The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito

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 effect on the population. We have recently develo...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	PLoS genetics Jg. 13; H. 10; S. e1007039
Hauptverfasser:	Hammond, Andrew M., Kyrou, Kyros, Bruttini, Marco, North, Ace, Galizi, Roberto, Karlsson, Xenia, Kranjc, Nace, Carpi, Francesco M., D’Aurizio, Romina, Crisanti, Andrea, Nolan, Tony
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 04.10.2017 Public Library of Science (PLoS)
Schlagworte:	Alleles Amino Acid Sequence Animals Anopheles - genetics Anopheles gambiae Bioinformatics Biology and life sciences Clustered Regularly Interspaced Short Palindromic Repeats - genetics Control Culicidae Female Fertility Fertility - genetics Fitness Gene Frequency Gene Library Gene mutation Genes Genes, Essential Genetic aspects Genetic Engineering Genetic research Genetics Genetics, Population Genomics Haplotypes Heredity High-Throughput Nucleotide Sequencing Homing Homology Insect Vectors - genetics Life sciences Malaria Malaria - prevention & control Male Medicine and Health Sciences Methods Models, Genetic Mosquito Control - methods Mosquitoes Mutation Nuclease Population Positive selection Reproductive fitness Research and Analysis Methods Selection, Genetic Sequence Analysis, RNA Technology assessment
ISSN:	1553-7404, 1553-7390, 1553-7404
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

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 effect on the population. We have recently developed gene drives based on CRISPR nuclease constructs that are 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, 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 observed a gradual decrease in its frequency that was accompanied by the spread of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations showed 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 in future gene drive applications.
AbstractList	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 effect on the population. We have recently developed gene drives based on CRISPR nuclease constructs that are 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, 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 observed a gradual decrease in its frequency that was accompanied by the spread of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations showed 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 in future gene drive applications.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 effect on the population. We have recently developed gene drives based on CRISPR nuclease constructs that are 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, 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 observed a gradual decrease in its frequency that was accompanied by the spread of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations showed 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 in future gene drive applications. 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 effect on the population. We have recently developed gene drives based on CRISPR nuclease constructs that are 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, 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 observed a gradual decrease in its frequency that was accompanied by the spread of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations showed 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 in future gene drive applications. 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 effect on the population. We have recently developed gene drives based on CRISPR nuclease constructs that are 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, 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 observed a gradual decrease in its frequency that was accompanied by the spread of small, nuclease-induced mutations at the target gene that are resistant to further cleavage and restore its functionality. Such mutations showed 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 in future gene drive applications. Gene drives are selfish genetic elements that are able to bias their own inheritance among offspring. Starting from very low frequencies they can rapidly invade a population in just a few generations, even when imposing a fitness cost. Gene drives based on the precise DNA cutting enzyme CRISPR have been shown recently to be highly efficient at copying themselves from one chromosome to the other during the process of gamete formation in mosquitoes, resulting in transmission to 99% of offspring instead of the 50% expected for a single gene copy. One proposed use for CRISPR-based gene drives is in the control of mosquitoes by designing the gene drive to target mosquito genes involved in fertility, thereby reducing their overall reproductive output and leading to population suppression. Like any intervention designed to suppress a population these gene drives are expected to select for mutations in the mosquito that are resistant to the drive and restore fertility to mosquitoes. We have analyzed the origin and selection of resistant alleles in caged populations of mosquitoes initiated with a gene drive construct targeting a female fertility gene. We find the selected alleles are in-frame insertions and deletions that are resistant to cleavage and restore female fertility. Our findings allow us to improve predictions on gene drive behaviour and to make concrete recommendations on how to improve future gene drive designs by decreasing the likelihood that they generate resistance.
Audience	Academic
Author	Hammond, Andrew M. Crisanti, Andrea D’Aurizio, Romina North, Ace Bruttini, Marco Nolan, Tony Kranjc, Nace Galizi, Roberto Carpi, Francesco M. Kyrou, Kyros Karlsson, Xenia
