A Primer of Genome Science

by Gibson, Greg; Muse, Spencer V.

• ISBN13: 9780878932320
• ISBN10: 0878932321
• Edition: 2nd
• Format: Paperback
• Copyright: 2004-12-01
• Publisher: Sinauer Associates Inc

Author Biography

Greg Gibson is Associate Professor in the Department of Genetics at North Carolina State University.

Table of Contents

Preface	xi
1 Genome Projects: Organization and Objectives
The Core Aims of Genome Science	1	(3)
Mapping Genomes	4	(9)
Genetic Maps	4	(4)
EXERCISE 1.1 Constructing a genetic map	7	(1)
Physical Maps	8	(1)
Cytological Maps	8	(2)
Comparative Genomics	10	(3)
The Human Genome Project	13	(12)
Objectives	13	(3)
The Content of the Human Genome	16	(6)
BOX 1.1 The Ethical, Legal, and Social Implications of the Human Genome Project	18	(4)
Internet Resources	22	(3)
EXERCISE 1.2 Use the NCBI and Ensembl genome browsers to examine a human disease gene	23	(2)
Animal Genome Projects	25	(16)
BOX 1.2 GenBank Files	26	(3)
Rodent Genome Projects	29	(4)
EXERCISE 1.3 Compare the structure of a gene in a mouse and a human	32	(1)
Other Vertebrate Biomedical Models	33	(1)
Animal Breeding Projects	34	(1)
Invertebrate Model Organisms	35	(3)
BOX 1.3 Managing and Distributing
Genome Data	38	(3)
Plant Genome Projects	41	(6)
Arabidopsis Thaliana	41	(2)
Grasses and Legumes	43	(3)
Other Flowering Plants	46	(1)
Microbial Genome Projects	47	(12)
The Minimal Genome	47	(4)
Sequenced Microbial Genomes	51	(2)
EXERCISE 1.4 Compare two microbial genomes using the CMR	52	(1)
Environmental Sequencing	53	(2)
Yeast	55	(2)
EXERCISE 1.5 Examining a gene in the Saccharomyces Genome Database	56	(1)
Parasite Genomics	57	(2)
Summary	59	(1)
Discussion Questions	60	(1)
Literature Cited	60	(5)
2 Genome Sequencing and Annotation
Automated DNA Sequencing	65	(16)
The Principle of Sanger Sequencing	65	(1)
High-Throughput Sequencing	66	(2)
Reading Sequence Traces	68	(4)
EXERCISE 2.1 Reading a sequence trace	71	(1)
Contig Assembly	72	(7)
BOX 2.1 Pairwise Sequence Alignment	74	(4)
EXERCISE 2.2 Computing an optimal sequence alignment	78	(1)
Emerging Sequencing Methods	79	(2)
Genome Sequencing	81	(12)
Hierarchical Sequencing	82	(4)
Shotgun Sequencing	86	(6)
BOX 2.2 Searching Sequence Databases Using BLAST	88	(4)
Sequence Verification	92	(1)
Genome Annotation	93	(40)
EST Sequencing	93	(3)
Ab Initio Gene Discovery	96	(37)
3 SNPs and Variation
The Nature of Single Nucleotide Polymorphisms	133	(14)
Classification of SNPs	133	(3)
Distribution of SNPs	136	(2)
Linkage Disequilibrium and Haplotype Maps	138	(9)
BOX 3.1 Disequilibrium between Alleles at Two Loci	140	(3)
EXERCISE 3.1 Quantifying heterozygosity and LD	143	(4)
Applications of SNP Technology	147
Population Genetics	147	(6)
BOX 3.2 The Coalescent	150	(3)
Recombination Mapping	153	(3)
EXERCISE 3.2 Inferring haplotype structure	154	(2)
QTL Mapping	156	(3)
Linkage Disequilibrium Mapping	159
BOX 3.3 Case-Control Association Studies	164
BOX 2.3 Hidden Markov Models and Gene Finding	97	(4)
Regulatory Sequences	101	(1)
Non-Protein Coding Genes	102	(3)
Structural Features of Genome Sequences	105	(5)
Functional Annotation and Gene Family Clusters	110	(16)
EXERCISE 2.3 Perform a BLAST search	111	(1)
Clustering of Genes by Sequence Similarity	112	(2)
Clusters of Orthologous Genes	114	(1)
Phylogenetic Classification of Genes	115	(7)
BOX 2.4 Phylogenetics	116	(4)
EXERCISE 2.4 A simple phylogenetic analysis	120	(2)
Gene Ontology	122	(50)
BOX 2.5 Gene Ontologies	124	(2)
