Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae

Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Redmond, Seth N. [verfasserIn] Eiglmeier, Karin Mitri, Christian Markianos, Kyriacos Guelbeogo, Wamdaogo M. Gneme, Awa Isaacs, Alison T. Coulibaly, Boubacar Brito-Fravallo, Emma Maslen, Gareth Mead, Daniel Niare, Oumou Traore, Sekou F. Sagnon, N’Fale Kwiatkowski, Dominic Riehle, Michelle M. Vernick, Kenneth D.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Mosquito Malaria Genetic analysis GWAS Host-pathogen interaction Population genomics Pooled sequencing

Anmerkung:	© Redmond et al. 2015

Übergeordnetes Werk:	Enthalten in: BMC genomics - London : BioMed Central, 2000, 16(2015), 1 vom: 13. Okt.
Übergeordnetes Werk:	volume:16 ; year:2015 ; number:1 ; day:13 ; month:10

Links:	Volltext

DOI / URN:	10.1186/s12864-015-2009-z

Katalog-ID:	SPR027111466

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100	1		\|a Redmond, Seth N. \|e verfasserin \|4 aut
245	1	0	\|a Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae
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520			\|a Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour.
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700	1		\|a Riehle, Michelle M. \|4 aut
700	1		\|a Vernick, Kenneth D. \|4 aut
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allfields	10.1186/s12864-015-2009-z doi (DE-627)SPR027111466 (SPR)s12864-015-2009-z-e DE-627 ger DE-627 rakwb eng Redmond, Seth N. verfasserin aut Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Redmond et al. 2015 Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. Mosquito (dpeaa)DE-He213 Malaria (dpeaa)DE-He213 Genetic analysis (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Host-pathogen interaction (dpeaa)DE-He213 Population genomics (dpeaa)DE-He213 Pooled sequencing (dpeaa)DE-He213 Eiglmeier, Karin aut Mitri, Christian aut Markianos, Kyriacos aut Guelbeogo, Wamdaogo M. aut Gneme, Awa aut Isaacs, Alison T. aut Coulibaly, Boubacar aut Brito-Fravallo, Emma aut Maslen, Gareth aut Mead, Daniel aut Niare, Oumou aut Traore, Sekou F. aut Sagnon, N’Fale aut Kwiatkowski, Dominic aut Riehle, Michelle M. aut Vernick, Kenneth D. aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 13. Okt. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:13 month:10 https://dx.doi.org/10.1186/s12864-015-2009-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 13 10
spelling	10.1186/s12864-015-2009-z doi (DE-627)SPR027111466 (SPR)s12864-015-2009-z-e DE-627 ger DE-627 rakwb eng Redmond, Seth N. verfasserin aut Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Redmond et al. 2015 Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. Mosquito (dpeaa)DE-He213 Malaria (dpeaa)DE-He213 Genetic analysis (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Host-pathogen interaction (dpeaa)DE-He213 Population genomics (dpeaa)DE-He213 Pooled sequencing (dpeaa)DE-He213 Eiglmeier, Karin aut Mitri, Christian aut Markianos, Kyriacos aut Guelbeogo, Wamdaogo M. aut Gneme, Awa aut Isaacs, Alison T. aut Coulibaly, Boubacar aut Brito-Fravallo, Emma aut Maslen, Gareth aut Mead, Daniel aut Niare, Oumou aut Traore, Sekou F. aut Sagnon, N’Fale aut Kwiatkowski, Dominic aut Riehle, Michelle M. aut Vernick, Kenneth D. aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 13. Okt. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:13 month:10 https://dx.doi.org/10.1186/s12864-015-2009-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 13 10
allfields_unstemmed	10.1186/s12864-015-2009-z doi (DE-627)SPR027111466 (SPR)s12864-015-2009-z-e DE-627 ger DE-627 rakwb eng Redmond, Seth N. verfasserin aut Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Redmond et al. 2015 Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. Mosquito (dpeaa)DE-He213 Malaria (dpeaa)DE-He213 Genetic analysis (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Host-pathogen interaction (dpeaa)DE-He213 Population genomics (dpeaa)DE-He213 Pooled sequencing (dpeaa)DE-He213 Eiglmeier, Karin aut Mitri, Christian aut Markianos, Kyriacos aut Guelbeogo, Wamdaogo M. aut Gneme, Awa aut Isaacs, Alison T. aut Coulibaly, Boubacar aut Brito-Fravallo, Emma aut Maslen, Gareth aut Mead, Daniel aut Niare, Oumou aut Traore, Sekou F. aut Sagnon, N’Fale aut Kwiatkowski, Dominic aut Riehle, Michelle M. aut Vernick, Kenneth D. aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 13. Okt. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:13 month:10 https://dx.doi.org/10.1186/s12864-015-2009-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 13 10