AuthorAffiliation	Institute of Science and Technology Austria (IST Austria), AUSTRIA 4 Laboratory of Integrative Systems Medicine (LISM), Institute of Informatics and Telematics (IIT), CNR, Pisa, Italy 3 Department of Zoology, University of Oxford, Oxford, England 1 Dept. of Life Sciences, Imperial College London, London, United Kingdom 2 Polo d’Innovazione Genomica, Genetica e Biologia, Siena, Italy
AuthorAffiliation_xml	– name: 2 Polo d’Innovazione Genomica, Genetica e Biologia, Siena, Italy – name: Institute of Science and Technology Austria (IST Austria), AUSTRIA – name: 3 Department of Zoology, University of Oxford, Oxford, England – name: 4 Laboratory of Integrative Systems Medicine (LISM), Institute of Informatics and Telematics (IIT), CNR, Pisa, Italy – name: 1 Dept. of Life Sciences, Imperial College London, London, United Kingdom
Author_xml	– sequence: 1 givenname: Andrew M. surname: Hammond fullname: Hammond, Andrew M. – sequence: 2 givenname: Kyros surname: Kyrou fullname: Kyrou, Kyros – sequence: 3 givenname: Marco orcidid: 0000-0003-1063-2522 surname: Bruttini fullname: Bruttini, Marco – sequence: 4 givenname: Ace orcidid: 0000-0002-4253-396X surname: North fullname: North, Ace – sequence: 5 givenname: Roberto orcidid: 0000-0003-3134-7480 surname: Galizi fullname: Galizi, Roberto – sequence: 6 givenname: Xenia surname: Karlsson fullname: Karlsson, Xenia – sequence: 7 givenname: Nace surname: Kranjc fullname: Kranjc, Nace – sequence: 8 givenname: Francesco M. surname: Carpi fullname: Carpi, Francesco M. – sequence: 9 givenname: Romina orcidid: 0000-0002-1728-6397 surname: D’Aurizio fullname: D’Aurizio, Romina – sequence: 10 givenname: Andrea surname: Crisanti fullname: Crisanti, Andrea – sequence: 11 givenname: Tony orcidid: 0000-0002-2982-8333 surname: Nolan fullname: Nolan, Tony
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/28976972$$D View this record in MEDLINE/PubMed
BookMark	eNqVk12L1DAUhousuB_6D0QLgujFjEnTJK0XwrL4MbC4oKu3IZOczmRIm9kkHfTfm850l5llEaUXaXKe9z3JSc5pdtS5DrLsOUZTTDh-t3K976SdrhfQTTFCHJH6UXaCKSUTXqLyaO__ODsNYYUQoVXNn2THRRpYzYuTLFwvIVceZDSuy2Wn8wAW1Hbmmrzt4zYScg_BhCi7mEeXyzwlhVx7s4HcbcAn0EaztrAN-FFjujwm-1Za6Y3MWxduehPd0-xxI22AZ-N4lv349PH64svk8urz7OL8cqJ4weIEinKugFSSQIlIpZs6TTngugRaKaiY5oiyWkJVVHNEUFU0nBRYck0xl4STs-zlzndtXRBjvYLANaOI1zXDiZjtCO3kSqy9aaX_LZw0Yrvg_EJIH42yIBCmpURIVzVWpa7IXGvNGJ0D5ow3VZm8PozZ-nkLWkEXvbQHpoeRzizFwm0EZWVV0GG7b0YD7256CFG0JiiwVnbg-mHfJWcFYuWQ69U99OHTjdRCpgOYrnEprxpMxTnFBeMMUZKo6QNU-jS0RqU315i0fiB4eyBITIRfcSH7EMTs-7f_YL_-O3v185B9vccuQdq4DM7223d3CL7Yv5W767jtgASUO0B5F4KH5g7BSAyNdltaMTSaGBstyd7fkymza5VUPWP_Lv4D9CguEA
CitedBy_id	crossref_primary_10_1093_molbev_msab352 crossref_primary_10_1186_s12936_024_04952_9 crossref_primary_10_1186_s13071_025_06905_w crossref_primary_10_1186_s12936_022_04242_2 crossref_primary_10_2174_0113892010316710240626042205 crossref_primary_10_1038_s41467_023_42183_9 crossref_primary_10_1073_pnas_1816928116 crossref_primary_10_1111_mec_17530 crossref_primary_10_1038_s41598_024_54498_8 crossref_primary_10_1186_s12864_024_10597_4 crossref_primary_10_1080_07853890_2024_2302504 crossref_primary_10_1111_eva_13032 crossref_primary_10_1089_hs_2018_0067 crossref_primary_10_3389_fbioe_2020_00452 crossref_primary_10_3389_finsc_2022_981974 crossref_primary_10_1038_s41598_018_34909_3 crossref_primary_10_1186_s13071_021_04789_0 crossref_primary_10_1038_s41467_020_14960_3 crossref_primary_10_1073_pnas_1901886116 crossref_primary_10_1128_JVI_00802_21 crossref_primary_10_1371_journal_pntd_0006769 crossref_primary_10_1038_s41564_018_0214_7 crossref_primary_10_1080_20477724_2018_1438880 crossref_primary_10_1073_pnas_1713825115 crossref_primary_10_5802_crbiol_182 crossref_primary_10_1038_s41467_024_46479_2 crossref_primary_10_1016_j_amjmed_2021_08_036 crossref_primary_10_1038_s41598_020_77544_7 crossref_primary_10_1038_s42003_024_07254_7 crossref_primary_10_1073_pnas_2107413118 crossref_primary_10_1186_s12864_024_11127_y crossref_primary_10_1038_nrg_2017_91 crossref_primary_10_1016_j_tibtech_2018_09_010 crossref_primary_10_1016_j_jglr_2021_10_018 crossref_primary_10_1371_journal_pcbi_1009660 crossref_primary_10_1093_g3journal_jkab086 crossref_primary_10_1007_s12033_025_01482_w crossref_primary_10_1038_s41467_024_51225_9 crossref_primary_10_7554_eLife_51701 crossref_primary_10_1186_s13071_018_3209_6 crossref_primary_10_3389_fagro_2023_1290781 crossref_primary_10_1534_g3_117_300557 crossref_primary_10_1016_j_jia_2022_11_003 crossref_primary_10_1016_j_jtbi_2021_110831 crossref_primary_10_1016_j_meegid_2023_105419 crossref_primary_10_7554_eLife_65939 crossref_primary_10_1089_crispr_2021_0129 crossref_primary_10_1371_journal_pgen_1009321 crossref_primary_10_1038_s41467_021_21771_7 crossref_primary_10_1186_s40694_019_0065_x crossref_primary_10_1038_s41598_022_10327_4 crossref_primary_10_1093_g3journal_jkac081 crossref_primary_10_1073_pnas_1713139115 crossref_primary_10_1073_pnas_2312456121 crossref_primary_10_1146_annurev_genet_031623_105059 crossref_primary_10_1093_g3journal_jkae025 crossref_primary_10_1038_s41467_019_13977_7 crossref_primary_10_1016_j_jgg_2024_04_001 crossref_primary_10_1038_s41598_019_51181_1 crossref_primary_10_1242_bio_037762 crossref_primary_10_1093_molbev_msaf048 crossref_primary_10_1002_bies_202100279 crossref_primary_10_1038_s41467_021_24790_6 crossref_primary_10_1186_s12936_025_05243_7 crossref_primary_10_1186_s12915_022_01292_5 crossref_primary_10_1371_journal_pgen_1011226 crossref_primary_10_1016_j_cois_2020_03_007 crossref_primary_10_1016_j_jenvman_2025_126189 crossref_primary_10_1038_s41467_024_53065_z crossref_primary_10_1038_s42003_024_06848_5 crossref_primary_10_1089_vbz_2019_2606 