Thompson & Thompson Genetics in Medicine: With STUDENT CONSULT Online Access by Robert L. Nussbaum, Roderick R. McInnes, Huntington F. Willard

Introduction     1
Genetics and Genomics in Medicine     1
Onward     2
The Human Genome and the Chromosomal Basis of Heredity     5
The Human Genome and Its Chromosomes     6
Cell Division     13
Human Gametogenesis and Fertilization     20
Medical Relevance of Mitosis and Meiosis     22
The Human Genome: Gene Structure and Function     25
Information Content of the Human Genome     25
The Central Dogma: DNA [right arrow] RNA [right arrow] Protein     26
Gene Organization and Structure     28
Fundamentals of Gene Expression     30
Gene Expression in Action: The [beta]-Globin Gene     33
Gene Regulation and Changes in Activity of the Genome     36
Variation in Gene Expression and its Relevance to Medicine     38
Tools of Human Molecular Genetics     41
Analysis of Individual DNA and RNA Sequences     41
Methods of Nucleic Acid Analysis     48
The Polymerase Chain Reaction     50
DNA Sequence Analysis     53
Advanced Techniques Using Digital Image Capture of Fluorescence-Tagged Nucleotides     55
Western Blot Analysis of Proteins     57
Principles ofClinical Cytogenetics     59
Introduction to Cytogenetics     59
Chromosome Abnormalities     65
Parent-of-Origin Effects     77
Studies of Chromosomes in Human Meiosis     81
Mendelian Disorders with Cytogenetic Effects     82
Cytogenetic Analysis in Cancer     82
Clinical Cytogenetics: Disorders of the Autosomes and the Sex Chromosomes     89
Autosomal Disorders     89
The Sex Chromosomes and Their Abnormalities     98
Disorders of Gonadal and Sexual Development     109
Patterns of Single-Gene Inheritance     115
Overview and Concepts     115
Mendelian Inheritance     118
Factors Affecting Pedigree Patterns     119
Correlating Genotype and Phenotype     121
Autosomal Patterns of Mendelian Inheritance     122
X-Linked Inheritance     129
Pseudoautosomal Inheritance     135
Mosaicism     135
Imprinting In Pedigrees     137
Unstable Repeat Expansions     139
Conditions that May Mimic Mendelian Inheritance of Single-Gene Disorders     144
Maternal Inheritance of Disorders Caused by Mutations in the Mitochondrial Genome     144
Family History as Personalized Medicine     146
Genetics of Common Disorders with Complex Inheritance     151
Qualitative and Quantitative Traits     152
Genetic and Environmental Modifiers of Single-Gene Disorders     159
Examples of Multifactorial Traits for which Genetic and Environmental Factors Are Known     160
Genetic Variation in Individuals and Populations: Mutation and Polymorphism     175
Mutation     175
Types of Mutations and Their Consequences     177
Human Genetic Diversity     183
Inherited Variation and Polymorphism in DNA     184
Inherited Variation and Polymorphism in Proteins     186
Genotypes and Phenotypes in Populations     192
Factors that Disturb Hardy-Weinberg Equilibrium     195
Ethnic Differences in the Frequency of Various Genetic Diseases     199
Human Gene Mapping and Disease Gene Identification     207
The Genetic Landscape of the Human Genome     207
Mapping Human Genes by Linkage Analysis     217
Mapping of Complex Traits     222
From Gene Mapping to Gene Identification     226
Clinical Case Studies Illustrating Genetic Principles     231
Principles of Molecular Disease: Lessons from the Hemoglobinopathies      323
The Effect of Mutation on Protein Function     323
How Mutations Disrupt the Formation of Biologically Normal Proteins     325
The Hemoglobins     326
The Hemoglobinopathies     329
The Molecular, Biochemical, and Cellular Basis of Genetic Disease     345
Diseases due to Mutations in Different Classes of Proteins     345
Diseases Involving Enzymes     348
Defects in Receptor Proteins     360
Transport Defects     364
Disorders of Structural Proteins     367
Neurodegenerative Disorders     377
The Treatment of Genetic Disease     393
The Current State of Treatment of Genetic Disease     393
Special Considerations in Treating Genetic Disease     395
Treatment Strategies     396
The Molecular Treatment of Disease     399
Developmental Genetics and Birth Defects   Leslie G. Biesecker, MD     419
Developmental Biology in Medicine     419
Introduction to Developmental Biology     422
Genes and Environment in Development     424
Basic Concepts of Developmental Biology     426
Cellular and Molecular Mechanisms in Development     434
Interaction of Developmental Mechanisms in Embryogenesis     440
Prenatal Diagnosis     443
Indications for Prenatal Diagnosis by Invasive Testing     443
Methods of Prenatal Diagnosis     444
Laboratory Studies     453
Emerging Technologies for Prenatal Diagnosis     456
Prenatal Prevention and Management of Genetic Disease     457
Genetic Counseling for Prenatal Diagnosis     458
Cancer Genetics and Genomics     461
Genetic Basis of Cancer     461
Oncogenes     464
Tumor-Suppressor Genes     467
Tumor Progression     479
Applying Genomics to Individualize Cancer Therapy     479
Cancer and the Environment     482
Personalized Genetic Medicine     485
Family History as Personalized Genetic Medicine     485
Genetic Screening in Populations     487
Screening for Genetic Susceptibility to Disease     490
Pharmacogenetics and Pharmacogenomics     497
Using Risk Information to Improve Care: Pharmacogenetics     497
Pharmacogenomics     504
Role of Ethnicity and Race in Personalized Medicine     504
Genetic Counseling and Risk Assessment     507
The Process of Genetic Counseling      507
Determining Recurrence Risks     509
Application of Molecular Genetics to Determination of Recurrence Risks     516
Empirical Recurrence Risks     519
Ethical Issues in Medical Genetics     523
Ethical Dilemmas Arising in Medical Genetics     523
Eugenic and Dysgenic Effects of Medical Genetics     528
Genetics in Medicine     529
Glossary     531
Answers to Problems     551
Index     567