Keywords: underdominance

Modeling-informed Engineered Genetic Incompatibility strategies to overcome resistance in the invasive Drosophila suzukii

A. Sychla, N. R. Feltman, W. D. Hutchison and M. J. Smanski,  Frontiers in Insect Science,  2. 2022.
Engineered Genetic Incompatibility (EGI) is an engineered extreme underdominance genetic system wherein hybrid animals are not viable, functioning as a synthetic speciation event. There are several strategies in which EGI could be leveraged for genetic biocontrol of pest ...
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Gene drives gaining speed

E. Bier,  Nature Reviews Genetics,  2021.
Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne ...
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Gene drive strategies of pest control in agricultural systems: challenges and opportunities

M. Legros, J. M. Marshall, S. Macfadyen, K. R. Hayes, A. Sheppard and L. G. Barrett,  Evolutionary Applications,  2021.
Abstract Recent advances in gene editing technologies have opened new avenues for genetic pest control strategies, in particular around the use of gene drives to suppress or modify pest populations. Significant uncertainty, however, surrounds the applicability of these strategies ...
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Combating mosquito-borne diseases using genetic control technologies

G.-H. Wang, S. Gamez, R. R. Raban, J. M. Marshall, L. Alphey, M. Li, J. L. Rasgon and O. S. Akbari,  Nature Communications,  12:4388. 2021.
Mosquito-borne diseases, such as dengue and malaria, pose significant global health burdens. Unfortunately, current control methods based on insecticides and environmental maintenance have fallen short of eliminating the disease burden. Scalable, deployable, genetic-based ...
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Gene tech to prevent crossbreeding could safely harness the power of gene drives

I. l. Guillou,  The Science Advisory Board,  2021.
A new gene engineering technology could allow scientists to harness the benefits of releasing genetically modified animals into the wild without the risk of uncontrolled spread. The new study, published in the journal Nature Communications on June 2, could help in the battle ...
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Design and analysis of CRISPR-based underdominance toxin-antidote gene drives

J. Champer, S. E. Champer, I. K. Kim, A. G. Clark and P. W. Messer,  Evolutionary Applications,  18. 2020.
We model drives which target essential genes that are either haplosufficient or haplolethal, using nuclease promoters with expression restricted to the germline, promoters that additionally result in cleavage activity in the early embryo from maternal deposition, and promoters ...
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Engineering the Composition and Fate of Wild Populations with Gene Drive

B. A. Hay, G. Oberhofer and M. Guo,  Annual Review of Entomology,  2020.
We describe technologies under consideration, progress that has been made, and remaining technological hurdles, particularly with respect to evolutionary stability and our ability to control the spread and ultimate fate of genes introduced into populations.
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Engineering multiple species-like genetic incompatibilities in insects

M. Maselko, N. Feltman, A. Upadhyay, A. Hayward, S. Das, N. Myslicki, A. J. Peterson, M. B. O’Connor and M. J. Smanski,  Nature Communications,  11:4468. 2020.
Here, we demonstrate a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster.
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Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations

H. M. Sánchez C, J. B. Bennett, S. L. Wu, G. Rašić, O. S. Akbari and J. M. Marshall,  BMC Biology,  18:50. 2020.
Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems—reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL—to explore their ability to be confined and remediated.
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Genetic Biocontrol – An Overview

GeneConvene Global Collaborative,,  GeneConvene Global Collaborative,  2020.
This video explains what genetic biocontrol is and surveys various technologies that can be consider genetic biocontrol technologies.  It offers a conceptual organization of the various technologies based on the potential of genetic biocontrol organisms to persist and spread in ...
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GeneConvene Global Collaborative,  GeneConvene Global Collaborative,  2020.
This video graphically explains the genetic concept of underdominance and illustrates how it can result in one allele replacing another allele in a population.  While 'gene drive', underdominance is a genetic phenomenon that can be recreated using genetic technologies and might ...
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Progress towards engineering gene drives for population control

R. R. Raban, J. M. Marshall and O. S. Akbari,  The Journal of Experimental Biology,  223:jeb208181. 2020.
Vector-borne diseases, such as dengue, Zika and malaria, are a major cause of morbidity and mortality worldwide. These diseases have proven difficult to control and currently available management tools are insufficient to eliminate them in many regions. Gene drives have the ...
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Design and analysis of CRISPR-based underdominance toxin-antidote gene drives

Champer, J., S. E. Champer, I. Kim, A. G. Clark and P. W. Messer,  bioRxiv,  861435:861435. 2019.
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we model and assess the performance of several CRISPR-based ...
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Gene drive and resilience through renewal with next generation Cleave and Rescue selfish genetic elements