crossref_primary_10_1002_moda_30 crossref_primary_10_2903_j_efsa_2020_6297 crossref_primary_10_1371_journal_pgen_1010370 crossref_primary_10_1038_s41434_024_00468_8 crossref_primary_10_1038_s41467_024_53631_5 crossref_primary_10_1111_eva_12945 crossref_primary_10_1111_eva_13119 crossref_primary_10_1073_pnas_2200567119 crossref_primary_10_1371_journal_pntd_0008876 crossref_primary_10_1016_j_ijbiomac_2025_146574 crossref_primary_10_1089_crispr_2018_29001_tno crossref_primary_10_1111_eva_13358 crossref_primary_10_1038_s41576_021_00386_0 crossref_primary_10_1186_s12915_020_00834_z crossref_primary_10_7554_eLife_79121 crossref_primary_10_1073_pnas_1805278115 crossref_primary_10_1111_conl_12593 crossref_primary_10_1111_jen_13314 crossref_primary_10_1534_g3_119_400985 crossref_primary_10_1038_s41467_024_50992_9 crossref_primary_10_1073_pnas_2414207122 crossref_primary_10_3389_fbioe_2022_856981 crossref_primary_10_7554_eLife_71809 crossref_primary_10_1073_pnas_1805874115 crossref_primary_10_1093_genetics_iyac055 crossref_primary_10_1073_pnas_1720354115 crossref_primary_10_3389_fgene_2022_891218 crossref_primary_10_1038_nbt_4245 crossref_primary_10_1089_crispr_2022_0026 crossref_primary_10_1016_j_cois_2018_07_014 crossref_primary_10_1016_j_semcdb_2019_04_008 crossref_primary_10_1186_s13071_020_04170_7 crossref_primary_10_1038_s41598_020_69259_6 crossref_primary_10_1186_s12936_021_03682_6 crossref_primary_10_1038_s41467_021_27333_1 crossref_primary_10_1371_journal_pntd_0008971 crossref_primary_10_3389_finsc_2025_1618382 crossref_primary_10_1016_j_isci_2023_108027 crossref_primary_10_1089_crispr_2023_0029 crossref_primary_10_1007_s11248_021_00262_x crossref_primary_10_1038_s42003_024_06348_6 crossref_primary_10_7554_eLife_93142 crossref_primary_10_7554_eLife_41439 crossref_primary_10_1007_s11569_023_00439_0 crossref_primary_10_1093_jme_tjab030 crossref_primary_10_1038_s41467_022_34739_y crossref_primary_10_1038_s42003_019_0717_7 crossref_primary_10_1051_jbio_2019006 crossref_primary_10_1371_journal_pgen_1008440 crossref_primary_10_1146_annurev_micro_011320_025557 crossref_primary_10_1016_j_pt_2017_10_012 crossref_primary_10_1111_pim_12762 crossref_primary_10_1089_crispr_2017_0012 crossref_primary_10_1080_21550085_2020_1848197 crossref_primary_10_1093_g3journal_jkab201 crossref_primary_10_1038_s41467_024_44956_2 crossref_primary_10_1038_s42003_023_05224_z crossref_primary_10_1073_pnas_2004838117 crossref_primary_10_1038_s41598_020_80436_5 crossref_primary_10_1534_genetics_119_302037 crossref_primary_10_1042_BST20180076 crossref_primary_10_1016_j_pt_2024_04_010 crossref_primary_10_1007_s41649_018_0071_y crossref_primary_10_1038_s41467_020_18678_0 crossref_primary_10_1111_mec_70028 crossref_primary_10_1016_j_cois_2025_101437 crossref_primary_10_1371_journal_pcbi_1009526 crossref_primary_10_1038_s41467_021_24654_z crossref_primary_10_1038_s41467_021_24214_5 crossref_primary_10_1139_cjfas_2018_0153 crossref_primary_10_70749_ijbr_v2i02_385 crossref_primary_10_1016_j_cois_2025_101430 crossref_primary_10_1007_s11673_022_10172_0 crossref_primary_10_1111_eva_12878 crossref_primary_10_1371_journal_pgen_1010060 crossref_primary_10_1073_pnas_2004373117 crossref_primary_10_1186_s12985_022_01859_2 crossref_primary_10_1186_s13071_018_3218_5 crossref_primary_10_1016_j_tig_2022_02_013 crossref_primary_10_1186_s12915_020_0761_2 crossref_primary_10_3389_finsc_2022_1063789 crossref_primary_10_3389_finsc_2022_957570 crossref_primary_10_1007_s10592_019_01165_5 crossref_primary_10_1016_j_pt_2019_03_004 crossref_primary_10_1111_eea_13093 crossref_primary_10_1111_jeb_13693 crossref_primary_10_1007_s44297_024_00038_9 crossref_primary_10_1038_d41586_019_02087_5 crossref_primary_10_1007_s40290_019_00276_1 crossref_primary_10_1098_rspb_2018_0776 crossref_primary_10_1146_annurev_ento_020117_043154 crossref_primary_10_1016_j_cois_2018_10_009 crossref_primary_10_1038_s41467_018_06580_9 crossref_primary_10_1371_journal_pgen_1009740 crossref_primary_10_1016_j_jtbi_2023_111654 crossref_primary_10_1371_journal_pgen_1008898 crossref_primary_10_1371_journal_ppat_1006898 crossref_primary_10_1016_j_jtbi_2019_06_024 crossref_primary_10_1038_s41467_020_19426_0 crossref_primary_10_1186_s13059_024_03455_9
Cites_doi	10.1534/genetics.108.089037 10.1038/nature15535 10.1126/science.aaa5945 10.1534/genetics.116.197285 10.7717/peerj.2584 10.1371/journal.pgen.1006796 10.1126/science.1258522 10.1038/nbt.3439 10.1093/bioinformatics/btu170 10.1093/jmedent/31.1.10 10.1038/nature09937 10.1093/genetics/143.4.1653 10.1098/rspb.2002.2319 10.1126/sciadv.1601964 10.1086/281969 10.1186/1471-2199-10-65 10.1073/pnas.1521077112 10.1038/218368a0 10.1073/pnas.1110717108 10.1093/bioinformatics/btt593 10.1073/pnas.1213431110
ContentType	Journal Article
Copyright	COPYRIGHT 2017 Public Library of Science 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hammond AM, Kyrou K, Bruttini M, North A, Galizi R, Karlsson X, et al. (2017) The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito. PLoS Genet13(10): e1007039. https://doi.org/10.1371/journal.pgen.1007039 2017 Hammond et al 2017 Hammond et al 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hammond AM, Kyrou K, Bruttini M, North A, Galizi R, Karlsson X, et al. (2017) The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito. PLoS Genet13(10): e1007039. https://doi.org/10.1371/journal.pgen.1007039
Copyright_xml	– notice: COPYRIGHT 2017 Public Library of Science – notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hammond AM, Kyrou K, Bruttini M, North A, Galizi R, Karlsson X, et al. (2017) The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito. PLoS Genet13(10): e1007039. https://doi.org/10.1371/journal.pgen.1007039 – notice: 2017 Hammond et al 2017 Hammond et al – notice: 2017 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hammond AM, Kyrou K, Bruttini M, North A, Galizi R, Karlsson X, et al. (2017) The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito. PLoS Genet13(10): e1007039. https://doi.org/10.1371/journal.pgen.1007039
