@article{ward_su_huang_lloyd_gould_hay_2010, title={Medea selfish genetic elements as tools for altering traits of wild populations: A theoretical analysis.}, volume={65}, ISSN={0014-3820}, url={http://dx.doi.org/10.1111/j.1558-5646.2010.01186.x}, DOI={10.1111/j.1558-5646.2010.01186.x}, abstractNote={One strategy for controlling transmission of insect‐borne disease involves replacing the native insect population with transgenic animals unable to transmit disease. Population replacement requires a drive mechanism to ensure the rapid spread of linked transgenes, the presence of which may result in a fitness cost to carriers. Medea selfish genetic elements have the feature that when present in a female, only offspring that inherit the element survive, a behavior that can lead to spread. Here, we derive equations that describe the conditions under which Medea elements with a fitness cost will spread, and the equilibrium allele frequencies are achieved. Of particular importance, we show that whenever Medea spreads, the non‐Medea genotype is driven out of the population, and we estimate the number of generations required to achieve this goal for Medea elements with different fitness costs and male‐only introduction frequencies. Finally, we characterize two contexts in which Medea elements with fitness costs drive the non‐Medea allele from the population: an autosomal element in which not all Medea‐bearing progeny of a Medea‐bearing mother survive, and an X‐linked element in species in which X/Y individuals are male. Our results suggest that Medea elements can drive population replacement under a wide range of conditions.}, number={4}, journal={Evolution}, publisher={Wiley}, author={Ward, Catherine M. and Su, Jessica T. and Huang, Yunxin and Lloyd, Alun L. and Gould, Fred and Hay, Bruce A.}, year={2010}, month={Dec}, pages={1149–1162} } @article{legros_lloyd_huang_gould_2009, title={Density-Dependent Intraspecific Competition in the Larval Stage of Aedes aegypti (Diptera: Culicidae): Revisiting the Current Paradigm}, volume={46}, ISSN={["0022-2585"]}, DOI={10.1603/033.046.0301}, abstractNote={ABSTRACT Density-dependent intraspecific competition has been considered an important determinant of the dynamics of larval stages of Aedes aegypti. A model was published in 1984 providing a mathematical description of this density dependence, based on field data, that has since been widely used. This description, however, is based on the strong assumption that all mortality is density-dependent. We re-examine the data without this premise and find a reduced importance of density dependence, as well as a different functional form. Based on these discrepancies, we emphasize that the characterization of density dependence in the larval stages of Ae. aegypti should be based on a more complete dataset, and we use artificially generated data to explore how such additional information could help developing a better description of this density dependence. We review other empirical studies on larval competition, discuss the need for further dedicated studies, and provide a few simple guidelines for the design of such studies.}, number={3}, journal={JOURNAL OF MEDICAL ENTOMOLOGY}, author={Legros, Mathieu and Lloyd, Alun L. and Huang, Yunxin and Gould, Fred}, year={2009}, month={May}, pages={409–419} } @article{huang_lloyd_legros_gould_2009, title={Gene-drive in age-structured insect populations}, volume={2}, ISSN={1752-4571 1752-4571}, url={http://dx.doi.org/10.1111/j.1752-4571.2008.00049.x}, DOI={10.1111/j.1752-4571.2008.00049.x}, abstractNote={Abstract}, number={2}, journal={Evolutionary Applications}, publisher={Wiley}, author={Huang, Yunxin and Lloyd, Alun L. and Legros, Mathieu and Gould, Fred}, year={2009}, month={May}, pages={143–159} } @article{gould_huang_legros_lloyd_2008, title={A Killer-Rescue system for self-limiting gene drive of anti-pathogen constructs}, volume={275}, ISSN={["0962-8452"]}, url={https://publons.com/publon/8709314/}, DOI={10.1098/rspb.2008.0846}, abstractNote={A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2 : 1 release (engineered : wild) or after four 1 : 2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.