Thompson & Thompson Genetics and Genomics in Medicine

9th Edition - June 26, 2023
Editors: Ronald Cohn, Stephen Scherer, Ada Hamosh
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 5 4 7 6 2 - 8

First published in 1966, Thompson and Thompson Genetics and Genomics in Medicine has become an essential textbook for medical students, genetic counseling students, students… Read more

Thompson & Thompson Genetics and Genomics in Medicine

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First published in 1966, Thompson and Thompson Genetics and Genomics in Medicine has become an essential textbook for medical students, genetic counseling students, students in laboratory medicine, and more advanced trainees. With its focus on fundamental principles in human genetics and genomics and their application to medicine, the book has served many as a well-thumbed resource they return to over and over.

Such students can continue to depend on this valuable text, joining those in newer fields of genome data analysis for all they need to know about genetics and genomics throughout their basic science training, clinical placements and beyond. Coverage includes new discoveries—such as the functional roles of non-coding RNAs, chromatin regulation and epigenetics—latest technologies, and new diagnoses they are enabling.

Under an expanded title, this ninth edition has been completely revised by a new editorial team overseeing a large cadre of contributing authors. Support groups have also assisted to update illustrations featuring beautiful images of those living with genetic conditions.

Cover image
Title page
Table of Contents
Any screen, Any time, Anywhere
Copyright
Chapter Contributors
Case Study Contributors
Preface
Clinical Cases
Case 1
Case 2
Case 3
Case 4
Case 5
Case 6
Case 7
Case 8
Case 9
Case 10
Case 11
Case 12
Case 13
Case 14
Case 15
Case 16
Case 17
Case 18
Case 19
Case 20
Case 21
Case 22
Case 23
Case 24
Case 25
Case 26
Case 27
Case 28
Case 29
Case 30
Case 31
Case 32
Case 33
Case 34
Case 35
Case 36
Case 37
Case 38
Case 39
Case 40
Case 41
Case 42
Case 43
Case 44
Case 45
Case 46
Case 47
Case 48
Case 49
Abbreviations
Chapter 1. Introduction
Abstract
The Birth and Development of Genetics and Genomics
Genetics and Genomics in Medicine
Evolution of Genetics in Medicine
Chapter 2. Introduction to the Human Genome
Abstract
The Human Genome and the Chromosomal Basis of Heredity
Variation in the Human Genome
Transmission of the Genome
Human Gametogenesis and Fertilization
Medical Relevance of Mitosis and Meiosis
General References
References for Specific Topics
Chapter 3. The Human Genome: Gene Structure and Function
Abstract
Information Content of the Human Genome
The Central Dogma: Dna → Rna → Protein
Gene Organization and Structure
Fundamentals of Gene Expression
Gene Expression in Action
Epigenetic and Epigenomic Aspects of Gene Expression
Gene Expression as the Integration of Genomic and Epigenomic Signals
Allelic Imbalance in Gene Expression
Variation in Gene Expression and its Relevance to Medicine
General References
References for Specific Topics
Chapter 4. Human Genetic Diversity: Human Genetic Diversity: Genomic Variation
Abstract
The Nature of Genetic Variation
Inherited Common Variation in Dna
The Origin and Frequency of Different Types of Mutation
Types of Mutation and Their Consequences
Variation in Individual Genomes
Impact of Genomic Variation
General References
References for Specific Topics
Chapter 5. Principles of Clinical Cytogenetics and Genome Analysis
Abstract
Introduction to Cytogenetics and Genome Analysis
Chromosome Abnormalities
Chromosome and Genome Analysis in Cancer
Acknowledgment
General References
References for Specific Topics
Chapter 6. The Chromosomal and Genomic Basis of Disease: Disorders of the Autosomes and Sex Chromosomes
Abstract
Mechanisms of Abnormalities
Whole Chromosome Aneuploidy
Uniparental Disomy
Structural Variants and Clinical Impact
The Impact of Genetic Diversity
Segmental Duplications, Copy Number Variants, and Nonallelic Homologous Recombination
The Impact of Inversions in Genomic Disorders
Deletion and Duplication Syndromes
Recurrent Structural variants
Nonrecurrent Structural Variants
Nonrecurrent Chromosome Abnormalities
Segregation of Familial Abnormalities
Neurodevelopmental Disorders and Intellectual Disability
Disorders Associated with Genomic Imprinting
The Sex Chromosomes and their Abnormalities
Databases of Genomic Variants
General References
References for Specific Topics
Chapter 7. Patterns of Single-Gene Inheritance
Abstract
Overview and Concepts
Pedigrees
Patterns of Inheritance
Autosomal Patterns of Mendelian Inheritance
Characteristics of Autosomal Recessive Inheritance
X-linked Inheritance
Pseudoautosomal Inheritance
