Genetic experimentation

The application of recombinant DNA techniques to the study of neuropeptide biosynthesis is essential because these techniques facilitate structural analyses and evolutionary studies, clarify biosynthetic pathways, provide the necessary background and probes for analysis of synthesis regulation at the levels of mRNA and gene transcription and assist in classical genetic experimentation. Examples of these benefits are cited and problems encountered in insect systems are discussed. 

Bernardi G. (1979a). The petite mutation in yeast. Trends in Biochem. Sci. 4 197-201 Bernardi G. (1979b). Organization and evolution of the eukaryotic genome. In Recombinant DNA and genetic experimentation (J. Morgan and W.J. Whelan, eds.) pp. 15-20, Pergamon, New York, NY, USA. 

These genetic experiments clearly demonstrated that the proposed structural model for the binding of these proteins to the phage operators was essentially correct. The second a helix in the helix-turn-helix motif is involved in recognizing operator sites as well as in the differential selection of operators by P22 Cro and repressor proteins. However, a note of caution is needed many other early models of DNA-protein interactions proved to be misleading, if not wrong. Modeling techniques are more sophisticated today but are still not infallible and are certainly not replacements for experimental determinations of structure. 

Animals may not be moved for 14 days after administration of the experimental product, and records on the disposition of trial animals must be retained for 2 years. Bio-security issues will be of particular concern to the environmental impact assessment where trials involve live organisms or genetically modified organisms, either in vaccine challenge studies or as experimental products. 

Fig. 3. One of the experimental systems in common use for genetic engineering of plants with Agrobacterium containing a recombinant Ti-plasmid (from Bryant, 1988).

The determination of an acceptable dose for humans involves the application of uncertainty factors to reflect the fact that, unlike the experimental animal, there is wide variability and susceptibility of response in the genetically diverse human population. Variations in gender, age, hormonal and disease status can affect the response to a chemical. In order to minimise any potential risks, uncertainty factors are applied to the NOAEL to arrive at a reduced exposure that is considered tolerable - namely the acceptable daily intake or ADI. These are usually tenfold for variations in susceptibility amongst the human population (the intra-species factor) and tenfold for the potential... 

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