DBID	AAYXX CITATION CGR CUY CVF ECM EIF NPM IOV ISN ISR 3V. 7QP 7QR 7SS 7TK 7TM 7TO 7X7 7XB 88E 8FD 8FE 8FH 8FI 8FJ 8FK ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FR3 FYUFA GHDGH GNUQQ H94 HCIFZ K9. LK8 M0S M1P M7P P64 PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQGLB PQQKQ PQUKI PRINS RC3 7X8 5PM DOA
DOI	10.1371/journal.pgen.1007039
DatabaseName	CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Gale In Context: Opposing Viewpoints Gale In Context: Canada Gale In Context: Science ProQuest Central (Corporate) Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Entomology Abstracts (Full archive) Neurosciences Abstracts Nucleic Acids Abstracts Oncogenes and Growth Factors Abstracts Health & Medical Collection (ProQuest) ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Technology Research Database ProQuest SciTech Collection ProQuest Natural Science Collection Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials - QC Biological Science Collection ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Engineering Research Database Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Central Student AIDS and Cancer Research Abstracts SciTech Collection (ProQuest) ProQuest Health & Medical Complete (Alumni) Biological Sciences ProQuest Health & Medical Collection Medical Database Biological Science Database Biotechnology and BioEngineering Abstracts ProQuest Central Premium ProQuest One Academic Publicly Available Content Database ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Applied & Life Sciences ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ: Directory of Open Access Journal (DOAJ)
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Publicly Available Content Database ProQuest Central Student Oncogenes and Growth Factors Abstracts Technology Research Database ProQuest One Academic Middle East (New) ProQuest Central Essentials Nucleic Acids Abstracts ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest One Health & Nursing ProQuest Natural Science Collection ProQuest Central China ProQuest Central ProQuest One Applied & Life Sciences ProQuest Health & Medical Research Collection Genetics Abstracts Health Research Premium Collection Health and Medicine Complete (Alumni Edition) Natural Science Collection ProQuest Central Korea Health & Medical Research Collection Biological Science Collection AIDS and Cancer Research Abstracts Chemoreception Abstracts ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest Biological Science Collection ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) Biological Science Database ProQuest SciTech Collection Neurosciences Abstracts ProQuest Hospital Collection (Alumni) Biotechnology and BioEngineering Abstracts Entomology Abstracts ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition Engineering Research Database ProQuest One Academic Calcium & Calcified Tissue Abstracts ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic
DatabaseTitleList	MEDLINE - Academic Publicly Available Content Database MEDLINE
Database_xml	– sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: PIMPY name: Publicly Available Content Database url: http://search.proquest.com/publiccontent sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Biology
DocumentTitleAlternate	Gene drive resistance in mosquito
EISSN	1553-7404
ExternalDocumentID	1965079961 oai_doaj_org_article_0154a00d891c4d83bddd665be1767f84 PMC5648257 A512676053 28976972 10_1371_journal_pgen_1007039
Genre	Journal Article
GrantInformation_xml	– fundername: ;
GroupedDBID	--- 123 29O 2WC 53G 5VS 7X7 88E 8FE 8FH 8FI 8FJ AAFWJ AAUCC AAWOE AAYXX ABDBF ABUWG ACCTH ACGFO ACIHN ACIWK ACPRK ACUHS ADBBV ADRAZ AEAQA AENEX AFFHD AFKRA AFPKN AHMBA ALMA_UNASSIGNED_HOLDINGS AOIJS B0M BAIFH BAWUL BBNVY BBTPI BCNDV BENPR BHPHI BPHCQ BVXVI BWKFM CCPQU CITATION CS3 DIK DU5 E3Z EAP EAS EBD EBS EJD EMK EMOBN ESX F5P FPL FYUFA GROUPED_DOAJ GX1 HCIFZ HMCUK HYE IAO IGS IHR IHW INH INR IOV ISN ISR ITC KQ8 LK8 M1P M48 M7P O5R O5S OK1 OVT P2P PHGZM PHGZT PIMPY PJZUB PPXIY PQGLB PQQKQ PROAC PSQYO PV9 QF4 QN7 RNS RPM RZL SV3 TR2 TUS UKHRP WOW XSB ~8M 3V. ALIPV C1A CGR CUY CVF ECM EIF H13 IPNFZ M~E NPM RIG WOQ 7QP 7QR 7SS 7TK 7TM 7TO 7XB 8FD 8FK AZQEC DWQXO FR3 GNUQQ H94 K9. P64 PKEHL PQEST PQUKI PRINS RC3 7X8 PUEGO 5PM - AAPBV ABPTK ADACO BBAFP
ID	FETCH-LOGICAL-c726t-e24bce38a3e4038df9bce7e194e58ce86d70569ae828b03082f7321a7d517a373
IEDL.DBID	FPL
ISICitedReferencesCount	214
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000414161300014&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1553-7404 1553-7390
IngestDate	Sun Apr 03 16:02:32 EDT 2022 Fri Oct 03 12:50:56 EDT 2025 Tue Nov 04 01:51:44 EST 2025 Wed Oct 01 14:10:24 EDT 2025 Sat Nov 29 14:53:58 EST 2025 Tue Nov 11 10:09:45 EST 2025 Tue Nov 04 17:32:46 EST 2025 Thu Nov 13 15:25:57 EST 2025 Thu Nov 13 15:30:30 EST 2025 Thu Nov 13 15:18:30 EST 2025 Thu May 22 21:18:11 EDT 2025 Wed Feb 19 02:43:43 EST 2025 Sat Nov 29 06:03:45 EST 2025 Tue Nov 18 21:10:24 EST 2025
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	10
Language	English
License	This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Creative Commons Attribution License
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c726t-e24bce38a3e4038df9bce7e194e58ce86d70569ae828b03082f7321a7d517a373
Notes	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 The authors have declared that no competing interests exist.
