Introduction to genomics:
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Format: | Buch |
Sprache: | English |
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Oxford, United Kingdom
Oxford University Press
[2017]
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Ausgabe: | Third edition |
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Beschreibung: | xxvii, 509 Seiten, 1 ungezählte Seite Illustrationen, Diagramme, Karten |
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Datensatz im Suchindex
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---|---|
adam_text | Titel: Introduction to genomics
Autor: Lesk, Arthur M
Jahr: 2017
CONTENTS
Preface vii
Plan of the third edition x
Recommended reading xiii
Introduction to genomics on the web xiii
Acknowledgements xiv
List of abbreviations xxv
1 Introduction and Background 1
Learning goals 1
Genomics: the hub of biology 2
Phenotype = genotype + environment + life history + epigenetics 2
Varieties of genome Organization 4
Chromosomes, organelles, and plasmids 4
Genes 6
The scope and applications of genome sequencing projects 9
Variations in genome sequences within species 10
Mutations and disease 10
Single-nucleotide polymorphisms 10
Haplotypes 13
A clinically important haplotype: the major histocompatibility complex 14
Populations 15
Species 17
The biosphere 18
Extinctions 19
The future? 22
Genome projects and our current library of genome Information 25
High-throughput sequencing 25
De novo sequencing 26
Resequencing 26
Exome sequencing 26
What s in a genome? 27
Some regions of the genome encode non-protein-coding RNA molecules 28
Some regions of the genome contain pseudogenes 28
Other regions contain binding sites for ligands responsible for regulation
of transcription 29
Repetitive elements of unknown function account for surprisingly large
fractions of our genomes 29
Dynamic components of genomes 30
Genomics and developmental biology 32
Genes and minds: neurogenomics 35
Genetics of behaviour 36
Contents
45
47
Proteomics 37
Protein evolution: divergence of sequences and structures
within and among species 39
Mechanisms of protein evolution 39
Organization and regulation 42
Some mechanisms of regulation act at the level of transcription 45
Some mechanisms of regulation act at the level of translation
Some regulatory mechanisms affect protein activity
On the web: genome browsers 47
Genomics and Computing 52
Archiving and analysis of genome sequences and related data 52
Databanks in molecular biology 53
Programming 54
Looking forward 55
Recommended reading 55
Exercises and problems 57
2 The Human Genome Project: Achievements and Applications 62
Learning goals 62
... the end of the beginning 63
Human genome sequencing 66
What makes us human? 67
Comparative genomics 68
Genomics and language 68
The human genome and medicine 71
Prevention of disease ^
Detection and precise diagnosis 72
Genetic counselling—carrier Status 72
Discovery and implementation of effective treatment 72
Tunable healthcare delivery: pharmacogenomics 74
Pop applications of genome sequencing 76
Genomics in personal identification 76
DNA fingerprinting 77
Personal identification by amplification of specific regions has
superseded the RFLP approach 79
Mitochondrial DNA 79
Analysis of non-human DNA sequences 82
Parentage testing 82
Inference of physical features, and even family name 88
Ethical, legal, and social issues 85
Databases containing human DNA sequence information 85
Use of DNA sequencing in research on human subjects 88
Looking forward 88
Recommended reading 88
Exercises and problems 90
Contents
3 Mapping, Sequencing, Annotation, and Databases
Learning goals
Classical genetics as background
What is a gene?
