Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa
ABSTRACT: Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described. Determinants of antimalarial drug susceptibility for P. vivax in the region have not been characterised. Our genomic analysis of gl...
- Autores:
-
Fernández, Diana
Tobón Castaño, Alberto
Vélez Tobón, Gabriel Jaime
Campos Aguiar, Anna Caroline
Batista Pereira, Dhelio
Diez Benavente, Ernest
Dombrowski, Jamille G.
Campino, Susana
Manko, Emilia
Marinho, Claudio R. F.
Moon, Robert
Nolder, Debbie
Nosten, Francois
Phelan, Jody
Sriprawat, Kanlaya
Sutherland, Colin J.
Clark, Taane G.
Campos, Mónica
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2021
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/42046
- Acceso en línea:
- https://hdl.handle.net/10495/42046
- Palabra clave:
- Antimaláricos
Antimalarials
Resistencia a Medicamentos
Drug Resistance
Sistema del Grupo Sanguíneo Duffy
Duffy Blood-Group System
Genes Protozoarios
Genes, Protozoan
Sitios Genéticos
Genetic Loci
Malaria Vivax
Malaria, Vivax
Plasmodium vivax
África Oriental
Africa, Eastern
Polimorfismo de Nucleótido Simple
Polymorphism, Single Nucleotide
Proteínas Protozoarias
Protozoan Proteins
Reticulocitos
Reticulocytes
Selección Genética
Selection, Genetic
https://id.nlm.nih.gov/mesh/D000962
https://id.nlm.nih.gov/mesh/D004351
https://id.nlm.nih.gov/mesh/D004375
https://id.nlm.nih.gov/mesh/D017125
https://id.nlm.nih.gov/mesh/D056426
https://id.nlm.nih.gov/mesh/D016780
https://id.nlm.nih.gov/mesh/D010966
https://id.nlm.nih.gov/mesh/D000351
https://id.nlm.nih.gov/mesh/D020641
https://id.nlm.nih.gov/mesh/D015800
https://id.nlm.nih.gov/mesh/D012156
https://id.nlm.nih.gov/mesh/D012641
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by/2.5/co/
| id |
UDEA2_e75c0ba12af254b48cfa1c8b9ec6187c |
|---|---|
| oai_identifier_str |
oai:bibliotecadigital.udea.edu.co:10495/42046 |
| network_acronym_str |
UDEA2 |
| network_name_str |
Repositorio UdeA |
| repository_id_str |
|
| dc.title.spa.fl_str_mv |
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa |
| title |
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa |
| spellingShingle |
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa Antimaláricos Antimalarials Resistencia a Medicamentos Drug Resistance Sistema del Grupo Sanguíneo Duffy Duffy Blood-Group System Genes Protozoarios Genes, Protozoan Sitios Genéticos Genetic Loci Malaria Vivax Malaria, Vivax Plasmodium vivax África Oriental Africa, Eastern Polimorfismo de Nucleótido Simple Polymorphism, Single Nucleotide Proteínas Protozoarias Protozoan Proteins Reticulocitos Reticulocytes Selección Genética Selection, Genetic https://id.nlm.nih.gov/mesh/D000962 https://id.nlm.nih.gov/mesh/D004351 https://id.nlm.nih.gov/mesh/D004375 https://id.nlm.nih.gov/mesh/D017125 https://id.nlm.nih.gov/mesh/D056426 https://id.nlm.nih.gov/mesh/D016780 https://id.nlm.nih.gov/mesh/D010966 https://id.nlm.nih.gov/mesh/D000351 https://id.nlm.nih.gov/mesh/D020641 https://id.nlm.nih.gov/mesh/D015800 https://id.nlm.nih.gov/mesh/D012156 https://id.nlm.nih.gov/mesh/D012641 |
| title_short |
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa |
| title_full |
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa |
| title_fullStr |
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa |
| title_full_unstemmed |
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa |
| title_sort |
Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa |
| dc.creator.fl_str_mv |
Fernández, Diana Tobón Castaño, Alberto Vélez Tobón, Gabriel Jaime Campos Aguiar, Anna Caroline Batista Pereira, Dhelio Diez Benavente, Ernest Dombrowski, Jamille G. Campino, Susana Manko, Emilia Marinho, Claudio R. F. Moon, Robert Nolder, Debbie Nosten, Francois Phelan, Jody Sriprawat, Kanlaya Sutherland, Colin J. Clark, Taane G. Campos, Mónica |
