| Foreword |
| Preface |
| Acknowledgments |
| Genome Sequences / Unit 1： |
| What's Wrong with My Child? / Chapter 1： |
| First Patients / 1.1： |
| Clinical Presentation / Phase I： |
| Family Pedigree / Phase II： |
| Karyotyping and Linkage Analysis / Phase III： |
| DNA Sequence Analysis / Phase IV： |
| Summary 1.1 |
| What Is an E-Value? / Math Minute 1.1： |
| The Next Steps in Understanding the Disease / 1.2： |
| The Need for an Animal Model System |
| What Was the Other Protein that Gave Lots of BLASTp Hits? |
| Does Utrophin Play a Role in Muscular Dystrophy, Too? |
| What Does Dystrophin Do? |
| What's Special about This Graph? / Math Minute 1.2： |
| Why Do DMD Patients' Muscles Deteriorate after the First Three Years? |
| Is It Possible to Have DMD and Be Wild-Type for Dystrophin? |
| How Can They Have Muscular Dystrophy if Their Dystrophin Genes Are Normal? |
| What Do You Mean by Highly Unlikely? / Math Minute 1.3： |
| Where Is the Muscular Dystrophy Field Now? |
| Sixth International Conference on Molecular Causes of Muscular Dystrophies |
| The Meeting Begins |
| Structural Weaknesses |
| Nonfunctional Mutations |
| New Paradigms: Nonstructural Causes for Muscular Dystrophies |
| Final Presentation |
| Is cGMP Production Elevated? / Math Minute 1.4： |
| Summary 1.2 |
| Chapter 1 Conclusions |
| References |
| Genome Sequence Acquisition / Chapter 2： |
| How Are Genomes Sequenced? / 2.1： |
| What Is Genomics? |
| How Are Whole Genomes Sequenced? |
| How Are Organisms Picked for Genome Sequencing? |
| What Can You Learn from a Dot Plot? / Math Minute 2.1： |
| How Do You Find Motifs? / Math Minute 2.2： |
| Can We Predict Protein Functions from DNA Sequence? |
| What Are "Positives" and What Do They Have to Do with E-values? / Math Minute 2.3： |
| What Shapes Are the Proteins? |
| Does Structure Reveal Function? |
| Why Do the Databases Contain So Many Partial Sequences? |
| Which Sequencing Method Worked Better? |
| Annotated Genomes Online |
| How Many Proteins Can One Gene Make? |
| Can the Genome Alter Gene Expression Without Changing the DNA Sequence? |
| What Is the Fifth Base in DNA? Methyl-Cytosine |
| Imprinting, Methylation, and Cancer |
| Summary 2.1 |
| What Have We Learned from Unicellular Genomes? / 2.2： |
| Why Do I Get So Many Pimples? |
| Which Genes Cause Pimples? |
| Are All Bacteria Living in Us Bad for Us? |
| Can Microbial Genomes Become Dependent upon Human Genes? |
| What Is the Minimum Number of Genes Possible? |
| Are All Viral Genomes Smaller than All Bacterial Genomes? |
| Is Mimivirus Alive? |
| Do Genomes Reflect an Organism's Ecological Niche? |
| Can You Estimate the Number of Inversions in a Dot Plot? / Math Minute 2.4： |
| Why Is MED4's Genome So Small? |
| How Many Genome Changes Are Required Before a New Species Is Created? |
| What Kind of Organism Causes Malaria? |
| What Sort of Genome Does Plasmodium Possess? |
| Is the Predicted Proteome Equally Bizarre? |
| Is There a Model Eukaryote Genome? |
| What Did the Investigators Predict for the Future of Genomics? |
| Epilog for the Yeast Genome |
| Summary 2.2 |
| What Have We Learned from Metazoan Genomes? / 2.3： |
| Are Animal Genomes Harder to Finish? |
| What Are Polythene Chromosomes? |
| What Makes a Fly Different from Other Eukaryotes? |
| Is the Fly Still a Good Model Organism? |
| Fly Genome Epilog |
| Do We Need Two Plant Genome Sequences? |
| Plants Seem Simpler than Animals, but Are Their Genomes? |
| Can We Draw Any Conclusions from Draft Sequences? |
| What Lessons Have We Learned? |
| Rice Epilog |
| What Can We Possibly Learn from a Puffer Fish Genome? |
| Did the Genome Reveal Any Surprises? |
| Are There More Big Lessons from Tetraodon? |
