuits Are Interconnected, Does Gene Order Matter? 402(1)
Observational Approach 402(1)
Computational Approach 403(1)
Does Gene 1 Have to Be First? 404(3)
Summary 11.2 407(1)
Conclusions 407(1)
References 407(2)
Modeling Whole-Genome Circuits 409(12)
Is Genomics a New Perspective? 410(1)
The People Involved: Who Is Doing Systems Biology? 410(1)
The Quality of the Message: What Questions Do Systems Biologists Ask? 411(1)
Can We Model Entire Eukaryotes with a Systems Approach? 411(7)
Does the Proteome Respond Like the Transcriptome? 415(1)
Can We Build a Systems Model? 416(1)
Context of the Message: What Is the Impact of this Research? 417(1)
Will Systems Biology Go Systemic? 418(3)
Conclusions 419(1)
References 419(2)
Glossary 421(14)
Credits 435(4)
Index 439