Maps and tour guides
Genetic maps
Linkage
Linkage disequilibrium
Chromosome banding pattern maps
Restriction maps
Discovery of the structure of DNA
DNA sequencing
Frederick Sanger and the development of DNA sequencing
DNA sequencing by termination of chain replication
The Maxam-Gilbert chemical cleavage method
Automation of DNA sequencing
Organizing a large-scale sequencing project
Bring on the clones: hierarchical—or BAC-to-BAC —genome
sequencing 116
Whole-genome shotgun sequencing 116
Next-generation sequencing 118
Roche 454 Life Sciences 120
lllumina 121
Ion Torrent/Personal Genome Machine (PGM) 124
PacBio 124
Oxford Nanopore 124
10XGenomics 125
The Bionano Irys system 125
Life in the fast lane 126
How much sequencing power is there in the world? 126
Databanks in molecular biology 128
Nucleic acid sequence databases 130
Protein sequence databases 130
Databases of genetic diseases—OMIM and OMIA 130
Databases of structu res 131
Specialized or boutique databases 132
Expression and proteomics databases 132
Databases of metabolic pathways 133
Bibliographie databases 133
Surveys of molecular biology databases and Servers 134
Computer programming in genomics 134
Programming languages 135
How to compute effectively 136
Looking forward 137
Recommended reading 137
Exercises and problems 138
97
97
98
99
99
100
101
102
103
106
107
110
111
111
114
114
116
Contents
4. Evolution and Genomic Change 143
Learning goals 143
Evolution is exploration 144
Biological systematics 146
Biological nomenclature 146
Measurement of biological similarities and differences 148
Homologues and families 150
Pattern matching—the basic tool of bioinformatics 151
Sequence alignment 151
Defining the optimum alignment 153
Scoring schemes 155
Varieties and extensions 157
Approximate methods for quick Screening of databases 158
Pattern matching in three-dimensional structures 160
Evolution of protein sequences, structures, and functions 161
Evolution of protein structure and function 164
Phylogeny 165
Calculation of phylogenetic trees 169
Short-circuiting evolution: genetic engineering 173
Looking forward 175
Recommended reading 176
Exercises and problems 177
5 Genomes of Prokaryotes and Viruses 179
Learning goals 179
Evolution and phylogenetic relationships in prokaryotes 18°
Major types of prokaryotes 180
Do we know the root of the tree of life? 182
Genome Organization in prokaryotes 183
Replication and transcription 184
Gene transfer 184
Archaea 184
The genome of Methanococcus jannaschii 186
Life at extreme temperatures 188
Comparative genomics of hyperthermophilic archaea:
Thermococcus kodakarensis and pyrococci 189
Bacteria 194
Genomes of pathogenic bacteria 195
Genomics and the development of vaccines 197
Viruses 198
Nucleocytoplasmic large DNA viruses (or giant viruses) 199
Viral genomes 199
Recombinant viruses 199
Viruses and evolution 201
Influenza: a past and current threat 201
Contents
Ome, ome, on the ränge: metagenomics, the genomes in a
coherent environmental sample 204
Marine cyanobacteria—an in-depth study 205
Looking forward 208
Recommended reading 208
Exercises and problems 210
6 Genomes of Eukaryotes 211
Learning goals 211
The origin and evolution of eukaryotes 212
Evolution and phylogenetic relationships in eukaryotes 212
The yeast genome 212
The evolution of plants 214
The Arabidopsis thaliana genome 214
Genomes of animals 216
The genome of the sea squirt (Ciona intestinalis) 216
The genome of the pufferfish (Tetraodon nigroviridis) 217
The genome of the chicken (Gallus gallus domesticus) 220
The genome of the platypus (Ornithorhynchus anatinus) 221
The genome of the dog 223
Palaeosequencing—ancient DNA 225
Recovery of DNA from ancient samples 225
DNA from extinct birds 226
High-throughput sequencing of mammoth DNA 227
The phylogeny of elephants 230
Looking forward 230
Recommended reading 231
Exercises and problems 231
7 Comparative Genomics 233
Learning goals 233
Introduction 234
Unity and diversity of life 234
Taxonomy based on sequences 235
Sizes and Organization of genomes 238
Genome sizes 238
Genome Organization in eukaryotes 241
Photosynthetic sea slugs: endosymbiosis of chloroplasts 242
How genomes differ 243
Variation at the level of individual nucleotides 243
Duplications 243
Duplication of genes 244
Contents
Family expansion: G protein-coupled receptors 247
Comparisons at the chromosome level: synteny 252
What makes us human? 252
Comparative genomics 252