Mosaicism
Parent-of-origin Effects on Inheritance Patterns
Dynamic Mutations: Unstable Repeat Expansions
Maternal Inheritance of Disorders Caused by Variants in the Mitochondrial Genome
Correlating Genotype And Phenotype
Importance of The Family History in Medical Practice
Acknowledgment
General References
Chapter 8. Principles of Clinical Epigenetics
Abstract
Introduction
Epigenetic Machinery
Epigenetics in Development
The Environment Interacts with the Epigenome
The Role of Epigenetics in Human Disease
Categories Of Epigenetic Disorders
Diagnostic Testing for Epigenetic Disorders
Dna Methylation and Cancer Diagnostics
Treatment for Neurodevelopmental Disorders Caused by Pathogenic Variants in Epigenetic Regulators
Future Directions
General References
Specific References
Chapter 9. Complex Inheritance of Common Multifactorial Disorders
Abstract
Qualitative and Quantitative Traits
Familial Aggregation and Correlation
Determining the Relative Contributions of Genes and Environment to Complex Disease
Examples of Common Multifactorial Diseases with a Genetic Contribution
Examples Of Multifactorial Traits For Which Specific Genetic And Environmental Factors are Known
The Challenge of Multifactorial Disease with Complex Inheritance
General References
References for Specific Topics
Chapter 10. Population Genetics for Genomic Medicine
Introduction to Population Genetics for Genomic Medicine
Human Origins and Founder Effects of Serial Migration
Defining Human Populations to Characterize Diversity
Allele and Genotype Frequencies
Genomic Variation and Biases in Population Datasets
Acknowledgment
General References
References For Specific Topics
Chapter 11. Identifying the Genetic Basis for Human Disease
Genetic Basis for Linkage Analysis and Association
Strategies for Discovery of Disease-Associated Genes
Mapping Human Disease Genes by Linkage Analysis
Finding Genes Responsible for Disease by Genome-Wide Sequencing
Filtering Strategies for Identification of Disease-Causing Genes
General References
References for Specific Topics
Chapter 12. The Molecular Basis of Genetic Disease
Abstract
General Principles and Lessons from the Hemoglobinopathies
Effect of Pathogenic Variants on Protein Function
How Variants Disrupt the Formation of Biologically Normal Proteins
The Relationship between Genotype and Phenotype in Genetic Disease
Human Hemoglobin and Associated Diseases
The Hemoglobinopathies
General References
References for Specific Topics
Chapter 13. The Molecular, Biochemical, and Cellular Basis of Genetic Disease
Abstract
Diseases Due to Pathogenic Variants in Different Classes of Proteins
Diseases Involving Enzymes
Altered Protein Function due to Abnormal Posttranslational Modification
Defects in Receptor Proteins
Transport Defects
Disorders of Structural Proteins
The Effect of Gene Duplication and Retained Function on Phenotype: Spinal Muscular Atrophy
Neurodegenerative Disorders
General References
References to Specific Topics
Useful Websites
Chapter 14. The Treatment of Genetic Disease
Abstract
The Current State of Treatment of Genetic Disease
Special Considerations in Treating Genetic Disease
Treatment by the Manipulation of Metabolism
Treatment to Increase the Function of the Affected Gene or Protein
Gene Therapy
Precision Medicine: The Present and Future of the Treatment of Mendelian Disease
General References
References for Specific Topics
Useful Websites
Chapter 15. Developmental Genetics and Birth Defects
Developmental Biology in Medicine
Introduction to Developmental Biology
Genes and Environment in Development
Basic Concepts of Developmental Biology
Cellular and Molecular Mechanisms in Development
Interaction of Developmental Mechanisms in Embryogenesis
Concluding Comments
General References
References Specific to Particular Topics
Chapter 16. Cancer Genetics and Genomics
Abstract
Germline Versus Somatic
Neoplasia
Genetic Basis of Cancer
Cancer in Families
Familial Occurrence of Cancer
Sporadic Cancer
Cytogenetic Changes in Cancer
The Role of Epigenetics in Cancer
Applying Genomics to Individualize Cancer Therapy
Cancer and the Environment
Acknowledgment
General References
Specific References
Useful Websites
Chapter 17. Genetic Counseling and Risk Assessment
Abstract
Genetic Counseling
Clinical Genetics
Risk Assessment
Family History Risk Assessment
Risk Communication and Perception
Determining Recurrence Risks
General Principles of Risk Estimation
Empirical Recurrence Risks
Reproductive Options
Genetic Counseling in the Era of Genomic Medicine
General References
References for Specific Topics
Chapter 18. Preconception and Prenatal Screening and Diagnosis
Abstract
Prenatal Screening Methods
Prenatal Diagnostic Procedures
Laboratory Studies
Preconception Genetic Screening and Testing
