Genetics and genomics in medicine:
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Boca Raton ; London ; New York
CRC Press, Taylor & Francis Group
[2022]
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| Ausgabe: | Second edition |
| Schriftenreihe: | A Garland science book
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Klappentext |
| Beschreibung: | Includes bibliographical references |
| Beschreibung: | xviii, 534 Seiten Illustrationen |
| ISBN: | 9780367490812 0367490811 9780367490829 |
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| 245 | 1 | 0 | |a Genetics and genomics in medicine |c Tom Strachan and Anneke Lucassen |
| 250 | |a Second edition | ||
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| 300 | |a xviii, 534 Seiten |b Illustrationen | ||
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| 490 | 0 | |a A Garland science book | |
| 500 | |a Includes bibliographical references | ||
| 650 | 2 | |a Genetic Phenomena | |
| 650 | 2 | |a Genomics | |
| 650 | 2 | |a Genetic Diseases, Inborn - therapy | |
| 650 | 2 | |a Individualized Medicine | |
| 650 | 2 | |a Examination Questions | |
| 650 | 2 | |a Genetic Phenomena | |
| 650 | 2 | |a Genomics | |
| 650 | 2 | |a Genetic Diseases, Inborn |a therapy | |
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Datensatz im Suchindex
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Contents Mitosis: the usual form of cell division. 13 Meiosis: a specialized reductive cell division giving rise to sperm and egg cells. 13 Why each of our gametes is unique. 16 Preface. xv Acknowledgements. xviii 1 FUNDAMENTALS OF DNA, CHROMOSOMES, AND CELLS. 1 1.1 THE STRUCTURE AND FUNCTION OF NUCLEIC ACIDS. 2 General concepts: the genetic material, genomes, and genes. 2 The underlying chemistry of nucleic acids. 2 Base pairing and the double helix. 4 DNA replication and DNA polymerases. 5 Genes, transcription, and the central dogma of molecular biology. 7 1.2 SUMMARY. 18 QUESTIONS. 19 FURTHER READING. 19 2 FUNDAMENTALSOFGENESTRUCTURE, GENE EXPRESSION, AND HUMAN GENOME ORGANIZATION. 21 2.1 THE STRUCTURE AND FUNCTION OF CHROMOSOMES.8 Gene organization: exons and introns. 22 RNA splicing: stitching together the genetic information in exons.23 Translation: decoding messenger RNA to make a polypeptide. 24 From newly synthesized polypeptide to mature protein.29 Why we need highly
structured chromosomes, and how they are organized. 8 Chromosome function: replication origins, centromeres, and telomeres. 9 1.3 DNA AND CHROMOSOMES IN CELL DIVISION AND THE CELL CYCLE. 10 Differences in DNA copy number between cells. 10 The cell cycle and segregation of replicated chromosomes and DNA molecules. 11 PROTEIN-CODING GENES: STRUCTURE AND EXPRESSION. 22 2.2 RNA GENES AND NONCODING RNA. 32 The extraordinary secondary structure and versatility of RNA. 33 RNAs that act as specific regulators: from quirky exceptions to the mainstream.34 V
Contents 2.3 WORKING OUT THE DETAILS OF OUR GENOME AND WHAT THEY MEAN. 35 3 PRINCIPLES UNDERLYING CORE DNA TECHNOLOGIES.57 3.1 The Human Genome Project: working out the details of the nuclear genome. 35 What the sequence didn't tell us and the goal of identifying all Amplifying desired DNA within bacterial cells. 59 The need for vector DNA molecules.59 Physical clone separation. 60 The need for restriction nucleases. 60 DNA libraries and the uses and limitations of DNA cloning. 61 functional human DNA sequences. 37 2.4 A QUICK TOUR OF SOME ELECTRONIC RESOURCES USED TO INTERROGATE THE HUMAN GENOME SEQUENCE AND GENE PRODUCTS. 39 Gene nomenclature and the HGNC gateway. 40 Databases storing nucleotide and protein sequences. 40 Finding related nucleotide and protein sequences. 40 Links to clinical databases.42 2.5 3.2 SUMMARY. 53 QUESTIONS.54 FURTHER READING. 54 AMPLIFYING DNA USING THE POLYMERASE CHAIN REACTION (PCR). 62 Basics of the polymerase chain reaction
(PCR).62 Quantitative PCR and real-time PCR. 63 3.3 PRINCIPLES OF NUCLEIC ACID HYBRIDIZATION. 63 Formation of artificial heteroduplexes. 66 Hybridization assays: using known nucleic acids to find related sequences in a test nucleic acid population. 66 Microarray hybridization: largescale parallel hybridization to immobilized probes.70 THE ORGANIZATION AND EVOLUTION OF THE HUMAN GENOME. 42 A brief overview of the evolutionary mechanisms that shaped our genome. 42 How much of our genome is functionally significant?. 43 The mitochondrial genome: economical usage but limited autonomy. 44 Gene distribution in the human genome. 45 The extent of repetitive DNA in the human genome. 46 The organization of gene families. 47 The significance of gene duplication and repetitive coding DNA.50 Highly repetitive noncoding DNA in the human genome 51 AMPLIFYING DNA BY DNA CLONING.58 3.4 PRINCIPLES OF DNA SEQUENCING. 71 Dideoxy DNA sequencing.72 Massively parallel DNA sequencing (next-generation sequencing). 74 SUMMARY. 75 QUESTIONS.