Genomes of chimpanzees and humans 252
Genomes of mice and rats 254
Model organisms for study of human diseases 255
The genome of Caenorhabditis elegans 256
The genome of Drosophila melanogaster 256
Homologous genes in humans, worms, and flies 257
Looking forward 258
Recommended reading 260
Exercises and problems 261
8 The Impact of Genome Sequences on Human
Health and Disease 264
Learning goals 264
Introduction 265
Some diseases are associated with mutations in specific genes 265
Haemoglobinopathies—molecular diseases caused by abnormal
haemoglobins 265
Phenylketonuria 266
Alzheimers disease 268
Identification of genes associated with inherited diseases 268
Genome-wide association studies 271
GWAS of sickle-cell disease 274
GWAS of type 2 diabetes 275
GWAS of schizophrenia 276
The human microbiome 278
Treatment of abnormal microbiome composition 281
Cancer genomics 281
SNPs and Cancer 284
Whole-genome sequencing association studies of breast cancer 285
Copy-number alterations in cancer 286
Chromosomal aberrations 288
Epigenetics and cancer 289
microRNAs and Cancer 290
Immunotherapy for cancer 291
Looking forward 292
Recommended reading 292
Exercises and problems 294
Contents
9 Genomics and Anthropology: Human Evolution,
Migration, and Domestication of Plants and Animals 295
Learning goals 295
Ancestry of Homo sapiens 296
The Neanderthal genome 297
The Denisovan genome 298
What do these data teil us? 299
What have Neanderthals and Denisovans done for us lately? 300
Ancient populations and migrations 300
Western civilization? I think it would be a good idea 308
Domestication of the dog 310
Domestication of the horse 311
Domestication of crops 313
Maize (Zea mays) 315
Rice (Oryza sativa) 317
Control of flowering time 318
History of rice domestication 320
Chocolate (Theobroma cacao) 321
The Theobroma cacao genome 322
Looking forward 324
Recommended reading 326
Exercises and problems 327
10 Transcriptomics 329
Learning goals 329
Introduction 330
Microarrays 331
Microarray data are semiquantitative 332
Applications of DNA microarrays 332
Analysis of microarray data 333
RNAseq 336
RNAseq versus microarrays 337
Expression patterns in different physiological states 339
Sleep in rats and fruit flies 340
Expression pattern changes in development 342
Variation of expression patterns during the life cyde of
Drosophila melanogaster 342
Flower formation in roses 344
Expression patterns in learning and memory: long-term potentiation 347
Conserved Clusters of co-expressing genes 350
Contents
Evolutionary changes in expression patterns
Applications of transcriptomics in medicine
Development of antibiotic resistance in bacteria
Childhood leukaemias
The Encyclopedia of DNA Elements (ENCODE)
Looking forward
Recommended reading
Exercises and problems
11 Proteomics
Learning goals
Introduction
Protein nature and types of proteins
Protein structure
The chemical structure of proteins
Conformation of the Polypeptide chain
Protein folding patterns
Domains
Disorder in proteins
Post-translational modifications
Why is there a common genetic code with 20 canonical amino acids? 374
Separation and analysis of proteins 375
Polyacrylamide gel electrophoresis (PAGE) 375
Two-dimensional PAGE 375
Mass spectrometry 376
Identification of components of a complex mixture 377
Protein sequencing by mass spectrometry 378
Quantitative analysis of relative abundance 378
Measuring deuterium exchange in proteins 379
Experimental methods of protein structure determination 381
X-ray crystallography of proteins 381
Interpretation of the electron density: model building and improvement 383
How accurate are the structures? 384
NMR spectroscopy in structural biology 386
Protein structure determination by NMR 386
Low-temperature electron microscopy (cryoEM) 387
Classifications of protein structures 388
SCOP 389
SCOP2 391
Protein complexes and aggregates 391
Protein aggregation diseases 392
Properties of protein-protein complexes 393
Stoichiometry—what is the composition of the complex? 393
Affinity—how stable is the complex? 394
351
353
353
357
359
359
360
361
363
363
364
364
365
365
367
367
370
370
372
Contents
How are complexes organized in three dimensions? 395
Multisubunit proteins 396
Many proteins change conformation as part of the mechanism
of their function 396
Conformational change during enzymatic catalysis 397
Motor proteins 399
Allosteric regulation of protein function 401
