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| Preface | |
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| Introduction | |
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| Mutation | |
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| Types of mutations | |
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| Muller's classification of mutants | |
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| Modern mutant terminology | |
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| DNA-level terminology | |
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| Dominance and recessivity | |
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| Dominance and recessivity at the level of the cell | |
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| Difficulties in applying the terms "dominant" and "recessive" to sex-linked mutants | |
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| The genetic utility of dominant and recessive mutants | |
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| Summary | |
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| Gallery of model organisms | |
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| Our favorite organism: Drosophila melanogaster | |
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| Our second favorite organism: Saccharomyces cerevisiae | |
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| Our third favorite organism: Caenorhabditis elegans | |
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| Our new favorite organism: zebrafish | |
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| Phage lambda | |
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| Phage T4 | |
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| Arabidopsis thaliana | |
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| Mus musculus (the mouse) | |
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| Mutant hunts | |
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| Why look for new mutants? | |
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| Reason 1: To identify genes required for a specific biological process | |
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| Reason 2: To isolate more mutations in a specific gene of interest | |
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| Reason 3: To obtain mutations tools for structure-function analysis | |
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| Reason 4: To isolate mutations in a gene so far identified only by molecular approaches | |
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| Mutagenesis and mutational mechanisms | |
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| Method 1: Ionizing radiation (usually X-rays and gamma-rays) | |
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| Method 2: Chemical mutagens | |
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| Method 3: Transposons as mutagens | |
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| Method 4: Targeted gene disruption (a variant on transposon mutagenesis) | |
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| What phenotype should you screen (or select) for? | |
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| Actually getting started | |
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| Your starting material | |
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| Pilot screens | |
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| Keeping too many, keeping too few | |
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| How many mutants is enough? | |
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| Summary | |
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| A screen for embryonic lethal mutations in Drosophila | |
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| The balancer chromosome | |
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| A screen for sex-linked lethal mutations in Drosophila | |
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| Making phenocopies by RNAi and co-suppression | |
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| Reviews of mutant isolation schemes and techniques in various organisms | |
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| The complementation test | |
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| The essence of the complementation test | |
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| Rules for using the complementation test | |
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| How might the complementation test lie to you? | |
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| Second-site non-complementation (SSNC) (non-allelic non-complementation) | |
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| Type 1 SSNC (poisonous interactions): the interaction is allele-specific at both loci | |
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| Type 2 SSNC (sequestration): the interaction is allele-specific at one locus | |
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| Type 3 SSNC (combined haplo-insufficiency): the interaction is allele-independent at both loci | |
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| Summary of SSNC | |
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| An extension of second-site non-complementation: dominant enhancers | |
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| A successful screen for dominant enhancers | |
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| Summary | |
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| A more rigorous definition of the complementation test | |
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| An example of using the complementation test in yeast | |
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| Transformation rescue is a variant of the complementation test | |
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| 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 | |
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| Pairing-dependent complementation: transvection | |
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| Synthetic lethality and genetic buffering | |
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| Suppression | |
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| A basic definition of genetic suppression | |
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| Intragenic suppression (pseudo-reversion) | |
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| Intragenic revertants can mediate translational suppression | |
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| Intragenic suppression as a result of compensatory mutants | |
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| Extragenic suppression | |
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| Transcriptional suppression | |
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| Suppression at the level of gene expression | |
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| Suppression of transposon insertion mutants by altering the control of mRNA processing | |
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| Suppression of nonsense mutants by messenger stabilization in C. elegans | |
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| Translational suppression | |
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| Simplicity: tRNA suppressors in E. coli | |
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| The numerical and functional redundancy of tRNA genes allowing suppressor mutations to be viable | |
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| Suppression of a frameshift mutation using a mutant tRNA gene | |
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| Suppressing a nonsense codon using unaltered tRNAs | |
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| Suppression by post-translational modification | |
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| Extragenic suppression as a result of protein-protein interaction | |
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| Searching for suppressors that act by protein-protein interaction in eukaryotes | |
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| Extragenic suppression as a result of "lock-and-key" conformational suppression | |