76 FURTHER READING. 76 4 PRINCIPLES OF GENETIC VARIATION. 77 4.1 DNA SEQUENCE VARIATION ORIGINS AND DNA REPAIR. 79 Genetic variation arising from errors in chromosome and DNA function. 79
Contents Various endogenous and exogenous sources can cause damage to DNA by altering its chemical structure. 81 The wide range of DNA repair mechanisms. 82 Repair of DNA damage or altered seguence on a single DNA strand. 82 Repair of DNA lesions that affect both DNA strands. 83 Undetected DNA damage, DNA damage tolerance, and translesion synthesis. 84 4.2 POPULATION GENOMICS AND THE SCALE OF HUMAN GENETIC VARIATION. 87 DNA variants, polymorphisms, and human population genomics. 87 Small-scale variation: single nucleotide variants and small insertions and deletions. 89 Microsatellites and other variable number of tandem repeat (VNTR) polymorphisms. 90 Structural variation and low copy number variation. 91 Taking stock of human genetic variation. 92 4.3 4.4 Programmed and random posi zygotic genetic variation. Као Somatic mechanisms allow cell-specific production ol immunoglobulins and T i ell receptors. ]()() MHC (HLA) proteins: fune tions and polymorphism. ю? The medical importance ol the HLA system.ЮИ SUMMARY. 107 QUESTIONS. 108 FURTHER
READING. 108 5 SINGLE-GENE DISORDERS: INHERITANCE PATTERNS, PHENOTYPE VARIABILITY, AND ALLELE FREQUENCIES.109 5.1 EXTRAORDINARY GENETIC VARIATION IN THE IMMUNE SYSTEM.99 Pronounced genetic variation in four classes of immune system proteins. 99 INTRODUCTION: TERMINOLOGY, ELECTRONIC RESOURCES, AND PEDIGREES. 110 Background terminology and electronic resources with information on single-gene disorders. 110 Investigating family history of disease and recording pedigrees. Ill 5.2 FUNCTIONAL GENETIC VARIATION AND PROTEIN POLYMORPHISM. 93 The vast majority of genetic variation has a neutral effect on the phenotype, but a small fraction is harmful.93 Different types of Darwinian natural selection operate in human lineages. 94 Generating protein diversity by gene duplication: the example of olfactory receptor genes. 98 vii THE BASICS OF MENDELIAN AND MITOCHONDRIAL DNA INHERITANCE PATTERNS. 112 Autosomal dominant inheritance. 112 Autosomal recessive inheritance. 113 Sex-linked inheritance. 116 Matrilineal inheritance for mitochondrial DNA disorders. 121 5.3 UNCERTAINTY, HETEROGENEITY, AND VARIABLE EXPRESSION OF MENDELIAN PHENOTYPES. 122 Difficulties in defining the mode of inheritance in small pedigrees. 122 Heterogeneity in the correspondence
between phenotypes and the underlying genes and mutations. 124
Contents viii Nonpenetrance and age-related penetrance. 126 5.4 6.2 ALLELE FREQUENCIES IN POPULATIONS. 129 An overview of the molecular basis of epigenetic mechanisms. 150 Allele frequencies and the Hardy-Weinberg law.130 Applications and limitations of the Hardy-Weinberg law. 131 Ways in which allele frequencies change in populations. 132 Population bottlenecks and founder effects. 133 Mutation versus selection in determining allele frequencies. 135 Heterozygote advantage: when natural selection favors carriers of recessive disease. 136 How changes in chromatin structure produce altered gene expression. 151 Histone modification and histone substitution in nucleosomes. 152 Modified histones and histone variants affect chromatin structure. 154 The function of DNA methylation in mammalian cells. 155 DNA methylation: mechanisms, heritability, and global roles during early development and gametogenesis . 156 Long noncoding RNAs in mammalian epigenetic regulation. 158 Genomic imprinting: differential expression of maternally and paternally inherited alleles. 160 X-chromosome inactivation: compensating for sex differences in gene dosage. 163
SUMMARY. 137 QUESTIONS. 138 FURTHER READING. 138 6 PRINCIPLES OF GENE REGULATION AND EPIGENETICS. Ί39 The two fundamental types of gene regulation. 139 Os-acting and rrans-acting effects in gene regulation. 140 6.1 GENETIC REGULATION OF GENE EXPRESSION. 141 Promoters: the major on֊off switches in genes. 141 Modulating transcription and tissue-specific regulation. 142 Transcription factor binding and specificity.143 Genetic regulation during RNA processing: RNA splicing and RNA editing. 144 Translational regulation by trans acting regulatory proteins. 147 Post-transcriptional gene silencing by microRNAs. 148 Repressing the repressors: competing endogenous RNAs sequester miRNA. 148 CHROMATIN MODIFICATION AND EPIGENETIC FACTORS IN GENE REGULATION. 150 6.3 ABNORMAL EPIGENETIC REGULATION IN MENDELIAN DISORDERS AND UNIPARENTAL DISOMY 165 Principles of epigenetic dysrégulation.165 "Chromatin diseases" due to mutations in genes specifying chromatin modifiers. 167 Disease resulting from dysrégulation of heterochromatin. 168 Uniparental disomy and
disorders of imprinting. 171 Abnormal gene regulation at imprinted loci. 172 SUMMARY. 176 QUESTIONS. 176 FURTHER READING. 177
Contents 7 HOW GENETIC VARIATION IN DNA AND CHROMOSOMES CAUSES DISEASE. 179 7.1 AN OVERVIEW OF HOW GENETIC VARIATION RESULTS IN DISEASE.180 Disease arising from stepna ке exchanges between disumtiv located repeats in nuclear DNA. ír 7.5 PATHOGENIC NUCLEOTIDE SUBSTITUTIONS AND TINY INSERTIONS AND DELETIONS. 183 Pathogenic single nucleotide substitutions within coding sequences. 183 Mutations that result in premature termination codons. 185 Genesis and frequency of pathogenic point mutations.188 Surveying and curating point mutations that cause disease. 191 7.3 7.6 7.7 PATHOGENESIS DUE TO VARIATION IN SHORT TANDEM REPEAT COPY NUMBER 192 EFFECTS ON THE PHENOTYPE OF PATHOGENIC VARIANTS IN NUCLEAR DNA. 217 Mutations affecting how a single gene works: an overview of loss of function and gain of function. 218 The effect of pathogenic variants depends on how the products of alleles interact: dominance and recessiveness revisited. 220 Gain-of-function and loss֊offunction mutations in the same gene can produce different phenotypes. 223 Multiple gene dysrégulation resulting from aneuploidies and mutations in regulatory genes. 224 PATHOGENESIS TRIGGERED BY LONG TANDEM REPEATS AND INTERSPERSED REPEATS. 198 Pathogenic exchanges between repeats occurs in both
