Les mythes fondateurs de Gilgamesh à Noé (Bibliothèque Européenne/essais) (French Edition)

Human Molecular Genetics has been carefully crafted over successive editions to provide an authoritative introduction to the molecular aspects of human genetics, genomics and cell biology. Maintaining the features that have made previous editions so popular, this fifth edition has been completely updated in line with the latest developments in the field. Older technologies such as cloning and hybridization have been merged and summarized, coverage of newer DNA sequencing technologies has been expanded, and powerful new gene editing and single-cell genomics technologies have been added. The coverage of GWAS, functional genomics, stem cells, and disease modeling has been expanded. Greater focus is given to inheritance and variation in the context of populations and on the role of epigenetics in gene regulation. Key features: Fully integrated approach to the molecular aspects of human genetics, genomics, and cell biology Accessible text is supported and enhanced throughout by superb artwork illustrating the key concepts and mechanisms Summary boxes at the end of each chapter provide clear learning points Annotated further reading helps readers navigate the wealth of additional information in this complex subject and provides direction for further study Reorganized into five sections for improved access to related topics Also new to this edition - brand new chapter on evolution and anthropology from the authors of the highly acclaimed Human Evolutionary Genetics A proven and popular textbook for upper-level undergraduates and graduate students, the new edition of Human Molecular Genetics remains the 'go-to' book for those studying human molecular genetics or genomics courses around the world. Cover 1 Title Page 4 Copyright Page 5 Contents 6 Preface 10 About the authors 12 Contributors 14 PART 1: BASICS OF DNA, CHROMOSOMES, CELLS, DEVELOPMENT AND INHERITANCE 16 Chapter 1: BASIC PRINCIPLES OF NUCLEIC ACID STRUCTURE AND GENE EXPRESSION 18 1.1 Composition of nucleic acids and polypeptides 19 1.2 Base pairing in DNA and RNA, the double helix, and DNA replication 24 1.3 RNA transcription and gene expression 33 1.4 RNA processing 36 1.5 Translation, post-translational processing, and protein structure 43 Summary 54 Further reading 55 Chapter 2: FUNDAMENTALS OF CELLS AND CHROMOSOMES 56 2.1 Cell structure and diversity, and cell evolution 57 2.2 DNA and chromosome copy number during the cell cycle 66 2.3 Cell division and transmission of DNA to daughter cells 68 2.4 Structure and function of chromosomes 74 Summary 82 Further reading 82 Chapter 3: FUNDAMENTALS OF CELL–CELL INTERACTIONS AND IMMUNE SYSTEM BIOLOGY 84 3.1 Principles of cell signaling 84 3.2 Cell proliferation and programmed cell death 91 3.3 Cell adhesion and tissue formation 98 3.4 Immune system biology 103 Summary 119 Further reading 119 Chapter 4: ASPECTS OF EARLY MAMMALIAN DEVELOPMENT, CELL DIFFERENTIATION, AND STEM CELLS 122 4.1 Cell lineages and tissue differentiation in early mammalian development 122 4.2 Stem cells and cell differentiation 139 Summary 149 Further reading 150 Chapter 5: PATTERNS OF INHERITANCE 152 5.1 Monogenic versus multifactorial inheritance 153 5.2 Mendelian pedigree patterns 154 5.3 Mosaicism and new mutations 161 5.4 Non-Mendelian characters 165 Summary 171 Further reading 171 PART 2: UNDERSTANDING GENOMES 174 Chapter 6: CORE DNA TECHNOLOGIES: AMPLIFYING DNA, NUCLEIC ACID HYBRIDIZATION, AND DNA SEQUENCING 176 6.1 Cloning DNA in bacterial cells 177 6.2 Amplifying DNA by in vitro DNA replication 185 6.3 Nucleic acid hybridization: principles and uses 189 6.4 DNA sequencing principles and Sanger dideoxy sequencing 198 6.5 Massively-parallel DNA sequencing (next-generation sequencing) 201 Summary 215 Further reading 216 Chapter 7: ANALYZING THE STRUCTURE AND EXPRESSION OF GENES AND GENOMES 218 7.1 Genome structure analysis and genome projects 218 7.2 Basic gene expression analyses 234 7.3 High-throughput gene expression analyses 239 7.4 Single-cell genomics 248 Summary 255 Further reading 