Discovering Genomics, Proteomics And Bioinformatics

by Campbell, A. Malcolm; Heyer, Laurie J.

• ISBN13: 9780805382198
• ISBN10: 0805382194
• Edition: 2nd
• Format: Paperback
• Copyright: 2006-03-02
• Publisher: Benjamin Cummings

Summary

KEY BENEFIT:Discovering Genomicsis 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 Editionallows 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: Whatrs"s wrong with my child? Genome Sequence Acquisition and Analysis, Comparative Genomics in Evolution and Medicine, Genome Variations, Genomic Medicine Case Study: Why Canrs"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 Canrs"t We Cure More Diseases? Genomic Circuits in Single Genes, Integrated Genomic Circuits, Modeling Whole-Genome Circuits.MARKET: For all readers interested in genomics.

Table of Contents

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