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Book Details
Abstract
Popular for its highly visual, clinical approach, Medical Genetics delivers an accessible yet thorough understanding of this active and fast-changing field. Key updates in this new edition cover the latest developments which are integrated with clinical practice to emphasize the central principles and how they apply to practice. Photographs, illustrations, and tables, along with boxes containing patient/family vignettes demonstrate clinical relevance and enhance visual impact of the material for easier and more effective learning and retention.
- Mini-summaries, study questions, suggested reading, and a detailed glossary supplement and reinforce what you learn from the text.
- More than 230 photographs, illustrations, and tables, along with patient/family vignettes clarify difficult concepts and demonstrate clinical significance.
- Clinical Commentary Boxes help demonstrate how the hard science of genetics has real applications to everyday patient problems and prepare you for problem-based integrated courses.
- Self-assessment study questions aid in retention and review of key material.
- The latest knowledge and research on gene identification, cancer genetics, gene testing and gene therapy, common disorders, ethical and social issues, and much more so you can keep up with current developments in genetics.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Inside Front Cover | ifc1 | ||
| Medical Genetics | i | ||
| Copyright Page | iv | ||
| Dedication | v | ||
| Foreword | vii | ||
| Preface | viii | ||
| Acknowledgments | ix | ||
| Table Of Contents | x | ||
| 1 Background and History | 1 | ||
| What Is Medical Genetics? | 1 | ||
| Why Is a Knowledge of Medical Genetics Important for Today’s Health-Care Practitioner? | 1 | ||
| A Brief History | 1 | ||
| Types of Genetic Diseases | 3 | ||
| The Clinical Impact of Genetic Disease | 3 | ||
| Suggested Readings | 4 | ||
| Internet Resources | 5 | ||
| 2 Basic Cell Biology: | 6 | ||
| DNA, RNA, and Proteins: Heredity at the Molecular Level | 6 | ||
| DNA | 6 | ||
| Composition and Structure of DNA | 6 | ||
| DNA Coiling | 7 | ||
| Replication of DNA | 8 | ||
| From Genes to Proteins | 11 | ||
| Transcription | 12 | ||
| Transcription and the Regulation of Gene Expression | 12 | ||
| Gene Splicing | 15 | ||
| The Genetic Code | 15 | ||
| Translation | 15 | ||
| The Structure of Genes and the Genome | 20 | ||
| Introns and Exons | 20 | ||
| Types of DNA | 21 | ||
| The Cell Cycle | 22 | ||
| Mitosis | 23 | ||
| Meiosis | 23 | ||
| The Relationship between Meiosis and Gametogenesis | 26 | ||
| Study Questions | 27 | ||
| Suggested Readings | 27 | ||
| Internet Resources | 27 | ||
| 3 Genetic Variation: | 28 | ||
| Mutation: The Source of Genetic Variation | 28 | ||
| Types of Mutation | 28 | ||
| Molecular Consequences of Mutation | 31 | ||
| Clinical Consequences of Mutation: The Hemoglobin Disorders | 32 | ||
| Sickle Cell Disease | 33 | ||
| Thalassemia | 33 | ||
| Causes of Mutation | 35 | ||
| DNA Repair | 39 | ||
| Mutation Rates | 39 | ||
| Detection and Measurement of Genetic Variation | 40 | ||
| Blood Groups | 40 | ||
| The ABO Blood Group | 40 | ||
| The Rh System | 41 | ||
| Protein Electrophoresis | 41 | ||
| Detecting Variation at the DNA Level | 42 | ||
| Southern Blotting and Restriction Fragment Analysis | 42 | ||
| Tandem Repeat Polymorphisms | 45 | ||
| Single Nucleotide Polymorphisms | 46 | ||