| What Makes Humans Different? |
| How Do You Fit a Line to Data? / Math Minute 2.5： |
| Whose DNA Did We Sequence? |
| Can We Describe a Typical Human Gene? |
| Human Genome Epilog |
| What Is the Next Goal in Human Genomics? |
| Summary 2.3 |
| Chapter 2 Conclusions |
| Comparative Genomics in Evolution and Medicine / Chapter 3： |
| Comparative Genomics / 3.1： |
| How Can E. coli Be Lethal and in Our Intestines at the Same Time? |
| How Can You Tell if Base Compositions Are Different? / Math Minute 3.1： |
| Two Hundred Genomes: What Can Comparative Genomics Tell Us about Prokaryotes? |
| Do All Prokaryotes Have One Circular Chromosome? |
| Are the Genomes Still Changing? |
| How Many Genomes Are There? |
| What Can We Learn by Comparing Many Whole Genomes? |
| What Can We See at the Chromosomal Perspective? |
| Summary 3.1 |
| Evolution of Genomes / 3.2： |
| What Organism Is the Root of the Tree of Life? |
| What Are the Origins of our Nuclear Genes? |
| Are the Hit Numbers Significantly Different / Math Minute 3.2： |
| Is There Evidence of Intermediate Stages in Genomic Evolution? |
| Are You Going to Eat That? |
| A Missing Link of Biblical Proportions |
| Could Nuclei Evolve without Symbiosis? |
| Are We Related to Rats? |
| What Is the Origin of Our Species? |
| Are We All of African Descent? |
| How Do You Know if the Tree Is Correct? / Math Minute 3.3： |
| Have We Stopped Evolving? |
| Summary 3.2 |
| Genomic Identifications / 3.3： |
| How Can We Identify Biological Weapons? |
| How Long Can DNA Survive? |
| How Did Tuberculosis Reach North America? |
| How Are Newly Emerging Diseases Identified? |
| What Other Outbreaks Are Coming? |
| Summary 3.3 |
| Biomedical Genome Research / 3.4： |
| Can We Use Genomic Sequences to Make New Vaccines? |
| Can We Make New Types of Antibiotics? |
| Can We Invent a New Class of Medication? |
| Is There an Alternative Way to Inhibit RNAs? |
| Are There More Stable RNA Genomes We Can Target? |
| Summary 3.4 |
| Chapter 3 Conclusions |
| Genomic Variations / Chapter 4： |
| Environmental Case Study / 4.1： |
| Can Genomic Diversity Affect Global Warming? |
| How Do You Measure Genetic Diversity? / Math Minute 4.1： |
| How Do You Model Population Diversity? / Math Minute 4.2： |
| Summary 4.1 |
| Human Genomic Variation / 4.2： |
| How Much Variation Is in the Human Genome? |
| What's the Difference Between a Mutation and an Allele? |
| Why Should We Care about NSPs? |
| Are All SNPs Really SNPs? / Math Minute 4.3： |
| Do Any SNPs Produce Common Phenotypes? |
| Are There Vital SNPs That Can Surprise Me? |
| Patent Law and Genomics |
| Why the SNP Frenzy? Pharmacogenomics! |
| Summary 4.2 |
| The Ultimate Genomic Phenotype-Death? / 4.3： |
| Why Do We Age? |
| Are There Hidden Costs for a Prolonged Life? |
| Do Bacteria Experience Genomic Tradeoffs Too? |
| Summary 4.3 |
| Ethical Consequences of Genomic Variations / 4.4： |
| Are Genetically Modified Organisms Bad? |
| Is Genetic Testing Good? |
| What Does a Positive Test Result Really Mean? / Math Minute 4.4： |
| Genomic Diversity Banks and Small Populations |
| Who Benefits from Genomic Medicine? |
| Are There Simple Applications for Complex Genomes? |
| Should I Get a Genetic Test? |
| Should Humans Be Cloned? |
| Summary 4.4 |
| Chapter 4 Conclusions |
| Genome Expression / Unit 2： |
| Why Can't I Just Take a Pill to Lose Weight? / Chapter 5： |
| Hungry for Knowledge |
| Saturday, 21 October. 7:30 A.M. |
| Library Opens at 8:30 A.M. on Saturdays |
| Building a Model for Weight Homeostasis |
| Cloning the Leptin Gene |
| Functional Tests for Leptin |
| Time to Visit Grandma |
| Grandma Gives You Homework! |
| Chapter 5 Conclusions |
