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Recessive Lethal Mutations - Essay Example

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George Streisinger pioneered the potential of zebrafish as a vertebrate organism suitable for forward genetics screening research, about twenty years ago. In the laboratory environment zebrafish are easily handled…
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Recessive Lethal Mutations
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In order to understand how genes specify a biological process of both phenotypes that can occure and the number of genes involve, it is important identifying the mutated genes. Because high mutation frequencies can be obtain with chemical mutagens. Actually the mutation frequency can vary widely for different loci, chemical mutagens can induce mutation in most genes. With all these advantages, there is still some disadvantage associate with it because cloning mutant gene is difficult, as these chemicals usually cause point mutations. Positioning cloning chemical induce mutants are made feasible over time, but cloning remain expensive and laborious in vertebrate animal with large genomes. A less effective approach to chemical mutagenesis that greatly speeds the cloning of mutant genes is known as insertional mutagenesis. The integration of exogenous DNA sequences into a genome can be mutagenic, and the inserted DNA serves as a tag to clone mutated genes, though fewer lesions are obtained per genome and also insertional mutagens seldom, if integrated randomly into host DNA.

When large-scale genetic screening is carried out, it results in successful identification of many genes that define embryological pathways. However, two scientists from Boston and Tubingen are inspired by the remarkable characteristic of the zebrafish, along with the first zebrafish genetic screening identified mutant embryonic phenotype in F3 generation. Some of the mutated developmental genes identified in the two screens have been cloned, which assist in the dissection of the gene network that controls the early development. For example, the mutated genes in the endoderm mutants such as casanova, bonnie and clyde, and faust can be assembled into a genetic pathway that have been shown tom encode transcription factors that are necessary for endoderm formation. Analysis of proviral insertions has revealed that different germ cell are infected independently in F1 progeny and with high titer virus stocks they often have multiple integrations and any given insertion is transmitted mosaically to between 1% and 40% of the F1 pronegy. Individual F1 fish can inherit multiple insertion and proviral insertions in F1 fish and transmitted in a mendelian fashion.
When outcrossing founder fish, identified F1 fish with single proviral insertion, generated an F2 family for each insertion, and then inbred transgenic F2 fish and examined F3 progeny to identify mutation. This system is not too efficient for large-scale screen because each insertion was inbred individually, therefore ...Download file to see next pagesRead More
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