| Copy Number Variants | 46 | ||
| DNA Amplification Using the Polymerase Chain Reaction | 48 | ||
| DNA Sequencing | 50 | ||
| High-Throughput DNA Sequencing | 50 | ||
| Detection of Mutations at the DNA Level | 52 | ||
| Genetic Variation in Populations | 53 | ||
| Basic Concepts of Probability | 54 | ||
| Gene and Genotype Frequencies | 55 | ||
| The Hardy–Weinberg Principle | 55 | ||
| Causes of Genetic Variation | 56 | ||
| Study Questions | 58 | ||
| Suggested Readings | 59 | ||
| Internet Resources | 59 | ||
| 4 Autosomal Dominant and Recessive Inheritance | 60 | ||
| Basic Concepts of Formal Genetics | 60 | ||
| Gregor Mendel’s Contributions | 60 | ||
| The Concept of Phenotype | 60 | ||
| Basic Pedigree Structure | 63 | ||
| Autosomal Dominant Inheritance | 63 | ||
| Characteristics of Autosomal Dominant Inheritance | 63 | ||
| Recurrence Risks | 64 | ||
| Autosomal Recessive Inheritance | 64 | ||
| Characteristics of Autosomal Recessive Inheritance | 65 | ||
| Recurrence Risks | 66 | ||
| “Dominant” Versus “Recessive”: Some Cautions | 66 | ||
| Factors that Affect Expression of Disease-Causing Genes | 67 | ||
| New Mutation | 67 | ||
| Germline Mosaicism | 68 | ||
| Reduced Penetrance | 68 | ||
| Age-Dependent Penetrance | 69 | ||
| Variable Expression | 69 | ||
| Locus Heterogeneity | 72 | ||
| Pleiotropy | 74 | ||
| Consanguinity in Human Populations | 74 | ||
| Consanguinity and the Frequency of Recessive Diseases | 74 | ||
| Health Consequences of Consanguinity | 74 | ||
| Study Questions | 77 | ||
| Suggested Readings | 78 | ||
| Internet Resources | 78 | ||
| 5 Sex-Linked and Nontraditional Modes of Inheritance | 79 | ||
| X Inactivation | 79 | ||
| Sex-Linked Inheritance | 81 | ||
| X-Linked Recessive Inheritance | 81 | ||
| X-Linked Dominant Inheritance | 90 | ||
| Y-Linked Inheritance | 91 | ||
| Sex-Limited and Sex-Influenced Traits | 91 | ||
| Mitochondrial Inheritance | 92 | ||
| Genomic Imprinting | 93 | ||
| Prader–Willi and Angelman Syndromes | 93 | ||
| Beckwith–Wiedemann Syndrome | 95 | ||
| Silver–Russell Syndrome | 96 | ||
| Anticipation and Repeat Expansion | 96 | ||
| The Fragile X Story: Molecular Genetics Explains a Puzzling Pattern of Inheritance | 99 | ||
| Study Questions | 101 | ||
| Suggested Readings | 102 | ||
| Internet Resources | 102 | ||
| 6 Clinical Cytogenetics: | 103 | ||
| Cytogenetic Technology and Nomenclature | 103 | ||
| Chromosome Banding | 104 | ||
| Fluorescence in Situ Hybridization | 105 | ||
| Comparative Genomic Hybridization | 107 | ||
| Abnormalities of Chromosome Number | 108 | ||
| Polyploidy | 108 | ||
| Autosomal Aneuploidy | 109 | ||
| Trisomy 21 | 110 | ||
| Trisomy 18 | 112 | ||
| Trisomy 13 | 113 | ||
| Trisomies, Nondisjunction, and Maternal Age | 114 | ||
| Sex Chromosome Aneuploidy | 114 | ||
| Monosomy of the X Chromosome (Turner Syndrome) | 114 | ||
| Klinefelter Syndrome | 116 | ||
| Trisomy X | 117 | ||
| 47,XYY Syndrome | 117 | ||
| Chromosome Abnormalities and Pregnancy Loss | 117 | ||
| Abnormalities of Chromosome Structure | 118 | ||
| Translocations | 118 | ||
| Reciprocal Translocations | 118 | ||
| Robertsonian Translocations | 119 | ||
| Deletions | 120 | ||
| Microdeletion Syndromes | 120 | ||
| Subtelomeric Rearrangements | 123 | ||
| Uniparental Disomy | 125 | ||
| Duplications | 126 | ||
| Ring Chromosomes | 126 | ||
| Inversions | 126 | ||
| Isochromosomes | 127 | ||
| Chromosome Abnormalities and Clinical Phenotypes | 127 | ||
