CONTENTS
CHAPTER 1 Introduction / 001
◎ 1. 1 The Birth and Development of Genetics and Genomics / 001
◎ 1.2 Categories of Genetic Disease / 001
◎ 1.3 Onward / 002
CHAPTER 2 Chromosomal Basis Heredity / 004
◎ 2. 1 The Human Genome and the Chromosomal Basis of
Heredity / 004
◎ 2.2 Transmission of the Genome / 012
◎ 2.3 Human Gametogenesis and Fertilization / 018
◎ 2.4 The Human Karyotype / 022
◎ 2.5 Medical Relevance of Mitosis and Meiosis / 024
CHAPTER 3 Patterns of Single-Gene Inheritance / 026
◎ 3. 1 Overview and Concepts / 026
◎ 3.2 Pedigrees / 029
◎ 3.3 Mendelian Inheritance / 031
◎ 3.4 Autosomal Patterns of Mendelian Inheritance / 032
◎ 3.5 X-Linked Inheritance / 040
◎ 3.6 Pseudoautosomal Inheritance / 047
◎ 3.7 Mosaicism / 048
◎ 3.8 Parent-of-Origin Effects on Inheritance Patterns / 050
◎ 3.9 Dynamic Mutations: Unstable Repeat Expansions / 051
◎ 3. 10 Correlating Genotype and Phenotype / 055
◎ 3. 11 Importance of the Family History in Medical Practice / 057
CHAPTER 4 ……
Principle of Clinical Cytogenetics / 060
◎ 4. 1 Introduction to Cytogenetics and Genome Analysis / 061
◎ 4.2 Chromosome Abnormalities / 069
◎ 4.3 Chromosome and Genome Analysis in Cancer / 082
CHAPTER 5 Chromosome Disease / 085
◎ 5. 1 Mechanisms of Abnormalities / 085
◎ 5.2 Aneuploidy / 086
◎ 5.3 Idiopathic Chromosome Abnormalities / 091
◎ 5.4 The Sex Chromosomes and Their Abnormalities / 094
CHAPTER 6 Multiple-Factor Inheritance / 108
◎ 6. 1 Qualitative and Quantitative Traits / 109
◎ 6.2 Familial Aggregation and Correlation / 111
◎ 6.3 Determining the Relative Contributions of Genes and
Environment to Complex Disease / 114
◎ 6.4 Examples of Common Multifactorial Diseases With a
Genetic Contribution / 120
◎ 6.5 Examples of Multifactorial Traits for Which Specific
Genetic and Environmental Factors are Known / 127
◎ 6.6 The Challenge of Multifactorial Disease With Complex
Inheritance / 135
002 / M edical G enetics
CONTENTS
CHAPTER 7 Epigenetics / 137
◎ 7. 1 Epigenetic and Epigenomic Aspects of Gene
Expression / 137
◎ 7.2 Gene Expression as the Integration of Genomic and
Epigenomic Signals / 142
◎ 7.3 Allelic Imbalance in Gene Expression / 142
◎ 7.4 Variation in Gene Expression and Its Relevance to
Medicine / 148
CHAPTER 8 Genetics of Cancer / 150
◎ 8. 1 Neoplasia / 150
◎ 8.2 Genetic Basis of Cancer / 152
◎ 8.3 Cancer in Families / 156
◎ 8.4 Familial Occurrence of Cancer / 169
◎ 8.5 Sporadic Cancer / 169
◎ 8.6 Cytogenetic Changes in Cancer / 173
◎ 8.7 Applying Genomics to Individualize Cancer Therapy / 174
CHAPTER 9 Genetic Variation in Individuals and Populations: Mutation
and Polymorphism / 180
◎ 9. 1 The Nature of Genetic Variation / 181
◎ 9.2 Inherited Variation and Polymorphism in DNA / 184
◎ 9.3 The Origin and Frequency of Different Types of
Mutations / 188
◎ 9.4 Types of Mutations and Their Consequences / 192
◎ 9.5 Variation in Individual Genomes / 196
◎ 9.6 Impact of Mutation and Polymorphism / 197
◎ 9.7 Genotypes and Phenotypes in Populations / 197
◎ 9.8 Factors That Disturb Hardy-Weinberg Equilibrium / 202
CHAPTER 10 The Treatment of Genetic Disease / 211
◎ 10. 1 The Current State of Treatment of Genetic Disease / 212
◎ 10.2 Special Considerations in Treating Genetic Disease / 215
◎ 10.3 Treatment by the Manipulation of Metabolism / 216
◎ 10.4 Treatment to Increase the Function of the Affected
Gene or Protein / 220
◎ 10.5 Gene Therapy / 237
◎ 10.6 Precision Medicine: the Present and Future of the
Treatment of Mendelian Disease / 245
CHAPTER 11 Genetic Counseling and Risk Assessment / 247
◎ ◎ ◎
◎ 11. 1 11.2 11.3
11.4 Family History in Risk Assessment / 247
Genetic Counseling in Clinical Practice / 248
Determining Recurrence Risks / 252
Empirical Recurrence Risks / 257
REFERENCES / 261
