Contents
1. Genome Projects: Organization and Objectives
* The Core Aims of Genome Science
* Mapping Genomes
o Genetic Maps
o Exercise 1.1. Constructing a genetic map
o Physical Maps
o Cytological Maps
o Comparative Genomics
* The Human Genome Project
o Objectives
o The Content of the Human Genome
o Internet Resources
o Exercise 1.2. Use the NCBI and Ensembl Genome Browsers to examine a human disease gene
* Animal Genome Projects
o Primate Genome Projects
o Rodent Genome Projects
o Exercise 1.3. Compare the structure of a gene in mouse and human
o Other Vertebrate Biomedical Models
o Animal Breeding Projects
o Invertebrate Model Organisms
* Plant Genome Projects
o Arabidopsis thaliana
o Grasses and Legumes
o Other Flowering Plants
* Microbial Genome Projects
o The Minimal Genome
o Sequenced Microbial Genomes
o Exercise 1.4. Compare two microbial genomes using the CMR
o Metagenomics
o Yeast
o Exercise 1.5. Examining a gene in the Saccharomyces Genome Database
o Parasite Genomics
* Summary
* Discussion Questions
* Literature Cited
* BOXES
o Ethical, Legal, and Social Implications of the Human Genome Project
o GenBank Files
o Managing and Distributing Genome Data
2. Genome Sequencing and Annotation
* Automated DNA Sequencing
o The Principle of Sanger Sequencing
o High-Throughput Sequencing
o Reading Sequence Traces
o Exercise 2.1. Reading a sequence trace
o Contig Assembly
o Exercise 2.2. Computing an optimal sequence alignment
o Emerging “Next Generation” Sequencing Methods
* Genome Sequencing
o Hierarchical Sequencing
o Shotgun Sequencing
o Sequence Verification
* Genome Annotation
o EST Sequencing
o Ab initio Gene Discovery
o Regulatory Sequences
o Non-Protein Coding Genes
o Structural Features of Genome Sequences
* Functional Annotation and Clusters of Gene Families
o Exercise 2.3. Perform a BLAST search
o Clustering of Genes by Sequence Similarity
o Clusters of Orthologous Genes
o Phylogenetic Classification of Genes
o Exercise 2.4. Simple phylogenetic analysis of a short sequence
o Gene Ontology
* Summary
* Discussion Questions
* Web Site Exercises
* Literature Cited
* BOXES
o Pairwise Sequence Alignment
o Searching Sequence Databases Using BLAST
o Hidden Markov Models and Gene Finding
o Phylogenetics
o Gene Ontologies
3. Genomic Variation
* The Nature of Single Nucleotide Polymorphisms
o Classification
o Distribution of SNPs
o Linkage Disequilibrium and Haplotype Maps
o Exercise 3.1. Quantitfying heterozygosity and LD
* Applications of SNP technology
o Population Genetics
o Recombination Mapping
o Exercise 3.2. Inferring haplotype structure
o QTL Mapping
o Linkage Disequilibrium Mapping
o Exercise 3.3. Perform a case-control association test
* SNP Genotyping
o SNP Discovery
o SNP Genotyping
o Exercise 3.4. Design a genotyping assay for a double polymorphism
o High-Throughput Genotyping Platforms
o Haplotype Phasing Methods
* Summary
* Discussion Questions
* Web Site Exercises
* Literature Cited
* BOXES
o Disequilibrium between Alleles at Two Loci
o The Coalescent
o Case-Control Association Studies
o Family-Based Association Tests
4. Gene Expression and the Transcriptome
* Parallel Analysis of Gene Expression: Microarrays
o Applications of Microarray Technology
o Experimental Design
o Exercise 4.1. Design a microarray experiment
o Microarray Technologies
o Labeling and Hybridization of cDNAs
o Statistical Analysis of cDNA Microarray Data
o Exercise 4.2. Calculate which of the following genes are differentially expressed
o Exercise 4.3. Evaluate the significance of the following gene expression differences
o Microarray Data Mining
o Exercise 4.4. Perform a cluster analysis on gene expression profiles
o ChIP Chips and Gene Regulation
o DNA Applications of Microarrays
* Parallel Analysis of Gene Expression: RNA-Sequencing
o Serial Analysis of Gene Expression
o RNA-Seq
* Single-Gene Analyses
o Northern Blots
o Quantitative PCR
* Properties of Transcriptomes
o Microbial Transcriptomics
o Cancer and Clinical Applications
o Development, Physiology, and Behavior
o Evolutionary and Ecological Functional Genomics
o Gene Expression Databases
* Summary
* Discussion Questions
* Web Site Exercises
* Literature Cited
* BOXES
o Microarray Image Processing
o Basis Statistics
o Clustering Methods
o Motif Detection in Promoter Sequences of Gene Clusters
5. Proteomics and Functional Genomics
* Functional Proteomics
o Protein Annotation
o Exercise 4.1. Structural annotation of a protein
o Protein Separation and 2D-PAGE
o Mass Spectrometry
o Exercise 4.2. Identification of a protein on the basis of a MS profile
o Immunochemistry
o Protein Microarrays
o Protein Interaction Maps
o Exercise 4.3. Formulating a network of protein interactions
* Structural Proteomics
o Objectives of Structural Proteomics
o Protein Structure Determination
o Protein Structure Prediction and Threading
* Functional Genomics
o Saturation Forward Genetics
o High-Throughput Reverse Genetics
o Fine-Structure Genetics
o Exercise 4.4. Designing a genetic screen
o Genetic Fingerprinting
* Summary
* Discussion Questions
* Web Site Exercises
* Literature Cited
* BOXES
o Hidden Markov Models in Domain Profiling
o Network Theory
o Transgenic Animals and Plants
6. Integrative Genomics
* Metabolomics
o Analysis of Cellular Constituents
o Metabolic profiling
o Metabolic and Biochemical Databases
* In silico Genomics
o Metabolic Control Analysis
o Systems-Level Modeling of Gene Networks
* Summary
* Discussion Questions
* Literature Cited
* BOXES
o Mathematical Modeling of Biochemical Pathways
o Genome-wide Association Studies
Glossary
Index