{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:02Z","timestamp":1787022062550,"version":"build-2736575974"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["14\/2013"],"award-info":[{"award-number":["14\/2013"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007382","name":"Universidade Federal do Par\u00e1","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0231651","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T13:27:31Z","timestamp":1586957251000},"page":"e0231651","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil"],"prefix":"10.1371","volume":"15","author":[{"given":"Juliana Carla Gomes","family":"Rodrigues","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane Piedade de","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Favacho","family":"Pastana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Maur\u00edcio","family":"Ribeiro dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1396-3442","authenticated-orcid":true,"given":"Marianne Rodrigues","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alayde Vieira","family":"Wanderley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro Jos\u00e9 de","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7657-9536","authenticated-orcid":true,"given":"Jos\u00e9 Eduardo","family":"Kroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adenilson Le\u00e3o","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Magalh\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00eds Reis das","family":"Merc\u00eas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Ferreira","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Vinasco-Sandoval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Chaves","family":"Cavalcante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Farias","family":"Guerreiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Pimentel de","family":"Assump\u00e7\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c2ndrea","family":"Ribeiro-dos-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ney Pereira Carneiro dos","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"issue":"9","key":"pone.0231651.ref001","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1136\/jmedgenet-2014-102530","article-title":"Genetic architectures of ADME genes in five Eurasian admixed populations and implications for drug safety and efficacy","volume":"51","author":"J Li","year":"2014","journal-title":"J Med Genet"},{"key":"pone.0231651.ref002","first-page":"3","article-title":"User considerations in assessing pharmacogenomic tests and their clinical support tools","volume":"11","author":"G Mukerjee","year":"2018","journal-title":"NPJ Genom. Med"},{"issue":"1","key":"pone.0231651.ref003","doi-asserted-by":"crossref","first-page":"7201","DOI":"10.1038\/s41598-019-43610-y","article-title":"Polymorphisms of ADME-related genes and their implications for drug safety and efficacy in Amazonian Amerindians","volume":"9","author":"JCG Rodrigues","year":"2019","journal-title":"Sci Rep"},{"issue":"18","key":"pone.0231651.ref004","doi-asserted-by":"crossref","first-page":"5501","DOI":"10.1158\/0008-5472.CAN-16-0584","article-title":"NUDT15 hydrolyzes 6-thio-deoxyGTP to mediate the anticancer efficacy of 6-thioguanine","volume":"76","author":"NC Valerie","year":"2016","journal-title":"Cancer Res"},{"issue":"22","key":"pone.0231651.ref005","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1182\/blood-2017-11-815506","article-title":"Preclinical evaluation of NUDT15-guided thiopurine therapy and its effects on toxicity and antileukemic efficacy","volume":"131","author":"R Nishii","year":"2018","journal-title":"Blood"},{"issue":"5","key":"pone.0231651.ref006","first-page":"4285","article-title":"Homozygous mutation in NUDT15 in childhood acute lymphoblastic leukemia with increased susceptibility to mercaptopurine toxicity: A case report","volume":"17","author":"J Cheng","year":"2019","journal-title":"Exp Ther Med"},{"key":"pone.0231651.ref007","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.leukres.2018.09.003","article-title":"Pharmacogenomics and variations in the risk of toxicity during the consolidation\/maintenance phases of the treatment of pediatric B-cell leukemia patients from an admixed population in the Brazilian Amazon","volume":"74","author":"DC Carvalho","year":"2018","journal-title":"Leuk Res"},{"issue":"2","key":"pone.0231651.ref008","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s00535-017-1416-0","article-title":"Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping","volume":"53","author":"Y Kakuta","year":"2018","journal-title":"J Gastroenterol"},{"key":"pone.0231651.ref009","unstructured":"PURIXAN\u00ae (mercaptopurine) [package insert on the internet]. United Kingdom: Nova Laboratories Ltd.; https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/205919s003lbl.pdf (2018)."},{"key":"pone.0231651.ref010","unstructured":"IMURAN \u00ae (azathioprine) [package insert on the internet]. Sebela Pharmaceuticals, Inc. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/016324s039lbl.pdf (2018)."},{"issue":"4","key":"pone.0231651.ref011","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/ng.3508","article-title":"NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity","volume":"48","author":"T Moriyama","year":"2016","journal-title":"Nat Genet"},{"issue":"1","key":"pone.0231651.ref012","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00535-019-01638-x","article-title":"High-resolution melt analysis enables simple genotyping of complicated polymorphisms of codon 18 rendering the NUDT15 diplotype","volume":"55","author":"Y Kakuta","year":"2020","journal-title":"J Gastroenterol"},{"issue":"11","key":"pone.0231651.ref013","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1200\/JCO.2014.59.4671","article-title":"Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia","volume":"33","author":"JJ Yang","year":"2015","journal-title":"J Clin