| dc.contributor.author.none.fl_str_mv |
Fernández, Diana Tobón Castaño, Alberto Vélez Tobón, Gabriel Jaime Campos Aguiar, Anna Caroline Batista Pereira, Dhelio Diez Benavente, Ernest Dombrowski, Jamille G. Campino, Susana Manko, Emilia Marinho, Claudio R. F. Moon, Robert Nolder, Debbie Nosten, Francois Phelan, Jody Sriprawat, Kanlaya Sutherland, Colin J. Clark, Taane G. Campos, Mónica |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo Malaria |
| dc.subject.decs.none.fl_str_mv |
Antimaláricos Antimalarials Resistencia a Medicamentos Drug Resistance Sistema del Grupo Sanguíneo Duffy Duffy Blood-Group System Genes Protozoarios Genes, Protozoan Sitios Genéticos Genetic Loci Malaria Vivax Malaria, Vivax Plasmodium vivax África Oriental Africa, Eastern Polimorfismo de Nucleótido Simple Polymorphism, Single Nucleotide Proteínas Protozoarias Protozoan Proteins Reticulocitos Reticulocytes Selección Genética Selection, Genetic |
| topic |
Antimaláricos Antimalarials Resistencia a Medicamentos Drug Resistance Sistema del Grupo Sanguíneo Duffy Duffy Blood-Group System Genes Protozoarios Genes, Protozoan Sitios Genéticos Genetic Loci Malaria Vivax Malaria, Vivax Plasmodium vivax África Oriental Africa, Eastern Polimorfismo de Nucleótido Simple Polymorphism, Single Nucleotide Proteínas Protozoarias Protozoan Proteins Reticulocitos Reticulocytes Selección Genética Selection, Genetic https://id.nlm.nih.gov/mesh/D000962 https://id.nlm.nih.gov/mesh/D004351 https://id.nlm.nih.gov/mesh/D004375 https://id.nlm.nih.gov/mesh/D017125 https://id.nlm.nih.gov/mesh/D056426 https://id.nlm.nih.gov/mesh/D016780 https://id.nlm.nih.gov/mesh/D010966 https://id.nlm.nih.gov/mesh/D000351 https://id.nlm.nih.gov/mesh/D020641 https://id.nlm.nih.gov/mesh/D015800 https://id.nlm.nih.gov/mesh/D012156 https://id.nlm.nih.gov/mesh/D012641 |
| dc.subject.meshuri.none.fl_str_mv |
https://id.nlm.nih.gov/mesh/D000962 https://id.nlm.nih.gov/mesh/D004351 https://id.nlm.nih.gov/mesh/D004375 https://id.nlm.nih.gov/mesh/D017125 https://id.nlm.nih.gov/mesh/D056426 https://id.nlm.nih.gov/mesh/D016780 https://id.nlm.nih.gov/mesh/D010966 https://id.nlm.nih.gov/mesh/D000351 https://id.nlm.nih.gov/mesh/D020641 https://id.nlm.nih.gov/mesh/D015800 https://id.nlm.nih.gov/mesh/D012156 https://id.nlm.nih.gov/mesh/D012641 |
| description |
ABSTRACT: Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described. Determinants of antimalarial drug susceptibility for P. vivax in the region have not been characterised. Our genomic analysis of global P. vivax (n = 558) establishes South Asian isolates (n = 92) as a distinct subpopulation, which shares ancestry with some East African and South East Asian parasites. Signals of positive selection are linked to drug resistance-associated loci including pvkelch10, pvmrp1, pvdhfr and pvdhps, and two loci linked to P. vivax invasion of reticulocytes, pvrbp1a and pvrbp1b. Significant identity-by-descent was found in extended chromosome regions common to P. vivax from India and Ethiopia, including the pvdbp gene associated with Duffy blood group binding. Our investigation provides new understanding of global P. vivax population structure and genomic diversity, and genetic evidence of recent directional selection in this important human pathogen. |
| publishDate |
2021 |
| dc.date.issued.none.fl_str_mv |
2021 |
| dc.date.accessioned.none.fl_str_mv |
2024-09-11T22:18:48Z |
| dc.date.available.none.fl_str_mv |
2024-09-11T22:18:48Z |
| dc.type.spa.fl_str_mv |
Artículo de investigación |
| dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
| dc.type.coarversion.spa.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/article |
| dc.type.version.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
| status_str |
publishedVersion |
| dc.identifier.citation.spa.fl_str_mv |
