A Primer of Genome Science, Third Edition

Greg Gibson and Spencer V. Muse

February 2009
344 pages, 129 illustrations
paper

About This Title

Genome science has matured as a discipline to the point where it is now incorporated as a regular part of the genetics curriculum in universities. A Primer of Genome Science, Third Edition bridges the gap between standard genetics textbooks and highly specialized, technical, and advanced treatments of the subdisciplines. It provides an affordable and up-to-date introduction to the field that is suited to advanced undergraduate or early graduate courses. Bioinformatic principles and experimental strategies are explained side-by-side with the experimental methods, establishing a framework that allows teachers to explore topics and the literature at their own pace.

The Primer is organized into six chapters dealing with the scope of genomics, genome sequencing, variation and complex traits, gene expression, proteomics, and metabolomics. Each chapter includes several boxes explaining the theory behind bioinformatic methods, discussion questions, and a summary. This edition has been updated to include the latest developments in next-generation sequencing, high-volume genotyping and expression profiling, and advances in metabolomics.

About the Authors

Greg Gibson is Professor in the School of Integrative Biology at the University of Queensland in Brisbane, Australia, and holds adjunct appointments at North Carolina State University and the Burnham Institute for Medical Research. He earned a Bachelor's Degree in Biology at the University of Sydney and a Ph.D. in Cell Biology at the University of Basel (with Walter J. Gehring). Dr. Gibson serves on the editorial boards of several leading journals, and is a Fellow of the American Association for the Advancement of Science. His research is in quantitative genetics and genomics, focusing both on the fruitfly, Drosophila melanogaster, and human variability.

Spencer V. Muse is Associate Professor in the Department of Statistics, Bioinformatics Research Center at North Carolina State University. He earned a Bachelor’s Degree in Statistics and a Ph.D. in Statistics and Genetics, both at NCSU (the latter with Bruce Weir and Trudy Mackay). Dr. Muse was the recipient of a Sloan Foundation Young Investigator Award (1997–2001). His research is in molecular evolution and bioinformatics.

NEW! eBook

New for the Third Edition, A Primer of Genome Science is available as an eBook via CourseSmart (www.coursesmart.com/9780878932368), at a substantial discount off the price of the printed textbook. The eBook reproduces the look of the printed book exactly, and is available either online or as a download. Features include convenient tools for searching the text, highlighting passages of text, and adding notes. For more information please contact:

Susan McGlew
mcglew@sinauer.com

Reviews and Commentary

“With the huge data sets that are produced in genomic studies, many mathematicians and computer sciences researchers, as well as cell biologists and classical geneticists, are being drawn into working on problems from a genomics perspective, and they will profit greatly from reading this book. The work also provides an affordable introduction that is suited to advanced academic coursework. As in earlier editions, the illustrations, special topic boxes, and hands-on exercises are superb. … Highly recommended.”
—K. A. Newman, Choice

1. Genome Projects: Organization and Objectives

The Core Aims of Genome Science
Mapping Genomes

Genetic Maps
Exercise 1.1. Constructing a genetic map
Physical Maps
Cytological Maps
Comparative Genomics

The Human Genome Project

Objectives
The Content of the Human Genome
Internet Resources
Exercise 1.2. Use the NCBI and Ensembl Genome Browsers to examine a human disease gene

Animal Genome Projects

Primate Genome Projects
Rodent Genome Projects
Exercise 1.3. Compare the structure of a gene in mouse and human
Other Vertebrate Biomedical Models
Animal Breeding Projects
Invertebrate Model Organisms

Plant Genome Projects

Arabidopsis thaliana
Grasses and Legumes
Other Flowering Plants

Microbial Genome Projects

The Minimal Genome
Sequenced Microbial Genomes
Exercise 1.4. Compare two microbial genomes using the CMR
Metagenomics
Yeast
Exercise 1.5. Examining a gene in the Saccharomyces Genome Database
Parasite Genomics

Summary
Discussion Questions
Literature Cited
BOXES

Ethical, Legal, and Social Implications of the Human Genome Project
GenBank Files
Managing and Distributing Genome Data

2. Genome Sequencing and Annotation

Automated DNA Sequencing

The Principle of Sanger Sequencing
High-Throughput Sequencing
Reading Sequence Traces
Exercise 2.1. Reading a sequence trace
Contig Assembly
Exercise 2.2. Computing an optimal sequence alignment
Emerging “Next Generation” Sequencing Methods

Genome Sequencing

Hierarchical Sequencing
Shotgun Sequencing
Sequence Verification

Genome Annotation

EST Sequencing
Ab initio Gene Discovery
Regulatory Sequences
Non-Protein Coding Genes
Structural Features of Genome Sequences