Oncol"},{"issue":"5","key":"pone.0231651.ref014","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1002\/cpt.1304","article-title":"Clinical Pharmacogenetics Implementation Consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 Update","volume":"105","author":"MV Relling","year":"2019","journal-title":"Clin Pharmacol Ther"},{"issue":"6","key":"pone.0231651.ref015","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1002\/cpt.1379","article-title":"NUDT15 Polymorphism in Native American Populations of Brazil","volume":"105","author":"G Suarez-Kurtz","year":"2019","journal-title":"Clin Pharmacol Ther"},{"issue":"10","key":"pone.0231651.ref016","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1182\/blood-2017-05-782383","article-title":"Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry","volume":"130","author":"T Moriyama","year":"2017","journal-title":"Blood"},{"issue":"3","key":"pone.0231651.ref017","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1200\/JCO.2013.48.6522","article-title":"Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002","volume":"32","author":"J Stary","year":"2014","journal-title":"J Clin Oncol"},{"issue":"2","key":"pone.0231651.ref018","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/humu.21159","article-title":"Assessing individual interethnic admixture and population substructure using a 48-insertion-deletion (INSEL) ancestry-informative marker (AIM) panel","volume":"31","author":"NP Santos","year":"2010","journal-title":"Hum Mutat"},{"issue":"3","key":"pone.0231651.ref019","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s10709-016-9894-1","article-title":"Neither self-reported ethnicity nor declared family origin are reliable indicators of genomic ancestry","volume":"144","author":"BR Ramos","year":"2016","journal-title":"Genetica"},{"key":"pone.0231651.ref020","volume-title":"Molecular cloning: a laboratory manual","author":"J Sambrook","year":"1989"},{"issue":"3","key":"pone.0231651.ref021","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1755-0998.2010.02847.x","article-title":"Arlequin suite ver 3.5: A new series of programs to perform population genetics analyses under Linux and Windows","volume":"10","author":"L. Excoffier","year":"2010","journal-title":"Mol Ecol Resour"},{"issue":"1","key":"pone.0231651.ref022","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2217\/pgs-2017-0147","article-title":"Predictive role of NUDT15 variants on thiopurine-induced myelotoxicity in Asian inflammatory bowel disease patients","volume":"19","author":"N Sutiman","year":"2018","journal-title":"Pharmacogenomics"},{"key":"pone.0231651.ref023","article-title":"Genotype-based treatment with thiopurine reduces incidence of myelosuppression in patients with inflammatory bowel diseases","author":"JY Chang","year":"2019","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"5","key":"pone.0231651.ref024","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1002\/cpt.1268","article-title":"Pharmacogene Variation Consortium Gene Introduction: NUDT15","volume":"105","author":"JJ Yang","year":"2019","journal-title":"Clin Pharmacol Ther"},{"issue":"7","key":"pone.0231651.ref025","doi-asserted-by":"crossref","first-page":"e293","DOI":"10.3324\/haematol.2018.187658","article-title":"Combination of common and novel rare NUDT15 variants improves predictive sensitivity of thiopurine-induced leukopenia in children with acute lymphoblastic leukemia","volume":"103","author":"Y Zhu","year":"2018","journal-title":"Haematologica"},{"issue":"3","key":"pone.0231651.ref026","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/ajpa.21505","article-title":"Autosome STRs in native South America-Testing models of association with geography and language","volume":"145","author":"SM Callegari-Jacques","year":"2011","journal-title":"Am J Phys Anthropol"},{"issue":"3","key":"pone.0231651.ref027","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/ajpa.1330790307","article-title":"Genetic variation within two linguistic Amerindian groups: relationship to geography and population size","volume":"79","author":"SM Callegari-Jacques","year":"1989","journal-title":"Am J Phys Anthropol"},{"issue":"3","key":"pone.0231651.ref028","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/ajhb.21110","article-title":"X-chromosomal genetic diversity and linkage disequilibrium patterns in Amerindians and non-Amerindian populations","volume":"23","author":"CE Amorim","year":"2011","journal-title":"Am J Hum Biol"},{"issue":"7","key":"pone.0231651.ref029","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/humu.23220","article-title":"Exomic variants of an elderly cohort of Brazilians in the ABraOM database","volume":"38","author":"MS Naslavsky","year":"2017","journal-title":"Hum Mutat"},{"issue":"1","key":"pone.0231651.ref030","doi-asserted-by":"crossref","first-page":"13900","DOI":"10.1038\/s41598-019-50362-2","article-title":"Distribution of local ancestry and evidence of adaptation in admixed populations","volume":"9","author":"R Secolin","year":"2019","journal-title":"Sci Rep"},{"issue":"12","key":"pone.0231651.ref031","doi-asserted-by":"crossref","first-page":"e1004023","DOI":"10.1371\/journal.pgen.1004023","article-title":"Reconstructing Native American migrations from whole-genome and whole-exome data","volume":"9","author":"S Gravel","year":"2013","journal-title":"PLoS Genet"},{"issue":"4","key":"pone.0231651.ref032","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.ajhg.2017.03.004","article-title":"Human demographic history impacts genetic risk prediction across diverse populations","volume":"100","author":"AR Martin","year":"2017","journal-title":"Am J Hum Genet"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0231651","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T13:28:02Z","timestamp":1586957282000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0231651"}},"subtitle":[],"editor":[{"given":"Francesc","family":"Calafell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0231651","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,15]]}}}