| Basic Research with DNA Microarrays / Chapter 6： |
| Introduction to Microarrays / 6.1： |
| What Happened to My Home Brew? |
| Where's the Probe? |
| Microarray Data Look Good, but Are They Real? |
| How Do You Analyze These Data? |
| Why Should You Log-Transform Microarray Data? / Math Minute 6.1： |
| How Do You Measure Similarity between Expression Patterns? / Math Minute 6.2： |
| How Do You Cluster Genes? / Math Minute 6.3： |
| Can Chips Reveal Regulatory Sequences? |
| Can We Formulate Testable Predictions with These Data? |
| Microarrays Seem Too Good to Be True-Are They? |
| Why Did the Beer Blow? |
| What Can We Learn from Stressed-Out Yeast? |
| Do Fungi Feel Stress? |
| What Goes Up? |
| Why Are There So Many Copies of Some Genes but Not Others? |
| How Well Do Promoters Control Gene Expression? |
| Do Promoters Work in Reverse? |
| Summary 6.1 |
| Alternative Uses of DNA Microarrays / 6.2： |
| Why Do So Many Unrelated Genes Share the Same Expression Profile? |
| Is It Useful to Compare the Columns of a Gene Expression Matrix? / Math Minute 6.4： |
| Can Cells Verify Their Own Genes? |
| Which Predicted Genes Are Real and Which Ones Aren't? |
| Can Microarrays Improve Annotations? |
| Could a Microarray Validate Annotation of an Entire Genome? |
| Summary 6.2 |
| Chapter 6 Conclusions |
| Applied Research with DNA Microarrays / Chapter 7： |
| Cancer and Genomic Microarrays / 7.1： |
| Are There Better Ways to Diagnose Cancer? |
| What Are Signature Genes, and How Do You Use Them? / Math Minute 7.1： |
| Can Breast Cancer Be Categorized with Microarrays? |
| What Genomic Changes Occur in Cancer Cells? |
| Summary 7.1 |
| Improving Health Care with DNA Microarrays / 7.2： |
| Why Is the Tuberculosis Vaccine Less Effective Now? |
| Can We Choose the Most Effective Medication for Each Cancer? |
| Can We Predict Effectiveness of Chemotherapy? |
| What Happens When You Accumulate Fat? |
| What Effect Does Leptin Have on wt Adipose Tissue? |
| Summary 7.2 |
| Chapter 7 Conclusions |
| Proteomics / Chapter 8： |
| Introduction / 8.1： |
| What Do All These Proteins Do? |
| Where Are These Proteins Located? |
| Which Proteins Are Needed in Different Conditions? |
| How Do You Know if You Have Sampled Enough Cells? / Math Minute 8.1： |
| Summary 8.1 |
| Protein 3D Structures / 8.2： |
| Does a Protein's Shape Reveal Its Function? |
| Can We Use Structures to Develop Better Drugs? |
| Can One Protein Kill You? |
| Summary 8.2 |
| Protein Interaction Networks / 8.3： |
| Which Proteins Interact with Each Other? |
| Can Sequence Analysis Uncover Interactions? |
| Can We Detect Protein Interactions? |
| Is Sup35 a Central Protein in the Network? / Math Minute 8.2： |
| Is It Possible to Understand Proteome-Wide Interactions? |
| Summary 8.3 |
| Measuring Proteins / 8.4： |
| Which Proteins Are Present? |
| What Are 2D Gels? |
| What Proteins Do Our White Blood Cells Need to Kill a Pathogen? |
| How Do You Identify Proteins on 2D Gels? / Math Minute 8.3： |
| How Much of Each Protein Is Present? |
| Can We Quantify Proteomes in Cultured Cells? |
| Can We Quantify Proteins in Any Cell? |
| Nice Idea, But Does ICAT Work? |
| Is the Last Unexplored Ecosystem on Earth Inside the Cell? |
| Can We Make Protein Microarrays? |
| Can Microarrays Detect Proteome Interactions? |
| Can Protein Microarrays Measure Kinase Activity? |
| Are All Cells Equal? |
| What Does a Proteome Produce? |
| Summary 8.4 |
| Chapter 8 Conclusions |
| Whole Genome Perspective / Unit 3： |
| Why Can't We Cure More Diseases? / Chapter 9： |
| How Are New Medications Developed? |
| Location, Location, Location / Focus 1： |
| Delivery Vehicles / Focus 2： |
| Specificity / Focus 3： |