Benavente ED, Manko E, Phelan J, Campos M, Nolder D, Fernandez D, Velez-Tobon G, Castaño AT, Dombrowski JG, Marinho CRF, Aguiar ACC, Pereira DB, Sriprawat K, Nosten F, Moon R, Sutherland CJ, Campino S, Clark TG. Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa. Nat Commun. 2021 May 26;12(1):3160. doi: 10.1038/s41467-021-23422-3. |
| dc.identifier.issn.none.fl_str_mv |
2041-1723 |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/10495/42046 |
| dc.identifier.doi.none.fl_str_mv |
10.1038/s41467-021-23422-3 |
| dc.identifier.eissn.none.fl_str_mv |
2041-1723 |
| identifier_str_mv |
Benavente ED, Manko E, Phelan J, Campos M, Nolder D, Fernandez D, Velez-Tobon G, Castaño AT, Dombrowski JG, Marinho CRF, Aguiar ACC, Pereira DB, Sriprawat K, Nosten F, Moon R, Sutherland CJ, Campino S, Clark TG. Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa. Nat Commun. 2021 May 26;12(1):3160. doi: 10.1038/s41467-021-23422-3. 2041-1723 10.1038/s41467-021-23422-3 |
| url |
https://hdl.handle.net/10495/42046 |
| dc.language.iso.spa.fl_str_mv |
eng |
| language |
eng |
| dc.relation.ispartofjournalabbrev.spa.fl_str_mv |
Nat. Commun. |
| dc.relation.citationendpage.spa.fl_str_mv |
11 |
| dc.relation.citationissue.spa.fl_str_mv |
1 |
| dc.relation.citationstartpage.spa.fl_str_mv |
1 |
| dc.relation.citationvolume.spa.fl_str_mv |
12 |
| dc.relation.ispartofjournal.spa.fl_str_mv |
Nature Communications |
| dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by/2.5/co/ |
| dc.rights.uri.spa.fl_str_mv |
https://creativecommons.org/licenses/by/4.0/ |
| dc.rights.accessrights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
| dc.rights.coar.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
| rights_invalid_str_mv |
http://creativecommons.org/licenses/by/2.5/co/ https://creativecommons.org/licenses/by/4.0/ http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.extent.spa.fl_str_mv |
11 páginas |
| dc.format.mimetype.spa.fl_str_mv |
application/pdf |
| dc.publisher.spa.fl_str_mv |
Nature Research |
| dc.publisher.place.spa.fl_str_mv |
Londres, Inglaterra |
| institution |
Universidad de Antioquia |
| bitstream.url.fl_str_mv |
https://bibliotecadigital.udea.edu.co/bitstreams/8e362849-53e2-4bbf-a9a7-8255c66afdee/download https://bibliotecadigital.udea.edu.co/bitstreams/b0f1b837-dcc9-417a-b563-55ea5f395749/download https://bibliotecadigital.udea.edu.co/bitstreams/a4c62d63-d824-41a6-9661-d7be0cc1509b/download https://bibliotecadigital.udea.edu.co/bitstreams/1b0ed652-08b4-4936-88ba-c95a8b957ef1/download https://bibliotecadigital.udea.edu.co/bitstreams/eda1f090-97e7-4ea9-976d-f21db05f1148/download |
| bitstream.checksum.fl_str_mv |
1646d1f6b96dbbbc38035efc9239ac9c 8a4605be74aa9ea9d79846c1fba20a33 2a362f0853e2de1d1fb5cefcb584cb84 dd08d948805a3308d27add4214ed6455 fe4b8e6ae4e9c527f94ce017cf066e9f |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositorio Institucional de la Universidad de Antioquia |
| repository.mail.fl_str_mv |
aplicacionbibliotecadigitalbiblioteca@udea.edu.co |
| _version_ |
1851052493367148544 |
| spelling |
Fernández, DianaTobón Castaño, AlbertoVélez Tobón, Gabriel JaimeCampos Aguiar, Anna CarolineBatista Pereira, DhelioDiez Benavente, ErnestDombrowski, Jamille G.Campino, SusanaManko, EmiliaMarinho, Claudio R. F.Moon, RobertNolder, DebbieNosten, FrancoisPhelan, JodySriprawat, KanlayaSutherland, Colin J.Clark, Taane G.Campos, MónicaGrupo Malaria2024-09-11T22:18:48Z2024-09-11T22:18:48Z2021Benavente ED, Manko E, Phelan J, Campos M, Nolder D, Fernandez D, Velez-Tobon G, Castaño AT, Dombrowski JG, Marinho CRF, Aguiar ACC, Pereira DB, Sriprawat K, Nosten F, Moon R, Sutherland CJ, Campino S, Clark TG. Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East Africa. Nat Commun. 