| Cancer Cytogenetics | 128 | ||
| Chromosome Instability Syndromes | 130 | ||
| Study Questions | 130 | ||
| Suggested Readings | 130 | ||
| Internet Resources | 131 | ||
| 7 Biochemical Genetics: | 132 | ||
| Variants of Metabolism | 132 | ||
| Prevalence of Metabolic Disease | 132 | ||
| Inheritance of Metabolic Defects | 133 | ||
| Types of Metabolic Processes | 133 | ||
| Defects of Metabolic Processes | 133 | ||
| Carbohydrate Metabolism | 133 | ||
| Galactose | 133 | ||
| Fructose | 136 | ||
| Glucose | 137 | ||
| Lactose | 137 | ||
| Glycogen | 137 | ||
| Amino Acid Metabolism | 138 | ||
| Phenylalanine | 138 | ||
| Tyrosine | 138 | ||
| Branched-Chain Amino Acids | 140 | ||
| Lipid Metabolism | 140 | ||
| Fatty Acids | 141 | ||
| Cholesterol | 141 | ||
| Steroid Hormones | 142 | ||
| Steroid Hormone Receptors | 143 | ||
| Peroxisomal Enzymes | 144 | ||
| Degradative Pathways | 144 | ||
| Lysosomal Storage Disorders | 144 | ||
| Mucopolysaccharidoses | 144 | ||
| Sphingolipidoses (Lipid Storage Diseases) | 145 | ||
| Urea Cycle Disorders | 147 | ||
| Energy Production | 148 | ||
| Transport Systems | 149 | ||
| Cystine | 149 | ||
| Heavy Metals | 149 | ||
| Copper | 149 | ||
| Zinc | 152 | ||
| Study Questions | 152 | ||
| Suggested Readings | 153 | ||
| 8 Disease-Gene Identification | 154 | ||
| Gene Mapping | 154 | ||
| Linkage Analysis | 154 | ||
| LOD Scores: Determining the Significance of Linkage Results | 157 | ||
| Linkage Analysis and the Human Gene Map | 157 | ||
| Linkage Disequilibrium: Nonrandom Association of Alleles at Linked Loci | 161 | ||
| Linkage Versus Association in Populations | 164 | ||
| Physical Mapping and Cloning | 166 | ||
| Chromosome Morphology | 166 | ||
| Deletions | 166 | ||
| Translocations | 167 | ||
| Dosage Mapping Using Deletions and Duplications | 167 | ||
| Positional Cloning | 167 | ||
| Functional versus Nonfunctional DNA | 168 | ||
| Computer Analysis of DNA Sequence | 168 | ||
| Screen for Mutations in the Sequence | 170 | ||
| Test for Gene Expression | 170 | ||
| Candidate Genes | 171 | ||
| Gene Mapping by Association: Genome-Wide Association Studies | 172 | ||
| Exome and Whole-Genome Sequencing | 173 | ||
| Study Questions | 176 | ||
| Suggested Readings | 178 | ||
| Internet Resources | 179 | ||
| 9 Immunogenetics | 180 | ||
| The Immune Response: Basic Concepts | 180 | ||
| The Innate Immune System | 180 | ||
| The Adaptive Immune System | 180 | ||
| The B-Cell Response: Humoral Immune System | 181 | ||
| The Cellular Immune System | 182 | ||
| The Innate, Humoral, and Cellular Immune Systems: A Comparison | 184 | ||
| Immune Response Proteins: Genetic Basis of Structure and Diversity | 185 | ||
| Immunoglobulin Molecules and Genes | 185 | ||
| The Genetic Basis of Antibody Diversity | 186 | ||
| 1. Multiple Germline Immunoglobulin Genes | 187 | ||
| 2. Somatic Recombination (VDJ Recombination) | 187 | ||
| 3. Junctional Diversity | 187 | ||
| 4. Somatic Hypermutation | 187 | ||
| 5. Multiple Combinations of Heavy and Light Chains | 188 | ||
| T-Cell Receptors | 188 | ||
| The Major Histocompatibility Complex | 188 | ||
| Class I, II, and III Genes | 188 | ||
| MHC and Disease Associations | 190 | ||
| The ABO and Rh Blood Groups | 192 | ||
| The ABO System | 192 | ||
| The Rh System | 193 | ||
| Immunodeficiency Diseases | 193 | ||
| Study Questions | 195 | ||
| Suggested Readings | 196 | ||
| Internet Resources | 196 | ||
| 10 Genetic Basis of Development | 197 | ||
