Introduction to Genetic Analysis

Front Cover
About the Authors
Title Page
Copyright Page
Contents in Brief
Contents
Preface
Chapter 1: The Genetics Revolution
	1.1 The Birth of Genetics
		Gregor Mendel—A monk in the garden
		Mendel rediscovered
		The central dogma of molecular biology
	1.2 After Cracking the Code
		Model organisms
		Tools for genetic analysis
	1.3 Genetics Today
		From classical genetics to medical genomics
		Investigating mutation and disease risk
		When rice gets its feet a little too wet
		Recent evolution in humans
		The complex genetics of color blindness
Part 1: Core Principles in Transmission Genetics
	Chapter 2: Single-Gene Inheritance
		2.1 Single-Gene Inheritance Patterns
			Mendel’s pioneering experiments
			Mendel’s law of equal segregation
		2.2 Genes and Chromosomes
			Single-gene inheritance in diploids
			Single-gene inheritance in haploids
		2.3 The Molecular Basis of Mendelian Inheritance Patterns
			Structural differences between alleles at the molecular level
			Molecular aspects of gene transmission
			Alleles at the molecular level
		2.4 Some Genes Discovered by Observing Segregation Ratios
			A gene active in the development of flower color
			A gene for wing development
			A gene for hyphal branching
			Predicting progeny proportions or parental genotypes by applying the principles of single-gene inheritance
		2.5 Sex-Linked Single-Gene Inheritance Patterns
			Sex chromosomes
			Sex-linked patterns of inheritance
			X-linked inheritance
		2.6 Human Pedigree Analysis
			Autosomal recessive disorders
			Autosomal dominant disorders
			Autosomal polymorphisms
			X-linked recessive disorders
			X-linked dominant disorders
			Y-linked inheritance
			Calculating risks in pedigree analysis
	Chapter 3: Independent Assortment of Genes
		3.1 Mendel’s Law of Independent Assortment
		3.2 Working with Independent Assortment
			Predicting progeny ratios
			Using the chi-square test on monohybrid and dihybrid ratios
			Synthesizing pure lines
			Hybrid vigor
		3.3 The Chromosomal Basis of Independent Assortment
			Independent assortment in diploid organisms
			Independent assortment in haploid organisms
			Recombination
		3.4 Polygenic Inheritance
		3.5 Organelle Genes: Inheritance Independent of the Nucleus
			Patterns of inheritance in organelles
			Cytoplasmic segregation
			Cytoplasmic mutations in humans
			mtDNA in evolutionary studies
	Chapter 4: Mapping Eukaryote Chromosomes by Recombination
		4.1 Diagnostics of Linkage
			Using recombinant frequency to recognize linkage
			How crossovers produce recombinants for linked genes
			Linkage symbolism and terminology
			Evidence that crossing over is a breakage-and-rejoining process
			Evidence that crossing over takes place at the four-chromatid stage
			Multiple crossovers can include two or more than two chromatids
		4.2 Mapping by Recombinant Frequency
			Map units
			Three-point testcross
			Deducing gene order by inspection
			Interference
			Using ratios as diagnostics
		4.3 Mapping with Molecular Markers
		4.4 Using the Chi-Square Test to Infer Linkage
		4.5 The Molecular Mechanism of Crossing Over
		4.6 Using Recombination-Based Maps in Conjunction with Physical Maps
	Chapter 5: Gene Interaction
		5.1 Interactions Between the Alleles of a Single Gene:
			Complete dominance and recessiveness
			Incomplete dominance
			Codominance
			Recessive lethal alleles
			Penetrance and expressivity
		5.2 Interaction of Genes in Pathways
			Biosynthetic pathways in Neurospora
			Gene interaction in other types of pathways
		5.3 Inferring Gene Interactions
			Sorting mutants using the complementation test
			Analyzing double mutants of random mutations
	Chapter 6: The Genetics of Bacteria and Their Viruses
		6.1 Working with Microorganisms
		6.2 Bacterial Conjugation
			Discovery of conjugation
			Discovery of the fertility factor (F)
			Hfr strains
			Mapping of bacterial chromosomes
			F plasmids that carry genomic fragments
			R plasmids
		6.3 Bacterial Transformation
			The nature of transformation
			Chromosome mapping using transformation
		6.4 Bacteriophage Genetics
			Infection of bacteria by phages
			Mapping phage chromosomes by using phage crosses
		6.5 Transduction
			Discovery of transduction
			Generalized transduction
			Specialized transduction
			Mechanism of specialized transduction
		6.6 Physical Maps and Linkage Maps Compared