ORCID	0000-0003-1063-2522 0000-0002-1728-6397 0000-0002-2982-8333 0000-0002-4253-396X 0000-0003-3134-7480
OpenAccessLink	http://dx.doi.org/10.1371/journal.pgen.1007039
PMID	28976972
PQID	1965079961
PQPubID	1436339
ParticipantIDs	plos_journals_1965079961 doaj_primary_oai_doaj_org_article_0154a00d891c4d83bddd665be1767f84 pubmedcentral_primary_oai_pubmedcentral_nih_gov_5648257 proquest_miscellaneous_1947620644 proquest_journals_1965079961 gale_infotracmisc_A512676053 gale_infotracacademiconefile_A512676053 gale_incontextgauss_ISR_A512676053 gale_incontextgauss_ISN_A512676053 gale_incontextgauss_IOV_A512676053 gale_healthsolutions_A512676053 pubmed_primary_28976972 crossref_primary_10_1371_journal_pgen_1007039 crossref_citationtrail_10_1371_journal_pgen_1007039
PublicationCentury	2000
PublicationDate	20171004
PublicationDateYYYYMMDD	2017-10-04
PublicationDate_xml	– month: 10 year: 2017 text: 20171004 day: 4
PublicationDecade	2010
PublicationPlace	United States
PublicationPlace_xml	– name: United States – name: San Francisco – name: San Francisco, CA USA
PublicationTitle	PLoS genetics
PublicationTitleAlternate	PLoS Genet
PublicationYear	2017
Publisher	Public Library of Science Public Library of Science (PLoS)
Publisher_xml	– name: Public Library of Science – name: Public Library of Science (PLoS)
References	VM Gantz (ref8) 2015; 112 RL Unckless (ref13) 2017; 205 LN Truong (ref16) 2013; 110 A Deredec (ref19) 2011; 108 M Vella (ref23) 2017 A Miles (ref22) 2016 CC Hong (ref15) 1996; 143 A Burt (ref1) 2003; 270 JM Marshall (ref20) 2016 AM Bolger (ref24) 2014; 30 JM Ribeiro (ref3) 1994; 31 A Deredec (ref18) 2008; 179 S Bhatt (ref5) 2015; 526 J Zhang (ref25) 2014; 30 KM Esvelt (ref12) 2014 T Rognes (ref26) 2016; 4 CF Curtis (ref2) 1968; 218 J Champer (ref10) 2017; 13 L Sandler (ref4) 1957; 91 PA Papathanos (ref17) 2009; 10 N Windbichler (ref9) 2011; 473 ref6 DE Neafsey (ref21) 2015; 347 VM Gantz (ref7) 2015; 348 A Hammond (ref11) 2016; 34 C Noble (ref14) 2017; 3 28727785 - PLoS Genet. 2017 Jul 20;13(7):e1006796 23610439 - Proc Natl Acad Sci U S A. 2013 May 7;110(19):7720-5 18660532 - Genetics. 2008 Aug;179(4):2013-26 24142950 - Bioinformatics. 2014 Mar 1;30(5):614-20 25908821 - Science. 2015 Apr 24;348(6233):442-4 28630470 - Sci Rep. 2017 Jun 19;7(1):3776 27781170 - PeerJ. 2016 Oct 18;4:e2584 21976487 - Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E874-80 26598698 - Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):E6736-43 26641531 - Nat Biotechnol. 2016 Jan;34(1):78-83 24695404 - Bioinformatics. 2014 Aug 1;30(15):2114-20 28435878 - Sci Adv. 2017 Apr 05;3(4):e1601964 25035423 - Elife. 2014 Jul 17;3 29062055 - Nat Rev Genet. 2017 Dec;18(12 ):704 19573226 - BMC Mol Biol. 2009 Jul 02;10:65 8158612 - J Med Entomol. 1994 Jan;31(1):10-6 26375008 - Nature. 2015 Oct 8;526(7572):207-211 28887462 - Sci Rep. 2017 Sep 8;7(1):11038 5649682 - Nature. 1968 Apr 27;218(5139):368-9 12803906 - Proc Biol Sci. 2003 May 7;270(1518):921-8 27941126 - Genetics. 2017 Feb;205(2):827-841 8844153 - Genetics. 1996 Aug;143(4):1653-61 21508956 - Nature. 2011 May 12;473(7346):212-5 25554792 - Science. 2015 Jan 2;347(6217):1258522
References_xml	– volume: 179 start-page: 2013 issue: 4 year: 2008 ident: ref18 article-title: The population genetics of using homing endonuclease genes in vector and pest management publication-title: Genetics doi: 10.1534/genetics.108.089037 – volume: 526 start-page: 207 issue: 7572 year: 2015 ident: ref5 article-title: The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015 publication-title: Nature doi: 10.1038/nature15535 – start-page: 144097 year: 2017 ident: ref23 article-title: Evaluating Strategies For Reversing CRISPR-Cas9 Gene Drives publication-title: bioRxiv – volume: 348 start-page: 442 issue: 6233 year: 2015 ident: ref7 article-title: Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations publication-title: Science doi: 10.1126/science.aaa5945 – volume: 205 start-page: 827 issue: 2 year: 2017 ident: ref13 article-title: Evolution of Resistance Against CRISPR/Cas9 Gene Drive publication-title: Genetics doi: 10.1534/genetics.116.197285 – volume: 4 start-page: e2584 year: 2016 ident: ref26 article-title: VSEARCH: a versatile open source tool for metagenomics publication-title: PeerJ doi: 10.7717/peerj.2584 – start-page: 3 year: 2014 ident: ref12 article-title: Concerning RNA-guided gene drives for the alteration of wild populations publication-title: Elife – volume: 13 start-page: e1006796 issue: 7 year: 2017 ident: ref10 article-title: Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations publication-title: PLoS Genet doi: 10.1371/journal.pgen.1006796 – volume: 347 start-page: 1258522 issue: 6217 year: 2015 ident: ref21 article-title: Mosquito genomics. Highly evolvable malaria vectors: the genomes of 16 Anopheles mosquitoes