}, number={1653}, journal={PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES}, publisher={The Royal Society}, author={Gould, Fred and Huang, Yunxin and Legros, Mathieu and Lloyd, Alun L.}, year={2008}, month={Dec}, pages={2823–2829} } @article{huang_magori_lloyd_gould_2007, title={Introducing desirable transgenes into insect populations using Y-linked meiotic drive - A theoretical assessment}, volume={61}, ISSN={["1558-5646"]}, url={https://publons.com/publon/8533052/}, DOI={10.1111/j.1558-5646.2007.00075.x}, abstractNote={Abstract The use of genetic drive mechanisms to replace native mosquito genotypes with individuals bearing antipathogen transgenes is a potential strategy for repressing insect transmission of human diseases such as malaria and dengue. Antipathogen transgenes have been developed and tested, but efficient gene drive mechanisms are lacking. Here we theoretically assess the feasibility of introducing antipathogen genes into wild Aedes aegypti populations by using a naturally occurring meiotic drive system. We consider the release of males having both a Y-linked meiotic drive gene and an X-linked drive-insensitive response allele to which an antipathogen gene is linked. We use mathematical models and computer simulations to determine how the post-introduction dynamics of the antipathogen gene are affected by specific genetic characteristics of the system. The results show that when the natural population is uniformly sensitive to the meiotic drive gene, the antipathogen gene may be driven close to fixation if the fitness costs of the drive gene, the insensitive response allele, and the antipathogen gene are low. However, when the natural population has a small proportion of an X-linked insensitive response allele or an autosomal gene that strongly reduces the effect of the drive gene, the antipathogen gene does not spread if it has an associated fitness cost. Our modeling results provide a theoretical foundation for further experimental tests.}, number={4}, journal={EVOLUTION}, publisher={Blackwell Publishing Inc}, author={Huang, Yunxin and Magori, Krisztian and Lloyd, Alun L. and Gould, Fred}, year={2007}, month={Apr}, pages={717–726} } @article{huang_magori_lloyd_gould_2007, title={Introducing transgenes into insect populations using combined gene-drive strategies: Modeling and analysis}, volume={37}, ISSN={["0965-1748"]}, DOI={10.1016/j.ibmb.2007.06.002}, abstractNote={Engineered underdominance (EU), meiotic drive (MD) and Wolbachia have been proposed as mechanisms for driving anti-pathogen transgenes into natural populations of insect vectors of human diseases. EU can drive transgenes to high and stable frequencies but requires the release of sizeable numbers of engineered insects. MD and Wolbachia either cannot maintain high frequencies of transgenes or lack appropriate expression in critical tissues, but both can drive the transgenes to spread from very low initial frequencies. Here we use mathematical models to assess the utility of combining EU with MD or with Wolbachia. Under some conditions, the combination of EU and MD results in a more efficient transgene-drive strategy than either mechanism alone. This combined strategy could drive the transgenes to stable fixation and would require fewer released insects than EU alone, especially when only males are released. However, a combination of EU and Wolbachia does not work better than EU alone because it requires the release of even more engineered insects.}, number={10}, journal={INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY}, author={Huang, Yunxin and Magori, Krisztian and Lloyd, Alun L. and Gould, Fred}, year={2007}, month={Oct}, pages={1054–1063} } @article{huang_rohani_2006, title={Age-structured effects and disease interference in childhood infections}, volume={273}, number={1591}, journal={Proceedings of the Royal Society of London. Series B. Biological Sciences}, author={Huang, Y. X. and Rohani, P.}, year={2006}, pages={1229–1237} } @article{gould_magori_huang_2006, title={Genetic strategies for controlling mosquito-borne diseases}, volume={94}, ISSN={["0003-0996"]}, DOI={10.1511/2006.3.238}, number={3}, journal={AMERICAN SCIENTIST}, author={Gould, F and Magori, K and Huang, YX}, year={2006}, pages={238–246} }