255 Chapter 8: PRINCIPLES OF GENETIC MANIPULATION OF MAMMALIAN CELLS 258 An overview of genome editing, gene silencing, and germ-line transgenesis 259 8.1 Artificial transfer of genetic material into mammalian cells 261 8.2 Principles of transgene expression in mammalian cells 272 8.3 Genome editing using homologous recombination 275 8.4 Genome editing using programmable site-specific endonucleases 278 8.5 Gene silencing 283 8.6 Germ-line transgenesis and transgenic animals 286 Summary 292 Further reading 293 Chapter 9: UNCOVERING THE ARCHITECTURE AND WORKINGS OF THE HUMAN GENOME 294 9.1 An overview of the human genome 294 9.2 Gene organization and distribution in the human genome 311 9.3 Heterochromatin DNA and transposon repeats 321 9.4 A start on working out how our genome functions 326 Summary 336 Further reading 337 Chapter 10: GENE REGULATION AND THE EPIGENOME 340 10.1 Chromatin accessibility and conformation 341 10.2 Histones and other DNA-binding proteins 343 10.3 Regulation by DNA methylation and noncoding RNAs 347 10.4 X-inactivation, imprinting, and epigenetic memory 352 10.5 Making the transcript: promoters and enhancers 360 10.6 Post-transcriptional regulation 365 Summary 370 Further Reading 371 PART 3: GENETIC VARIATION BETWEEN INDIVIDUALS AND SPECIES 374 Chapter 11: AN OVERVIEW OF HUMAN GENETIC VARIATION 376 11.1 Origins of DNA sequence variation 377 11.2 DNA repair 381 11.3 Population genomics and the scale of human genetic variation 386 11.4 Functional genetic variation and protein variation 396 11.5 Extraordinary genetic variation in the adaptive immune system 401 Summary 410 Further reading 411 Chapter 12: HUMAN POPULATION GENETICS 412 12.1 Allele frequencies and genotype frequencies: the Hardy–Weinberg relationship 412 12.2 Haplotype frequencies and linkage disequilibrium 414 12.3 Changing allele frequencies 419 12.4 Population structure and inbreeding 426 Summary 430 Further Reading 431 Chapter 13: COMPARATIVE GENOMICS AND GENOME EVOLUTION 434 13.1 Comparative genomics 434 13.2 Gene duplication, species differences in gene number, and evolutionary advantages of exons 447 13.3 Evolution of mammalian chromosomes 455 13.4 Regulatory sequence evolution and transposon origins of functional sequences 463 13.5 Phylogenetics and our place in the tree of life 469 Summary 472 Further reading 473 Chapter 14: HUMAN EVOLUTION 476 14.1 Human origins 476 14.2 Human evolutionary history from genome sequences 482 14.3 Inferring female and male histories using mitochondrial DNA and the Y chromosome 491 14.4 Health consequences of our evolutionary history 495 Summary 501 Further reading 502 PART 4: HUMAN GENETIC DISEASE 504 Chapter 15: CHROMOSOMAL ABNORMALITIES AND STRUCTURAL VARIANTS 506 15.1 Studying human chromosomes 506 15.2 Gross chromosome abnormalities 512 15.3 Structural variants, microdeletions, and microduplications 519 Summary 527 Further Reading 528 Chapter 16: MOLECULAR PATHOLOGY: CONNECTING PHENOTYPES TO GENOTYPES 530 16.1 Loss of function 531 16.2 Gain of function 542 16.3 Dynamic mutations: unstable repeat expansions 547 16.4 Molecular pathology of mitochondrial disorders 550 16.5 Genotype–phenotype correlations 553 Summary 561 Further reading 562 Chapter 17: MAPPING AND IDENTIFYING GENES FOR MONOGENIC DISORDERS 564 17.1 Positional cloning seeks to identify disease genes by first mapping them to a precise chromosomal location 565 17.2 Haplotype sharing and autozygosity 571 17.3 Whole-exome and whole-genome sequencing allow an unbiased and hypothesis-free approach to identifying the cause of a monogenic condition 574 17.4 Strategies for exome-based disease-gene identification 577 17.5 Confirming that the candidate gene is the correct one 581 Summary 585 Further reading 585 Chapter 18: COMPLEX DISEASE: IDENTIFYING SUSCEPTIBILITY FACTORS AND UNDERSTANDING PATHOGENESIS 588 Introduction 588 18.1 Investigation of complex disease: epidemiological approaches 589 18.2 Investigation of complex disease using linkage 592 18.3 Investigation of complex disease using association 594 18.4 The limitations of genome-wide association studies 603 18.5 What have we learned about the genetics of complex characters? 