Part 2: Core Principles in Molecular and Developmental Genetics
	Chapter 7: DNA: Structure and Replication
		7.1 DNA Is the Genetic Material
			The discovery of bacterial transformation: the Griffith experiment
			Evidence that DNA is the genetic material in bacteria: the Avery, MacLeod, and McCarty experiments
			Evidence that DNA is the genetic material in phage: the Hershey–Chase experiment
		7.2 DNA Structure
			DNA structure before Watson and Crick
			The DNA double helix structure: Watson and Crick
		7.3 DNA Replication Is Semiconservative
			Evidence that DNA replication is semiconservative: the Meselson–Stahl experiment
			Evidence for a replication fork: the Cairns experiment
		7.4 DNA Replication in Bacteria
			Unwinding the DNA double helix
			Assembling the replisome: replication initiation
			DNA polymerases catalyze DNA chain elongation
			DNA replication is semidiscontinuous
			DNA replication is accurate and rapid
		7.5 DNA Replication in Eukaryotes
			Eukaryotic origins of replication
			DNA replication and the yeast cell cycle
			Replication origins in higher eukaryotes
			Telomeres and telomerase: replication termination
	Chapter 8: RNA: Transcription, Processing, and Decay
		8.1 RNA Structure
			RNA is the information-carrying intermediate between DNA and proteins
			Consequences of the distinct chemical properties of RNA
			Classes of RNA
		8.2 Transcription and Decay of mRNA in Bacteria
			Overview: DNA as transcription template
			Stages of transcription
			mRNA decay in bacteria
		8.3 Transcription in Eukaryotes
			Transcription initiation in eukaryotes
			RNA polymerase II transcription elongation
			Transcription termination in eukaryotes
		8.4 Processing of mRNA in Eukaryotes
			Capping
			Polyadenylation
			The discovery of splicing
			The splicing mechanism
			snRNAs in the spliceosome may carry out the catalytic steps of splicing
			Alternative splicing can expand the proteome
			RNA editing
			RNA nucleotide modification
			RNA export from the nucleus
		8.5 Decay of mRNA in Eukaryotes
			mRNA decay mechanisms
			The discovery of RNA interference (RNAi)
			siRNA-mediated RNA decay and transcriptional silencing
			RNAi protects the genome from foreign DNA
	Chapter 9: Proteins and Their Synthesis
		9.1 Protein Structure
		9.2 The Genetic Code
			A degenerate three-letter genetic code specifies the 20 amino acids
			The genetic code is nonoverlapping and continuous
			Cracking the code
			Stop codons
			Degeneracy of the genetic code limits the effects of point mutations
		9.3 tRNAs and Ribosomes
			tRNAs are adaptors
			Wobble base pairing allows tRNAs to recognize more than one codon
			Ribosome structure and function
		9.4 Translation
			Translation initiation
			Translation elongation
			Translation termination
			Nonsense suppressor mutations
		9.5 Translational and Post-Translational Regulation
			Protein folding
			Post-translational modification of amino acid side chains
			Protein targeting
	Chapter 10: Gene Isolation and Manipulation
		10.1 Detecting and Quantifying DNA, RNA, and Protein
			Detecting and quantifying molecules by Southern, Northern, and Western blot analysis
			Detecting and amplifying DNA by the polymerase chain reaction
		10.2 Generating Recombinant DNA
			DNA cloning
			DNA libraries
			Identifying a clone of interest from a genomic or cDNA library
			Genomic and cDNA clones are used in different ways
			Cloning by PCR
		10.3 Sequencing DNA
		10.4 Engineering Genomes
			Genetic engineering in Saccharomyces cerevisiae
			Genetic engineering in plants
			Genetic engineering in animals
			CRISPR-Cas9 genome engineering
	Chapter 11: Regulation of Gene Expression in Bacteria and Their Viruses
		11.1 Gene Regulation
			The basics of bacterial transcriptional regulation: genetic switches
			A first look at the lac regulatory circuit
		11.2 Discovery of the lac System: Negative Regulation
			Genes controlled together
			Genetic evidence for the operator and repressor
			Genetic evidence for allostery
			Genetic analysis of the lac promoter
			Molecular characterization of the Lac repressor and the lac operator
		11.3 Catabolite Repression of the lac Operon: Positive Regulation
			The basics of lac catabolite repression: choosing the best sugar to metabolize
			The structures of target DNA sites
			A summary of the lac operon
		11.4 Dual Positive and Negative Regulation: The Arabinose Operon
		11.5 Metabolic Pathways and Additional Levels of Regulation: Attenuation