publication-title: Science doi: 10.1126/science.1258522 – volume: 34 start-page: 78 issue: 1 year: 2016 ident: ref11 article-title: A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae publication-title: Nat Biotechnol doi: 10.1038/nbt.3439 – volume: 30 start-page: 2114 issue: 15 year: 2014 ident: ref24 article-title: Trimmomatic: a flexible trimmer for Illumina sequence data publication-title: Bioinformatics doi: 10.1093/bioinformatics/btu170 – volume: 31 start-page: 10 issue: 1 year: 1994 ident: ref3 article-title: Transposable elements as population drive mechanisms: specification of critical parameter values publication-title: J Med Entomol doi: 10.1093/jmedent/31.1.10 – volume: 473 start-page: 212 issue: 7346 year: 2011 ident: ref9 article-title: A synthetic homing endonuclease-based gene drive system in the human malaria mosquito publication-title: Nature doi: 10.1038/nature09937 – volume: 143 start-page: 1653 issue: 4 year: 1996 ident: ref15 article-title: The maternal nudel protein of Drosophila has two distinct roles important for embryogenesis publication-title: Genetics doi: 10.1093/genetics/143.4.1653 – volume: 270 start-page: 921 issue: 1518 year: 2003 ident: ref1 article-title: Site-specific selfish genes as tools for the control and genetic engineering of natural populations publication-title: Proc Biol Sci doi: 10.1098/rspb.2002.2319 – volume: 3 start-page: e1601964 issue: 4 year: 2017 ident: ref14 article-title: Evolutionary dynamics of CRISPR gene drives publication-title: Sci Adv doi: 10.1126/sciadv.1601964 – volume: 91 start-page: 105 issue: 857 year: 1957 ident: ref4 article-title: Meiotic Drive as an Evolutionary Force publication-title: The American Naturalist doi: 10.1086/281969 – start-page: 096289 year: 2016 ident: ref22 article-title: Natural diversity of the malaria vector Anopheles gambiae publication-title: bioRxiv – ident: ref6 – volume: 10 start-page: 65 year: 2009 ident: ref17 article-title: The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies publication-title: BMC Mol Biol doi: 10.1186/1471-2199-10-65 – volume: 112 start-page: E6736 issue: 49 year: 2015 ident: ref8 article-title: Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1521077112 – volume: 218 start-page: 368 issue: 5139 year: 1968 ident: ref2 article-title: Possible use of translocations to fix desirable genes in insect pest populations publication-title: Nature doi: 10.1038/218368a0 – volume: 108 start-page: E874 issue: 43 year: 2011 ident: ref19 article-title: Requirements for effective malaria control with homing endonuclease genes publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1110717108 – volume: 30 start-page: 614 issue: 5 year: 2014 ident: ref25 article-title: PEAR: a fast and accurate Illumina Paired-End reAd mergeR publication-title: Bioinformatics doi: 10.1093/bioinformatics/btt593 – volume: 110 start-page: 7720 issue: 19 year: 2013 ident: ref16 article-title: Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1213431110 – start-page: 088427 year: 2016 ident: ref20 article-title: Overcoming evolved resistance to population-suppressing homing-based gene drives publication-title: biorXiv – reference: 27941126 - Genetics. 2017 Feb;205(2):827-841 – reference: 18660532 - Genetics. 2008 Aug;179(4):2013-26 – reference: 8844153 - Genetics. 1996 Aug;143(4):1653-61 – reference: 21976487 - Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E874-80 – reference: 25908821 - Science. 2015 Apr 24;348(6233):442-4 – reference: 29062055 - Nat Rev Genet. 2017 Dec;18(12 ):704 – reference: 24142950 - Bioinformatics. 2014 Mar 1;30(5):614-20 – reference: 28727785 - PLoS Genet. 2017 Jul 20;13(7):e1006796 – reference: 25035423 - Elife. 2014 Jul 17;3: – reference: 26641531 - Nat Biotechnol. 2016 Jan;34(1):78-83 – reference: 27781170 - PeerJ. 2016 Oct 18;4:e2584 – reference: 26598698 - Proc Natl Acad Sci U S A. 2015 Dec 8;112(49):E6736-43 – reference: 24695404 - Bioinformatics. 2014 Aug 1;30(15):2114-20 – reference: 23610439 - Proc Natl Acad Sci U S A. 2013 May 7;110(19):7720-5 – reference: 8158612 - J Med Entomol. 1994 Jan;31(1):10-6 – reference: 28630470 - Sci Rep. 2017 Jun 19;7(1):3776 – reference: 19573226 - BMC Mol Biol. 2009 Jul 02;10:65 – reference: 28435878 - Sci Adv. 2017 Apr 05;3(4):e1601964 – reference: 12803906 - Proc Biol Sci. 2003 May 7;270(1518):921-8 – reference: 26375008 - Nature. 2015 Oct 8;526(7572):207-211 – reference: 28887462 - Sci Rep. 2017 Sep 8;7(1):11038 – reference: 25554792 - Science. 2015 Jan 2;347(6217):1258522 – reference: 5649682 - Nature. 1968 Apr 27;218(5139):368-9 – reference: 21508956 - Nature. 2011 May 12;473(7346):212-5
SSID	ssj0035897
Score	2.6255262
Snippet	Gene drives have enormous potential for the control of insect populations of medical and agricultural relevance. By preferentially biasing their own...
