Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/jspui/handle/123456789/28820 |
Resumo: | Introduction The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. Methods The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. Results Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. Conclusion Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines. |
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Rodrigues, Juliana Carla GomesSouza, Tatiane Piedade dePastana, Lucas FavachoSantos, André Maurício Ribeiro dosFernandes, Marianne RodriguesPinto, PabloWanderley, Alayde VieiraSouza, Sandro José deKroll, José EduardoPereira, Adenilson LeãoMagalhães, LeandroMercês, Laís Reis dasVidal, Amanda FerreiraVinasco-Sandoval, TatianaCavalcante, Giovanna ChavesGuerreiro, João FariasAssumpção, Paulo Pimentel deRibeiro-dos-Santos, ÂndreaSantos, SidneySantos, Ney Pereira Carneiro dos2020-04-20T19:12:24Z2020-04-20T19:12:24Z2020-04-15RODRIGUES, J. C. G. et al. Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil. PLoS One, [S. l.], v. 15, n. 4, p. e0231651, abr. 2020.https://repositorio.ufrn.br/jspui/handle/123456789/2882010.1371/journal.pone.0231651Nudix hydrolase 15 (NUDT15)MercaptopurineIdentification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazilinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleIntroduction The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. Methods The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. Results Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. Conclusion Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines.engreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNinfo:eu-repo/semantics/openAccessORIGINALSandroSouza_ICe_2020_Identification of NUDT15.pdfSandroSouza_ICe_2020_Identification of NUDT15.pdfSandroSouza_ICe_2020_Identification of NUDT15application/pdf651472https://repositorio.ufrn.br/bitstream/123456789/28820/1/SandroSouza_ICe_2020_Identification%20of%20NUDT15.pdf7f780a11acac1377eb7946614a1cc3ecMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81484https://repositorio.ufrn.br/bitstream/123456789/28820/2/license.txte9597aa2854d128fd968be5edc8a28d9MD52TEXTSandroSouza_ICe_2020_Identification of NUDT15.pdf.txtSandroSouza_ICe_2020_Identification of NUDT15.pdf.txtExtracted texttext/plain41035https://repositorio.ufrn.br/bitstream/123456789/28820/3/SandroSouza_ICe_2020_Identification%20of%20NUDT15.pdf.txtee8b123fa78fab4e1c189c8d9dc024ffMD53THUMBNAILSandroSouza_ICe_2020_Identification of NUDT15.pdf.jpgSandroSouza_ICe_2020_Identification of NUDT15.pdf.jpgGenerated Thumbnailimage/jpeg1772https://repositorio.ufrn.br/bitstream/123456789/28820/4/SandroSouza_ICe_2020_Identification%20of%20NUDT15.pdf.jpg8f029a1ffff9e85c3978d30dfd66a745MD54123456789/288202020-04-26 04:30:22.868oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2020-04-26T07:30:22Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil |
title |
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil |
spellingShingle |
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil Rodrigues, Juliana Carla Gomes Nudix hydrolase 15 (NUDT15) Mercaptopurine |
title_short |
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil |
title_full |
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil |
title_fullStr |
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil |
title_full_unstemmed |
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil |
title_sort |
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil |
author |
Rodrigues, Juliana Carla Gomes |
author_facet |
Rodrigues, Juliana Carla Gomes Souza, Tatiane Piedade de Pastana, Lucas Favacho Santos, André Maurício Ribeiro dos Fernandes, Marianne Rodrigues Pinto, Pablo Wanderley, Alayde Vieira Souza, Sandro José de Kroll, José Eduardo Pereira, Adenilson Leão Magalhães, Leandro Mercês, Laís Reis das Vidal, Amanda Ferreira Vinasco-Sandoval, Tatiana Cavalcante, Giovanna Chaves Guerreiro, João Farias Assumpção, Paulo Pimentel de Ribeiro-dos-Santos, Ândrea Santos, Sidney Santos, Ney Pereira Carneiro dos |
author_role |
author |
author2 |
Souza, Tatiane Piedade de Pastana, Lucas Favacho Santos, André Maurício Ribeiro dos Fernandes, Marianne Rodrigues Pinto, Pablo Wanderley, Alayde Vieira Souza, Sandro José de Kroll, José Eduardo Pereira, Adenilson Leão Magalhães, Leandro Mercês, Laís Reis das Vidal, Amanda Ferreira Vinasco-Sandoval, Tatiana Cavalcante, Giovanna Chaves Guerreiro, João Farias Assumpção, Paulo Pimentel de Ribeiro-dos-Santos, Ândrea Santos, Sidney Santos, Ney Pereira Carneiro dos |
author2_role |
author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Rodrigues, Juliana Carla Gomes Souza, Tatiane Piedade de Pastana, Lucas Favacho Santos, André Maurício Ribeiro dos Fernandes, Marianne Rodrigues Pinto, Pablo Wanderley, Alayde Vieira Souza, Sandro José de Kroll, José Eduardo Pereira, Adenilson Leão Magalhães, Leandro Mercês, Laís Reis das Vidal, Amanda Ferreira Vinasco-Sandoval, Tatiana Cavalcante, Giovanna Chaves Guerreiro, João Farias Assumpção, Paulo Pimentel de Ribeiro-dos-Santos, Ândrea Santos, Sidney Santos, Ney Pereira Carneiro dos |
dc.subject.por.fl_str_mv |
Nudix hydrolase 15 (NUDT15) Mercaptopurine |
topic |
Nudix hydrolase 15 (NUDT15) Mercaptopurine |
description |
Introduction The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. Methods The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. Results Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. Conclusion Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-04-20T19:12:24Z |
dc.date.available.fl_str_mv |
2020-04-20T19:12:24Z |
dc.date.issued.fl_str_mv |
2020-04-15 |
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info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
RODRIGUES, J. C. G. et al. Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil. PLoS One, [S. l.], v. 15, n. 4, p. e0231651, abr. 2020. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/jspui/handle/123456789/28820 |
dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pone.0231651 |
identifier_str_mv |
RODRIGUES, J. C. G. et al. Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil. PLoS One, [S. l.], v. 15, n. 4, p. e0231651, abr. 2020. 10.1371/journal.pone.0231651 |
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https://repositorio.ufrn.br/jspui/handle/123456789/28820 |
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eng |
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