Summary	126	(2)
Discussion Questions	128	(1)
Web Site Exercises	128	(1)
Literature Cited	129	(43)
BOX 3.4 Family-Based Association Tests	168	(3)
EXERCISE 3.3 Perform a case-control association test	171	(1)
SNP Discovery	172	(4)
Resequencing	172	(2)
Sequence-Free Polymorphism Detection	174	(2)
SNP Genotyping	176	(12)
Low-Technology Methods	178	(1)
Minisequencing Methods	178	(6)
EXERCISE 3.4 Designing a genotyping assay for a double polymorphism	184	(1)
Homogeneous Fluorogenic Dye-Based Methods	184	(4)
Haplotype Phasing Methods	188	(1)
Summary	188	(2)
Discussion Questions	190	(1)
Web Site Exercises	190	(1)
Literature Cited	190	(5)
4 Gene Expression and the Transcriptome
Parallel Analysis of Gene Expression. Microarrays	195	(37)
Applications of Microarray Technology	196	(2)
Experimental Design	198	(4)
EXERCISE 4.1 Design a microarray experiment	200	(2)
Microarray Technologies	202	(9)
Statistical Analysis of cDNA Microarray Data	211	(13)
BOX 4.1 Microarray Image Processing	214	(2)
EXERCISE 4.2 Calculate which genes are differentially expressed	216	(4)
BOX 4.2 Basic Statistical Methods	220	(3)
EXERCISE 4.3 Evaluate the significance of the following gene expression differences	223	(1)
Microarray Data Mining	224	(6)
BOX 4.3 Clustering Methods	226	(3)
EXERCISE 4.4 Perform a cluster analysis on gene expression profiles	229	(1)
ChIP Chips and Gene Regulation	230	(2)
SAGE and Microbeads	232	(7)
Serial Analysis of Gene Expression	232	(7)
BOX 4.4 Motif Detection in Promoter Sequences	234	(5)
Microbead-Based Expression Profiling	239	(1)
Single-Gene Analyses	239	(3)
Northern Blots	239	(2)
Quantitative PCR	241	(1)
Properties of Transcriptomes	242	(13)
Microbial Transcriptomics	243	(4)
Cancer and Clinical Applications	247	(3)
Development, Physiology, and Behavior	250	(3)
Evolutionary and Ecological Functional Genomics	253	(2)
Gene Expression Databases	255	(3)
Summary	258	(1)
Discussion Questions	259	(1)
Web Site Exercises	260	(1)
A Literature Cited	260	(5)
5 Proteomics and Functional Genomics
Functional Proteomics	265	(24)
Protein Annotation	265	(8)
EXERCISE 5.1 Structural annotation of a protein	268	(2)
BOX 5.1 Hidden Markov Models in Domain Profiling	270	(3)
Protein Separation and 2D-PAGE	273	(4)
Mass Spectrometry and Protein Identification	277	(6)
EXERCISE 5.2 Identification of a protein on the basis of a MS profile	280	(3)
Protein Microarrays	283	(2)
Protein Interaction Maps	285	(4)
EXERCISE 5.3 Formulating a network of protein interactions	287	(2)
Structural Proteomics	289	(11)
Objectives of Structural Proteomics	289	(5)
BOX 5.2 Biological Networks In Genome Science	290	(4)
Protein Structure Determination	294	(3)
Protein Structure Prediction and Threading	297	(3)
Functional Genomics	300	(22)
Saturation Forward Genetics	301	(5)
High-Throughput Reverse Genetics	306	(8)
BOX 5.3 Transgenic Animals and Plants	312	(2)
Fine-Structure Genetics	314	(7)
EXERCISE 5.4 Designing a genetic screen	316	(5)
Genetic Fingerprinting	321	(1)
Summary	322	(3)
Discussion Questions	325	(1)
Web Site Exercises	325	(1)
Literature Cited	325	(8)
6 Integrative Genomics
Metabolomics	333	(6)
Analysis of Cellular Constituents	333	(4)
Metabolic and Biochemical Databases	337	(2)
In Silico Genomics	339	(9)
Metabolic Control Analysis	339	(4)
Systems-Level Modeling of Gene Networks	343	(5)
Summary	348	(1)
Discussion Questions	348	(1)
Literature Cited	349	(2)
Glossary	351	(12)
List of Abbreviations	363	(2)
Index	365