Oberhofer, G., T. Ivy and B. A. Hay,  bioRxiv,  2019:2019.2012.2013.876169. 2019.
Gene drive-based strategies for modifying populations face the problem that genes encoding cargo and the drive mechanism are subject to separation, mutational inactivation, and loss of efficacy. Resilience, an ability to respond to these eventualities in ways that restore ...
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Genetic Control of Mosquitoes

Alphey, L.,  Annual Review of Entomology,  59:205-224. 2019.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their ...
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Modeling the mutation and reversal of engineered underdominance gene drives

Edgington, MPA, Luke S.,  Journal of Theoretical Biology,  479:14-21. 2019.
A range of gene drive systems have been proposed that are predicted to increase their frequency and that of associated desirable genetic material even if they confer a fitness cost on individuals carrying them. Engineered underdominance (UD) is such a system and, in one version, ...
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Ecological effects on underdominance threshold drives for vector control

D. Khamis, C. El Mouden, K. Kura and M. B. Bonsall,  Journal of Theoretical Biology,  456:1-15. 2018.
Here, ecological and epidemiological dynamics are coupled to a model of mosquito genetics to investigate theoretically the impact of different types of underdominance gene drive on disease prevalence. We model systems with two engineered alleles carried either on the same pair ...
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Synthetic biology mosquitoes: Pioneering solution emerges to counter fears over using genetic engineerting to control Zika

English, C,  Genetic Literacy Project,  2018.
In fall 2015, the biotech company Oxitec planned to release genetically engineered mosquitoes throughout the Florida Keys capable of stopping their wild relatives from spreading Zika, a dangerous virus that causes birth defects and damages the nervous system. These lab-bread ...
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Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila

Buchman, ABI, Tobin; Marshall, John M.; Akbari, Omar S.; Hay, Bruce A.,  ACS Synthetic Biology,  7:1359-1370. 2018.
Replacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions using gene drive provides a self-perpetuating method of disease prevention. Mechanisms that require the gene drive element and ...
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Population dynamics of engineered underdominance and killer-rescue gene drives in the control of disease vectors

Edgington, MPA, Luke S.,  PLOS Computational Biology,  14:e1006059. 2018.
Vector-borne diseases represent a severe burden to both human and animal health worldwide. The methods currently being used to control a range of these diseases do not appear sufficient to address the issues at hand. As such, alternate methods for the control of vector-borne ...
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Invasion and migration of spatially self-limiting gene drives: A comparative analysis

Dhole, S.; Vella, M. R; Lloyd, A. L.; Gould, F.,  Evolutionary Applications,  11:794-808. 2018.
Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical ...
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Can CRISPR-based gene drive be confined in the Wild? A question for molecular and population biology

Marshall, JMA, Omar S.,  ACS Chemical Biology,  13:424-430. 2018.
The recent discovery of CRISPR and its application as a gene editing tool has enabled a range of gene drive systems to be engineered with greater ease. In order for the benefits of this technology to be realized, in some circumstances drive systems should be developed that are ...
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Population dynamics of underdominance gene drive systems in continuous space

Champer, JZ, Joanna; Champer, Sam; Liu, Jingxian; Messer, Philipp W.,  bioRxiv,  449355:1-23. 2018.
Underdominance gene drive systems promise a mechanism for rapidly spreading payload alleles through a local population while otherwise remaining confined, unable to spread into neighboring populations due to their frequency-dependent dynamics. Such systems could provide a new ...
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Recent advances in threshold-dependent gene drives for mosquitoes

Leftwich, PTE, Matthew P.; Harvey-Samuel, Tim; Carabajal Paladino, Leonela Z.; Norman, Victoria C.; Alphey, Luke,  Biochemical Society Transactions,  46:1203-1212. 2018.
Mosquito-borne diseases, such as malaria, dengue and chikungunya, cause morbidity and mortality around the world. Recent advances in gene drives have produced control methods that could theoretically modify all populations of a disease vector, from a single release, making whole ...
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RPM-Drive: A robust, safe, and reversible gene drive system that remains functional after 200+ generations

Reed, FAA-M, Todd G.; Costantini, Maria S.; Láruson, Áki J.; Sutton, Jolene T.,  arXiv,  1806.05304:1-19. 2018.
Despite the advent of several novel, synthetic gene drive mechanisms and their potential to one-day control a number of devastating diseases, among other applications, practical use of these systems remains contentious and risky. In particular, there is little in the way of ...
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Conditions for success of engineered underdominance gene drive systems

Edgington, MPA, L. S.,  Journal of Theoretical Biology,  430:128-140. 2017.
Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually ...
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Stability of underdominant genetic polymorphisms in population networks

Laruson, AJR, F. A.,  Journal of Theoretical Biology,  390:156-163. 2016.
Heterozygote disadvantage is potentially a potent driver of population genetic divergence. Also referred to as underdominance, this phenomena describes a situation where a genetic heterozygote has a lower overall fitness than either homozygote. Attention so far has mostly been ...
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Genetic Control of Mosquitoes.