Allosteric changes in haemoglobin 402
Conformational states of serine protease inhibitors (serpins) 404
Protein structure prediction and modelling 405
Homology modelling 406
Secondary structure prediction 408
Prediction of novel folds: ROSETTA 408
Available protocols for protein structure prediction 409
Structural genomics 411
Directed evolution and protein design 412
Directed evolution of subtilisin E 412
Looking forward 414
Recommended reading 414
Exercises and problems 415
12 Metabolomics 419
Learning goals 419
Introduction 419
Classification and assignment of protein function 420
The Enzyme Commission 420
The Gene Ontology™ Consortium protein function Classification 421
Comparison of EC and GO classifications 423
Metabolie networks 424
Databases of metabolic pathways 425
EcoCyc 425
The Kyoto Encyclopedia of Genes and Genomes 427
The Human Metabolome Database 428
Evolution and phylogeny of metabolic pathways 429
Alignment and comparison of metabolic pathways 431
Comparing linear metabolic pathways 432
Reconstruction of metabolic networks 432
Comparing non-linear metabolic pathways: the pentose phosphate
pathway and the Calvin-Benson cycle 434
Metabolomics in ecology 435
Dynamic modelling of metabolic pathways 437
Looking forward 439
Recommended reading 439
Exercises and problems 441
Contents
13 Systems Biology 443
Learning goals 443
Introduction 444
Regulatory mechanisms 444
Two parallel networks: physical and logical 445
Networks and graphs 446
Robustness and redundancy 447
Connectivity in networks 448
Dynamics, stability, and robustness 449
Protein complexes and aggregates 451
Protein interaction networks 451
Protein-DNA interactions 456
DNA-protein complexes 456
Structural themes in protein-DNA binding and sequence recognition 457
Bacteriophage T7 DNA Polymerase 458
Some protein-DNA complexes that regulate gene transcription 459
Regulatory networks 463
Structures of regulatory networks 464
Structural biology of regulatory networks 465
Gene regulation 466
The transcriptional regulatory network of Escherichia coli 466
The genetic switch of bacteriophage X 469
Regulation of the lactose Operon in Escherichia coli 472
The genetic regulatory network of Saccharomyces cerevisiae 474
Adaptability of the yeast regulatory network 476
Looking forward 479
Recommended reading 479
Exercises and problems 480
Epilogue 483
Glossary 484
Index 493
CONTENTS
Preface vii
Plan of the third edition x
Recommended reading xiii
Introduction to genomics on the web xiii
Acknowledgements xiv
List of abbreviations xxv
1 Introduction and Background 1
Learning goals 1
Genomics: the hub of biology 2
Phenotype = genotype + environment + life history + epigenetics 2
Varieties of genome organization 4
Chromosomes, organelles, and plasmids 4
Genes 6
The scope and applications of genome sequencing projects 9
Variations in genome sequences within species 10
Mutations and disease 10
Singfe-nucleotide polymorphisms 10
Haplotypes 13
A clinically important haplotype: the major histocompatibility complex 14
Populations 15
Species 17
The biosphere 18
Extinctions 19
The future? 22
Genome projects and our current library of genome information 25
High-throughput sequencing 25
De novo sequencing 26
Resequencing 26
Exome sequencing 26
What s in a genome? 27
Some regions of the genome encode non-protein-coding RNA molecules 28
Some regions of the genome contain pseudogenes 28
Other regions contain binding sites for ligands responsible for regulation
of transcription 29
Repetitive elements of unknown function account for surprisingly large
fractions of our genomes 29
Dynamic components of genomes 30
Genomics and developmental biology 32
Genes and minds: neurogenomics 35
Genetics of behaviour 36
Contents
Proteomics
Protein evolution: divergence of sequences and structures
within and among species
Mechanisms of protein evolution
Organization and regulation
Some mechanisms of regulation act at the level of transcription
Some mechanisms of regulation act at the level of translation
Some regulatory mechanisms affect protein activity
On the web: genome browsers
Genomics and computing
Archiving and analysis of genome sequences and related data
Databanks in molecular biology
Programming
Looking forward
Recommended reading
Exercises and problems
2 The Human Genome Project: Achievements and Applications
Learning goals
... the end of the beginning
Human genome sequencing
What makes us human?