nuclear DNA and mtDNA.198 Nonallelic homologous recombination and transposition.199 Pathogenic sequence exchanges between chromatids at mispaired tandem repeats. 199 MOLECULAR PATHOLOGY OF MITOCHONDRIAL DISORDERS.212 Mitochondrial disorders dur֊ to mtDNA mutation show maternal inheritance and variable proportions of mutant genotypes. 211 The two major classes of pathogenic DNA variant in mtDNA: large deletions and point mutations.215 The two main classes of pathogenic variation in short tandem repeat copy-number. 192 Dynamic disease-causing mutations due to unstable expansion of short tandem repeats. 194 Unstable expansion of short tandem repeats can cause disease in different ways. 197 7.4 CHROMOSOME ABNORMALITIES 204 Structural chromosomal abnormalities. »աո Chromosomal abnormalit ies involving gain or loss of compitar֊ chromosomes . ton The importance of repeat sequences in triggering pathogenesis. 182 7.2 ix 7.8 A PROTEIN STRUCTURE PERSPECTIVE OF MOLECULAR PATHOLOGY. 225 Pathogenesis arising from protein misfolding. 226
Contents x Estimating heritability: the contribution made by genetic factors to the variance of complex diseases. 256 The very limited success of linkage analyses in identifying genes underlying complex genetic diseases. 259 The fundamentals of allelic association and the importance of HLA-disease associations. 262 Linkage disequilibrium as the basis of allelic associations.266 How genomewide association studies are carried out. 270 Moving from candidate subchromosomal region to identify causal genetic variants in complex disease can be challenging. 273 The limitations of GWA studies and the issue of missing heritability. 274 Alternative genome-wide studies and the role of rare variants and copy number variants in complex disease. 276 The assessment and prediction of risk for common genetic diseases and the development of polygenic risk scores. 278 The many different ways in which protein aggregation can result in disease. 226 7.9 GENOTYPE-PHENOTYPE CORRELATIONS AND WHY MONOGENIC DISORDERS ARE OFTEN NOT SIMPLE. 231 The difficulty in getting reliable genotype-phenotype correlations. 231 Modifier genes and environmental factors: common explanations for poor genotype-phenotype correlations. 232
SUMMARY. 236 QUESTIONS.237 FURTHER READING. 237 8 IDENTIFYING DISEASE GENES AND GENETIC SUSCEPTIBILITY TO COMPLEX DISEASE. 239 8.1 IDENTIFYING GENES IN MONOGENIC DISORDERS. 240 A historical overview of identifying genes in monogenic disorders. 240 Linkage analysis to map genes for monogenic disorders to defined subchromosomal regions. 241 Chromosome abnormalities and other large-scale mutations as routes to identifying disease genes.248 Exorne sequencing: let's not bother getting a position for disease genes!. 248 8.2 APPROACHES TO MAPPING AND IDENTIFYING GENETIC SUSCEPTIBILITY TO COMPLEX DISEASE. 251 The polygenic and multifactorial nature of common genetic disorders. 252 Difficulties with lack of penetrance and phenotype classification in complex disease. 255 8.3 ASPECTS OF THE GENETIC ARCHITECTURE OF COMPLEX DISEASE AND THE CONTRIBUTIONS OF ENVIRONMENTAL AND EPIGENETIC FACTORS. 280 Common neurodegenerative disease: from monogenic to polygenic disease. 283 The importance of immune system pathways in common genetic disease. 287 The importance of protective factors and how a susceptibility factor for one complex disease may be a protective
factor for another disease. 289
Contents Gene-environment interactions in complex disease. 290 Epigenetics in complex disease and aging: significance and experimental approaches.294 Translating genomic advances ami developing generic drugs as u way of overcoming the problem of too few drug targets. Developing biological drugs: therapeutic proteins produced by genetic engineering.vú Genetically engineered therapeutic antibodies with improved therapeutic potential. VO SUMMARY. 297 QUESTIONS.298 FURTHER READING. 298 9 GENETIC APPROACHES TO TREATING DISEASE. 301 9.1 PRINCIPLES OF GENE AND CELL THERAPY.329 AN OVERVIEW OF TREATING GENETIC DISEASE AND OF GENETIC TREATMENT OF DISEASE. 303 Two broad strategies in somatic gene therapy. 329 The delivery problem: designing optimal and safe strategies for getting genetic constructs into the cells of patients. »0 Different ways of delivering therapeutic genetic constructs, and the advantages of ex vivo gene therapy. 334 Viral delivery of therapeutic gene1 constructs: relatively high efficiency but safety concerns. 330 Virus vectors used in gene therapy. 330 The importance of disease models for testing potential therapies in
humans. 33/ Three different broad approaches to treating genetic disorders. 303 Very different treatment options for different inborn errors of metabolism. 305 Genetic treatment of disease may be conducted at many different levels.309 9.2 GENETIC INPUTS INTO TREATING DISEASE WITH SMALL MOLECULE DRUGS AND THERAPEUTIC PROTEINS.310 An overview of how genetic differences affect the metabolism and performance of small molecule drugs 311 Phenotype differences arising from genetic variation in drug metabolism.313 Genetic variation in enzymes that work in phase II drug metabolism. 317 Altered drug responses resulting from genetic variation in drug targets. 318 When genotypes at multiple loci in patients are important in drug treatment: the example of warfarin. 321 Translating genetic advances: from identifying novel disease genes to therapeutic small molecule drugs. 322 xi 94 GENE THERAPY FOR INHERITED DISORDERS: PRACTICE AND FUTURE DIRECTIONS. 340 Multiple successes for ex vivo gene supplementation therapy targeted at hematopoietic stem cells. 340 in vivo gene therapy: approaches, barriers, and recent successes. 342 An overview of RNA and oligonucleotide therapeutics. 344 RNA interference therapy. 347 Future therapeutic prospects using CRISPR-Cas gene
editing. 349 Therapeutic applications of stem cells and cell reprogramming. 353 Obstacles to overcome in cell therapy. 353
xii Contents A special case: preventing transmission of severe mitochondrial DNA disorders by mitochondrial replacement. 355 SUMMARY. 356 QUESTIONS. 358 FURTHER READING. 358 10 CANCER GENETICS AND GENOMICS. 361 10.1 FUNDAMENTAL CHARACTERISTICS AND EVOLUTION OF CANCER. 362 The defining features of unregulated cell growth and cancer. 362 Why cancers are different from other diseases: the contest between natural selection operating at the level of the cell and the level of the organism. 364 Cancer cells acquire several distinguishing biological characteristics during their evolution. 366 The initiation and multistage nature of cancer evolution and why most human cancers develop over many decades. 369 Intratumor heterogeneity arises through cell infiltration, clonal evolution, and differentiation of cancer stem cells. 372 10.2 ONCOGENES AND TUMOR SUPPRESSOR GENES. 375 Two fundamental classes of cancer gene. 375 Viral oncogenes and the natural roles of cellular oncogenes.376 How normal cellular proto oncogenes are activated to become cancer genes. 376 Tumor suppressor genes: normal functions, the two-hit paradigm, and loss of heterozygosity in linked markers.