| What's the Right Dose? / Math Minute 9.1： |
| How Many Drugs Does It Take to Cure a Disease? |
| What Type of Drug Works Best? |
| Can Medication Do More than Simply Mask Symptoms? |
| Do We Know the Answers? |
| Chapter 9 Conclusions |
| Genomic Circuits in Single Genes / Chapter 10： |
| Dissecting a Gene's Circuitry / 10.1： |
| How Are Genes Regulated? |
| Molecular Dissection of Development |
| Expression of Endo16 |
| How Does a Gene Control Location, Timing, and Quantity of Transcription? |
| Which Modules Control Location? |
| Why Do Modules F, E, and DC Promote Expression in the Wrong Cells? |
| How Does Lithium Affect Transcription? |
| What Controls the Timing of Endo16 Transcription? |
| Does Module G Have a Function? |
| Can We Draw a Transcription Circuit for Endo16? |
| What Makes Module A So Special? |
| How Do Module A-Binding Proteins Work? |
| Which Module A Sites Respond to Repression by Modules DC, E, and F? |
| How Does Module A Interact with the Basic Promoter? |
| Are Genes Hard-Wired? |
| Do Genes Contain Miniature Computer Programs? |
| How Do You Make a Computer Understand Gene Regulation? / Math Minute 10.1： |
| Summary 10.1 |
| Integrating Single-Gene Circuits / 10.2： |
| How Can We Describe to Others What We Know About a Genome Circuit? |
| Does Interactivity Enhance Understanding? |
| Technical Hints |
| Summary 10.2 |
| Chapter 10 Conclusions |
| Integrated Genomic Circuits / Chapter 11： |
| Natural Gene Circuits / 11.1： |
| Can Genes Form Toggle Switches and Make Choices? |
| How Do Toggle Switches Work? |
| What Effect Do Noise and Stochastic Behavior Have on a Cell? |
| How Are Stochastic Models Applied to Cellular Processes? / Math Minute 11.1： |
| Theory Is Nice, but Do Toggle Switches Really Exist? |
| How Can Multicellular Organisms Develop with Noisy Circuits? |
| Redundancy: Does Gene Duplication Really Increase Genome Reliability? |
| Does Memory Formation Require Toggle Switches? |
| Are Simple Models of Complex Circuits Worthwhile? |
| How Much Math Is Required to Model Memory? |
| How Do You Build Complex Models? |
| Can a Transient Stimulus Produce Persistent Kinase Activation? |
| Why Does 100 Minutes of 5 nM EGF Achieve Long-Term Activation? |
| Is It Possible to Predict Steady-State Behavior? / Math Minute 11.2： |
| Can the Modeled Circuit Accommodate Learning and Forgetting? |
| What Roles Do Other Integrated Circuits Play in LTP? |
| Do They Need a More Complex Model to Match Reality? |
| Are LTP and Long-Term Memory Related? |
| What Have We Learned (How Much LTP Have We Generated)? |
| Can We Understand Cancer Better by Visualizing Its Circuitry? |
| Summary 11.1 |
| Synthetic Biology / 11.2： |
| Can Humans Engineer a Genetic Toggle Switch? |
| How to Build a Toggle Switch |
| Can We Build a Synthetic Oscillating Clock? |
| How Can You Visualize Gene Regulation Logic? / Math Minute 11.3： |
| Can Synthetic Devices Alter Gene Expression? |
| If Circuits Are Interconnected, Does Gene Order Matter? |
| Observational Approach |
| Computational Approach |
| Does Gene1 Have to Be First? |
| Summary 11.2 |
| Chapter 11 Conclusions |
| Modeling Whole-Genome Circuits / Chapter 12： |
| Is Genomics a New Perspective? / 12.1： |
| The People Involved: Who Is Doing Systems Biology? |
| The Quality of the Message: What Questions Do Systems Biologists Ask? |
| Can We Model Entire Eukaryotes with a Systems Approach? / 12.2： |
| Does the Proteome Respond Like the Transcriptome? |
| Can We Build a Systems Model? |
| Context of the Message: What Is the Impact of this Research? |
| Will Systems Biology Go Systemic? / 12.3： |
| Chapter 12 Conclusions |
| Glossary |
| Credits |
| Index |