Comparative genomics
Genomics and language
The human genome and medicine
Prevention of disease
Detection and precise diagnosis
Genetic counselling—carrier status
Discovery and implementation of effective treatment
Tunable healthcare delivery: pharmacogenomics
jPopF applications of genome sequencing
Genomics in personal identification
DNA fingerprinting
Personal identification by amplification of specific regions has
superseded the RFLP approach
Mitochondrial DNA
Analysis of non-human DNA sequences
Parentage testing
Inference of physical features, and even family name
Ethical, legal, and social Issues
Databases containing human DNA sequence information
Use of DNA sequencing in research on human subjects
Looking forward
Recommended reading
Exercises and problems
37
39
39
42
45
45
47
47
52
52
53
54
55
5d
57
62
62
66
Of
68
68
71
71
72
72
72
74
76
76
77
79
79
82
82
83
85
85
88
88
88
90
Contents
3 Mapping, Sequencing, Annotation, and Databases 97
Learning goals 97
Classical genetics as background 98
What is a gene? 99
Maps and tour guides 99
Genetic maps 100
Linkage 101
Linkage disequilibrium 102
Chromosome banding pattern maps 103
Restriction maps 106
Discovery of the structure of DNA 107
DNA sequencing 110
Frederick Sanger and the development of DNA sequencing 111
DNA sequencing by termination of chain replication 111
The Maxam-Gilbert chemical cleavage method 114
Automation of DNA sequencing 114
Organizing a large-scale sequencing project 116
Bring on the clones: hierarchical—or BAC-to-BAC—genome
sequencing 116
Whole-genome shotgun sequencing 116
Next-generation sequencing 118
Roche 454 Life Sciences 120
Illumina 121
Ion Torrent/Personal Genome Machine (PGM) 124
PacBio 124
Oxford Nanopore 124
10X Genomics 125
The Bionano Irys system 125
Life in the fast lane 126
How much sequencing power is there in the world? 126
Databanks in molecular biology 128
Nucleic acid sequence databases 130
Protein sequence databases 130
Databases of genetic diseases—OMIM and OMIA 130
Databases of structures 131
Specialized or boutique databases 132
Expression and proteomics databases 132
Databases of metabolic pathways 133
Bibliographic databases 133
Surveys of molecular biology databases and servers 134
Computer programming in genomics 134
Programming languages 135
How to compute effectively 136
Looking forward 137
Recommended reading 137
Exercises and problems 138
Contents
4. Evolution and Genomic Change
143
Learning goals
Evolution is exploration
Biological systematics
Biological nomenclature
Measurement of biological similarities and differences
Homologues and families
Pattern matching—the basic tool of bioinformatics
Sequence alignment
Defining the optimum alignment
Scoring schemes
Varieties and extensions
Approximate methods for quick screening of databases
Pattern matching in three-dimensional structures
Evolution of protein sequences, structures, and functions
Evolution of protein structure and function
Phylogeny
Calculation of phylogenetic trees
Short-circuiting evolution: genetic engineering
Looking forward
Recommended reading
Exercises and problems
143
144
146
146
145
150
151
151
153
155
157
153
160
161
164
165
169
173
175
176
5 Genomes of Prokaryotes and Viruses 179
Learning goals 175)
Evolution and phylogenetic relationships in prokaryotes 180
Major types of prokaryotes 180
Do we know the root of the tree of life? 182
Genome organization in prokaryotes 183
Replication and transcription 184
Gene transfer 184
Archaea 184
The genome of Methanococcus jannaschii 186
Life at extreme temperatures 188
Comparative genomics of hyperthermophilic archaea:
Thermococcus kodakarensis and pyrococci 189
Bacteria 194
Genomes of pathogenic bacteria 195
Genomics and the development of vaccines 197
Viruses 198
Nucleocytoplasmic large DNA viruses (or giant viruses) 199
Viral genomes 199
Recombinant viruses 199
Viruses and evolution 201
Influenza: a past and current threat 201
Contents
Ome, ome, on the range: metagenomics, the genomes in a
coherent environmental sample 204
Marine cyanobacteria—an in-depth study 205
Looking forward 208
Recommended reading 208
Exercises and problems 210
6 Genomes of Eukaryotes 211