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| Suppression without physical interaction | |
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| Bypass suppression | |
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| "Push me, pull you" bypass selection by counterbalancing of opposite activities | |
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| Extra-copy suppression as a form of bypass suppression | |
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| Suppression of dominant mutations | |
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| Designing your own screen for suppressor mutations | |
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| Summary and a warning | |
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| Intragenic suppression of antimorphic mutations that produce a poisonous protein | |
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| Bypass suppression of a telomere defect in the yeast S. pombe | |
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| Determining when and where genes function | |
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| Epistasis: ordering gene function in pathways | |
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| Ordering gene function in a biosynthetic pathway | |
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| The use of epistasis in non-biosynthetic pathways: determining if two genes act in the same or different pathways | |
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| The real value of epistasis analysis is in the dissection of regulatory hierarchies | |
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| How might an epistasis experiment mislead you? | |
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| Mosaic analysis: where does a given gene act? | |
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| Tissure transplantation studies | |
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| Loss of the unstable ring X chromosome | |
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| Mitotic recombination | |
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| Genetically controllable mitotic recombination: the FLP-FRT system | |
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| Summary | |
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| Genetic fine-structure analysis | |
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| Intragenic mapping (then) | |
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| The first efforts towards finding structure within a gene | |
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| The unit of recombination and mutation is the base pair | |
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| Intragenic mapping (now) | |
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| Intragenic complementation meets intragenic recombination: the basis of fine-structure analysis | |
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| The formal analysis of intragenic complementation | |
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| An example of fine-structure analysis for a eukaryotic gene encoding a multifunctional protein | |
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| A genetic and functional dissection of the HIS4 gene in yeast | |
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| Fine-structure analysis of genes with complex regulatory elements in eukaryotes | |
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| Genetic and functional dissection of the cut gene in Drosophila | |
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| Pairing-dependent intragenic complementation | |
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| Genetic and functional dissection of the yellow gene in Drosophila | |
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| The influence of the zeste gene on pairing-dependent complementation at the white locus in Drosophila | |
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| Genetic and functional dissection of BX-C in Drosophila | |
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| Summary | |
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| Genetic and functional dissection of the rudimentary gene in Drosophila | |
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| Meiotic recombination | |
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| An introduction to meiosis | |
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| A cytological description of meiosis | |
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| A more detailed description of meiotic prophase | |
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| Crossingover and chiasmata: recombination involves the physical interchange of genetic material and ensures homolog separation | |
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| The classical analysis of recombination | |
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| Measuring the frequency of recombination | |
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| The curious relationship between the frequency of recombination and chiasma frequency (and why it matters) | |
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| Map lengths and recombination frequency | |
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| Determining the fraction of bivalents with zero, one, two, or more exchanges (tetrad analysis) | |
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| Statistical estimation of recombination frequencies (LOD scores) | |
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| The actual distribution of exchange events | |
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| Practicalities of mapping | |
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| The mechanism of recombination | |
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| Gene conversion | |
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| Previous models | |
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| The currently accepted mechanism of recombination: the DSBR model | |
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| Summary | |
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| The molecular biology of synapsis | |
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| Do specific chromosomal sites mediate pairing? | |
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| Crossingover in compound X chromosomes | |
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| Does any sister chromatid exchange occur during meiosis? | |
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| Using tetrad analysis to determine linkage | |
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| Mapping centromeres in fungi with unordered tetrads | |
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| Meiotic chromosome segregation | |
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| Types and consequences of failed segregation | |
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| The origin of spontaneous nondisjunction | |
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| The centromere | |
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| The isolation and analysis of the S. cerevisiae centromere | |
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| The isolation and analysis of the Drosophila centromere | |
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| Segregational mechanisms | |
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| How chiasmata ensure segregation | |
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| Achiasmate segregation | |
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| Summary | |
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| Identifying genes that encode centromere-binding proteins in yeast | |
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| The concept of the epigenetic centromere in Drosophila and humans | |
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| Achiasmate heterologous segregation in Drosophila females | |
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| Epilogue | |
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| References | |
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| Partial author index | |
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| Subject index | |