Chapter 1

Introduction

    The Role of Genetics in Medicine  1

    Classification of Genetic Disorders  2

    Onward  2

Chapter 2

Chromosomal Basis of Heredity

    The Human Chromosomes  5

    The Life Cycle of a Somatic Cell  5

    Meiosis  9

    Human Gametogenesis and Fertilization  12

    Medical Relevance of Mitosis

      and Meiosis  15

Chapter 3

The Human Genome: Structure

and Function of Genes and

Chromosomes

    DNA Structure: A Brief Review  17

    The Central Dogma:

      DNA ~ RNA ~ Protein  18

    Fundamentals of Gene Expression  22

    Structure of Human Chromosomes  27

    Organization of the Human Genome  30

    Variation in Gene Expression and Its

      Relevance to Medicine  31

Chapter 4

Tools of Human Molecular Genetics ...

    Analysis of Individual DNA and

      RNA Sequences  33

    Methods of Nucleic Acid Analysis  41

    The Polymerase Chain Reaction  44

    In Situ Hybridization to Chromosomes  46

    DNA Sequence Analysis  48

    Methods of Protein Analysis  49

Chapter 5

Patterns of Single-Gene Inheritance

    Terminology  51

    Genetic Disorders with Classical

     Mendelian Inheritance  53

    Autosomal Recessive Inheritance  56

    Patterns of Autosomal Dominant

     Inheritance  61

    X-linked Inheritance  65

    Patterns of Pseudoautosomal Inheritance  71

    Atypical Patterns of Inheritance  72

    Summary  77

Chapter 6

Genetic Variation in Individuals:

Mutation and Polymorphism

    Mutation  79

    The Molecular Basis of Mutations and

      Their Detection  81

    Human Genetic Diversity  87

    Inherited Variation and Polymorphism

      in Proteins  87

    Inherited Variation and Polymorphism in

      DNA  90

    Uses of Polymorphisms in

      Medical Genetics  93

Chapter 7

Genetic Variation in Populations  

    Genetic Diversity in Human Populations  95

    Phenotypes, Genotypes, and Gene

      Frequencies  96

    The Hardy-Weinberg Law  97

    Frequency of X-Linked Genes and

      Genotypes  98

    Factors That Disturb Hardy-Weinberg

      Equilibrium  99

    Conclusion  108

Chapter 8

Gene Mapping and the Human Genome

Project  1

    Physical Mapping of Human Genes  111

    Mapping Human Genes by Linkage

      Analysis  118

    Applications of Human Gene Mapping  125

    The Human Genome Project  132

Chapter 9

Principles of Clinical

Cytogenetics

     Introduction to Cytogenetics  135

     Chromosome Abnormalities  140

     Parent-of-Origin Effects  151

     Studies of Chromosomes in

      Human Meiosis  153

     Mendelian Disorders with

      Cytogenetic Effects  153

     Cytogenetic Analysis in Cancer  154

Chapter 10

Clinical Cytogenetics: Disorders

of the Autosomes and the

Sex Chromosomes

    Autosomal Disorders  157

    The Sex Chromosomes and

      Their Abnormalities  165

Clinical Case Studies Illustrating

Genetic Principles

Chapter 11

Principles of Molecular Disease:

Lessons from the

Hemoglobinopathies

     The Effect of Mutation on

      Protein Function  181

     How Mutations Disrupt the

      Formation of Biologically Normal

      Proteins  183

     Hemoglobins and Their Diseases  184

     Genetic Disorders of Hemoglobin  187

     Conclusion  201

Chapter 12

The Molecular and Biochemical

Basis of Genetic Disease

     Diseases Due to Mutations in

      Different Classes of Proteins  203

     Enzyme Defects  206

     Defects in Receptor Proteins  218

     Transport Defects  222

     Disorders of Structural

      Proteins  225

     Neurodegenerative Disorders  234

     Pharmacogenetic Diseases  249

     Conclusion  253

Chapter 13

The Treatment of Genetic

Disease  255

     The Current State of Treatment of

      Genetic Disease  255

     Special Considerations in

      Treating Genetic Disease  257

    Treatment Strategies  258

Chapter 14

Genetics of the Immune System

    The Major Histocompatibility

      Complex  277

    Immunoglobulins  281

    The