Learning goals 211
The origin and evolution of eukaryotes 212
Evolution and phylogenetic relationships in eukaryotes 212
The yeast genome 212
The evolution of plants 214
The Arabidopsis thaliana genome 214
Genomes of animals 216
The genome of the sea squirt {dona intestinalis) 216
The genome of the pufferfish (Tetraodon nigroviridis) 217
The genome of the chicken (Gallus gallus domesticus) 220
The genome of the platypus (Ornithorhynchus anatinus) 221
The genome of the dog 223
Palaeosequencing—ancient DNA 225
Recovery of DNA from ancient samples 225
DNA from extinct birds 226
High-throughput sequencing of mammoth DNA 227
The phylogeny of elephants 230
Looking forward 230
Recommended reading 231
Exercises and problems 231
7 Comparative Genomics 233
Learning goals 233
Introduction 234
Unity and diversity of life 234
Taxonomy based on sequences 235
Sizes and organization of genomes 238
Genome sizes 238
Genome organization in eukaryotes 241
Photosynthetic sea slugs: endosymbiosis of chloroplasts 242
How genomes differ 243
Variation at the level of individual nucleotides 243
Duplications 243
Duplication of genes 244
Family expansion: G protein-coupled receptors 247
Comparisons at the chromosome level: synteny 252
What makes us human? 252
Comparative genomics 252
Genomes of chimpanzees and humans 252
Genomes of mice and rats 254
Model organisms for study of human diseases 255
The genome of Caenorhabditis elegans 256
The genome of Drosophila melanogaster 256
Homologous genes in humans, worms, and flies 257
Looking forward 253
Recommended reading 260
Exercises and problems 261
8 The Impact of Genome Sequences on Human
Health and Disease 264
Learning goals 264
Introduction 265
Some diseases are associated with mutations in specific genes 265
Haemoglobinopathies—molecular diseases caused by abnormal
haemoglobins 265
Phenylketonuria 266
Alzheimer s disease 268
Identification of genes associated with inherited diseases 268
Genome-wide association studies 271
GWAS of sickle-cell disease 274
GWAS of type 2 diabetes 275
GWAS of schizophrenia 276
The human microbiome 278
Treatment of abnormal microbiome composition 281
Cancer genomics 281
SNPs and cancer 284
Whole-genome sequencing association studies of breast cancer 285
Copy-number alterations in cancer 286
Chromosomal aberrations 288
Epigenetics and cancer 289
microRNAs and cancer 290
Immunotherapy for cancer 291
Looking forward 292
Recommended reading 292
Exercises and problems 294
Contents
9 Genomics and Anthropology: Human Evolution,
Migration, and Domestication of Plants and Animals 295
Learning goals 295
Ancestry of Homo sapiens 296
The Neanderthal genome 297
The Denisovan genome 298
What do these data tell us? 299
What have Neanderthals and Denisovans done for us lately? 300
Ancient populations and migrations 300
Western civilization? Jl think it would be a good idea 308
Domestication of the dog 310
Domestication of the horse 311
Domestication of crops 313
Maize (Zea mays) 315
R ice (Oryza sa tiva) 317
Control of flowering time 318
History of rice domestication 320
Chocolate (Theobroma cacao) 321
The Theobroma cacao genome 322
Looking forward 324
Recommended reading 326
Exercises and problems 327
10 Transcriptomics 329
Learning goals 329
Introduction 330
Microarrays 331
Microarray data are semiquantitative 332
Applications of DNA microarrays 332
Analysis of microarray data 333
RNAseq 336
RNAseq versus microarrays 337
Expression patterns in different physiological states 339
Sleep in rats and fruit flies 340
Expression pattern changes in development 342
Variation of expression patterns during the life cycle of
Drosophila melanogaster 342
Flower formation in roses 344
Expression patterns in learning and memory: long-term potentiation 347
Conserved clusters of со-expressing genes 350
Evolutionary changes in expression patterns 351
Applications of transcriptomics in medicine 353
353
Development of antibiotic resistance in bacteria 357
Childhood leukaemias
The Encyclopedia of DNA Elements (ENCODE) 359
Looking forward 359
Recommended reading 360
Exercises and problems 361
Proteomics 363
Learning goals 363
Introduction 364