380 The key roles of gatekeeper tumor suppressor genes in suppressing GrS transition in the cell cycle. 383 The additional role of p53 in activating different apoptosis pathways to ensure that rogue cells are destroyed.384 Tumor suppressor involvement in rare familial cancers and non-classical tumor suppressors. 384 The significance of miRNAs and long noncoding RNAs in cancer. 388 10.3 GENOMIC INSTABILITY AND EPIGENETIC DYSREGULATION IN CANCER.389 Different types of chromosomal instability in cancer. 390 Deficiency in mismatch repair results in unrepaired replication errors and global DNA instability. 392 Different classes of cancer susceptibility gene according to epigenetic function, epigenetic dysrégulation, and epigenome genome interaction . 395 10.4 NEW INSIGHTS FROM GENOME-WIDE STUDIES OF CANCERS. 397 Genome sequencing has revealed extraordinary mutational diversity in tumors and insights into cancer evolution. 398 Defining the landscape of driver mutations in cancer and establishing a complete inventory of cancer-susceptibility genes. 401 Tracing the mutational history of cancers: just one of the diverse applications of single-cell genomics and transcriptomics in cancer. 404 Genome-wide RNA sequencing enables insights into the link
Contents between cancer genomes and cancer biology and aids tumor classification. 405 10.5 GENETIC INROADS INTO CANCER THERAPY. 407 Targeted anticancer therapies are directed against key cancer cell proteins involved in oncogenesis or in escaping immunosurveillance. 408 CAR-T Cell therapy and the use of genetically engineered T cells to treat cancer. 410 The molecular basis of tumor recurrence and the evolution of drug resistance in cancers. 411 The promise of combinatorial drug therapies. 413 SUMMARY. 413 QUESTIONS. 415 FURTHER READING.415 11 GENETIC AND GENOMIC TESTING IN HEALTHCARE: PRACTICAL AND ETHICAL ASPECTS. 417 11.1 AN OVERVIEW OF GENETIC TESTING. 418 The different source materials and different levels of genetic testing. 419 11.2 GENETIC TESTING FOR CHROMOSOME ABNORMALITIES AND PATHOGENIC STRUCTURAL VARIATION. 423 Screening for aneuploidies using quantitative fluorescence PCR. 424 Detecting large-scale copy number variants using chromosome SNP microarray analysis.425 Detecting and scanning for oncogenic fusion genes using, respectively, chromosome FISH and targeted RNA
sequencing. 428 xiii Detecting pathogemc modetatc to small-scale deletions and duplications at defined loc i о often achieved usi tig the ML PA or ddPCR met hods. g зо Two very different routes towaids universal genome-wide screens for structural variation: genome wide sequencing and optical genome mapping.433 11.3 GENETIC AND GENOMIC TESTING FOR PATHOGENIC POINT MUTATIONS AND DNA METHYLATION TESTING. 433 Diverse methods permit rapid genotyping of specific point mutations. 4 36 The advantages of multiplex genotyping.4 38 Mutation scanning: from genes and gene panels to whole exorne and whole genome sequencing. 440 Interpreting and validating sequence variants can be aided by extensive online resources. 442 Detecting aberrant DNA methylation profiles associated with disease. 448 11.4 GENETIC AND GENOMIC TESTING: ORGANIZATION OF SERVICES AND PRACTICAL APPLICATIONS. 450 The developing transformation of genetic services into mainstream genomic medicine. 450 An overview of diagnostic and pre-symptomatic or predictive genetic testing. 453 The different ways in which diagnosis of genetic conditions is carried out in the prenatal period.456 Preimplantation genetic testing is carried out to prevent
xiv Contents the transmission of a harmful genetic defect using in vitro fertilization. 460 Noninvasive prenatal testing (NIPT) and whole genome testing of the fetus. 461 An overview of the different types of genetic screening. 463 Pregnancy screening for fetal abnormalities. 463 Newborn screening allows the possibility of early medical intervention. 464 Different types of carrier screening can be carried out for autosomal recessive conditions. 466 New genomic technologies are being exploited in cancer diagnostics. 468 Bypassing healthcare services: the rise of direct-to֊consumer (DTC) genetic testing. 470 The downsides of improved sensitivity through whole genome sequencing: increased uncertainty about what variants mean. 472 11.5 ETHICAL, LEGAL, AND SOCIETAL ISSUES (ELSI) IN GENETIC TESTING. 473 Genetic information as family information. 473 Consent issues in genetic testing. 474 The generation of genetic data is outstripping the ability to provide clinical interpretation. 477 New disease gene discovery and changing concepts of diagnosis. 479 Complications in diagnosing mitochondrial disease. 479 Complications arising from incidental, additional, secondary, or
unexpected information. 480 Consent issues in testing children. 482 Ethical and societal issues in prenatal diagnosis and testing. 483 Ethical and social issues in some emerging treatments for genetic disorders. 485 The ethics of germline gene modification for gene therapy and genetic enhancement.487 SUMMARY. 489 QUESTIONS. 491 FURTHER READING. 491 Glossary. 493 Index. 509
GENETICS AND GENOMICS IN MEDICINE Second Edition The second edition of this textbook written for undergraduate students, graduate students and medical researchers, Genetics and Genomics in Medicine explains the science behind the uses of genetics and genomics in medicine today, and how it is being applied. Maintaining the features that made the first edition so popular, this second edition has been thoroughly updated in line with the latest developments in the field. DNA technologies are explained, with emphasis on the modern techniques that are revolutionizing the use of genetic information in medicine and indicating the role of genetics in common diseases. Epigenetics and non-coding RNA are covered in-depth as are genetic approaches to treatment and prevention, including pharmacogenomics, genetic testing and personalized medicine. A dedicated chapter charts the latest insights into the molecular basis of cancers, cancer genomics and novel approaches to cancer detection. Coverage of genetic testing at the level of genes, chromosomes and genomes has been significantly expanded and updated. Extra prominence has been given to additional genomic analyses, ethical aspects and novel therapeutic approaches. Various case studies illustrate selected clinical applications. Key Features • Comprehensive and integrated account of how genetics and genomics affect the entire spectrum of human health and disease • Exquisite artwork illuminates the key concepts and mechanisms • Summary points at the end of each chapter help to consolidate learning • For each chapter, an abundance of
