Abbreviations |
Preface |
Supplementary learning aids |
Before we start - Intelligent use of the Internet |
The Basics / Part 1: |
DNA structure and gene expression / Chapter 1: |
Building blocks and chemical bonds in DNA, RNA and polypeptides / 1.1: |
DNA structure and replication / 1.2: |
Examples of the importance of hydrogen bonding in nucleic acids and proteins / Box 1.1: |
Major classes of proteins used in the DNA replication machinery / Box 1.2: |
RNA transcription and gene expression / 1.3: |
RNA processing / 1.4: |
Translation, post-translational processing and protein structure / 1.5: |
Chromosome structure and function / Chapter 2: |
Ploidy and the cell cycle / 2.1: |
Structure and function of chromosomes / 2.2: |
The mitotic spindle and its components / Box 2.1: |
Mitosis and meiosis are the two types of cell division / 2.3: |
Studying human chromosomes / 2.4: |
Chromosome banding / Box 2.2: |
Human chromosome nomenclature / Box 2.3: |
Chromosome abnormalities / 2.5: |
Nomenclature of chromosome abnormalities / Box 2.4: |
Cells and development / Chapter 3: |
The structure and diversity of cells / 3.1: |
Intracellular organization of animal cells / Box 3.1: |
The cytoskeleton: the key to cell movement and cell shape and a major framework for intracellular transport / Box 3.2: |
Cell interactions / 3.2: |
An overview of development / 3.3: |
The specialization of cells during development / 3.4: |
Animal models of development / Box 3.3: |
Twinning in human embryos / Box 3.4: |
Where our tissues come from - the developmental hierarchy in mammals / Box 3.5: |
The diversity of human cells / Box 3.6: |
Pattern formation in development / 3.5: |
Morphogenesis / 3.6: |
Polarizing the mammalian embryo - signals and gene products / Box 3.7: |
Early human development: fertilization to gastrulation / 3.7: |
Extra-embryonic membranes and the placenta / Box 3.8: |
Sex determination: genes and the environment in development / Box 3.9: |
Neural development / 3.8: |
Conservation of developmental pathways / 3.9: |
Genes in pedigrees and populations / Chapter 4: |
Monogenic versus multifactorial inheritance / 4.1: |
Mendelian pedigree patterns / 4.2: |
Characteristics of the Mendelian patterns of inheritance / Box 4.1: |
The complementation test to discover whether two recessive characters are determined by allelic genes / Box 4.2: |
Complications to the basic Mendelian pedigree patterns / 4.3: |
Genetics of multifactorial characters: the polygenic-threshold theory / 4.4: |
Two common misconceptions about regression to the mean / Box 4.3: |
Partitioning of variance / Box 4.4: |
Factors affecting gene frequencies / 4.5: |
Hardy-Weinberg equilibrium genotype frequencies for allele frequencies p(A1) and q (A2) / Box 4.5: |
The Hardy-Weinberg distribution can be used (with caution) to calculate carrier frequencies and simple risks for counseling / Box 4.6: |
Mutation-selection equilibrium / Box 4.7: |
Selection in favor of heterozygotes for CF / Box 4.8: |
Amplifying DNA: PCR and cell-based DNA cloning / Chapter 5: |
The importance of DNA cloning / 5.1: |
PCR: basic features and applications / 5.2: |
A glossary of PCR methods / Box 5.1: |
Principles of cell-based DNA cloning / 5.3: |
Restriction endonucleases and modification-restriction systems / Box 5.2: |
Nonsense suppressor mutations / Box 5.3: |
The importance of sequence tagged sites (STSs) / Box 5.4: |
Cloning systems for amplifying different sized fragments / 5.4: |
Cloning systems for producing single-stranded and mutagenized DNA / 5.5: |
Cloning systems designed to express genes / 5.6: |
Transferring genes into cultured animal cells / Box 5.5: |
Nucleic acid hybridization: principles and applications / Chapter 6: |
Preparation of nucleic acid probes / 6.1: |
Principles of autoradiography / Box 6.1: |
Principles of nucleic acid hybridization / 6.2: |
Fluorescence labeling and detection systems / Box 6.2: |
A glossary of nucleic acid hybridization / Box 6.3: |
Nucleic acid hybridization assays using cloned DNA probes to screen uncloned nucleic acid populations / 6.3: |
Standard and reverse nucleic acid hybridization assays / Box 6.4: |
Hybridization assays using cloned target DNA and microarrays / 6.4: |
Analyzing DNA and gene structure, variation and expression / Chapter 7: |
Sequencing and genotyping DNA / 7.1: |
Producing single-stranded DNA sequencing templates / Box 7.1: |
Identifying genes in cloned DNA and establishing their structure / 7.2: |
Common classes of DNA polymorphism which are amenable to simple genotyping methods / Box 7.2: |
Studying gene expression / 7.3: |
Database homology searching / Box 7.3: |
Obtaining antibodies / Box 7.4: |
The human genome and its relationship to other genomes / Part 2: |
Genome projects and model organisms / Chapter 8: |
The ground-breaking importance of genome projects / 8.1: |
A genomics glossary / Box 8.1: |
Background and organization of the Human Genome Project / 8.2: |
