The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito
Publication Date
October 04, 2017
Journal
PLOS Genetics
Authors
Andrew M. Hammond, Kyros Kyrou, Marco Bruttini, Ace North, et al
Volume
13
Issue
10
Pages
e1007039
DOI
https://dx.plos.org/10.1371/journal.pgen.1007039
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1007039
Scopus
85032170581
Mendeley
http://www.mendeley.com/research/creation-selection-mutations-resistant-gene-drive-multiple-generations-malaria-mosquito
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Mendeley | Further Information

{"title"=>"The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito", "type"=>"journal", "authors"=>[{"first_name"=>"Andrew M.", "last_name"=>"Hammond", "scopus_author_id"=>"56596929300"}, {"first_name"=>"Kyros", "last_name"=>"Kyrou", "scopus_author_id"=>"57044652700"}, {"first_name"=>"Marco", "last_name"=>"Bruttini", "scopus_author_id"=>"57196176256"}, {"first_name"=>"Ace", "last_name"=>"North", "scopus_author_id"=>"16643278200"}, {"first_name"=>"Roberto", "last_name"=>"Galizi", "scopus_author_id"=>"24502634500"}, {"first_name"=>"Xenia", "last_name"=>"Karlsson", "scopus_author_id"=>"57196184857"}, {"first_name"=>"Nace", "last_name"=>"Kranjc", "scopus_author_id"=>"57195980004"}, {"first_name"=>"Francesco M.", "last_name"=>"Carpi", "scopus_author_id"=>"36550196700"}, {"first_name"=>"Romina", "last_name"=>"D’Aurizio", "scopus_author_id"=>"57194897659"}, {"first_name"=>"Andrea", "last_name"=>"Crisanti", "scopus_author_id"=>"7006134060"}, {"first_name"=>"Tony", "last_name"=>"Nolan", "scopus_author_id"=>"7102073672"}], "year"=>2017, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"619157984", "pmid"=>"28976972", "doi"=>"10.1371/journal.pgen.1007039", "issn"=>"15537404", "scopus"=>"2-s2.0-85032170581", "arxiv"=>"149005", "sgr"=>"85032170581", "isbn"=>"1111111111"}, "id"=>"3888efc1-28fe-3509-81a0-baa69670e29a", "abstract"=>"Gene drives have enormous potential for the control of insect populations of medical and agricultural relevance. By preferentially biasing their own inheritance gene drives can rapidly introduce genetic traits even if these confer a negative fitness on the population. We have recently developed gene drives based on a CRISPR nuclease construct that is designed to disrupt key genes essential for female fertility in the malaria mosquito. The construct copies itself and the associated genetic disruption from one homologous chromosome to another during gamete formation, in a process called homing that ensures the majority of offspring inherit the drive. Such drives have the potential to cause long-lasting, sustainable population suppression though they are also expected to impose a large selection pressure for resistance in the mosquito. One of these population suppression gene drives showed rapid invasion of a caged population over 4 generations, establishing proof of principle for this technology. In order to assess the potential for the emergence of resistance to the gene drive in this population we allowed it to run for 25 generations and monitored the frequency of the gene drive over time. Following the initial increase of the gene drive we noticed a gradual decrease in its frequency that was accompanied emergence of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations show rates of increase consistent with positive selection in the face of the gene drive. Our findings represent the first documented example of selection for resistance to a synthetic gene drive and lead to important design recommendations and considerations in order to mitigate for resistance for future gene drive applications.", "link"=>"http://www.mendeley.com/research/creation-selection-mutations-resistant-gene-drive-multiple-generations-malaria-mosquito", "reader_count"=>77, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>3, "Researcher"=>16, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>6, "Student > Bachelor"=>17, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>3, "Researcher"=>16, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>17, "Student > Postgraduate"=>1, "Student > Master"=>8, "Other"=>6, "Student > Bachelor"=>17, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>8, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>27, "Agricultural and Biological Sciences"=>30, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Social Sciences"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>27}, "Unspecified"=>{"Unspecified"=>8}, "Environmental Science"=>{"Environmental Science"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>8}

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Scopus | Further Information

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