further reading to help provide the reader with direction for further study • Inclusive online question bank to test understanding • Standard boxes summarizing certain key principles in genetics • Clinical boxes summarizing selected case studies, pathogenesis mechanisms or novel therapies for selected diseases This book is equally suited for newcomers to the field as well as for engineers and scientists that have basic knowledge in this field but are interested in obtaining more information about specific future applications. About the Authors Tom Strachan is Emeritus Professor of Human Molecular Genetics at Newcastle University, UK. Together with a former colleague, Andrew Read, he writes the popular Human Molecular Genetics textbook, now in its Fifth Edition. Anneke Lucassen is Professor of Genomic Medicine and Director of the Centre for Personalised Medicine at the University of Oxford, UK к |
| adam_txt |
Contents Mitosis: the usual form of cell division. 13 Meiosis: a specialized reductive cell division giving rise to sperm and egg cells. 13 Why each of our gametes is unique. 16 Preface. xv Acknowledgements. xviii 1 FUNDAMENTALS OF DNA, CHROMOSOMES, AND CELLS. 1 1.1 THE STRUCTURE AND FUNCTION OF NUCLEIC ACIDS. 2 General concepts: the genetic material, genomes, and genes. 2 The underlying chemistry of nucleic acids. 2 Base pairing and the double helix. 4 DNA replication and DNA polymerases. 5 Genes, transcription, and the central dogma of molecular biology. 7 1.2 SUMMARY. 18 QUESTIONS. 19 FURTHER READING. 19 2 FUNDAMENTALSOFGENESTRUCTURE, GENE EXPRESSION, AND HUMAN GENOME ORGANIZATION. 21 2.1 THE STRUCTURE AND FUNCTION OF CHROMOSOMES.8 Gene organization: exons and introns. 22 RNA splicing: stitching together the genetic information in exons.23 Translation: decoding messenger RNA to make a polypeptide. 24 From newly synthesized polypeptide to mature protein.29 Why we need highly
structured chromosomes, and how they are organized. 8 Chromosome function: replication origins, centromeres, and telomeres. 9 1.3 DNA AND CHROMOSOMES IN CELL DIVISION AND THE CELL CYCLE. 10 Differences in DNA copy number between cells. 10 The cell cycle and segregation of replicated chromosomes and DNA molecules. 11 PROTEIN-CODING GENES: STRUCTURE AND EXPRESSION. 22 2.2 RNA GENES AND NONCODING RNA. 32 The extraordinary secondary structure and versatility of RNA. 33 RNAs that act as specific regulators: from quirky exceptions to the mainstream.34 V
Contents 2.3 WORKING OUT THE DETAILS OF OUR GENOME AND WHAT THEY MEAN. 35 3 PRINCIPLES UNDERLYING CORE DNA TECHNOLOGIES.57 3.1 The Human Genome Project: working out the details of the nuclear genome. 35 What the sequence didn't tell us and the goal of identifying all Amplifying desired DNA within bacterial cells. 59 The need for vector DNA molecules.59 Physical clone separation. 60 The need for restriction nucleases. 60 DNA libraries and the uses and limitations of DNA cloning. 61 functional human DNA sequences. 37 2.4 A QUICK TOUR OF SOME ELECTRONIC RESOURCES USED TO INTERROGATE THE HUMAN GENOME SEQUENCE AND GENE PRODUCTS. 39 Gene nomenclature and the HGNC gateway. 40 Databases storing nucleotide and protein sequences. 40 Finding related nucleotide and protein sequences. 40 Links to clinical databases.42 2.5 3.2 SUMMARY. 53 QUESTIONS.54 FURTHER READING. 54 AMPLIFYING DNA USING THE POLYMERASE CHAIN REACTION (PCR). 62 Basics of the polymerase chain reaction
(PCR).62 Quantitative PCR and real-time PCR. 63 3.3 PRINCIPLES OF NUCLEIC ACID HYBRIDIZATION. 63 Formation of artificial heteroduplexes. 66 Hybridization assays: using known nucleic acids to find related sequences in a test nucleic acid population. 66 Microarray hybridization: largescale parallel hybridization to immobilized probes.70 THE ORGANIZATION AND EVOLUTION OF THE HUMAN GENOME. 42 A brief overview of the evolutionary mechanisms that shaped our genome. 42 How much of our genome is functionally significant?. 43 The mitochondrial genome: economical usage but limited autonomy. 44 Gene distribution in the human genome. 45 The extent of repetitive DNA in the human genome. 46 The organization of gene families. 47 The significance of gene duplication and repetitive coding DNA.50 Highly repetitive noncoding DNA in the human genome 51 AMPLIFYING DNA BY DNA CLONING.58 3.4 PRINCIPLES OF DNA SEQUENCING. 71 Dideoxy DNA sequencing.72 Massively parallel DNA sequencing (next-generation sequencing). 74 SUMMARY. 75 QUESTIONS.
76 FURTHER READING. 76 4 PRINCIPLES OF GENETIC VARIATION. 77 4.1 DNA SEQUENCE VARIATION ORIGINS AND DNA REPAIR. 79 Genetic variation arising from errors in chromosome and DNA function. 79
Contents Various endogenous and exogenous sources can cause damage to DNA by altering its chemical structure. 81 The wide range of DNA repair mechanisms. 82 Repair of DNA damage or altered seguence on a single DNA strand. 82 Repair of DNA lesions that affect both DNA strands. 83 Undetected DNA damage, DNA damage tolerance, and translesion synthesis. 84 4.2 POPULATION GENOMICS AND THE SCALE OF HUMAN GENETIC VARIATION. 87 DNA variants, polymorphisms, and human population genomics. 87 Small-scale variation: single nucleotide variants and small insertions and deletions. 89 Microsatellites and other variable number of tandem repeat (VNTR) polymorphisms. 90 Structural variation and low copy number variation. 91 Taking stock of human genetic variation. 92 4.3 4.4 Programmed and random posi zygotic genetic variation. Као Somatic mechanisms allow cell-specific production ol immunoglobulins and T i ell receptors. ]()() MHC (HLA) proteins: fune tions and polymorphism. ю? The medical importance ol the HLA system.ЮИ SUMMARY. 107 QUESTIONS. 108 FURTHER
READING. 108 5 SINGLE-GENE DISORDERS: INHERITANCE PATTERNS, PHENOTYPE VARIABILITY, AND ALLELE FREQUENCIES.109 5.1 EXTRAORDINARY GENETIC VARIATION IN THE IMMUNE SYSTEM.99 Pronounced genetic variation in four classes of immune system proteins. 99 INTRODUCTION: TERMINOLOGY, ELECTRONIC RESOURCES, AND PEDIGREES. 110 Background terminology and electronic resources with information on single-gene disorders. 110 Investigating family history of disease and recording pedigrees. Ill 5.2 FUNCTIONAL GENETIC VARIATION AND PROTEIN POLYMORPHISM. 93 The vast majority of genetic variation has a neutral effect on the phenotype, but a small fraction is harmful.93 Different types of Darwinian natural selection operate in human lineages. 94 Generating protein diversity by gene duplication: the example of olfactory receptor genes. 98 vii THE BASICS OF MENDELIAN AND MITOCHONDRIAL DNA INHERITANCE PATTERNS. 112 Autosomal dominant inheritance. 112 Autosomal recessive inheritance. 113 Sex-linked inheritance. 116 Matrilineal inheritance for mitochondrial DNA disorders. 121 5.3 UNCERTAINTY, HETEROGENEITY, AND VARIABLE EXPRESSION OF MENDELIAN PHENOTYPES. 122 Difficulties in defining the mode of inheritance in small pedigrees. 122 Heterogeneity in the correspondence
between phenotypes and the underlying genes and mutations. 124
