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Tables of Contents for Advanced Genetic Analysis
Chapter/Section Title
Page #
Page Count
Preface
x
Introduction
xiv
Mutation
1
30
Types of mutations
1
10
Muller's classification of mutants
2
7
Modern mutant terminology
9
1
DNA-level terminology
10
1
Dominance and recessivity
11
3
Dominance and recessivity at the level of the cell
12
1
Difficulties in applying the terms ``dominant'' and ``recessive'' to sex-linked mutants
13
1
The genetic utility of dominant and recessive mutants
14
17
Summary
14
1
Gallery of model organisms
15
1
Our favorite organism: Drosophila melanogaster
15
3
Our second favorite organism: Saccharomyces cerevisiae
18
1
Our third favorite organism: Caenorhabditis elegans
19
2
Our new favorite organism: zebrafish
21
2
Phage lambda
23
2
Phage T4
25
2
Arabidopsis thaliana
27
1
Mus musculus (the mouse)
28
3
Mutant hunts
31
24
Why look for new mutants?
32
6
Reason 1: To identify genes required for a specific biological process
32
3
Reason 2: To isolate more mutations in a specific gene of interest
35
3
Reason 3: To obtain mutations tools for structure--function analysis
38
1
Reason 4: To isolate mutations in a gene so far identified only by molecular approaches
38
1
Mutagenesis and mutational mechanisms
38
8
Method 1: Ionizing radiation (usually X-rays and gamma-rays)
39
1
Method 2: Chemical mutagens
40
2
Method 3: Transposons as mutagens
42
2
Method 4: Targeted gene disruption (a variant on transposon mutagenesis)
44
2
What phenotype should you screen (or select) for?
46
1
Actually getting started
47
8
Your starting material
47
1
Pilot screens
47
1
Keeping too many, keeping too few
48
1
How many mutants is enough?
48
2
Summary
50
A screen for embryonic lethal mutations in Drosophila
33
1
The balancer chromosome
34
2
A screen for sex-linked lethal mutations in Drosophila
36
9
Making phenocopies by RNAi and co-suppression
45
6
Reviews of mutant isolation schemes and techniques in various organisms
51
4
The complementation test
55
27
The essence of the complementation test
55
3
Rules for using the complementation test
58
2
How might the complementation test lie to you?
60
1
Second-site non-complementation (SSNC) (non-allelic non-complementation)
61
18
Type 1 SSNC (poisonous interactions): the interaction is allele-specific at both loci
62
8
Type 2 SSNC (sequestration): the interaction is allele-specific at one locus
70
6
Type 3 SSNC (combined haplo-insufficiency): the interaction is allele-independent at both loci
76
1
Summary of SSNC
77
2
An extension of second-site non-complementation: dominant enhancers
79
3
A successful screen for dominant enhancers
79
2
Summary
81
A more rigorous definition of the complementation test
56
1
An example of using the complementation test in yeast
57
1
Transformation rescue is a variant of the complementation test
58
1
One method for determining whether or not a dominant mutation is an allele of a given gene, or how to make dominants into recessives by pseudo-reversion
59
3
Pairing-dependent complementation: transvection
62
5
Synthetic lethality and genetic buffering
67
15
Suppression
82
25
A basic definition of genetic suppression
82
1
Intragenic suppression (pseudo-reversion)
83
5
Intragenic revertants can mediate translational suppression
84
2
Intragenic suppression as a result of compensatory mutants
86
2
Extragenic suppression
88
1
Transcriptional suppression
88
2
Suppression at the level of gene expression
88
1
Suppression of transposon insertion mutants by altering the control of mRNA processing
89
1
Suppression of nonsense mutants by messenger stabilization in C. elegans
89
1
Translational suppression
90
3
Simplicity: tRNA suppressors in E. coli
90
2
The numerical and functional redundancy of tRNA genes allowing suppressor mutations to be viable
92
1
Suppression of a frameshift mutation using a mutant tRNA gene
93
1
Suppressing a nonsense codon using unaltered tRNAs
93
1
Suppression by post-translational modification
93
1
Extragenic suppression as a result of protein-protein interaction
94
6
Searching for suppressors that act by protein-protein interaction in eukaryotes
95
5
Extragenic suppression as a result of ``lock-and-key'' conformational suppression
100
1
Suppression without physical interaction
100
5
Bypass suppression
101
1
``Push me, pull you'' bypass selection by counterbalancing of opposite activities
102
1
Extra-copy suppression as a form of bypass suppression
103
2
Suppression of dominant mutations
105
1
Designing your own screen for suppressor mutations
105
2
Summary and a warning
106
Intragenic suppression of antimorphic mutations that produce a poisonous protein
87
15
Bypass suppression of a telomere defect in the yeast S. pombe
102
5
Determining when and where genes function
107
20
Epistasis: ordering gene function in pathways
107
11
Ordering gene function in a biosynthetic pathway
108
1
The use of epistasis in non-biosynthetic pathways: determining if two genes act in the same or different pathways
109
2
The real value of epistasis analysis is in the dissection of regulatory hierarchies
111
7
How might an epistasis experiment mislead you?
