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Advantages and Limitations of Transgenic Vector Control: Sterile Males versus Gene Drivers

This chapter appears in the following book:

Genetically Modified Mosquitoes for Malaria Control

Edited by: Christophe Boëte
ISBN: 1-58706-096-5
» Get more information about this book at landesbioscience.com «

Chapter authors:
Christopher Curtis, Paul G. Coleman, David W. Kelly and Diarmid H. Campbell-Lendrum


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Transgenesis might be used to produce fitter and more acceptable sterile males than those hitherto produced with radiation or chemosterilants. It is possible to engineer a dominant lethal construct which can be conditionally switched off so that males carrying it can be reared for release. Sterile males can eradicate pest populations provided that one can exclude immigrant, monogamous females that have already made a fertile mating outside the release area. “Urban island” populations of vectors may meet the required conditions for successful eradication. The genetic engineering of strains which are not susceptible to Plasmodium spp. development is also likely to be possible. For such ‘refractory genes’ to be useful it will be necessary to drive them to fixation so that they completely replace wild vector populations. A system for driving refractory genes through populations should require smaller releases to initiate the population replacement process than does the Sterile Male Technique (SIT), and the driving system should be “resistant” to the effects of immigration. Among the driving systems which have been suggested are: (i) negatively heterotic systems; (ii) uni-directional cytoplasmic incompatibility due to the bacterial endosymbiont Wolbachia; and (iii) transposons. An assumption underlying the driving of genes into populations is that the driver and the gene to be driven will remain genetically linked. In fact, some degree of recombination is inevitable and, if the driver without the refractory gene is fitter than the driver linked to this gene, the end result could be fixation of the driver alone, and loss of the refractory gene from the population with no reduction in disease transmission. We modelled the above three types of driving system with incomplete linkage to the refractory gene and with a fitness cost associated with that gene. We conclude that the systems will only confer permanent refractory protection if there is perfect linkage between the driver and refractory genes. There may be some public health benefits associated with a reduction in disease transmission as the refractory gene initially spreads through the vector population. However, within a time horizon of about 10 years, under a range of assumptions of fitness costs and recombination rates, our simulations show that any short-term gains associated with an increased frequency of the desired refractory genotypes are lost as the driving mechanism, freed from the costs associated with the transgene, drives itself to fixation and the refractory trait is lost from the population.

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