Contents viii Nonpenetrance and age-related penetrance. 126 5.4 6.2 ALLELE FREQUENCIES IN POPULATIONS. 129 An overview of the molecular basis of epigenetic mechanisms. 150 Allele frequencies and the Hardy-Weinberg law.130 Applications and limitations of the Hardy-Weinberg law. 131 Ways in which allele frequencies change in populations. 132 Population bottlenecks and founder effects. 133 Mutation versus selection in determining allele frequencies. 135 Heterozygote advantage: when natural selection favors carriers of recessive disease. 136 How changes in chromatin structure produce altered gene expression. 151 Histone modification and histone substitution in nucleosomes. 152 Modified histones and histone variants affect chromatin structure. 154 The function of DNA methylation in mammalian cells. 155 DNA methylation: mechanisms, heritability, and global roles during early development and gametogenesis . 156 Long noncoding RNAs in mammalian epigenetic regulation. 158 Genomic imprinting: differential expression of maternally and paternally inherited alleles. 160 X-chromosome inactivation: compensating for sex differences in gene dosage. 163
SUMMARY. 137 QUESTIONS. 138 FURTHER READING. 138 6 PRINCIPLES OF GENE REGULATION AND EPIGENETICS. Ί39 The two fundamental types of gene regulation. 139 Os-acting and rrans-acting effects in gene regulation. 140 6.1 GENETIC REGULATION OF GENE EXPRESSION. 141 Promoters: the major on֊off switches in genes. 141 Modulating transcription and tissue-specific regulation. 142 Transcription factor binding and specificity.143 Genetic regulation during RNA processing: RNA splicing and RNA editing. 144 Translational regulation by trans acting regulatory proteins. 147 Post-transcriptional gene silencing by microRNAs. 148 Repressing the repressors: competing endogenous RNAs sequester miRNA. 148 CHROMATIN MODIFICATION AND EPIGENETIC FACTORS IN GENE REGULATION. 150 6.3 ABNORMAL EPIGENETIC REGULATION IN MENDELIAN DISORDERS AND UNIPARENTAL DISOMY 165 Principles of epigenetic dysrégulation.165 "Chromatin diseases" due to mutations in genes specifying chromatin modifiers. 167 Disease resulting from dysrégulation of heterochromatin. 168 Uniparental disomy and
disorders of imprinting. 171 Abnormal gene regulation at imprinted loci. 172 SUMMARY. 176 QUESTIONS. 176 FURTHER READING. 177
Contents 7 HOW GENETIC VARIATION IN DNA AND CHROMOSOMES CAUSES DISEASE. 179 7.1 AN OVERVIEW OF HOW GENETIC VARIATION RESULTS IN DISEASE.180 Disease arising from stepna ке exchanges between disumtiv located repeats in nuclear DNA. ír 7.5 PATHOGENIC NUCLEOTIDE SUBSTITUTIONS AND TINY INSERTIONS AND DELETIONS. 183 Pathogenic single nucleotide substitutions within coding sequences. 183 Mutations that result in premature termination codons. 185 Genesis and frequency of pathogenic point mutations.188 Surveying and curating point mutations that cause disease. 191 7.3 7.6 7.7 PATHOGENESIS DUE TO VARIATION IN SHORT TANDEM REPEAT COPY NUMBER 192 EFFECTS ON THE PHENOTYPE OF PATHOGENIC VARIANTS IN NUCLEAR DNA. 217 Mutations affecting how a single gene works: an overview of loss of function and gain of function. 218 The effect of pathogenic variants depends on how the products of alleles interact: dominance and recessiveness revisited. 220 Gain-of-function and loss֊offunction mutations in the same gene can produce different phenotypes. 223 Multiple gene dysrégulation resulting from aneuploidies and mutations in regulatory genes. 224 PATHOGENESIS TRIGGERED BY LONG TANDEM REPEATS AND INTERSPERSED REPEATS. 198 Pathogenic exchanges between repeats occurs in both
nuclear DNA and mtDNA.198 Nonallelic homologous recombination and transposition.199 Pathogenic sequence exchanges between chromatids at mispaired tandem repeats. 199 MOLECULAR PATHOLOGY OF MITOCHONDRIAL DISORDERS.212 Mitochondrial disorders dur֊ to mtDNA mutation show maternal inheritance and variable proportions of mutant genotypes. 211 The two major classes of pathogenic DNA variant in mtDNA: large deletions and point mutations.215 The two main classes of pathogenic variation in short tandem repeat copy-number. 192 Dynamic disease-causing mutations due to unstable expansion of short tandem repeats. 194 Unstable expansion of short tandem repeats can cause disease in different ways. 197 7.4 CHROMOSOME ABNORMALITIES 204 Structural chromosomal abnormalities. »աո Chromosomal abnormalit ies involving gain or loss of compitar֊ chromosomes . ton The importance of repeat sequences in triggering pathogenesis. 182 7.2 ix 7.8 A PROTEIN STRUCTURE PERSPECTIVE OF MOLECULAR PATHOLOGY. 225 Pathogenesis arising from protein misfolding. 226
Contents x Estimating heritability: the contribution made by genetic factors to the variance of complex diseases. 256 The very limited success of linkage analyses in identifying genes underlying complex genetic diseases. 259 The fundamentals of allelic association and the importance of HLA-disease associations. 262 Linkage disequilibrium as the basis of allelic associations.266 How genomewide association studies are carried out. 270 Moving from candidate subchromosomal region to identify causal genetic variants in complex disease can be challenging. 273 The limitations of GWA studies and the issue of missing heritability. 274 Alternative genome-wide studies and the role of rare variants and copy number variants in complex disease. 276 The assessment and prediction of risk for common genetic diseases and the development of polygenic risk scores. 278 The many different ways in which protein aggregation can result in disease. 226 7.9 GENOTYPE-PHENOTYPE CORRELATIONS AND WHY MONOGENIC DISORDERS ARE OFTEN NOT SIMPLE. 231 The difficulty in getting reliable genotype-phenotype correlations. 231 Modifier genes and environmental factors: common explanations for poor genotype-phenotype correlations. 232
SUMMARY. 236 QUESTIONS.237 FURTHER READING. 237 8 IDENTIFYING DISEASE GENES AND GENETIC SUSCEPTIBILITY TO COMPLEX DISEASE. 239 8.1 IDENTIFYING GENES IN MONOGENIC DISORDERS. 240 A historical overview of identifying genes in monogenic disorders. 240 Linkage analysis to map genes for monogenic disorders to defined subchromosomal regions. 241 Chromosome abnormalities and other large-scale mutations as routes to identifying disease genes.248 Exorne sequencing: let's not bother getting a position for disease genes!. 248 8.2 APPROACHES TO MAPPING AND IDENTIFYING GENETIC SUSCEPTIBILITY TO COMPLEX DISEASE. 251 The polygenic and multifactorial nature of common genetic disorders. 252 Difficulties with lack of penetrance and phenotype classification in complex disease. 255 8.3 ASPECTS OF THE GENETIC ARCHITECTURE OF COMPLEX DISEASE AND THE CONTRIBUTIONS OF ENVIRONMENTAL AND EPIGENETIC FACTORS. 280 Common neurodegenerative disease: from monogenic to polygenic disease. 283 The importance of immune system pathways in common genetic disease. 287 The importance of protective factors and how a susceptibility factor for one complex disease may be a protective
factor for another disease. 289