| Development | 197 | ||
| Basic Concepts | 197 | ||
| A Brief Overview of Major Processes in Embryonic Development | 198 | ||
| Genetic Mediators of Development: The Molecular Toolbox | 199 | ||
| Paracrine Signaling Molecules | 199 | ||
| DNA Transcription Factors | 203 | ||
| Extracellular Matrix Proteins | 205 | ||
| Pattern Formation | 205 | ||
| Gastrulation | 206 | ||
| Neurulation and Ectoderm | 206 | ||
| Mesoderm and Endoderm | 206 | ||
| Axis Specification | 208 | ||
| Formation of the Anterior/Posterior Axis | 208 | ||
| Formation of the Dorsal/Ventral Axis | 208 | ||
| Formation of Organs and Appendages | 208 | ||
| Craniofacial Development | 208 | ||
| Development of the Limb | 213 | ||
| Organ Formation | 215 | ||
| Study Questions | 215 | ||
| Suggested Readings | 216 | ||
| 11 Cancer Genetics | 217 | ||
| Causes of Cancer | 217 | ||
| Genetic Considerations | 217 | ||
| Environmental Considerations | 218 | ||
| Cancer Genes | 219 | ||
| Genetic Control of Cell Growth and Differentiation | 219 | ||
| The Inherited Cancer Gene versus the Somatically Altered Gene | 220 | ||
| Major Classes of Cancer Genes | 221 | ||
| Tumor Suppressor Genes | 222 | ||
| Oncogenes | 223 | ||
| DNA Repair Genes, Chromosome Integrity, and Tumorigenesis | 225 | ||
| Genetic Alterations and Cancer Cell Immortality | 225 | ||
| Identification of Inherited Cancer-Causing Genes | 226 | ||
| Neurofibromatosis Type 1 | 228 | ||
| The TP53 Gene | 228 | ||
| The Familial Adenomatous Polyposis Gene, APC | 229 | ||
| The Hereditary Nonpolyposis Colon Cancer Genes | 233 | ||
| Inherited Breast Cancer | 233 | ||
| Familial Melanoma | 235 | ||
| The RET Proto-Oncogene and Multiple Endocrine Neoplasia | 236 | ||
| Is Genetic Inheritance Important in Common Cancers? | 237 | ||
| Study Questions | 237 | ||
| Suggested Readings | 237 | ||
| Internet Resources | 238 | ||
| 12 Multifactorial Inheritance and Common Diseases | 239 | ||
| Principles of Multifactorial Inheritance | 239 | ||
| The Multifactorial Model | 239 | ||
| The Threshold Model | 239 | ||
| Recurrence Risks and Transmission Patterns | 241 | ||
| Multifactorial versus Single-Gene Inheritance | 243 | ||
| Nature and Nurture: Disentangling the Effects of Genes and Environment | 244 | ||
| Twin Studies | 244 | ||
| Adoption Studies | 246 | ||
| The Genetics of Common Diseases | 247 | ||
| Congenital Malformations | 247 | ||
| Multifactorial Disorders in the Adult Population | 247 | ||
| Cardiovascular Disorders | 247 | ||
| Heart disease. | 247 | ||
| Stroke. | 252 | ||
| Hypertension. | 254 | ||
| Cancer | 255 | ||
| Breast cancer. | 256 | ||
| Colorectal cancer. | 256 | ||
| Prostate cancer. | 256 | ||
| Diabetes Mellitus | 257 | ||
| Type 1 diabetes. | 257 | ||
| Type 2 diabetes. | 257 | ||
| Maturity-onset diabetes of the young. | 258 | ||
| Obesity | 258 | ||
| Alzheimer Disease | 259 | ||
| Alcoholism | 260 | ||
| Psychiatric Disorders | 261 | ||
| Schizophrenia. | 261 | ||
| Bipolar disorder. | 262 | ||
| Autism spectrum disorder. | 262 | ||
| Other Complex Disorders | 262 | ||
| Some General Principles and Conclusions | 262 | ||
| Study Questions | 263 | ||
| Suggested Readings | 263 | ||
| Internet Resources | 264 | ||
| 13 Genetic Testing and Gene Therapy | 265 | ||
| Population Screening for Genetic Disease | 265 | ||
| Principles of Screening | 265 | ||
| Newborn Screening for Inborn Errors of Metabolism | 268 | ||
| Heterozygote Screening | 268 | ||