		11.6 Bacteriophage Life Cycles: More Regulators, Complex Operons
			Regulation of the bacteriophage λ life cycle
			Molecular anatomy of the genetic switch
			Sequence-specific binding of regulatory proteins to DNA
		11.7 Alternative Sigma Factors Regulate Large Sets of Genes
	Chapter 12: Regulation of Transcription in Eukaryotes
		12.1 Transcription Factors Regulate Transcription
			Transcription factors bind distal and proximal enhancers
			Transcription factors: lessons from the yeast GAL system
			Gal4 domains function independently of one another
			Regulation of Gal4
			Combinatorial control of transcription: lessons from yeast mating type
		12.2 Chromatin Structure
			Histones
			Nucleosomes
			Chromatin folding
		12.3 Chromatin Regulates Transcription
			Histone modification: a type of chromatin modification
			The histone code hypothesis
			DNA modification: another type of chromatin modification
			Chromatin remodeling
			Connecting chromatin structure to transcription: lessons from the interferon-β gene
		12.4 Chromatin in Epigenetic Regulation
			Cellular memory
			Position-effect variegation
			Genomic imprinting
			X-chromosome inactivation
	Chapter 13: The Genetic Control of Development
		13.1 The Genetic Approach to Development
		13.2 The Genetic Toolkit for Drosophila Development
			Classification of genes by developmental function
			Homeotic genes and segmental identity
			Organization and expression of Hox genes
			The homeobox
			Clusters of Hox genes control development in most animals
		13.3 Defining the Entire Toolkit
			The anteroposterior axis
			Expression of toolkit genes
		13.4 Spatial Regulation of Gene Expression in Development
			Maternal gradients and gene activation
			Drawing stripes: integration of gap-protein inputs
			Making segments different: integration of Hox inputs
		13.5 Post-transcriptional Regulation of Gene Expression in Development
			RNA splicing and sex determination in Drosophila
			Regulation of mRNA translation and cell lineage in C. elegans
			Translational control in the early embryo
			miRNA control of developmental timing in C. elegans and other species
		13.6 From Flies to Fingers, Feathers, and Floor Plates: The Many Roles of Individual Toolkit Genes
		13.7 Development and Disease
			Polydactyly
			Holoprosencephaly
			Cancer as a developmental disease
	Chapter 14: Genomes and Genomics
		14.1 The Genomics Revolution
		14.2 Obtaining the Sequence of a Genome
			Turning sequence reads into an assembled sequence
			Whole-genome sequencing
			Traditional WGS sequencing
			Next-generation WGS sequencing
			Whole-genome-sequence assembly
		14.3 Bioinformatics: Meaning from Genomic Sequence
			The nature of the information content of DNA
			Deducing the protein-encoding genes from genomic sequence
		14.4 The Structure of the Human Genome
			Noncoding functional elements in the genome
		14.5 The Comparative Genomics of Humans with Other Species
			Phylogenetic inference
			Of mice and humans
			Comparative genomics of chimpanzees and humans
		14.6 Comparative Genomics and Human Medicine
			The evolutionary history of human disease genes
			The exome and personalized genomics
			Comparative genomics of nonpathogenic and pathogenic E. coli
		14.7 Functional Genomics and Reverse Genetics
			“’Omics”
			Reverse genetics
Part 3: Core Principles in Mutation, Variation, and Evolution
	Chapter 15: DNA Damage, Repair, and Mutation
		15.1 Molecular Consequences of Point Mutations
			The types of point mutations
			The molecular consequences of a point mutation in an open reading frame
			The molecular consequences of a point mutation in a noncoding region
		15.2 Molecular Basis of Spontaneous Mutations
			Evidence for spontaneous mutations: the Luria and Delbrück fluctuation test
			Mechanisms of spontaneous mutations
		15.3 Molecular Basis of Induced Mutations
			Mechanisms of induced mutagenesis
			Identifying mutagens in the environment: the Ames test
		15.4 DNA Repair Mechanisms
			Direct repair of damaged DNA
			Base excision repair
			Nucleotide excision repair
			Mismatch repair
			Translesion synthesis
			Repair of double-strand breaks
	Chapter 16: The Dynamic Genome: Transposable Elements
		16.1 Discovery of Transposable Elements in Maize
			McClintock’s experiments: the Ds element
			Ac (Activator) and Ds (Dissociation) today
			Transposable elements: only in maize?
