scholarly journals Assessing connectivity despite high diversity in island populations of a malaria mosquito

2018 ◽  
Author(s):  
Christina M. Bergey ◽  
Martin Lukindu ◽  
Rachel M. Wiltshire ◽  
Michael C. Fontaine ◽  
Jonathan K. Kayondo ◽  
...  
Keyword(s):  
Lake Victoria ◽  
Field Testing ◽  
Accurate Estimation ◽  
Gene Drive ◽  
Classical Analysis ◽  
Isolated Populations ◽  
Island Populations ◽  
Polymorphic Species ◽  
Drive Systems ◽  
Shared Variation

AbstractDocumenting isolation is notoriously difficult for species with vast polymorphic populations. High proportions of shared variation impede estimation of connectivity, even despite leveraging information from many genetic markers. We overcome these impediments by combining classical analysis of neutral variation with assays of the structure of selected variation, demonstrated using populations of the principal African malaria vector Anopheles gambiae. Accurate estimation of mosquito migration is crucial for efforts to combat malaria. Modeling and cage experiments suggest that mosquito gene drive systems will enable malaria eradication, but establishing safety and efficacy requires identification of isolated populations in which to conduct field-testing. We assess Lake Victoria islands as candidate sites, finding one island 30 kilometers offshore is as differentiated from mainland samples as populations from across the continent. Collectively, our results suggest sufficient contemporary isolation of these islands to warrant consideration as field-testing locations and illustrate shared adaptive variation as a useful proxy for connectivity in highly polymorphic species.

scholarly journals Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations

2019 ◽  
Author(s):  
Héctor M. Sánchez C. ◽  
Jared B. Bennett ◽  
Sean L. Wu ◽  
Gordana Rašić ◽  
Omar S. Akbari ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Disease Transmission ◽  
Release Site ◽  
Field Trials ◽  
Mosquito Vector ◽  
Gene Drive ◽  
Isolated Populations ◽  
Dependent Behavior ◽  
Wide Scale ◽  
Drive Systems

AbstractBackgroundThe discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could potentially be used during the trial phase of this technology, or when localized control is otherwise desired, as simple models predict them to spread into partially isolated populations in a confineable manner, and to be reversible through releases of wild-type organisms. 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.ResultsWe simulate releases of Aedes aegypti, the mosquito vector of dengue, Zika and other arboviruses, in Yorkeys Knob, a suburb of Cairns, Australia, where previous biological control interventions have been undertaken on this species. We monitor spread to the neighboring suburb of Trinity Park to assess confinement. Results suggest that translocations could be introduced on a suburban scale, and remediated through releases of non-disease-transmitting male mosquitoes with release sizes on the scale of what has been previously implemented. UDMEL requires fewer releases to introduce, but more releases to remediate, including of females capable of disease transmission. Both systems are expected to be confineable to the release site; however, spillover of translocations into neighboring populations is less likely.ConclusionsOur analysis supports the use of translocations as a threshold-dependent drive system capable of spreading disease-refractory genes into Ae. aegypti populations in a confineable and reversible manner. It also highlights increased release requirements when incorporating life history and population structure into models. As the technology nears implementation, further ecological work will be essential to enhance model predictions in preparation for field trials.

scholarly journals Digital droplet PCR and IDAA for the detection of CRISPR indel edits in the malaria species Anopheles stephensi

BioTechniques ◽  
2020 ◽  
Vol 68 (4) ◽  
pp. 172-179 ◽  
Author(s):  
Rebeca Carballar-Lejarazú ◽  
Adam Kelsey ◽  
Thai Binh Pham ◽  
Eric P Bennett ◽  
Anthony A James
Keyword(s):  
Anopheles Stephensi ◽  
Field Testing ◽  
Nonhomologous End Joining ◽  
Mosquito Vector ◽  
Gene Drive ◽  
End Joining ◽  
Indel Detection ◽  
Vector Mosquito ◽  
Droplet Pcr ◽  
Drive Systems

CRISPR/Cas9 technology is a powerful tool for the design of gene-drive systems to control and/or modify mosquito vector populations; however, CRISPR/Cas9-mediated nonhomologous end joining mutations can have an important impact on generating alleles resistant to the drive and thus on drive efficiency. We demonstrate and compare the insertions or deletions (indels) detection capabilities of two techniques in the malaria vector mosquito Anopheles stephensi: Indel Detection by Amplicon Analysis (IDAA™) and Droplet Digital™ PCR (ddPCR™). Both techniques showed accuracy and reproducibility for indel frequencies across mosquito samples containing different ratios of indels of various sizes. Moreover, these techniques have advantages that make them potentially better suited for high-throughput nonhomologous end joining analysis in cage trials and contained field testing of gene-drive mosquitoes.

scholarly journals Retargeting: an unrecognized consideration in endonuclease-based gene drive biology

