Beddington- Mouse mutagenesis- From gene to phenotype and back agai

Beddington- Mouse mutagenesis- From gene to phenotype and back agai

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R840 Dispatch Mouse mutagenesis: From gene to phenotype and back again Rosa Beddington Screens for genetic mutations have been instrumental in identifying genes needed to execute particular biological processes. They have also helped to resolve the function of individual genes. Now the notion of large-scale mutagenesis screens in mouse, an experimental model for humans, is becoming a reality. Address: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Current Biology 1998, 8:R840–R842 http://biomednet.com/elecref/09609822008R0840 © Current Biology Ltd ISSN 0960-9822 At the heart of genetics lie screens for mutations that cause detectable and heritable changes in biological form or function. If altering a particular gene alters a biological process, then probably that gene’s normal protein product operates in that process. Genetic screens thus provide a relatively unbiassed route for identifying the genes required for a given biological process. They may also indicate when in that process the product of a particular gene is needed, and how it interacts with or relates to other genes operating in the same process. In this way, a hierarchy of genetic requirements can be compiled, even before the molecular nature of the gene products is known. Can large scale mutagenesis screens be used to dissect mammalian biology? The success of a genetic screen depends on several factors. Scale is important: the phenotypes of enough individuals need to be studied to ensure that mutations in as many genes as possible — ideally, all genes — are represented. Indeed, more than one mutation per gene is desirable, different mutations exposing different facets of function. In reality, however, some mutations will be lethal before the phenotype is examined, which means that the ideal of saturation is seldom realised. How sensi- tive the screen will be depends on how good the criteria are for distinguishing between normal and abnormal phenotype. Often it is easier to identify mutations in organisms that otherwise have identical genomes and minimal phenotypic variability between individuals. The type of mutation being sought will also be important. Removing or attenuating gene function generally reveals more about normality than adding to or changing gene function. If a plant is deprived of water, it will die because normally it needs water. If it is given detergent it will also die, not because normally it needs detergent, but because the addition of soap changes water into a poison. So loss- of-function mutations, which tend to be recessive in diploid organisms, are usually more informative than gain- of-function mutations, which tend to be dominant. The ability to map mutations to their location in the genome — on which chromosome they reside and where — is essential, not only in helping to distinguish between dif- ferent genes with similar effects, but also in cloning the mutated gene and determining the molecular function of
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This note was uploaded on 02/15/2012 for the course PMB 13 taught by Professor Freeling during the Spring '09 term at Berkeley.

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Beddington- Mouse mutagenesis- From gene to phenotype and back agai

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