2021 May 26;12(1):3160. doi: 10.1038/s41467-021-23422-3.2041-1723https://hdl.handle.net/10495/4204610.1038/s41467-021-23422-32041-1723ABSTRACT: Despite the high burden of Plasmodium vivax malaria in South Asian countries, the genetic diversity of circulating parasite populations is not well described. Determinants of antimalarial drug susceptibility for P. vivax in the region have not been characterised. Our genomic analysis of global P. vivax (n = 558) establishes South Asian isolates (n = 92) as a distinct subpopulation, which shares ancestry with some East African and South East Asian parasites. Signals of positive selection are linked to drug resistance-associated loci including pvkelch10, pvmrp1, pvdhfr and pvdhps, and two loci linked to P. vivax invasion of reticulocytes, pvrbp1a and pvrbp1b. Significant identity-by-descent was found in extended chromosome regions common to P. vivax from India and Ethiopia, including the pvdbp gene associated with Duffy blood group binding. Our investigation provides new understanding of global P. vivax population structure and genomic diversity, and genetic evidence of recent directional selection in this important human pathogen.Wellcome TrustMedical Research CouncilCOL000752411 páginasapplication/pdfengNature ResearchLondres, Inglaterrahttp://creativecommons.org/licenses/by/2.5/co/https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Distinctive genetic structure and selection patterns in Plasmodium vivax from South Asia and East AfricaArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAntimaláricosAntimalarialsResistencia a MedicamentosDrug ResistanceSistema del Grupo Sanguíneo DuffyDuffy Blood-Group SystemGenes ProtozoariosGenes, ProtozoanSitios GenéticosGenetic LociMalaria VivaxMalaria, VivaxPlasmodium vivaxÁfrica OrientalAfrica, EasternPolimorfismo de Nucleótido SimplePolymorphism, Single NucleotideProteínas ProtozoariasProtozoan ProteinsReticulocitosReticulocytesSelección GenéticaSelection, Genetichttps://id.nlm.nih.gov/mesh/D000962https://id.nlm.nih.gov/mesh/D004351https://id.nlm.nih.gov/mesh/D004375https://id.nlm.nih.gov/mesh/D017125https://id.nlm.nih.gov/mesh/D056426https://id.nlm.nih.gov/mesh/D016780https://id.nlm.nih.gov/mesh/D010966https://id.nlm.nih.gov/mesh/D000351https://id.nlm.nih.gov/mesh/D020641https://id.nlm.nih.gov/mesh/D015800https://id.nlm.nih.gov/mesh/D012156https://id.nlm.nih.gov/mesh/D012641Nat. Commun.111112Nature CommunicationsWT 106698MRC MR/M01360X/1, MR/N010469/1, MR/R025576/1 y MR/R020973/1RoR:029chgv08RoR:03x94j517PublicationCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8927https://bibliotecadigital.udea.edu.co/bitstreams/8e362849-53e2-4bbf-a9a7-8255c66afdee/download1646d1f6b96dbbbc38035efc9239ac9cMD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/b0f1b837-dcc9-417a-b563-55ea5f395749/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADORIGINALTobonAlberto_2021_Genetic_Structure_Plasmodium.pdfTobonAlberto_2021_Genetic_Structure_Plasmodium.pdfArtículo de investigaciónapplication/pdf1313876https://bibliotecadigital.udea.edu.co/bitstreams/a4c62d63-d824-41a6-9661-d7be0cc1509b/download2a362f0853e2de1d1fb5cefcb584cb84MD51trueAnonymousREADTEXTTobonAlberto_2021_Genetic_Structure_Plasmodium.pdf.txtTobonAlberto_2021_Genetic_Structure_Plasmodium.pdf.txtExtracted texttext/plain70614https://bibliotecadigital.udea.edu.co/bitstreams/1b0ed652-08b4-4936-88ba-c95a8b957ef1/downloaddd08d948805a3308d27add4214ed6455MD54falseAnonymousREADTHUMBNAILTobonAlberto_2021_Genetic_Structure_Plasmodium.pdf.jpgTobonAlberto_2021_Genetic_Structure_Plasmodium.pdf.jpgGenerated Thumbnailimage/jpeg12738https://bibliotecadigital.udea.edu.co/bitstreams/eda1f090-97e7-4ea9-976d-f21db05f1148/downloadfe4b8e6ae4e9c527f94ce017cf066e9fMD55falseAnonymousREAD10495/42046oai:bibliotecadigital.udea.edu.co:10495/420462025-03-26 23:15:18.202http://creativecommons.org/licenses/by/2.5/co/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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 |