How the human genome was mapped and sequenced / 8.3: |
Human gene and DNA segment nomenclature / Box 8.2: |
Major milestones in mapping and sequencing the human genome / Box 8.3: |
Hybrid cell mapping / Box 8.4: |
Physical mapping by building clone contigs / Box 8.5: |
Co-operation, competition and controversy in the genome projects / Box 8.6: |
Genome projects for model organisms / 8.4: |
Model unicellular organisms / Box 8.7: |
Model multicellular animals for understanding development, disease and gene function / Box 8.8: |
Organization of the human genome / Chapter 9: |
General organization of the human genome / 9.1: |
Genome copy number variation in human cells / Box 9.1: |
The limited autonomy of the mitochondrial genome / Box 9.2: |
DNA methylation and CpG islands / Box 9.3: |
Organization, distribution and function of human RNA genes / 9.2: |
Anticodon specificity of eukaryotic cytoplasmic tRNAs / Box 9.4: |
Organization, distribution and function of human polypeptide-encoding genes / 9.3: |
Human genome and human gene statistics / Box 9.5: |
Tandemly repeated noncoding DNA / 9.4: |
Interspersed repetitive noncoding DNA / 9.5: |
Human gene expression / Chapter 10: |
An overview of gene expression in human cells / 10.1: |
Spatial and temporal restriction of gene expression in mammalian cells / Box 10.1: |
Control of gene expression by binding of trans-acting protein factors to cis-acting regulatory sequences in DNA and RNA / 10.2: |
Classes of cis-acting sequence elements involved in regulating transcription of polypeptide-encoding genes / Box 10.2: |
Alternative transcription and processing of individual genes / 10.3: |
Alternative splicing can alter the functional properties of a protein / Box 10.3: |
Differential gene expression: origins through asymmetry and perpetuation through epigenetic mechanisms such as DNA methylation / 10.4: |
Long range control of gene expression and imprinting / 10.5: |
Mechanisms resulting in monoallelic expression from biallelic genes in human cells / Box 10.4: |
The nonequivalence of the maternal and paternal genomes / Box 10.5: |
The unique organization and expression of Ig and TCR genes / 10.6: |
Instability of the human genome: mutation and DNA repair / Chapter 11: |
An overview of mutation, polymorphism, and DNA repair / 11.1: |
Simple mutations / 11.2: |
Classes of genetic polymorphisms and sequence variation / Box 11.1: |
Mechanisms that affect the population frequency of alleles / Box 11.2: |
Classes of single base substitution in polypeptide-encoding DNA / Box 11.3: |
Sex differences in mutation rate and the question of male-driven evolution / Box 11.4: |
Genetic mechanisms which result in sequence exchanges between repeats / 11.3: |
Pathogenic mutations / 11.4: |
The pathogenic potential of repeated sequences / 11.5: |
DNA repair / 11.6: |
Our place in the tree of life / Chapter 12: |
Evolution of gene structure and duplicated genes / 12.1: |
Intron groups / Box 12.1: |
Symmetrical exons and intron phases / Box 12.2: |
Gene duplication mechanisms and paralogy / Box 12.3: |
Evolution of chromosomes and genomes / 12.2: |
The universal tree of life and horizontal gene transfer / Box 12.4: |
Molecular phylogenetics and comparative genomics / 12.3: |
What makes us human? / 12.4: |
A glossary of common metazoan phylogenetic groups and terms / Box 12.5: |
Evolution of human populations / 12.5: |
Coalescence analyses / Box 12.6: |
Mapping and identifying disease genes and mutations / Part 3: |
Genetic mapping of Mendelian characters / Chapter 13: |
Recombinants and nonrecombinants / 13.1: |
Genetic markers / 13.2: |
The development of human genetic markers / Box 13.1: |
Informative and uninformative meioses / Box 13.2: |
Two-point mapping / 13.3: |
Calculation of lod scores for the families in Figure 13.6 / Box 13.3: |
Multipoint mapping is more efficient than two-point mapping / 13.4: |
Bayesian calculation of linkage threshold / Box 13.4: |
Fine-mapping using extended pedigrees and ancestral haplotypes / 13.5: |
Standard lod score analysis is not without problems / 13.6: |
Identifying human disease genes / Chapter 14: |
Principles and strategies in identifying disease genes / 14.1: |
Position-independent strategies for identifying disease genes / 14.2: |
Positional cloning / 14.3: |
Transcript mapping: laboratory methods that supplement database analysis for identifying expressed sequences within genomic clones / Box 14.1: |
Use of chromosomal abnormalities / 14.4: |
Mapping mouse genes / Box 14.2: |
Pointers to the presence of chromosome abnormalities / Box 14.3: |
Position effects - a pitfall in disease gene identification / Box 14.4: |
Confirming a candidate gene / 14.5: |
CGH for detecting submicroscopic chromosomal imbalances / Box 14.5: |
Eight examples illustrate various ways disease genes have been identified / 14.6: |
Mapping and identifying genes conferring susceptibility to complex diseases / Chapter 15: |