| Presymptomatic Diagnosis | 270 | ||
| Psychosocial Implications of Genetic Screening and Diagnosis | 270 | ||
| Molecular Tools for Screening and Diagnosis | 271 | ||
| Linkage Analysis | 271 | ||
| Direct Mutation Analysis | 271 | ||
| Prenatal Diagnosis of Genetic Disorders and Congenital Defects | 275 | ||
| Amniocentesis | 275 | ||
| Chorionic Villus Sampling | 277 | ||
| Other Methods of Fetal Tissue Sampling | 278 | ||
| Ultrasonography | 279 | ||
| Maternal Serum Screening in the First and Second Trimesters | 279 | ||
| Analysis of Fetal DNA in Maternal Circulation | 281 | ||
| Preimplantation Genetic Diagnosis | 281 | ||
| Fetal Treatment | 282 | ||
| Gene Therapy | 282 | ||
| Somatic Cell Therapy | 282 | ||
| Gene Replacement Therapy | 282 | ||
| Retroviral Vectors | 282 | ||
| Adenoviral Vectors | 283 | ||
| Adeno-Associated Viral Vectors | 283 | ||
| Lentiviral Vectors | 283 | ||
| Challenges in Viral Gene Therapy | 285 | ||
| Nonviral Vectors | 285 | ||
| Gene-Blocking Therapies | 285 | ||
| Antisense Therapy | 285 | ||
| Ribozyme Therapy | 287 | ||
| RNA Interference | 287 | ||
| Gene Therapy for Noninherited Diseases | 287 | ||
| Germline Therapy | 288 | ||
| Gene Therapy: A Perspective | 288 | ||
| Study Questions | 289 | ||
| Suggested Readings | 290 | ||
| Internet Resources | 291 | ||
| 14 Genetics and Precision Medicine | 292 | ||
| A Technology-Driven Transformation | 292 | ||
| The Impact of Genomics | 293 | ||
| Pharmacogenetics | 293 | ||
| Genetic Prediction of Serious Adverse Drug Responses | 293 | ||
| Individualized Drug Therapy | 293 | ||
| Diagnosing and Monitoring Common Disease | 296 | ||
| Cancer Genomics | 297 | ||
| Common Disease | 298 | ||
| Race and Genetic Assessment of Individual Ancestry | 298 | ||
| The Future of Predictive Medicine | 299 | ||
| Study Questions | 300 | ||
| Suggested Readings | 300 | ||
| Internet Resources | 300 | ||
| 15 Clinical Genetics and Genetic Counseling | 301 | ||
| The Principles and Practice of Clinical Genetics | 301 | ||
| Accurate Diagnosis | 301 | ||
| Application of the Principles of Medical Genetics | 302 | ||
| Genetic Counseling: Definition and Principles | 303 | ||
| Genetic Counselors and the Delivery of Genetic Counseling | 308 | ||
| Genetic Advocacy Groups | 309 | ||
| Clinical Genetics Evaluation and Services | 309 | ||
| Dysmorphology and Clinical Teratology | 312 | ||
| Principles of Dysmorphology | 313 | ||
| Clinical Teratology | 314 | ||
| Prevention of Congenital Malformations | 314 | ||
| Bioethics and Medical Genetics | 317 | ||
| Study Questions | 319 | ||
| Suggested Readings | 319 | ||
| Internet Resources | 320 | ||
| Glossary | 321 | ||
| Answers to Study Questions | 332 | ||
| Chapter 2 | 332 | ||
| Chapter 3 | 332 | ||
| Chapter 4 | 333 | ||
| Chapter 5 | 334 | ||
| Chapter 6 | 334 | ||
| Chapter 7 | 335 | ||
| Chapter 8 | 336 | ||
| Chapter 9 | 337 | ||
| Chapter 10 | 338 | ||
| Chapter 11 | 339 | ||
| Chapter 12 | 339 | ||
| Chapter 13 | 340 | ||
| Chapter 14 | 340 | ||
| Chapter 15 | 341 | ||
| Index | 342 | ||
| A | 342 | ||
| B | 343 | ||
| C | 343 | ||
| D | 345 | ||
| E | 346 | ||
| F | 346 | ||
| G | 346 | ||
| H | 347 | ||
| I | 348 | ||
| J | 348 | ||
| K | 349 | ||
| L | 349 | ||
| M | 349 | ||
| N | 351 | ||
| O | 351 | ||
| P | 351 | ||
| Q | 353 | ||
| R | 353 | ||
| S | 353 | ||
| T | 354 | ||
| U | 355 | ||
| V | 355 | ||
| W | 355 | ||
| X | 355 | ||
| Y | 356 | ||
| Z | 356 | ||
| Inside Back Cover | ibc1 |