2016 ◽  
Author(s):  
Andrew M. Scharenberg ◽  
Barry L Stoddard ◽  
Raymond J Monnat ◽  
Anthony Nolan
Keyword(s):  
Gene Editing ◽  
Insect Pests ◽  
Field Testing ◽  
Nuclease Activity ◽  
Genome Replication ◽  
Gene Drive ◽  
Regulatory Issues ◽  
Guide Rna ◽  
Insect Populations ◽  
Drive Systems

AbstractThere is intense interest surrounding the use of gene editing nucleases in gene drive systems to control agricultural insect pests and insect vectors of infectious diseases such as malaria, dengue and Zika virus. While gene drive systems offer immense promise for the beneficial modification of deleterious insect populations, their unique mechanism of action also raises novel safety concerns and regulatory issues. A recent US National Academies of Science report provides a list of potential regulatory issues associated with implementation of homologous recombination (HR)-mediated gene drive systems, based on the premise that all such systems would exhibit similar biological behaviors. Here we examine how HR-mediated gene drive systems based on different gene editing nuclease platforms could be affected by mutations that occur during host cell transcription, genome replication, and, in conjunction with gene editing nuclease activity, during HR-mediated gene drive. Our analysis suggests that the same feature that makes RNA-guided nucleases such attractive research tools—their ease of reprogramming by alterations to their guide RNA components—might also contribute to increased rates of retargeting that could influence the long term behavior of RNA-guided gene drive systems. Predictability of behavior over time is an issue that should be addressed by in-depth risk assessment before field testing of organisms incorporating nuclease-mediated gene drives.

scholarly journals Optimized CRISPR tools and site-directed transgenesis in Culex quinquefasciatus mosquitoes for gene drive development

2021 ◽  
Author(s):  
Xuechun Feng ◽  
Víctor López Del Amo ◽  
Enzo Mameli ◽  
Megan Lee ◽  
Alena L. Bishop ◽  
...  
Keyword(s):  
Culex Quinquefasciatus ◽  
Technology Development ◽  
Companion Animals ◽  
Fruit Fly ◽  
Valuable Insight ◽  
Gene Drive ◽  
Future Technology ◽  
Drive Systems ◽  
Global Vector ◽  
Human And Animal Diseases

ABSTRACTCulex mosquitoes are a global vector for multiple human and animal diseases, including West Nile virus, lymphatic filariasis, and avian malaria, posing a constant threat to public health, livestock, companion animals, and endangered birds. While rising insecticide resistance has threatened the control of Culex mosquitoes, advances in CRISPR genome-editing tools have fostered the development of alternative genetic strategies such as gene drive systems to fight disease vectors. However, though gene-drive technology has quickly progressed in other mosquitoes, advances have been lacking in Culex. Here, we developed a Culex-specific Cas9/gRNA expression toolkit and used site-directed homology-based transgenesis to generate and validate a Culex quinquefasciatus Cas9-expressing line. We showed that gRNA scaffold variants improve transgenesis efficiency in both Culex and Drosophila and boost gene-drive performance in the fruit fly. These findings support future technology development to control Culex mosquitoes and provide valuable insight for improving these tools in other species.

Variability in Island Populations of the House Finch

The Auk ◽  
1983 ◽  
Vol 100 (1) ◽  
pp. 180-187 ◽  
Author(s):  
Dennis M. Power
Keyword(s):  
Morphological Characters ◽  
Population Variation ◽  
Carpodacus Mexicanus ◽  
House Finch ◽  
Isolated Populations ◽  
Island Populations ◽  
Coefficients Of Variation ◽  
Variation Parameter ◽  
Guadalupe Island

Abstract Coefficients of variation and generalized variances are compared for nine morphological characters from five mainland and four island populations of the House Finch (Carpodacus mexicanus). The purpose is to test the idea that variability is reduced in isolated populations and that there is a "population variation parameter" that determines the level of variation in most characters. Variability is greater in bill characters for Guadalupe and San Benito Islands than for mainland and other island populations. There are no consistent differences among samples in variability of wing, tail, or hind-limb characters, except for a tendency toward increased tarsus-length variability in a southern Baja California population and reduced variability in this character in San Clemente Island and Guadalupe Island populations. In bill characters, increased variability is found in the most divergent populations. The results do not support the generalization that geographic (= genetic) isolation per se causes much of a change in variability in island populations of birds, nor is there support for the idea of a pervasive quality of the gene pool that determines the level of variability in most characters.

No evidence for Galapagos Plasmodium lineage arriving via Humboldt Current seabirds.

