Universidad Peruana Cayetano Heredia

Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis

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dc.contributor.author Coll, Francesc
dc.contributor.author Phelan, Jody
dc.contributor.author Hill-Cawthorne, Grant A.
dc.contributor.author Nair, Mridul B.
dc.contributor.author Mallard, Kim
dc.contributor.author Ali, Shahjahan
dc.contributor.author Abdallah, Abdallah M.
dc.contributor.author Alghamdi, Saad
dc.contributor.author Alsomali, Mona
dc.contributor.author Ahmed, Abdallah O.
dc.contributor.author Portelli, Stephanie
dc.contributor.author Oppong, Yaa
dc.contributor.author Alves, Adriana
dc.contributor.author Bessa, Theolis Barbosa
dc.contributor.author Campino, Susana
dc.contributor.author Caws, Maxine
dc.contributor.author Chatterjee, Anirvan
dc.contributor.author Crampin, Amelia C.
dc.contributor.author Dheda, Keertan
dc.contributor.author Furnham, Nicholas
dc.contributor.author Glynn, Judith R.
dc.contributor.author Grandjean, Louis
dc.contributor.author Minh Ha, Dang
dc.contributor.author Hasan, Rumina
dc.contributor.author Hasan, Zahra
dc.contributor.author Hibberd, Martin L.
dc.contributor.author Joloba, Moses
dc.contributor.author Jones-López, Edward C.
dc.contributor.author Matsumoto, Tomoshige
dc.contributor.author Miranda, Anabela
dc.contributor.author Moore, David Alexander James
dc.contributor.author Mocillo, Nora
dc.contributor.author Panaiotov, Stefan
dc.contributor.author Parkhill, Julian
dc.contributor.author Penha, Carlos
dc.contributor.author Perdigão, João
dc.contributor.author Portugal, Isabel
dc.contributor.author Rchiad, Zineb
dc.contributor.author Robledo, Jaime
dc.contributor.author Sheen Cortavarria, Patricia
dc.contributor.author Shesha, Nashwa Talaat
dc.contributor.author Sirgel, Frik A.
dc.contributor.author Sola, Christophe
dc.contributor.author Oliveira Sousa, Erivelton
dc.contributor.author Streicher, Elizabeth M.
dc.contributor.author Helden, Paul Van
dc.contributor.author Viveiros, Miguel
dc.contributor.author Warren, Robert M.
dc.contributor.author McNerney, Ruth
dc.contributor.author Pain, Arnab
dc.contributor.author Clark, Taane G.
dc.date.accessioned 2018-11-30T03:10:47Z
dc.date.available 2018-11-30T03:10:47Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/4080
dc.description.abstract To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps (drrA and Rv2688c) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms. en_US
dc.language.iso eng
dc.publisher Springer Nature
dc.relation.ispartofseries Nature Genetics
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Genome-wide association studies en_US
dc.subject Microbial genetics en_US
dc.subject Tuberculosis en_US
dc.title Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1038/s41588-017-0029-0
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.07
dc.relation.issn 1546-1718


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