1. IX
Table of Contents
Introduction
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Chronology . . . . . . . . . . . . . . . . . . . . . . . .
Important Advances that Contributed
to the Development of Genetics . . . . .
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Fundamentals
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Prologue . . . . . . . . . . . . . . . . . . . . . . . . . .
Phylogenetic Tree of Living Organisms
Origins of Humans . . . . . . . . . . . . . . . .
Out of Africa: Toward Modern
Humans . . . . . . . . . . . . . . . . . . . . . . . .
Molecular Basis of Genetics . . . . . . . . . .
The Cell and its Components . . . . . . .
Some Types of Chemical Bonds . . . . .
Carbohydrates . . . . . . . . . . . . . . . . . . .
Lipids (Fatty Acids) . . . . . . . . . . . . . . .
Nucleotides and Nucleic Acids . . . . . .
Amino Acids . . . . . . . . . . . . . . . . . . . . .
Proteins . . . . . . . . . . . . . . . . . . . . . . . .
DNA as a Carrier of Genetic
Information . . . . . . . . . . . . . . . . . . . . .
DNA and its Components . . . . . . . . . .
DNA Structure . . . . . . . . . . . . . . . . . . .
Alternative DNA Structures . . . . . . . . .
DNA Replication . . . . . . . . . . . . . . . . . .
The Flow of Genetic Information:
Transcription and Translation . . . . . . .
Genetic Code . . . . . . . . . . . . . . . . . . . .
Eukaryotic Gene Structure . . . . . . . . .
Analysis of DNA . . . . . . . . . . . . . . . . . . . .
Restriction Enzymes . . . . . . . . . . . . . .
DNA Amplification by Polymerase
Chain Reaction (PCR) . . . . . . . . . . . . . .
DNA Sequencing . . . . . . . . . . . . . . . . .
Parallel DNA Sequencing . . . . . . . . . . .
DNA Cloning . . . . . . . . . . . . . . . . . . . . .
cDNA Cloning . . . . . . . . . . . . . . . . . . . .
DNA Libraries . . . . . . . . . . . . . . . . . . . .
Southern Blot Hybridization . . . . . . . .
Variability of DNA . . . . . . . . . . . . . . . . . .
DNA Polymorphism . . . . . . . . . . . . . . .
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Genes and Mutation . . . . . . . . . . . . . .
Mutations Due to Base Modifications .
Mutations Due to Errors in Replication
Processing of DNA . . . . . . . . . . . . . . . . . .
DNA Repair Systems . . . . . . . . . . . . . .
Recombination . . . . . . . . . . . . . . . . . . .
Transposition . . . . . . . . . . . . . . . . . . . .
Trinucleotide Repeat Expansion . . . . .
Eukaryotic Cells . . . . . . . . . . . . . . . . . . . .
Cell Communication . . . . . . . . . . . . . .
Haploid and Diploid Yeast Cells . . . . .
Mating Type Determination in Yeast
Cells and Yeast Two-Hybrid System . .
Cell Division: Mitosis . . . . . . . . . . . . . .
Meiosis in Germ Cells . . . . . . . . . . . . .
Meiosis Prophase I . . . . . . . . . . . . . . . .
Formation of Gametes . . . . . . . . . . . . .
Cell Cycle Control . . . . . . . . . . . . . . . . .
Programmed Cell Death . . . . . . . . . . .
Cultured Cells . . . . . . . . . . . . . . . . . . . .
Formal Genetics . . . . . . . . . . . . . . . . . . . .
The Mendelian Traits . . . . . . . . . . . . . .
Transmission to the Next Generation .
Independent Distribution . . . . . . . . . .
Phenotype and Genotype . . . . . . . . . .
Segregation of Parental Genotypes . . .
Monogenic Inheritance . . . . . . . . . . . .
Genetic Linkage and Recombination .
Genetic Linkage and Association
Analysis . . . . . . . . . . . . . . . . . . . . . . . .
Quantitative Differences in Genetic
Traits . . . . . . . . . . . . . . . . . . . . . . . . . . .
Polygenic Threshold Model . . . . . . . . .
Allelic Distribution in a Population . .
Hardy–Weinberg Equilibrium
Principle . . . . . . . . . . . . . . . . . . . . . . . .
Geographical Differences in Allelic
Distribution . . . . . . . . . . . . . . . . . . . . .
Inbreeding . . . . . . . . . . . . . . . . . . . . . .
Twins . . . . . . . . . . . . . . . . . . . . . . . . . .
Chromosomes . . . . . . . . . . . . . . . . . . . . .
Chromosomes in Metaphase . . . . . . . .
Visible Functional Structures of
Chromosomes . . . . . . . . . . . . . . . . . . .
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2. X
Table of Contents
Chromosome Organization . . . . . . . . .