Alphey, L.,  Annual Review of Entomology,  59:205-224. 2014.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their ...
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Dynamics of a combined medea-underdominant population transformation system

Gokhale, CSR, R. G.; Reed, F. A.,  BMC Evolutionary Biology,  14:98. 2014.
: Transgenic constructs intended to be stably established at high frequencies in wild populations have been demonstrated to "drive" from low frequencies in experimental insect populations. Linking such population transformation constructs to genes which render them unable to ...
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Modeling the dynamics of a non-limited and a self-limited gene drive system in structured Aedes aegypti populations

Legros, MX, C. G.; Morrison, A.; Scott, T. W.; Lloyd, A. L.; Gould, F.,  PLOS One,  8:e83354. 2013.
Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local ...
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A Synthetic Gene Drive System for Local, Reversible Modification and Suppression of Insect Populations

Akbari, OSM, K. D.; Marshall, J. M.; Huang, H. X.; Ward, C. M.; Hay, B. A.,  Current Biology,  23:671-677. 2013.
Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a self-perpetuating method of disease prevention but requires a gene drive mechanism to spread these traits to high frequency [1-3]. Drive mechanisms requiring that ...
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Confinement of gene drive systems to local populations: A comparative analysis

Marshall, JMH, B. A.,  Journal of Theoretical Biology,  294:153-171. 2012.
Mosquito-borne diseases such as malaria and dengue fever pose a major health problem through much of the world. One approach to disease prevention involves the use of selfish genetic elements to drive disease-refractory genes into wild mosquito populations. Recently engineered ...
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Stability properties of underdominance in finite subdivided populations

Altrock, PMT, A.; Reed, F. A.,  PLOS Computational Biology,  7:10. 2011.
In isolated populations underdominance leads to bistable evolutionary dynamics: below a certain mutant allele frequency the wildtype succeeds. Above this point, the potentially underdominant mutant allele fixes. In subdivided populations with gene flow there can be stable states ...
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Using underdominance to bi-stably transform local populations

Altrock, PMT, A.; Reeves, R. G.; Reed, F. A.,  Journal of Theoretical Biology,  267:62-75. 2010.
Underdominance refers to natural selection against individuals with a heterozygous genotype. Here, we analyze a single-locus underdominant system of two large local populations that exchange individuals at a certain migration rate. The system can be characterized by fixed points ...
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Gene-drive in age-structured insect populations

Huang, YXL, A. L.; Legros, M.; Gould, F.,  Evolutionary Applications,  2:143-159. 2009.
To date, models of gene-drive mechanisms proposed for replacing wild-type mosquitoes with transgenic strains that cannot transmit diseases have assumed no age or mating structure. We developed a more detailed model to analyze the effects of age and mating-related factors on the ...
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A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs

Gould, FH, Yunxin; Legros, Mathieu; Lloyd, Alun L.,  Proceedings of the Royal Society B: Biological Sciences,  275:2823-2829. 2008.
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. ...
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Introducing transgenes into insect populations using combined gene-drive strategies: Modeling and analysis

Huang, YXM, K.; Lloyd, A. L.; Gould, F.,  Insect Biochemistry and Molecular Biology,  37:1054-1063. 2007.
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 ...
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Genetic strategies for controlling mosquito-borne diseases

F. Gould, K. Magori and Y. Huang,  American Scientist,  94:238. 2006.
Malaria kills more than a million people each year, primarily children under the age of six. Dengue fever is less deadly, but an outbreak can debilitate millions of people and easily overwhelm doctors and hospitals in tropical cities.
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Genetic strategies for controlling mosquito-borne diseases

F. Gould, K. Magori and Y. Huang,  American Scientist,  94:238. 2006.
Malaria kills more than a million people each year, primarily children under the age of six. Dengue fever is less deadly, but an outbreak can debilitate millions of people and easily overwhelm doctors and hospitals in tropical cities
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Genetics-driving genes and chromosomes

Charlesworth, B,  Nature,  332:394-395. 1988.
Thereare several genetic and chromosomal systems in which Mendel's first law - the equal probability of transmission of maternal and paternal alternative alleles or homologues - is violated. This phenomenon was named 'meiotic drive' in 1957 by Sandler and Novitski, who drew ...
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On the possibility of a new method for the control of insect pests.

A. S. Serebrovskii,  Zoologicheskiĭ zhurnal,  19:618-630 (in Russian). 1940.
ON THE POSSIBILITY OF A NEW METHOD FOR THE CONTROL OF INSECT PESTS. The new principle of insect control consists in disturbing the propagation of the pest population by means of translocations. It is well known that individuals heterozygous for some translocations usually form a ...
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