Variation is the crux of genetics. Mutagenesis screens in organisms from bacteria to fish have provided a battery of mutants that define protein functions within complex pathways. Large-scale mutation isolation has been carried out in Caenorhabditis elegans, Drosophila melanogaster and zebrafish, and has been recently reported in the mouse in two screens that have generated many new, clinically relevant mutations to reveal the power of phenotype-driven screens in a mammal.
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Acknowledgements
The author thanks H. Bellen for the critical reading of this manuscript and for sharing his knowledge of the history and current status of Drosophila melanogaster genetics, and Andrew Sallinger for photographing the mice in Fig. 3. This work was supported by a United States Public Health Service grant.
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German ENU-mouse mutagenesis screen project
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Glossary
- GENE TRAPPING
-
A mutation strategy that uses insertion vectors to trap or isolate transcripts from flanking genes. The inserted sequence acts as a tag from which to clone the mutated gene.
- ALLELIC SERIES
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An array of possible mutant forms of a gene, which usually cause multiple phenotypes.
- HYPOMORPH
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A mutant allele that does not eliminate the wild-type function of a gene and may give a less severe phenotype than a loss-of-function mutant.
- COMPLEMENTATION
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When two mutations are combined in an organism and the phenotype is wild type, the mutations are said to complement each other.
- ANTIMORPH
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A mutant allele that antagonizes gene function and acts in a semi-dominant manner.
- MISSENSE MUTATION
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A mutation that results in the substitution of an amino acid in a protein.
- NONSENSE MUTATION
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A mutation that results in the introduction of a stop codon to cause the premature termination of the protein.
- HAPLOINSUFFICIENT
-
A phenotype that arises in diploid organisms owing to the loss of one functional copy of a gene.
- ELISA (ENZYME-LINKED IMMUNOSORBENT ASSAY.)
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A sensitive antibody-based method for the detection of an antigen such as a protein.
- BACKCROSS
-
The mating of an individual with its parent, or with an individual of the same genotype as its parent, to follow the inheritance of alleles and phenotypes.
- DNA POOLING
-
A mapping strategy that pools DNA from phenotypically distinct backcross or intercross progeny to identify marker alleles that are linked to the genes that determine phenotype; it reduces the time and expense of genotyping individual mice from linkage crosses.
- FORWARD GENETICS
-
A genetic analysis that proceeds from phenotype to genotype by positional cloning or candidate-gene analysis.
- REVERSE GENETICS
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A genetic analysis that proceeds from genotype to phenotype by gene-manipulation techniques, such as homologous recombination in ES cells.
- PARTHENOGENESIS
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The production of offspring by a female with no genetic contribution from a male.
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Justice, M. Capitalizing on large-scale mouse mutagenesis screens. Nat Rev Genet 1, 109–115 (2000). https://doi.org/10.1038/35038549
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DOI: https://doi.org/10.1038/35038549
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