Functional Elements of Chromosomes
DNA and Nucleosomes . . . . . . . . . . . .
DNA in Chromosomes . . . . . . . . . . . . .
The Telomere . . . . . . . . . . . . . . . . . . . .
The Banding Patterns of Human
Chromosomes . . . . . . . . . . . . . . . . . . .
Karyotype of Man and Mouse . . . . . . .
Preparation of Metaphase
Chromosomes for Analysis . . . . . . . . .
Fluorescence In-Situ Hybridization
(FISH) . . . . . . . . . . . . . . . . . . . . . . . . . .
Multicolor FISH Identification of
Chromosomes . . . . . . . . . . . . . . . . . . .
Aneuploidy . . . . . . . . . . . . . . . . . . . . . .
Chromosome Translocation . . . . . . . . .
Structural Chromosomal Aberrations .
Regulation of Gene Function . . . . . . . . . .
Ribosomal RNA and Protein Assembly
Transcription . . . . . . . . . . . . . . . . . . . .
Basic Principles of Gene Control . . . . .
Regulation of Gene Expression in
Eukaryotes . . . . . . . . . . . . . . . . . . . . . .
DNA–Protein Interaction . . . . . . . . . . .
Transcription Activation . . . . . . . . . . .
RNA Interference (RNAi) . . . . . . . . . . .
Targeted Gene Disruption . . . . . . . . . .
Epigenetic Modifications . . . . . . . . . . . . .
DNA Methylation . . . . . . . . . . . . . . . . .
Reversible Changes in Chromatin
Structure . . . . . . . . . . . . . . . . . . . . . . .
Genomic Imprinting . . . . . . . . . . . . . .
Mammalian X Chromosome
Inactivation . . . . . . . . . . . . . . . . . . . . .
Genetic Signal Pathways . . . . . . . . . . . . .
Cellular Signal Transduction . . . . . . . .
Heterotrimeric G Proteins . . . . . . . . . .
TGFβ and Wnt/β-Catenin Signaling
Pathways . . . . . . . . . . . . . . . . . . . . . . .
The Hedgehog and TNFα Signal
Transduction Pathways . . . . . . . . . . . .
The Notch/Delta Signaling Pathway . .
Genes in Embryonic Development . . . . .
Embryonic Development Genes in
Drosophila melanogaster . . . . . . . . . . .
Hox Genes . . . . . . . . . . . . . . . . . . . . . .
Zebrafish: A Translucent Vertebrate . .
Cell Lineage in a Nematode,
C. elegans . . . . . . . . . . . . . . . . . . . . . . .
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Genomics . . . . . . . . . . . . . . . . . . . . . . .
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Genomics . . . . . . . . . . . . . . . . . . . . . . . . .
Genomics, the Study of the
Organization of Genomes . . . . . . . . . .
Identification of Disease-related
Genes . . . . . . . . . . . . . . . . . . . . . . . . . .
Genomes of Microorganisms . . . . . . .
Architecture of the Human Genome .
Genome Analysis with DNA
Microarrays . . . . . . . . . . . . . . . . . . . . .
Genome Scan and Array CGH . . . . . . .
Comparative Genomic Hybridization .
Genome-Wide Association Study
(GWAS) . . . . . . . . . . . . . . . . . . . . . . . .
The Dynamic Genome: Mobile Genetic
Elements . . . . . . . . . . . . . . . . . . . . . . . .
Evolution of Genes and Genomes . . . .
Comparative Genomics . . . . . . . . . . . .
Genomic Structure of the Human X
and Y Chromosomes . . . . . . . . . . . . . .
Genomic Disorders . . . . . . . . . . . . . . .
The Mitochondrial Genome of Man . .
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Genetics and Medicine
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247
Imbalanced Homeostasis . . . . . . . . . . . . .
Chloride Channel Defects: Cystic
Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . .
Genetic Defects in Ion Channels: LQT
Syndromes . . . . . . . . . . . . . . . . . . . . . .
α1-Antitrypsin Deficiency . . . . . . . . . .
Hemophilia A and B . . . . . . . . . . . . . .
von Willebrand Bleeding Disease . . . .
Pharmacogenetics . . . . . . . . . . . . . . . .
Cytochrome P450 (CYP) Genes . . . . . .
Mitochondrial Diseases . . . . . . . . . . . .
Metabolic Disorders . . . . . . . . . . . . . . . . .
Diabetes Mellitus . . . . . . . . . . . . . . . . .
Amino Acid Degradation and Urea
Cycle Disorders . . . . . . . . . . . . . . . . . .
Cholesterol Biosynthesis Pathway . . . .
Distal Cholesterol Biosynthesis
Pathway . . . . . . . . . . . . . . . . . . . . . . . .
Familial Hypercholesterolemia . . . . . .
LDL Receptor Mutations . . . . . . . . . . .