118
1
Mosaic analysis: where does a given gene act?
118
9
Tissure transplantation studies
119
1
Loss of the unstable ring X chromosome
120
3
Mitotic recombination
123
1
Genetically controllable mitotic recombination: the FLP-FRT system
124
2
Summary
126
1
Genetic fine-structure analysis
127
24
Intragenic mapping (then)
127
7
The first efforts towards finding structure within a gene
127
2
The unit of recombination and mutation is the base pair
129
5
Intragenic mapping (now)
134
1
Intragenic complementation meets intragenic recombination: the basis of fine-structure analysis
135
3
The formal analysis of intragenic complementation
136
2
An example of fine-structure analysis for a eukaryotic gene encoding a multifunctional protein
138
1
A genetic and functional dissection of the HIS4 gene in yeast
138
1
Fine-structure analysis of genes with complex regulatory elements in eukaryotes
139
3
Genetic and functional dissection of the cut gene in Drosophila
139
3
Pairing-dependent intragenic complementation
142
9
Genetic and functional dissection of the yellow gene in Drosophila
142
1
The influence of the zeste gene on pairing-dependent complementation at the white locus in Drosophila
143
2
Genetic and functional dissection of BX-C in Drosophila
145
1
Summary
146
1
Genetic and functional dissection of the rudimentary gene in Drosophila
147
4
Meiotic recombination
151
49
An introduction to meiosis
151
9
A cytological description of meiosis
158
2
A more detailed description of meiotic prophase
160
1
Crossingover and chiasmata: recombination involves the physical interchange of genetic material and ensures homolog separation
160
2
The classical analysis of recombination
162
5
Measuring the frequency of recombination
167
26
The curious relationship between the frequency of recombination and chiasma frequency (and why it matters)
167
1
Map lengths and recombination frequency
168
3
Determining the fraction of bivalents with zero, one, two, or more exchanges (tetrad analysis)
171
11
Statistical estimation of recombination frequencies (LOD scores)
182
10
The actual distribution of exchange events
192
1
Practicalities of mapping
193
1
The mechanism of recombination
193
7
Gene conversion
193
2
Previous models
195
3
The currently accepted mechanism of recombination: the DSBR model
198
1
Summary
199
The molecular biology of synapsis
155
1
Do specific chromosomal sites mediate pairing?
156
7
Crossingover in compound X chromosomes
163
3
Does any sister chromatid exchange occur during meiosis?
166
11
Using tetrad analysis to determine linkage
177
1
Mapping centromeres in fungi with unordered tetrads
177
23
Meiotic chromosome segregation
200
19
Types and consequences of failed segregation
201
1
The origin of spontaneous nondisjunction
202
2
The centromere
204
9
The isolation and analysis of the S. cerevisiae centromere
204
3
The isolation and analysis of the Drosophila centromere
207
6
Segregational mechanisms
213
6
How chiasmata ensure segregation
213
1
Achiasmate segregation
214
4
Summary
218
Identifying genes that encode centromere-binding proteins in yeast
206
6
The concept of the epigenetic centromere in Drosophila and humans
212
5
Achiasmate heterologous segregation in Drosophila females
217
2
Epilogue
219
1
References
220
16
Partial author index
236
2
Subject index
238