2014 ◽  
Vol 20 (1) ◽  
pp. 37 ◽  
Author(s):  
Iris I Levin ◽  
Michael J Adkesson ◽  
Maranda Evans ◽  
Cindee K Rettke ◽  
Patricia G Parker
Keyword(s):  
South American ◽  
Wildlife Diseases ◽  
Isolated Populations ◽  
Humboldt Current ◽  
Island Populations ◽  
Negative Results ◽  
Contact Rates ◽  
Haemosporidian Parasites ◽  
Genus Plasmodium ◽  
Current Flows

Avian malaria, caused by parasites in the genus Plasmodium, has recently been detected in the endangered Galapagos penguin (Spheniscus mendiculus). Understanding possible routes of parasite and pathogen introduction is important for management of small and isolated populations, because island populations can be at higher risk of adverse effects due to lower immunity. One possible means of introduction could be through contact with pelagic birds from coastal South America. In order to better understand the origins of Plasmodium in Galapagos penguins, we used a PCR protocol to test for haemosporidian parasites in Humboldt penguins (Spheniscus humboldti), the sister species of Galapagos penguins, and two other Humboldt Current endemics, the guanay cormorant (Phalacrocorax bougainvillii) and the Peruvian pelican (Pelecanus thagus). None of these seabirds, all sampled at Punta San Juan, Peru, tested positive for haemosporidian parasites. Although the strong Humboldt Current flows from Antarctica up the South American coast and towards Galapagos at the equator, contact rates between these Humboldt endemics and Galapagos birds might still be rare. Despite negative results, this information is important for furthering our knowledge of Plasmodium in Galapagos and in our efforts to effectively manage wildlife diseases.

scholarly journals Integral Gene Drives: an “operating system” for population replacement

2018 ◽  
Author(s):  
Alexander Nash ◽  
Giulia Mignini Urdaneta ◽  
Andrea K. Beaghton ◽  
Astrid Hoermann ◽  
Philippos Aris Papathanos ◽  
...  
Keyword(s):  
Field Testing ◽  
Target Site ◽  
Gene Drive ◽  
Population Replacement ◽  
Pathogen Effector ◽  
Site Variation ◽  
The Face ◽  
Endogenous Genes ◽  
Target Site Resistance ◽  
Gene Drives

AbstractFirst generation CRISPR-based gene drives have now been tested in the laboratory in a number of organisms including malaria vector mosquitoes. A number of challenges for their use in the area-wide genetic control of vector-borne disease have been identified. These include the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and the practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. To address these challenges, we have evaluated the concept of Integral Gene Drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including both the drive and the anti-pathogen effector elements directly embedded within endogenous genes – an arrangement which we refer to as gene “hijacking”. This design would allow autonomous and non-autonomous IGD traits and strains to be generated, tested, optimized, regulated and imported independently. We performed quantitative modelling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population while hedging drive over multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target-site variation. IGD thus has the potential to yield more durable and flexible population replacement traits.

scholarly journals Gene Therapy: A Promising Therapeutic Strategy for Malaria

2018 ◽  
Vol 8 (2) ◽  
pp. 40-44
Author(s):  
Raafay Shehzad
Keyword(s):  
Gene Therapy ◽  
Therapeutic Strategy ◽  
Homing Endonuclease ◽  
Genetic Material ◽  
Gene Drive ◽  
Treatment And Prevention ◽  
Preventative Measures ◽  
Drive Systems ◽  
Embryonic Arrest ◽  
Diabetes And Obesity

Malaria is a serious illness caused by the Plasmodium parasite, which places approximately 3.5 billion people at risk. Currently, preventative measures are key in combatting this disease. However, gene therapy is an emerging field that shows promising results for the treatment of malaria, by modifying cells through the delivery of genetic material. Most notable was the discovery of CRISPR-Cas9, which not only allows deleterious mutations to be repaired, but does so with specificity, speed, and simplicity. There are numerous ongoing trials focusing on gene therapy in malaria treatment and prevention. They involve different approaches such as the genetic modification of vector mosquitoes to interfere with malaria transmission, use of CRISPR-Cas9, maternal-effect dominant embryonic arrest, homing endonuclease gene drive systems, and the design of specific Morpholino oligomers to interfere with the expression of parasitic characteristics. Overall, this emerging field shows promising results to treat and prevent not just malaria, but other diseases such as cancer, diabetes, and obesity.

scholarly journals Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

2020 ◽  
Author(s):  
Adriana Adolfi ◽  
Valentino M. Gantz ◽  
Nijole Jasinskiene ◽  
Hsu-Feng Lee ◽  
Kristy Hwang ◽  
...  
Keyword(s):  
Anopheles Stephensi ◽  
Pathogen Transmission ◽  
Gene Drive ◽  
Initial Release ◽  
Genetic Technologies ◽  
Rescue System ◽  
Vector Borne ◽  
Kynurenine Hydroxylase ◽  
Drive Systems ◽  
Population Suppression

ABSTRACTThe development of Cas9/gRNA-mediated gene-drive systems has bolstered the advancement of genetic technologies for controlling vector-borne pathogen transmission. These include population suppression approaches, genetic analogs of insecticidal techniques that reduce the number of vector insects, and population modification (replacement/alteration) approaches, which interfere with competence to transmit pathogens. We developed a recoded gene-drive rescue system for population modification in the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant alleles are eliminated via a dominantly-acting maternal effect combined with slower-acting standard negative selection, and a functional resistant allele does not prevent drive invasion. Small cage trials show that single releases of gene-drive males robustly result in efficient population modification with ≥95% of mosquitoes carrying the drive within 5-11 generations over a range of initial release ratios.

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