Protein nature and types of proteins 364
Protein structure 365
The chemical structure of proteins 365
Conformation of the polypeptide chain 367
Protein folding patterns 367
Domains 370
Disorder in proteins 370
Post-translational modifications 372
Why is there a common genetic code with 20 canonical amino acids? 374
Separation and analysis of proteins 37E
Polyacrylamide gel electrophoresis (PAGE) 375
Two-dimensional PAGE 375
Mass spectrometry 376
Identification of components of a complex mixture 377
Protein sequencing by mass spectrometry 378
Quantitative analysis of relative abundance 378
Measuring deuterium exchange in proteins 379
Experimental methods of protein structure determination 381
X-ray crystallography of proteins 381
Interpretation of the electron density: model building and improvement 383
How accurate are the structures? 384
NMR spectroscopy in structural biology 386
Protein structure determination by NMR 386
Low-temperature electron microscopy (cryoEM) 387
Classifications of protein structures 388
SCOP 389
SCOP2 391
Protein complexes and aggregates 391
Protein aggregation diseases 392
Properties of protein-protein complexes 393
Stoichiometry what is the composition of the complex? 393
Affinity—how stable is the complex? 394
Contents
How are complexes organized in three dimensions? 395
Multisubunit proteins 396
Many proteins change conformation as part of the mechanism
of their function 396
Conformational change during enzymatic catalysis 397
Motor proteins 399
Allosteric regulation of protein function 401
Allosteric changes in haemoglobin 402
Conformational states of serine protease inhibitors (serpins) 404
Protein structure prediction and modelling 405
Homology modelling 406
Secondary structure prediction 408
Prediction of novel folds: ROSETTA 408
Available protocols for protein structure prediction 409
Structural genomics 411
Directed evolution and protein design 412
Directed evolution of subtilisin E 412
Looking forward 414
Recommended reading 414
Exercises and problems 415
12 Metabolomics 419
Learning goals 419
Introduction 419
Classification and assignment of protein function 420
The Enzyme Commission 420
The Gene Ontology™ Consortium protein function classification 421
Comparison of EC and GO classifications 423
Metabolic networks 424
Databases of metabolic pathways 425
EcoCyc 425
The Kyoto Encyclopedia of Genes and Genomes 427
The Human Metabolome Database 428
Evolution and phylogeny of metabolic pathways 429
Alignment and comparison of metabolic pathways 431
Comparing linear metabolic pathways 432
Reconstruction of metabolic networks 432
Comparing non-linear metabolic pathways: the pentose phosphate
pathway and the Calvin-Benson cycle 434
Metabolomics in ecology 435
Dynamic modelling of metabolic pathways 437
Looking forward 439
Recommended reading 439
Exercises and problems 441
Contents
13 Systems Biology 443
Learning goals 443
Introduction 444
Regulatory mechanisms 444
Two parallel networks: physical and logical 445
Networks and graphs 446
Robustness and redundancy 447
Connectivity in networks 448
Dynamics, stability, and robustness 449
Protein complexes and aggregates 451
Protein interaction networks 451
Protein-DNA interactions 456
DNA-protein complexes 456
Structural themes in protein-DNA binding and sequence recognition 457
Bacteriophage T7 DNA polymerase 458
Some protein-DNA complexes that regulate gene transcription 459
Regulatory networks 463
Structures of regulatory networks 464
Structural biology of regulatory networks 465
Gene regulation 46*6
The transcriptional regulatory network of Escherichia coli 466
The genetic switch of bacteriophage X 469
Regulation of the lactose operon in Escherichia coli 472
The genetic regulatory network of Saccharomyces cerevisiae 474
Adaptability of the yeast regulatory network 476
Looking forward 479
Recommended reading 479
Exercises and problems 480
Epilogue 483
Glossary 484
Index 493
New to this edition:
• Two new chapters, focused on human genomics
and applications to health and disease, lay out the
concrete outcomes of the human genome project
and the most recent advances in cancer genomics.