SourceID	plos doaj pubmedcentral proquest gale pubmed crossref
SourceType	Open Website Open Access Repository Aggregation Database Index Database Enrichment Source
StartPage	e1007039
SubjectTerms	Alleles Amino Acid Sequence Animals Anopheles - genetics Anopheles gambiae Bioinformatics Biology and life sciences Clustered Regularly Interspaced Short Palindromic Repeats - genetics Control Culicidae Female Fertility Fertility - genetics Fitness Gene Frequency Gene Library Gene mutation Genes Genes, Essential Genetic aspects Genetic Engineering Genetic research Genetics Genetics, Population Genomics Haplotypes Heredity High-Throughput Nucleotide Sequencing Homing Homology Insect Vectors - genetics Life sciences Malaria Malaria - prevention & control Male Medicine and Health Sciences Methods Models, Genetic Mosquito Control - methods Mosquitoes Mutation Nuclease Population Positive selection Reproductive fitness Research and Analysis Methods Selection, Genetic Sequence Analysis, RNA Technology assessment
SummonAdditionalLinks	– databaseName: DOAJ: Directory of Open Access Journal (DOAJ) dbid: DOA link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3di9QwEA-yKPgift_qqVEEn-q1TZq0j6d4KMgqfhz3FtIm0YXbdt22gv-9M0lbtnJw9-DLQjfT0p2ZzvxmO_kNIS9TJAgRzkRVCh8cGyy05VnEXGm1tokMf12cfpSrVX52VnzeG_WFPWGBHjgo7ghzvI5jkxdJxU3OSmOMEFkJlxHS5Z4JFFDPWEyFGMyyPIxVyTIWSSjrh01zTCZHg41eb8FAvkcgxkHhe0nJc_dPEXqxPW_ai-Dnv12Ue2np5Da5NeBJehx-xx1yzdZ3yY0wYfLPPdKCG9ARGFJdG9r6wTd41Di66cOb-JZC1Y1Isu5o11BN4a4tNTsIhRR7POnYd-gXdsM565oCfKQbDdXxWtNN0_7qIUDcJ99P3n17-z4a5ixElUxFF9mUl5VluWaWxyw3roBDaZOC2yyvbC6MBJhUaAvVWen5bZxkaaKlyRKpmWQPyKJuantAqBCpY6XlWkLaFwWgoTJxpXY2iZ3mLF4SNipaVQMJOc7COFf-zZqEYiToTaF51GCeJYmms7aBhOMS-Tdow0kWKbT9F-BYanAsdZljLckz9AAV9qNOgUAdA0QSEqpAtiQvvATSaNTYp_ND922rPnw6vYLQ19VVhL7MhF4NQq4BnVV62EABmkcOr5nk4UwSIkY1Wz5Apx5V1ypklYwlVL4JnDk6-sXLz6dlvCg26NW26VGGQ1oFfAt6exiei0n9UNNLUch0SeTsiZnZZ75Sr396qvNM8BySyqP_YdDH5GaKmAy7P_ghWXS73j4h16vf3brdPfXx4y81PXRR priority: 102 providerName: Directory of Open Access Journals – databaseName: ProQuest Central dbid: BENPR link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3db9QwDI_gBtJexjc7GBAQEk9lbZMm7RPa0CaQ0DENmPZWpU0yTtq1t34g8d9jt2lZ0QSTeDmpZ-d0tR3n58SxCXkdYoEQYbWXh_DBMcFCGR55zGZGKRPIfuvi5JNcLOLT0-TIbbjVLq1y8Imdo9Zljnvku1j5zpeAzoN36wsPu0bh6aproXGTbGClMj4jG_sHi6PjwRezKO7bq0QR8ySE9-7yHJPBrtPV2zUoqssV8LFh-KXFqavhP3rq2fq8rK-CoX9mU15ang7v_O-L3SVbDpjSvd6S7pEbprhPbvetKn8-IDXYEx0QJlWFpnXXQQefSktXbX-kX1MI3xGSFg1tSqoovLahugKfSjFZlA4JjB2hcmOWBQUcSlcKwuyloquyvmjB0zwk3w4Pvr7_4LmGDV4uQ9F4JuRZblismOE-i7VN4FEaUIyJ4tzEQkvAW4kyEOZlXaEcK1kYKKmjQCom2SMyK8rCbBMqRGhZZriSgB9EArAqC2ymrAl8qzjz54QNmkpzV80cm2qcp90RnYSoppdbivpNnX7nxBtHrftqHv_g30cjGHmxFnf3RVmdpW5qp4hCle_rOAlyrmOWaa2FiDIwdCFtzOfkBZpQ2l9sHT1KugdYS0gIJ9mcvOo4sB5HgQk_Z6qt6_Tj55NrMH1ZXIfpeML0xjHZEmSWK3cTAySPxcAmnDsTTnA9-YS8jbNiEF2d_rZlGDlY-9XklyMZfxQz_QpTtsjDYX0GoAxye9xPrFH8IcxmkchwTuRkyk30M6UUy-9dzfRI8BhWpyd__1tPyWaIsA0TRPgOmTVVa56RW_mPZllXz51z-QV3IIQe priority: 102 providerName: ProQuest
Title	The creation and selection of mutations resistant to a gene drive over multiple generations in the malaria mosquito
URI	https://www.ncbi.nlm.nih.gov/pubmed/28976972 https://www.proquest.com/docview/1965079961 https://www.proquest.com/docview/1947620644 https://pubmed.ncbi.nlm.nih.gov/PMC5648257 https://doaj.org/article/0154a00d891c4d83bddd665be1767f84 http://dx.doi.org/10.1371/journal.pgen.1007039
Volume	13
WOSCitedRecordID	wos000414161300014&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: DOA dateStart: 20050101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVPQU databaseName: Biological Science Database customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: M7P dateStart: 20050701 isFulltext: true titleUrlDefault: http://search.proquest.com/biologicalscijournals providerName: ProQuest – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: 7X7 dateStart: 20050701 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: BENPR dateStart: 20050701 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: Publicly Available Content Database customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: PIMPY dateStart: 20050701 isFulltext: true titleUrlDefault: http://search.proquest.com/publiccontent providerName: ProQuest – providerCode: PRVATS databaseName: Public Library of Science (PLoS) Journals Open Access customDbUrl: eissn: 1553-7404 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0035897 issn: 1553-7404 databaseCode: FPL dateStart: 20050701 isFulltext: true titleUrlDefault: http://www.plos.org/publications/ providerName: Public Library of Science