Lysosomal Disorders . . . . . . . . . . . . . .
Lysosomal Enzyme Defects . . . . . . . . .
Mucopolysaccharide Storage Diseases
Peroxisomal Disorders . . . . . . . . . . . . .
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3. Table of Contents
Immune System . . . . . . . . . . . . . . . . . . . .
Components of the Immune System .
Immunoglobulin Molecules . . . . . . . . .
Generation of Antibody Diversity . . . .
Immunoglobulin Gene
Rearrangement . . . . . . . . . . . . . . . . . . .
T-cell Receptor . . . . . . . . . . . . . . . . . . .
The MHC Region . . . . . . . . . . . . . . . . .
Evolution of the Immunoglobulin
Super Family . . . . . . . . . . . . . . . . . . . .
Primary Immunodeficiency Diseases .
Origins of Cancer . . . . . . . . . . . . . . . . . . .
Genetic Causes of Cancer: Background
Categories of Cancer Genes . . . . . . . . .
Cancer Genomes . . . . . . . . . . . . . . . . .
The p53 Tumor Suppressor Gene . . . .
The APC Gene and Polyposis coli . . . .
Breast and Ovarian Cancer
Susceptibility Genes . . . . . . . . . . . . . .
Oncogenic Chromosome
Translocation . . . . . . . . . . . . . . . . . . . .
Retinoblastoma . . . . . . . . . . . . . . . . . .
Neurofibromatosis . . . . . . . . . . . . . . . .
Genomic Instability Diseases . . . . . . .
DNA Excision Repair Disorders . . . . . .
Impaired Cell and Tissue Structure . . . . .
Cytoskeletal Proteins in Erythrocytes .
Hereditary Muscle Diseases . . . . . . . .
Duchenne Muscular Dystrophy . . . . . .
FGF Receptor Mutations in Skeletal
Dysplasias . . . . . . . . . . . . . . . . . . . . . . .
Marfan and Loeys–Dietz Syndromes .
Collagen Molecules . . . . . . . . . . . . . . .
Osteogenesis Imperfecta . . . . . . . . . . .
Molecular Basis of Bone Development
Ciliopathies . . . . . . . . . . . . . . . . . . . . . .
Neurocristopathies . . . . . . . . . . . . . . . .
Dysregulated RAS-MAPK Signaling
Pathway . . . . . . . . . . . . . . . . . . . . . . . .
Hemoglobin Disorders . . . . . . . . . . . . . . .
Hemoglobin . . . . . . . . . . . . . . . . . . . . .
Hemoglobin Genes . . . . . . . . . . . . . . .
Sickle Cell Disease . . . . . . . . . . . . . . . .
Mutations in Globin Genes . . . . . . . . .
The Thalassemias . . . . . . . . . . . . . . . . .
Hereditary Persistence of Fetal
Hemoglobin (HPFH) . . . . . . . . . . . . . . .
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Sex Determination and Differentiation . .
Mammalian Sex Determination . . . . .
Sex Differentiation . . . . . . . . . . . . . . . .
Disorders of Sexual Development . . . .
Congenital Adrenal Hyperplasia . . . . .
Atypical Patterns of Genetic
Transmission . . . . . . . . . . . . . . . . . . . . . .
Unstable Repeat Expansion . . . . . . . . .
Fragile X Syndrome . . . . . . . . . . . . . . .
Imprinting Disorders . . . . . . . . . . . . . .
Sensory Perception . . . . . . . . . . . . . . . . .
Rhodopsin, a Photoreceptor . . . . . . . .
Pigmentary Retinal Degeneration . . . .
Color Vision . . . . . . . . . . . . . . . . . . . . .
Auditory System . . . . . . . . . . . . . . . . .
Odorant Receptors . . . . . . . . . . . . . . . .
Mammalian Taste Receptors . . . . . . . .
Karyotype–Phenotype Relationship . . . .
Autosomal Trisomies . . . . . . . . . . . . . .
Triploidy, Monosomy X, Additional X
or Y Chromosome . . . . . . . . . . . . . . . .
Microdeletion Syndromes . . . . . . . . . .
A Brief Guide to Genetic Diagnosis . . . . .
Principles of Genetic Diagnostics . . . .
Segregation Analysis with Linked
Genetic Markers . . . . . . . . . . . . . . . . . .
Indirect DNA Analysis . . . . . . . . . . . . .
Detection of Mutations without
Sequencing . . . . . . . . . . . . . . . . . . . . . .
Gene and Stem Cell Therapy . . . . . . . .
Morbid Anatomy of the Human Genome
Chromosomal Locations of Human
Genetic Diseases . . . . . . . . . . . . . . . . .
Chromosomal Locations—
Alphabetical List . . . . . . . . . . . . . . . . . . .
Appendix
Supplementary Data
Glossary
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Picture Credits
Index
XI
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