Fetal Surgical and Medical Interventions
Genetic Counseling for Preconception and Prenatal Diagnosis and Screening
General References
Specific References
Chapter 19. Application of Genomics to Medicine and Individualized Health Care
Abstract
Genetic Screening in Populations
Pharmacogenomics
Pharmacogenomics as a Complex Trait
Screening for Genetic Susceptibility to Disease
Individualized Genomic Medicine
Precision Child Health
General References
References for Specific Topics
Chapter 20. Ethical and Social Issues in Genetics and Genomics
Abstract
Principles of Biomedical Ethics
Ethical Dilemmas Arising in Medical Genetics
Privacy of Genetic Information
Artificial Intelligence and Increased Digitization
Use of Genetic Information by Employers and Insurers
Eugenic and Dysgenic Effects of Medical Genetics
Genetics and Genomics in Medicine
Acknowledgments
General References
References for Specific Topics
Clinical Case Studies Illustrating Genetic Principles
Case Presentations
1. Abacavir-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (MIM 608579) (Genetically Determined Immunological Adverse Drug Reaction)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Inheritance
Questions for Small Group Discussion
References
2. Achondroplasia (MIM 100800) (FGFR3 Pathogenic Variant)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
3. Age-Related Macular Degeneration (MIM 603075) (Complement Factor H Variants)
Principles
Major Phenotypic Features
History and Physical Examination
Background
Questions for Small Group Discussion
References
4. Alzheimer Disease (MIM 104300)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
5. 16p11.2 Deletion Syndrome (MIM 611913)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
6. Beckwith-Wiedemann Syndrome (MIM 130650) (Uniparental Disomy and Imprinting Defect)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
7. Hereditary Breast and Ovarian Cancer (MIM 604370, 612555) (BRCA1 and BRCA2 Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
8. Charcot-Marie-Tooth Disease Type 1 A (MIM 118220) (PMP22 Sequence Variant or Duplication)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
9. CHARGE Syndrome (MIM 214800) (CHD7 Disorder)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Inheritance
Questions for Small Group Discussion
10. Chronic Myelogenous Leukemia (MIM 608232) (BCR-ABL1 Oncogene)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
11. Inflammatory Bowel Disease (MIM 266600)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
Key References
12. Cystic Fibrosis (MIM 219700) (CFTR Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
13. Hearing Loss (NonSyndromic) (MIM 220290) (GJB2 Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
14. Duchenne Muscular Dystrophy (MIM 310200) (Dystrophin [DMD] Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
15. Monogenic Diabetes (MIM 600496) (Single Gene Pathogenic Variants Impacting Pancreatic Islet β Cell Development and/or Function)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
16. Familial Hypercholesterolemia (MIM 143890) (Low-Density Lipoprotein Receptor [LDLR] Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
17. Fragile X Syndrome (MIM 300624), Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS) (MIM 300623), and Fragile X–Associated Primary Ovarian Insufficiency (FXPOI) (MIM 311360) (Pathogenic FMR1 Repeat Expansion)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
18. GAUCHER DISEASE Type I (Non-Neuronopathic) (MIM 230800) (GBA Pathogenic Variants)
Principles
Major Phenotypic Features
Case Presentation
Background
Questions for Small Group Discussion
References
19. Glucose-6-Phosphate Dehydrogenase Deficiency (MIM 300908) (G6PD Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
20. Hereditary Hemochromatosis (MIM 235200) (HFE Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
21. Hemophilia (MIM 306700 and MIM 306900) (F8 or F9 Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
22. 22q11.2 Deletion Syndrome (MIM 188400 DiGeorge Syndrome or MIM 192430 Velocardiofacial Syndrome)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
23. Holoprosencephaly (Nonsyndromic Form) (MIM 142945) (Sonic Hedgehog [SHH] variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
24. Huntington Disease (MIM 143100) (HTT Pathogenic Variant [CAG Expansion])
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
25. Hypertrophic Cardiomyopathy (MIM 192600) (Cardiac Sarcomere Gene Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
26. Proteus Syndrome (MIM 176920) (AKT1 Gene de novo Mosaic Variant)
Principles
Major Phenotypic Findings
History and Physical Findings
Questions for Small Group Discussion
References
27. Fetal Growth Restriction (Abnormal Fetal Karyotype)