		16.2 Transposable Elements in Bacteria
			Evidence for transposable elements in bacteria
			Simple and composite transposons
			Mechanism of transposition
		16.3 Transposable Elements in Eukaryotes
			Class 1: retrotransposons
			Class 2: DNA transposons
			Utility of DNA transposons as tools for genetic research
		16.4 The Dynamic Genome: More Transposable Elements Than Ever Imagined
			Large genomes are largely transposable elements
			Transposable elements in the human genome
			Plants: LTR-retrotransposons thrive in large genomes
			Safe havens
		16.5 Regulation of Transposable Element Movement by the Host
			RNAi silencing of transposable elements
			Genome surveillance
	Chapter 17: Large-Scale Chromosomal Changes
		17.1 Changes in Chromosome Number
			Aberrant euploidy
			Aneuploidy
			The concept of gene balance
		17.2 Changes in Chromosome Structure
			Deletions
			Duplications
			Inversions
			Reciprocal translocations
			Robertsonian translocations
			Applications of inversions and translocations
		17.3 Phenotypic Consequences of Chromosomal Changes
			Chromosome rearrangements and evolution
			Chromosome rearrangements and cancer
			Overall incidence of human chromosome mutations
	Chapter 18: Population Genetics
		18.1 Detecting Genetic Variation
			Single nucleotide polymorphisms (SNPs)
			Microsatellites
			Haplotypes
			Other sources and forms of variation
		18.2 The Gene-Pool Concept and the Hardy–Weinberg Law
		18.3 Mating Systems
			Assortative mating
			Isolation by distance
			Inbreeding
			The inbreeding coefficient
			Population size and inbreeding
		18.4 Genetic Variation and Its Measurement
		18.5 The Modulation of Genetic Variation
			New alleles enter the population: mutation and migration
			Recombination and linkage disequilibrium
			Genetic drift and population size
			Selection
			Forms of selection
			Balance between mutation and drift
			Balance between mutation and selection
		18.6 Biological and Social Applications
			Conservation genetics
			Calculating disease risks
			DNA forensics
	Chapter 19: The Inheritance of Complex Traits
		19.1 Measuring Quantitative Variation
			Types of traits and inheritance
			The mean
			The variance
			The normal distribution
		19.2 A Simple Genetic Model for Quantitative Traits
			Genetic and environmental deviations
			Genetic and environmental variances
			Correlation between variables
		19.3 Broad-Sense Heritability: Nature versus Nurture
			Measuring heritability in humans using twin studies
		19.4 Narrow-Sense Heritability: Predicting Phenotypes
			Gene action and the transmission of genetic variation
			The additive and dominance effects
			A model with additivity and dominance
			Narrow-sense heritability
			Predicting offspring phenotypes
			Selection on complex traits
		19.5 Mapping QTL in Populations with Known Pedigrees
			The basic method for QTL mapping
			From QTL to gene
		19.6 Association Mapping in Random-Mating Populations
			The basic method for GWAS
			GWA, genes, disease, and heritability
	Chapter 20: Evolution of Genes, Traits, and Species
		20.1 Evolution by Natural Selection
		20.2 Natural Selection in Action: An Exemplary Case
			The selective advantage of HbS
			The molecular origins of HbS
		20.3 Molecular Evolution
			The development of the neutral theory of evolution
			The rate of neutral substitutions
			The signature of purifying selection on DNA sequences
			The signature of positive selection on DNA sequences
		20.4 Evolution of Genes and Genomes
			Expanding gene number
			The fate of duplicated genes
			The fate of duplicated genomes
		20.5 Evolution of Traits
			Adaptive changes in a pigment-regulating protein
			Gene inactivation
			Regulatory-sequence evolution
			Loss of characters through regulatory-sequence evolution
			Regulatory evolution in humans
		20.6 Evolution of Species
			Species concepts
			Mechanisms of reproductive isolation
			Genetics of reproductive isolation
A Brief Guide to Model Organisms
Appendix A: Genetic Nomenclature
Appendix B: Bioinformatic Resources for Genetics and Genomics
Glossary
Answers to Selected Problems
Index
Back Cover