allfieldsGer	10.1186/s12864-015-2009-z doi (DE-627)SPR027111466 (SPR)s12864-015-2009-z-e DE-627 ger DE-627 rakwb eng Redmond, Seth N. verfasserin aut Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Redmond et al. 2015 Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. Mosquito (dpeaa)DE-He213 Malaria (dpeaa)DE-He213 Genetic analysis (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Host-pathogen interaction (dpeaa)DE-He213 Population genomics (dpeaa)DE-He213 Pooled sequencing (dpeaa)DE-He213 Eiglmeier, Karin aut Mitri, Christian aut Markianos, Kyriacos aut Guelbeogo, Wamdaogo M. aut Gneme, Awa aut Isaacs, Alison T. aut Coulibaly, Boubacar aut Brito-Fravallo, Emma aut Maslen, Gareth aut Mead, Daniel aut Niare, Oumou aut Traore, Sekou F. aut Sagnon, N’Fale aut Kwiatkowski, Dominic aut Riehle, Michelle M. aut Vernick, Kenneth D. aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 13. Okt. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:13 month:10 https://dx.doi.org/10.1186/s12864-015-2009-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 13 10
allfieldsSound	10.1186/s12864-015-2009-z doi (DE-627)SPR027111466 (SPR)s12864-015-2009-z-e DE-627 ger DE-627 rakwb eng Redmond, Seth N. verfasserin aut Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Redmond et al. 2015 Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. Mosquito (dpeaa)DE-He213 Malaria (dpeaa)DE-He213 Genetic analysis (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Host-pathogen interaction (dpeaa)DE-He213 Population genomics (dpeaa)DE-He213 Pooled sequencing (dpeaa)DE-He213 Eiglmeier, Karin aut Mitri, Christian aut Markianos, Kyriacos aut Guelbeogo, Wamdaogo M. aut Gneme, Awa aut Isaacs, Alison T. aut Coulibaly, Boubacar aut Brito-Fravallo, Emma aut Maslen, Gareth aut Mead, Daniel aut Niare, Oumou aut Traore, Sekou F. aut Sagnon, N’Fale aut Kwiatkowski, Dominic aut Riehle, Michelle M. aut Vernick, Kenneth D. aut Enthalten in BMC genomics London : BioMed Central, 2000 16(2015), 1 vom: 13. Okt. (DE-627)326644954 (DE-600)2041499-7 1471-2164 nnns volume:16 year:2015 number:1 day:13 month:10 https://dx.doi.org/10.1186/s12864-015-2009-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2015 1 13 10
language	English
source	Enthalten in BMC genomics 16(2015), 1 vom: 13. Okt. volume:16 year:2015 number:1 day:13 month:10
sourceStr	Enthalten in BMC genomics 16(2015), 1 vom: 13. Okt. volume:16 year:2015 number:1 day:13 month:10
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Mosquito Malaria Genetic analysis GWAS Host-pathogen interaction Population genomics Pooled sequencing
isfreeaccess_bool	true
container_title	BMC genomics
authorswithroles_txt_mv	Redmond, Seth N. @@aut@@ Eiglmeier, Karin @@aut@@ Mitri, Christian @@aut@@ Markianos, Kyriacos @@aut@@ Guelbeogo, Wamdaogo M. @@aut@@ Gneme, Awa @@aut@@ Isaacs, Alison T. @@aut@@ Coulibaly, Boubacar @@aut@@ Brito-Fravallo, Emma @@aut@@ Maslen, Gareth @@aut@@ Mead, Daniel @@aut@@ Niare, Oumou @@aut@@ Traore, Sekou F. @@aut@@ Sagnon, N’Fale @@aut@@ Kwiatkowski, Dominic @@aut@@ Riehle, Michelle M. @@aut@@ Vernick, Kenneth D. @@aut@@
publishDateDaySort_date	2015-10-13T00:00:00Z
hierarchy_top_id	326644954
id	SPR027111466
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR027111466</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519081157.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2015 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s12864-015-2009-z</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR027111466</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s12864-015-2009-z-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Redmond, Seth N.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Redmond et al. 2015</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. 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author	Redmond, Seth N.
spellingShingle	Redmond, Seth N. misc Mosquito misc Malaria misc Genetic analysis misc GWAS misc Host-pathogen interaction misc Population genomics misc Pooled sequencing Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae
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topic_title	Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae Mosquito (dpeaa)DE-He213 Malaria (dpeaa)DE-He213 Genetic analysis (dpeaa)DE-He213 GWAS (dpeaa)DE-He213 Host-pathogen interaction (dpeaa)DE-He213 Population genomics (dpeaa)DE-He213 Pooled sequencing (dpeaa)DE-He213
topic	misc Mosquito misc Malaria misc Genetic analysis misc GWAS misc Host-pathogen interaction misc Population genomics misc Pooled sequencing
topic_unstemmed	misc Mosquito misc Malaria misc Genetic analysis misc GWAS misc Host-pathogen interaction misc Population genomics misc Pooled sequencing
topic_browse	misc Mosquito misc Malaria misc Genetic analysis misc GWAS misc Host-pathogen interaction misc Population genomics misc Pooled sequencing
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title	Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae
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title_full	Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae
author_sort	Redmond, Seth N.
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author_browse	Redmond, Seth N. Eiglmeier, Karin Mitri, Christian Markianos, Kyriacos Guelbeogo, Wamdaogo M. Gneme, Awa Isaacs, Alison T. Coulibaly, Boubacar Brito-Fravallo, Emma Maslen, Gareth Mead, Daniel Niare, Oumou Traore, Sekou F. Sagnon, N’Fale Kwiatkowski, Dominic Riehle, Michelle M. Vernick, Kenneth D.
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title_sort	association mapping by pooled sequencing identifies toll 11 as a protective factor against plasmodium falciparum in anopheles gambiae
title_auth	Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae
abstract	Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. © Redmond et al. 2015
abstractGer	Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. © Redmond et al. 2015
abstract_unstemmed	Background The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. This design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour. © Redmond et al. 2015
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title_short	Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae
url	https://dx.doi.org/10.1186/s12864-015-2009-z
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author2	Eiglmeier, Karin Mitri, Christian Markianos, Kyriacos Guelbeogo, Wamdaogo M. Gneme, Awa Isaacs, Alison T. Coulibaly, Boubacar Brito-Fravallo, Emma Maslen, Gareth Mead, Daniel Niare, Oumou Traore, Sekou F. Sagnon, N’Fale Kwiatkowski, Dominic Riehle, Michelle M. Vernick, Kenneth D.
author2Str	Eiglmeier, Karin Mitri, Christian Markianos, Kyriacos Guelbeogo, Wamdaogo M. Gneme, Awa Isaacs, Alison T. Coulibaly, Boubacar Brito-Fravallo, Emma Maslen, Gareth Mead, Daniel Niare, Oumou Traore, Sekou F. Sagnon, N’Fale Kwiatkowski, Dominic Riehle, Michelle M. Vernick, Kenneth D.
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Methods We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colonies from West Africa, controlled for diversity, linkage disequilibrium and population stratification. Colonies were challenged by feeding on the infectious stage of the human malaria parasite, Plasmodium falciparum, mosquitoes were phenotyped for parasite load, and DNA pools for phenotypically similar mosquitoes were Illumina sequenced. Phenotype-genotype mapping was carried out in two stages, coarse and fine. Results In the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. In the second mapping stage, focused genotyping of SNPs from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. The second stage confirmed significant SNPs in a locus encoding two Toll-family proteins. RNAi-mediated gene silencing and infection challenge revealed that TOLL 11 protects mosquitoes against P. falciparum infection. Conclusions We present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent Anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. This approach is a practical and preferred alternative to population-based GWAS for first-pass mapping of phenotypes in Anopheles. 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Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae

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