Functional Annotation and Clusters of Gene Families

Exercise 2.3. Perform a BLAST search
Clustering of Genes by Sequence Similarity
Clusters of Orthologous Genes
Phylogenetic Classification of Genes
Exercise 2.4. Simple phylogenetic analysis of a short sequence
Gene Ontology

Summary
Discussion Questions
Web Site Exercises
Literature Cited
BOXES

Pairwise Sequence Alignment
Searching Sequence Databases Using BLAST
Hidden Markov Models and Gene Finding
Phylogenetics
Gene Ontologies

3. Genomic Variation

The Nature of Single Nucleotide Polymorphisms

Classification
Distribution of SNPs
Linkage Disequilibrium and Haplotype Maps
Exercise 3.1. Quantitfying heterozygosity and LD

Applications of SNP technology

Population Genetics
Recombination Mapping
Exercise 3.2. Inferring haplotype structure
QTL Mapping
Linkage Disequilibrium Mapping
Exercise 3.3. Perform a case-control association test

SNP Genotyping

SNP Discovery
SNP Genotyping
Exercise 3.4. Design a genotyping assay for a double polymorphism
High-Throughput Genotyping Platforms
Haplotype Phasing Methods

Summary
Discussion Questions
Web Site Exercises
Literature Cited
BOXES

Disequilibrium between Alleles at Two Loci
The Coalescent
Case-Control Association Studies
Family-Based Association Tests

4. Gene Expression and the Transcriptome

Parallel Analysis of Gene Expression: Microarrays

Applications of Microarray Technology
Experimental Design
Exercise 4.1. Design a microarray experiment
Microarray Technologies
Labeling and Hybridization of cDNAs
Statistical Analysis of cDNA Microarray Data
Exercise 4.2. Calculate which of the following genes are differentially expressed
Exercise 4.3. Evaluate the significance of the following gene expression differences
Microarray Data Mining
Exercise 4.4. Perform a cluster analysis on gene expression profiles
ChIP Chips and Gene Regulation
DNA Applications of Microarrays

Parallel Analysis of Gene Expression: RNA-Sequencing

Serial Analysis of Gene Expression
RNA-Seq

Single-Gene Analyses

Northern Blots
Quantitative PCR

Properties of Transcriptomes

Microbial Transcriptomics
Cancer and Clinical Applications
Development, Physiology, and Behavior
Evolutionary and Ecological Functional Genomics
Gene Expression Databases

Summary
Discussion Questions
Web Site Exercises
Literature Cited
BOXES

Microarray Image Processing
Basis Statistics
Clustering Methods
Motif Detection in Promoter Sequences of Gene Clusters

5. Proteomics and Functional Genomics

Functional Proteomics

Protein Annotation
Exercise 4.1. Structural annotation of a protein
Protein Separation and 2D-PAGE
Mass Spectrometry
Exercise 4.2. Identification of a protein on the basis of a MS profile
Immunochemistry
Protein Microarrays
Protein Interaction Maps
Exercise 4.3. Formulating a network of protein interactions

Structural Proteomics

Objectives of Structural Proteomics
Protein Structure Determination
Protein Structure Prediction and Threading

Functional Genomics

Saturation Forward Genetics
High-Throughput Reverse Genetics
Fine-Structure Genetics
Exercise 4.4. Designing a genetic screen
Genetic Fingerprinting

Summary
Discussion Questions
Web Site Exercises
Literature Cited
BOXES
- Hidden Markov Models in Domain Profiling
- Network Theory
- Transgenic Animals and Plants

6. Integrative Genomics

Metabolomics

Analysis of Cellular Constituents
Metabolic profiling
Metabolic and Biochemical Databases

In silico Genomics

Metabolic Control Analysis
Systems-Level Modeling of Gene Networks

Summary
Discussion Questions
Literature Cited
BOXES

Mathematical Modeling of Biochemical Pathways
Genome-wide Association Studies

Glossary

Index

Media & Supplements

Companion Website
(www.sinauer.com/genomics)
The Primer of Genome Science Companion Website includes the end-of-chapter exercises with links and downloadable files, as well as links to all of the websites referenced throughout the textbook.

Instructor's Resource Library
This resource includes all the full-color illustrations and all the tables from the textbook, in JPEG format, reformatted and relabeled for optimal readability. Also included are ready-to-use PowerPoint® presentations of all illustrations and tables.

If you have adopted this text for course use (within the U.S., Canada, or the Caribbean) and are interested in the instructor's supplements that accompany the text, please contact Susan McGlew at mcglew@sinauer.com. Outside the U.S., Canada, or the Caribbean? Check our ordering page for your local distributor.

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