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Main Author:	Lesk, Arthur M. (Author)
Format:	Book
Language:	English
Published:	Oxford, United Kingdom Oxford University Press [2017]
Edition:	Third edition
Subjects:	Genómica Génomique Genomics Genomik Evolution Genanalyse Lehrbuch
Online Access:	Inhaltsverzeichnis Inhaltsverzeichnis Klappentext
Physical Description:	xxvii, 509 Seiten, 1 ungezählte Seite Illustrationen, Diagramme, Karten
ISBN:	9780198754831 0198754833

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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.
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indexdate	2024-07-10T07:40:51Z
institution	BVB
isbn	9780198754831 0198754833
language	English
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physical	xxvii, 509 Seiten, 1 ungezählte Seite Illustrationen, Diagramme, Karten
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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
url	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 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 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
work_keys_str_mv	AT leskarthurm introductiontogenomics

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