• An expanded introductory chapter sets the scene
for your first encounter with the subject.
• A new Looking forward feature links the topics
covered in each chapter to help you make
connections between seemingly different topics.
• A glossary of key terms defines all the concepts
and abbreviations you need to know.
This fully updated and restructured new edition
takes account of new developments and technologies
to present a logical and coherent overview of
genome science today. Covering the similarities
and differences between organisms; how different
organisms evolved; how the genome is constructed
and how it operates; and what our understanding
of genomics means in terms of our future health
and wellbeing, Introduction to Genomics is the most
up-to-date and complete textbook for students
approaching the subject for the first time.
Key features:
• The author s widely-praised writing style leads you
through a conceptually challenging subject in a clear
and lucid way.
• Numerous learning features throughout help you
master the subject by encouraging and supporting
independent study.
• Broad and fascinating range of examples ground the
study of genomics in the real world , inspiring you to
apply your knowledge of the subject more widely.
Arthur N. Lesk is Professor of Biochemistry and Molecular Biology at The Pennsylvania State University, USA.
|
any_adam_object | 1 |
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dewey-ones | 572 - Biochemistry |
dewey-raw | 572.86 |
dewey-search | 572.86 |
dewey-sort | 3572.86 |
dewey-tens | 570 - Biology |
discipline | Biologie |
edition | Third edition |
format | Book |
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spelling | Lesk, Arthur M. Verfasser (DE-588)1047454270 aut Introduction to genomics Arthur M. Lesk, The Pennsylvania State University Third edition Oxford, United Kingdom Oxford University Press [2017] xxvii, 509 Seiten, 1 ungezählte Seite Illustrationen, Diagramme, Karten txt rdacontent n rdamedia nc rdacarrier Genómica Génomique Genomics Genomik (DE-588)4776397-8 gnd rswk-swf Evolution (DE-588)4071050-6 gnd rswk-swf Genanalyse (DE-588)4200230-8 gnd rswk-swf (DE-588)4123623-3 Lehrbuch gnd-content Genomik (DE-588)4776397-8 s DE-604 Evolution (DE-588)4071050-6 s Genanalyse (DE-588)4200230-8 s HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029409626&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Regensburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029409626&sequence=000003&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Regensburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=029409626&sequence=000004&line_number=0003&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
spellingShingle | Lesk, Arthur M. Introduction to genomics Genómica Génomique Genomics Genomik (DE-588)4776397-8 gnd Evolution (DE-588)4071050-6 gnd Genanalyse (DE-588)4200230-8 gnd |
subject_GND | (DE-588)4776397-8 (DE-588)4071050-6 (DE-588)4200230-8 (DE-588)4123623-3 |
title | Introduction to genomics |
title_auth | Introduction to genomics |
title_exact_search | Introduction to genomics |
title_full | Introduction to genomics Arthur M. Lesk, The Pennsylvania State University |
title_fullStr | Introduction to genomics Arthur M. Lesk, The Pennsylvania State University |
title_full_unstemmed | Introduction to genomics Arthur M. Lesk, The Pennsylvania State University |
title_short | Introduction to genomics |
title_sort | introduction to genomics |
topic | Genómica Génomique Genomics Genomik (DE-588)4776397-8 gnd Evolution (DE-588)4071050-6 gnd Genanalyse (DE-588)4200230-8 gnd |
topic_facet | Genómica Génomique Genomics Genomik Evolution Genanalyse Lehrbuch |
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