606 Summary 609 Further reading 610 Chapter 19: CANCER GENETICS AND GENOMICS 612 Introduction 612 19.1 Oncogenes 614 19.2 Tumor suppressor genes 620 19.3 Key oncogenes and tumor suppressor genes work mainly to regulate cell cycle checkpoints and genome maintenance 625 19.4 A genome-wide view of cancer 629 19.5 Using our new understanding of cancer 638 Summary 642 Further Reading 642 PART 5: APPLIED HUMAN MOLECULAR GENETICS 644 Chapter 20: GENETIC TESTING IN HEALTHCARE AND THE LAW 646 20.1 What to test and why 647 20.2 Testing for a specific genetic variant 648 20.3 Clinical diagnostic testing 652 20.4 Population screening 657 20.5 Pharmacogenetics and personalized medicine 666 20.6 DNA forensics: identifying individuals and relationships 672 Summary 679 Further Reading 680 Chapter 21: MODEL ORGANISMS AND MODELING DISEASE 682 21.1 An overview of model organisms 682 21.2 Cellular disease models 688 21.3 Origins of animal models of genetic disorders 693 21.4 How useful are animal models of genetic disorders? 700 Summary 706 Further reading 707 Chapter 22: GENETIC APPROACHES TO TREATING DISEASE 710 22.1 An overview of treating genetic disease and of genetic treatment of disease 711 22.2 Treating disease with genetically-engineered therapeutic proteins 714 22.3 Basic principles of gene therapy and RNA therapeutics 718 22.4 The practice of gene augmentation therapy for treating recessively inherited disorders 725 22.5 RNA therapeutics, therapeutic genome editing prospects, and genetic approaches to preventing disease 729 Summary 735 Further reading 736 Glossary 738 Index 758 Human Molecular Genetics has been carefully crafted over successive editions to provide an authoritative introduction to the molecular aspects of human genetics, genomics and cell biology. Maintaining the features that have made previous editions so popular, this fifth edition has been completely updated in line with the latest developments in the field. Older technologies such as cloning and hybridization have been merged and summarized, coverage of newer DNA sequencing technologies has been expanded, and powerful new gene editing and single-cell genomics technologies have been added. The coverage of GWAS, functional genomics, stem cells, and disease modeling has been expanded. Greater focus is given to inheritance and variation in the context of populations and on the role of epigenetics in gene regulation. Table of Contents Part 1: Basics of DNA, Chromosomes, Cells, Development, and Inheritance 1. Basic Principles of Nucleic Acid Structure and Gene Expression. 2. Fundamentals of Cells and Chromosomes. 3. Fundamentals of Cell-Cell Interactions and Immune System Biology. 4. Aspects of Early Mammalian Development, Cell Differentiation, and Stem Cells. 5. Patterns of Inheritance. Part 2: Understanding Genomes 6. Core DNA Technologies: Amplifying DNA, Nucleic Acid Hybirdization, and DNA Sequencing. 7. Analyzing the Structure and Expression of Genes and Genomes. 8. Principles of Genetic Manipulation of Mammalian Cells. 9. Uncovering the Architecture and Workings of the Human Genome. 10. Gene Regulation and the Epigenome. Part 3: Genetic Variation Between Individuals and Species 11. An Overview of Human Genetic Variation. 12. Human Population Genetics. 13. Comparative Genomics and Genome Evolution. 14. Human Evolution. Part 4: Human Genetic Disease 15. Chromosomal Abnormalities and Structural Variants. 16. Molecular Pathology: Connecting Phenotypes to Genotypes. 17. Mapping and Identifying Genes for Monogenic Disorders. 18. Complex Disease: Identifying Susceptibility Factors and Understanding Pathogenesis. 19. Cancer Genetics and Genomics. Part 5: Applied Human Molecular Genetics 20. Genetic Testing in Healthcare and the Law. 21. Model Organisms and Modeling Disease. 22. Genetic Approaches to Treating Disease This book is offers fully integrated approach to the molecular aspects of human genetics, genomics, and cell biology, accessible text is supported and enhanced throughout by artwork illustrating the key concepts and mechanisms