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV3db9MwELdYBxIvfMMKoxiExFNGEju287ihVUwaJRowjafISWyotCalaZH477lzPiDTJsZLpPTOTXT2nX8Xn38m5HWIBCHCFl4ewoVjgYU2PPKYzYzWJpDNp4vTYzmbqbOzOPmTKF5YwWcyeNvadG8JBnVr-j6Lt8h2yITAEq5pctxFXhapWLbb465qOZh-HEt_H4tHy_OqvgxoXqyX_GsCmt7931e_R-60UJPuN2PjPrlhygfkVnP45K-HpIYRQjvMSHVZ0NqdiYN3laWLTbNIX1NIyBFklmu6rqim8BRDixVESYrln7QrSXSCVdtmXlJAlnShIXGea7qo6h8biB2PyJfp4ed37732CAYvl6FYeybkWW6Y0sxwn6nCxnArTRBzE6ncKFFIQFCxNpC4ZY76xkoWBloWUSA1k-wxGZVVaXYIFSK0LDNcS0AEIgaglAU209YEvtWc-WPCup5J85afHI_JOE_dopuEPKWxW4rmTFtzjonXt1o2_Bz_0D_ATu91kV3b_QD9lrbOmiKu1L5fqDjIeaFYVhSFEFEGQ1dIq_iYvMAhkzZbVfsYke4DehISEkQ2Jq-cBjJslFjC801v6jo9-nh6DaVPs-sonQyU3rRKtgKb5brdWwGWR3qvgebuQBOCST4Q76AXdKarUySc9CUkxQG07DzjcvHLXox_irV7pak2qMNhxgXoC3Z70jhSb35I96WIZTgmcuBig_4ZSsr5d8eCHgmuYL55evUbPyO3QwRhWO7Bd8lovdqY5-Rm_nM9r1cTsiXPpLuqCdk-OJwlJxP3RWbigsoEq4ATkCRHH5KvvwHq0nYZ
linkProvider	Public Library of Science
linkToHtml	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9QwELbKAoILb2igUINAnEKTOLGTA0LlUXXVZUFQqr0FJ7bLSrvJNtkF9U_xG5nJiwZV0EsPXCIlHke7k5nxN8nnGUKeelgghBtlpx4cfCRYSO0HNjOJllK7on51cTAS43E4mUQf18jPdi8M0irbmFgFapWn-I58CyvfOQLQuftqcWRj1yj8utq20KjNYk8f_4CUrXw5fAvP95nn7bzbf7NrN10F7FR4fGlrz09SzULJtO-wUJkIToWGZF4HYapDrgSAgkhqyEWSqpqLEcxzpVCBKyQTDO57gVyEOC6QQiYmXYLHgrBu5hIEzBYscpqteky4W41lvFiAWVTMBAfbk59YCquOAd26MFjM8vI00Psnd_PEYrhz_X9T4w1yrYHddLv2k5tkTWe3yOW6EefxbVKCt9AWP1OZKVpW_YHwLDd0vqoJCyUtdImAO1vSZU4lBTVrqgpYMShSYWlLz6wGimbONKOAsulcziR4O53n5dEK4ugd8uVc_vFdMsjyTK8TyrlnWKJ9KQAd8QhAY-KaRBrtOkb6zLEIay0jTpta7dgyZBZXHyAF5Gy13mK0p7ixJ4vY3axFXavkH_Kv0eg6Waw0Xl3Ii8O4CVwxYmzpOCqM3NRXIUuUUpwHCbgxFyb0LbKJJhvX23a7eBlvA5LkApJlZpEnlQRWG8mQznQoV2UZDz8cnEHo8_gsQp96Qs8bIZODzlLZ7DMBzWOps57kRk8SAmvaG15HL2xVV8a_fQdmtt51-vDjbhhvijzGTOcrlPEBfUAaAHq7Vztyp34PogePhGcR0XPx3vPpj2TTb1VF-ID7Iay99__-szbJld3996N4NBzvPSBXPQSoSIXxN8hgWaz0Q3Ip_b6clsWjKqxR8vW8A8Avg5jfBA
linkToPdf	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9NAEF6VFBAX3tBAoQsCcTKxvfaufUCopY2IWoWq0Ko3s_bulkiJndoJqH-NX8eMX9Sogl564BLJ2c9WMp7HN_bsDCGvXGwQwo2yEhc-PCywkNrzLWZiLaV2RPXo4mhPjMfB8XG4v0J-NnthsKyy8Ymlo1ZZgs_IB9j5zhbAzp2Bqcsi9reH7-enFk6QwjetzTiNSkV29dkPSN-Kd6NtuNevXXe48-XDR6ueMGAlwuULS7tenGgWSKY9mwXKhHAoNCT22g8SHXAlgCCEUkNeEpedXYxgriOF8h0hmWBw3WtkVQDJAOta3doZ7x80cYD5QTXaxfeZBQi73rjHhDOo9eTtHJSkrFOwcVj5ucBYzg9oo0RvPs2Kiyjwn5Wc50Lj8M7_LNS75HZNyOlmZUH3yIpO75Mb1YjOswekADuiDbOmMlW0KCcH4VFm6GxZlTIUNNcFUvF0QRcZlRRErqnKIZZQLJKlTeFmuZDX50xSCvybzuRUgh-gs6w4XYKHfUgOr-QfPyK9NEv1GqGcu4bF2pMCeBMPgU7Gjoml0Y5tpMfsPmGNlkRJ3cUdh4lMo_LVpIBsrpJbhLoV1brVJ1Z71rzqYvIP_BYqYIvFHuTlF1l-EtUuLUL2LW1bBaGTeCpgsVKKcz8GA-fCBF6fbKD6RtWG3taTRpvAMbmANJr1ycsSgX1IUlS-E7ksimj06egSoM_jy4AOOqA3NchkILNE1jtQQPLYBK2DXO8gweUmneU1tMhGdEX0247gzMbSLl5-0S7jRbHCMdXZEjEe8BJIEEBujyujbsXvgifhoXD7RHTMvXN_uivp5FvZK97nXgBR-cnff9YGuQl2H-2NxrtPyS0XmSvWyHjrpLfIl_oZuZ58X0yK_Hnt4yj5etUe4Bfk8ukl
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+creation+and+selection+of+mutations+resistant+to+a+gene+drive+over+multiple+generations+in+the+malaria+mosquito&rft.jtitle=PLoS+genetics&rft.au=Hammond%2C+Andrew+M&rft.au=Kyrou%2C+Kyros&rft.au=Bruttini%2C+Marco&rft.au=North%2C+Ace&rft.date=2017-10-04&rft.pub=Public+Library+of+Science&rft.issn=1553-7390&rft.volume=13&rft.issue=10&rft_id=info:doi/10.1371%2Fjournal.pgen.1007039&rft.externalDBID=ISN&rft.externalDocID=A512676053
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1553-7404&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1553-7404&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1553-7404&client=summon