Deciding whether a non-Mendelian character is genetic: the role of family, twin and adoption studies / 15.1: |
Segregation analysis allows analysis of characters that are anywhere on the spectrum between purely Mendelian and purely polygenic / 15.2: |
Linkage analysis of complex characters / 15.3: |
Correcting the segregation ratio / Box 15.1: |
Association studies and linkage disequilibrium / 15.4: |
Measures of linkage disequilibrium / Box 15.2: |
The transmission disequilibrium test (TDT) to determine whether marker allele M[subscript 1] is associated with a disease / Box 15.3: |
Identifying the susceptibility alleles / 15.5: |
Sample sizes needed to find a disease susceptibility locus by a whole genome scan using either affected sib pairs (ASP) or the transmission disequilibrium test (TDT) / Box 15.4: |
Eight examples illustrate the varying success of genetic dissection of complex diseases / 15.6: |
Alzheimer disease, ApoE testing and discrimination / Ethics Box 1: |
Overview and summary / 15.7: |
Molecular pathology / Chapter 16: |
Introduction / 16.1: |
The convenient nomenclature of A and a alleles hides a vast diversity of DNA sequences / 16.2: |
A first classification of mutations is into loss of function vs. gain of function mutations / 16.3: |
The main classes of mutation / Box 16.1: |
Nomenclature for describing sequence changes / Box 16.2: |
A nomenclature for describing the effect of an allele / Box 16.3: |
Loss of function mutations / 16.4: |
Hemoglobinopathies / Box 16.4: |
Guidelines for assessing the significance of a DNA sequence change / Box 16.5: |
Gain of function mutations / 16.5: |
Molecular pathology: from gene to disease / 16.6: |
Molecular pathology of Prader-Willi and Angelman syndromes / Box 16.6: |
Molecular pathology: from disease to gene / 16.7: |
Molecular pathology of chromosomal disorders / 16.8: |
Cancer genetics / Chapter 17: |
The evolution of cancer / 17.1: |
Oncogenes / 17.3: |
Two ways of making a series of successive mutations more likely / Box 17.1: |
Tumor suppressor genes / 17.4: |
Stability of the genome / 17.5: |
Control of the cell cycle / 17.6: |
Integrating the data: pathways and capabilities / 17.7: |
What use is all this knowledge? / 17.8: |
Genetic testing in individuals and populations / Chapter 18: |
The choice of material to test: DNA, RNA or protein / 18.1: |
Scanning a gene for mutations / 18.3: |
Testing for a specified sequence change / 18.4: |
Multiplex amplifiable probe hybridization (MAPH) / Box 18.1: |
Gene tracking / 18.5: |
Two methods for high-throughput genotyping |
The logic of gene tracking / Box 18.3: |
Population screening / 18.6: |
Use of Bayes' theorem for combining probabilities / Box 18.4: |
DNA profiling can be used for identifying individuals and determining relationships / 18.7: |
The Prosecutor's Fallacy / Box 18.5: |
New horizons: into the 21st century / Part 4: |
Beyond the genome project: functional genomics, proteomics and bioinformatics / Chapter 19: |
An overview of functional genomics / 19.1: |
The function of glucokinase / Box 19.1: |
Functional annotation by sequence comparison / 19.2: |
Global mRNA profiling (transcriptomics) / 19.3: |
Sequence sampling techniques for the global analysis of gene expression / Box 19.2: |
Proteomics / 19.4: |
Protein chips / Box 19.3: |
Mass spectrometry in proteomics / Box 19.4: |
Determination of protein structures / Box 19.5: |
Structural classification of proteins / Box 19.6: |
Summary / 19.5: |
Genetic manipulation of cells and animals / Chapter 20: |
An overview of gene transfer technology / 20.1: |
Principles of gene transfer / 20.2: |
Methods of gene transfer to animal cells in culture / Box 20.1: |
Selectable markers for animal cells / Box 20.2: |
Isolation and manipulation of mammalian embryonic stem cells / Box 20.3: |
Using gene transfer to study gene expression and function / 20.3: |
Reporter genes for animal cells / Box 20.4: |
Sophisticated vectors used for insertional mutagenesis / Box 20.5: |
Creating disease models using gene transfer and gene targeting technology / 20.4: |
The potential of animals for modeling human disease / Box 20.6: |
New approaches to treating disease / Chapter 21: |
Treatment of genetic disease is not the same as genetic treatment of disease / 21.1: |
Treatment of genetic disease / 21.2: |
Using genetic knowledge to improve existing treatments and develop new versions of conventional treatments / 21.3: |
The ethics of human cloning |
Principles of gene therapy / 21.4: |
Methods for inserting and expressing a gene in a target cell or tissue / 21.5: |
Germ line versus somatic gene therapy / Ethics Box 2: |
1995 NIH Panel report on gene therapy (Orkin-Motulsky report) / Box 21.1: |
Designer babies / Ethics Box 3: |
Methods for repairing or inactivating a pathogenic gene in a cell or tissue / 21.6: |
Some examples of attempts at human gene therapy / 21.7: |
Glossary |
Disease index |
Index |