Contents Gene-environment interactions in complex disease. 290 Epigenetics in complex disease and aging: significance and experimental approaches.294 Translating genomic advances ami developing generic drugs as u way of overcoming the problem of too few drug targets. Developing biological drugs: therapeutic proteins produced by genetic engineering.vú Genetically engineered therapeutic antibodies with improved therapeutic potential. VO SUMMARY. 297 QUESTIONS.298 FURTHER READING. 298 9 GENETIC APPROACHES TO TREATING DISEASE. 301 9.1 PRINCIPLES OF GENE AND CELL THERAPY.329 AN OVERVIEW OF TREATING GENETIC DISEASE AND OF GENETIC TREATMENT OF DISEASE. 303 Two broad strategies in somatic gene therapy. 329 The delivery problem: designing optimal and safe strategies for getting genetic constructs into the cells of patients. »0 Different ways of delivering therapeutic genetic constructs, and the advantages of ex vivo gene therapy. 334 Viral delivery of therapeutic gene1 constructs: relatively high efficiency but safety concerns. 330 Virus vectors used in gene therapy. 330 The importance of disease models for testing potential therapies in
humans. 33/ Three different broad approaches to treating genetic disorders. 303 Very different treatment options for different inborn errors of metabolism. 305 Genetic treatment of disease may be conducted at many different levels.309 9.2 GENETIC INPUTS INTO TREATING DISEASE WITH SMALL MOLECULE DRUGS AND THERAPEUTIC PROTEINS.310 An overview of how genetic differences affect the metabolism and performance of small molecule drugs 311 Phenotype differences arising from genetic variation in drug metabolism.313 Genetic variation in enzymes that work in phase II drug metabolism. 317 Altered drug responses resulting from genetic variation in drug targets. 318 When genotypes at multiple loci in patients are important in drug treatment: the example of warfarin. 321 Translating genetic advances: from identifying novel disease genes to therapeutic small molecule drugs. 322 xi 94 GENE THERAPY FOR INHERITED DISORDERS: PRACTICE AND FUTURE DIRECTIONS. 340 Multiple successes for ex vivo gene supplementation therapy targeted at hematopoietic stem cells. 340 in vivo gene therapy: approaches, barriers, and recent successes. 342 An overview of RNA and oligonucleotide therapeutics. 344 RNA interference therapy. 347 Future therapeutic prospects using CRISPR-Cas gene
editing. 349 Therapeutic applications of stem cells and cell reprogramming. 353 Obstacles to overcome in cell therapy. 353
xii Contents A special case: preventing transmission of severe mitochondrial DNA disorders by mitochondrial replacement. 355 SUMMARY. 356 QUESTIONS. 358 FURTHER READING. 358 10 CANCER GENETICS AND GENOMICS. 361 10.1 FUNDAMENTAL CHARACTERISTICS AND EVOLUTION OF CANCER. 362 The defining features of unregulated cell growth and cancer. 362 Why cancers are different from other diseases: the contest between natural selection operating at the level of the cell and the level of the organism. 364 Cancer cells acquire several distinguishing biological characteristics during their evolution. 366 The initiation and multistage nature of cancer evolution and why most human cancers develop over many decades. 369 Intratumor heterogeneity arises through cell infiltration, clonal evolution, and differentiation of cancer stem cells. 372 10.2 ONCOGENES AND TUMOR SUPPRESSOR GENES. 375 Two fundamental classes of cancer gene. 375 Viral oncogenes and the natural roles of cellular oncogenes.376 How normal cellular proto oncogenes are activated to become cancer genes. 376 Tumor suppressor genes: normal functions, the two-hit paradigm, and loss of heterozygosity in linked markers.
380 The key roles of gatekeeper tumor suppressor genes in suppressing GrS transition in the cell cycle. 383 The additional role of p53 in activating different apoptosis pathways to ensure that rogue cells are destroyed.384 Tumor suppressor involvement in rare familial cancers and non-classical tumor suppressors. 384 The significance of miRNAs and long noncoding RNAs in cancer. 388 10.3 GENOMIC INSTABILITY AND EPIGENETIC DYSREGULATION IN CANCER.389 Different types of chromosomal instability in cancer. 390 Deficiency in mismatch repair results in unrepaired replication errors and global DNA instability. 392 Different classes of cancer susceptibility gene according to epigenetic function, epigenetic dysrégulation, and epigenome genome interaction . 395 10.4 NEW INSIGHTS FROM GENOME-WIDE STUDIES OF CANCERS. 397 Genome sequencing has revealed extraordinary mutational diversity in tumors and insights into cancer evolution. 398 Defining the landscape of driver mutations in cancer and establishing a complete inventory of cancer-susceptibility genes. 401 Tracing the mutational history of cancers: just one of the diverse applications of single-cell genomics and transcriptomics in cancer. 404 Genome-wide RNA sequencing enables insights into the link
Contents between cancer genomes and cancer biology and aids tumor classification. 405 10.5 GENETIC INROADS INTO CANCER THERAPY. 407 Targeted anticancer therapies are directed against key cancer cell proteins involved in oncogenesis or in escaping immunosurveillance. 408 CAR-T Cell therapy and the use of genetically engineered T cells to treat cancer. 410 The molecular basis of tumor recurrence and the evolution of drug resistance in cancers. 411 The promise of combinatorial drug therapies. 413 SUMMARY. 413 QUESTIONS. 415 FURTHER READING.415 11 GENETIC AND GENOMIC TESTING IN HEALTHCARE: PRACTICAL AND ETHICAL ASPECTS. 417 11.1 AN OVERVIEW OF GENETIC TESTING. 418 The different source materials and different levels of genetic testing. 419 11.2 GENETIC TESTING FOR CHROMOSOME ABNORMALITIES AND PATHOGENIC STRUCTURAL VARIATION. 423 Screening for aneuploidies using quantitative fluorescence PCR. 424 Detecting large-scale copy number variants using chromosome SNP microarray analysis.425 Detecting and scanning for oncogenic fusion genes using, respectively, chromosome FISH and targeted RNA
sequencing. 428 xiii Detecting pathogemc modetatc to small-scale deletions and duplications at defined loc i о often achieved usi tig the ML PA or ddPCR met hods. g зо Two very different routes towaids universal genome-wide screens for structural variation: genome wide sequencing and optical genome mapping.433 11.3 GENETIC AND GENOMIC TESTING FOR PATHOGENIC POINT MUTATIONS AND DNA METHYLATION TESTING. 433 Diverse methods permit rapid genotyping of specific point mutations. 4 36 The advantages of multiplex genotyping.4 38 Mutation scanning: from genes and gene panels to whole exorne and whole genome sequencing. 440 Interpreting and validating sequence variants can be aided by extensive online resources. 442 Detecting aberrant DNA methylation profiles associated with disease. 448 11.4 GENETIC AND GENOMIC TESTING: ORGANIZATION OF SERVICES AND PRACTICAL APPLICATIONS. 450 The developing transformation of genetic services into mainstream genomic medicine. 450 An overview of diagnostic and pre-symptomatic or predictive genetic testing. 453 The different ways in which diagnosis of genetic conditions is carried out in the prenatal period.456 Preimplantation genetic testing is carried out to prevent