Principles
Major Phenotypic Features
Case Description
Background
Questions for Small Group Discussion
References
28. Long QT Syndrome (MIM 192500) (Cardiac Ion Channel Gene)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
29. Lynch Syndrome (MIM 120435) (DNA Mismatch Repair Genes Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Questions for Small Group Discussion
References
30. Marfan Syndrome (MIM 154700) (FBN1 Pathogenic Variants)
Principles
Major Phenotypic Features
Case Presentation
Background
Questions for Small Group Discussion
References
31. Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MIM 201450) (ACADM Pathogenic Variation)
Principles
Major Phenotypic Features
Case Report
Background
Questions for Small Group Discussion
References
32. Miller-Dieker Syndrome (MIM 247200) (17p13.3 Heterozygous Deletion)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Management
Questions for Small Group Discussion
References
33. Myoclonic Epilepsy With Ragged-Red Fibers (MIM 545000) (Mitochondrial tRNAlys Variant)
Principles
Major Phenotypic Features
Case Report
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
34. Neurofibromatosis 1 (MIM 162200) (NF1 Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
35. Roifman Syndrome (MIM 616651) RNU4ATAC Noncoding RNA Gene Pathogenic Variants
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
36. Ornithine Transcarbamylase Deficiency (MIM 311250) (OTC Pathogenic Variant)
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
Reference
37. Polycystic Kidney Disease (MIM 173900 and MIM 613095) (PKD1 or PKD2 Pathogenic Variants)
Principles
Major Phenotypic Findings
Case Example
Background
Phenotype and Natural History
Management
Indications for Adpkd Molecular Testing
Inheritance
Questions for Small Group Discussion
References
38. Prader-Willi Syndrome (MIM 176270) (Absence of Paternally Derived 15q11-q13)
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
39. Retinoblastoma (MIM 180200) (RB1 Pathogenic Variants)
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
40. Rett Syndrome (MIM 312750) (MECP2 Variants)
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
41. Noonan Syndrome (RASopathies) (MIM 163950)
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
42. Sickle Cell Disease (MIM 603903)
Principles
Major Phenotypic Findings
Case Report
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
43. Tay-TAY-Sachs Disease (MIM 272800) (HEXA Pathogenic Variants)
Principles
Major Phenotypic Findings
Case Report
Background
Phenotype and Natural History
Diagnosis and Management
Carrier Screening
Inheritance
Questions for Small Group Discussion
References
44. α-Thalassemia (α-Globin Deficiency) (MIM 604131)
Principles
Major Phenotypic Findings
Case Report
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
Reference
45. Thiopurine S-Methyltransferase Deficiency (MIM 610460) (TPMT Variants)
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
46. Thrombophilia (MIM 188055 and 176860) (FV and PROC Pathogenic Variants)
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
47. Turner Syndrome (Female Monosomy X) Chromosomal
Principles
Major Phenotypic Features
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
48. Xeroderma Pigmentosum (MIM 278700) (Defect of Nucleotide Excision Repair, XPA Pathogenic Variants)
Principles
Major Phenotypic Findings
History and Physical Findings
Background
Phenotype and Natural History
Management
Inheritance
Questions for Small Group Discussion
References
49. Telomere-Related Pulmonary Fibrosis and/or Bone Marrow Failure (MIM 614742) (TERT Pathogenic Variants)
Principles
Major Phenotypic Features
History and Physical Findings
Background
Inheritance
Questions for Small Group Discussion
References
Glossary
Answers to Problems
Chapter 2 Ada Hamosh and Stephen W. Scherer
Chapter 3 Stephen W. Scherer
Chapter 4 Stephen W. Scherer and Ada Hamosh
Chapter 5 Dimitri J. Stavropoulos
Chapter 6 Feyza Yilmaz, Christine R. Beck, Charles Lee
Chapter 7 Neal Sondheimer
Chapter 8 Sarah Goodman, Cheryl Cytrynbaum, Rosanna Weksberg
Chapter 9 Cristen J. Willer and Gonçalo R. Abecasisa
Chapter 10 Alice B. Popejoy
Chapter 11 Christian R. Marshall
Chapter 12 Gregory Costain
Chapter 13 Ada Hamosh
Chapter 14 Ronald Doron Cohn and Ada Hamosh
Chapter 15 Anthony Wynshaw-Boris and Ophir Klein
Chapter 16 Michael F. Walsh
Chapter 17 Carolyn Dinsmore Applegate and Jodie Marie Vento
Chapter 18 Angie Child Jelin and Ignatia B. Van den Veyver
Chapter 19 Ronald Doran Cohn and Iris Cohn
Chapter 20 Bartha Maria Knoppers and Ma’n H. Zawati
Index
Confidence is ClinicalKey

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Thompson & Thompson Genetics and Genomics in Medicine

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