xiv Contents the transmission of a harmful genetic defect using in vitro fertilization. 460 Noninvasive prenatal testing (NIPT) and whole genome testing of the fetus. 461 An overview of the different types of genetic screening. 463 Pregnancy screening for fetal abnormalities. 463 Newborn screening allows the possibility of early medical intervention. 464 Different types of carrier screening can be carried out for autosomal recessive conditions. 466 New genomic technologies are being exploited in cancer diagnostics. 468 Bypassing healthcare services: the rise of direct-to֊consumer (DTC) genetic testing. 470 The downsides of improved sensitivity through whole genome sequencing: increased uncertainty about what variants mean. 472 11.5 ETHICAL, LEGAL, AND SOCIETAL ISSUES (ELSI) IN GENETIC TESTING. 473 Genetic information as family information. 473 Consent issues in genetic testing. 474 The generation of genetic data is outstripping the ability to provide clinical interpretation. 477 New disease gene discovery and changing concepts of diagnosis. 479 Complications in diagnosing mitochondrial disease. 479 Complications arising from incidental, additional, secondary, or
unexpected information. 480 Consent issues in testing children. 482 Ethical and societal issues in prenatal diagnosis and testing. 483 Ethical and social issues in some emerging treatments for genetic disorders. 485 The ethics of germline gene modification for gene therapy and genetic enhancement.487 SUMMARY. 489 QUESTIONS. 491 FURTHER READING. 491 Glossary. 493 Index. 509
GENETICS AND GENOMICS IN MEDICINE Second Edition The second edition of this textbook written for undergraduate students, graduate students and medical researchers, Genetics and Genomics in Medicine explains the science behind the uses of genetics and genomics in medicine today, and how it is being applied. Maintaining the features that made the first edition so popular, this second edition has been thoroughly updated in line with the latest developments in the field. DNA technologies are explained, with emphasis on the modern techniques that are revolutionizing the use of genetic information in medicine and indicating the role of genetics in common diseases. Epigenetics and non-coding RNA are covered in-depth as are genetic approaches to treatment and prevention, including pharmacogenomics, genetic testing and personalized medicine. A dedicated chapter charts the latest insights into the molecular basis of cancers, cancer genomics and novel approaches to cancer detection. Coverage of genetic testing at the level of genes, chromosomes and genomes has been significantly expanded and updated. Extra prominence has been given to additional genomic analyses, ethical aspects and novel therapeutic approaches. Various case studies illustrate selected clinical applications. Key Features • Comprehensive and integrated account of how genetics and genomics affect the entire spectrum of human health and disease • Exquisite artwork illuminates the key concepts and mechanisms • Summary points at the end of each chapter help to consolidate learning • For each chapter, an abundance of
further reading to help provide the reader with direction for further study • Inclusive online question bank to test understanding • Standard boxes summarizing certain key principles in genetics • Clinical boxes summarizing selected case studies, pathogenesis mechanisms or novel therapies for selected diseases This book is equally suited for newcomers to the field as well as for engineers and scientists that have basic knowledge in this field but are interested in obtaining more information about specific future applications. About the Authors Tom Strachan is Emeritus Professor of Human Molecular Genetics at Newcastle University, UK. Together with a former colleague, Andrew Read, he writes the popular Human Molecular Genetics textbook, now in its Fifth Edition. Anneke Lucassen is Professor of Genomic Medicine and Director of the Centre for Personalised Medicine at the University of Oxford, UK к |
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| spelling | Strachan, Tom 1952- Verfasser (DE-588)11355785X aut Genetics and genomics in medicine Tom Strachan and Anneke Lucassen Second edition Boca Raton ; London ; New York CRC Press, Taylor & Francis Group [2022] xviii, 534 Seiten Illustrationen txt rdacontent n rdamedia nc rdacarrier A Garland science book Includes bibliographical references Genetic Phenomena Genomics Genetic Diseases, Inborn - therapy Individualized Medicine Examination Questions Genetic Diseases, Inborn therapy Krankheit (DE-588)4032844-2 gnd rswk-swf Humangenetik (DE-588)4072653-8 gnd rswk-swf Genomik (DE-588)4776397-8 gnd rswk-swf Humangenetik (DE-588)4072653-8 s DE-604 Genomik (DE-588)4776397-8 s Krankheit (DE-588)4032844-2 s b DE-604 Lucassen, Anneke Verfasser (DE-588)1078752737 aut Erscheint auch als Online-Ausgabe 978-1-003-04440-6 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=033912820&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=033912820&sequence=000003&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
| spellingShingle | Strachan, Tom 1952- Lucassen, Anneke Genetics and genomics in medicine Genetic Phenomena Genomics Genetic Diseases, Inborn - therapy Individualized Medicine Examination Questions Genetic Diseases, Inborn therapy Krankheit (DE-588)4032844-2 gnd Humangenetik (DE-588)4072653-8 gnd Genomik (DE-588)4776397-8 gnd |
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| title | Genetics and genomics in medicine |
| title_auth | Genetics and genomics in medicine |
| title_exact_search | Genetics and genomics in medicine |
| title_exact_search_txtP | Genetics and genomics in medicine |
| title_full | Genetics and genomics in medicine Tom Strachan and Anneke Lucassen |
| title_fullStr | Genetics and genomics in medicine Tom Strachan and Anneke Lucassen |
| title_full_unstemmed | Genetics and genomics in medicine Tom Strachan and Anneke Lucassen |
| title_short | Genetics and genomics in medicine |
| title_sort | genetics and genomics in medicine |
| topic | Genetic Phenomena Genomics Genetic Diseases, Inborn - therapy Individualized Medicine Examination Questions Genetic Diseases, Inborn therapy Krankheit (DE-588)4032844-2 gnd Humangenetik (DE-588)4072653-8 gnd Genomik (DE-588)4776397-8 gnd |
| topic_facet | Genetic Phenomena Genomics Genetic Diseases, Inborn - therapy Individualized Medicine Examination Questions Genetic Diseases, Inborn therapy Krankheit Humangenetik Genomik |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=033912820&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=033912820&sequence=000003&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT strachantom geneticsandgenomicsinmedicine AT lucassenanneke geneticsandgenomicsinmedicine |