Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil

Abstract

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

Identification of Variants (rs11571707, rs144848, and rs11571769) in the BRCA2 Gene Associated with Hereditary Breast Cancer in Indigenous Populations of the Brazilian Amazon

“…There is a lack of evidence in the literature about current information concerning breast cancer in the population of the Americas, probably due to an underreporting of cases in local communities [ 8 , 14 ]. Furthermore, the traditional populations of Latin America constitute a complex study group due to their human history of miscegenation, which confers them with high levels of interpopulation genetic diversity [ 10 ].…”

“…The sample of the American population of the 1000 Genomes Project includes several countries of Latin America, such as Mexico, Peru, Colombia, and Puerto Rico [ 11 ]. Although there is a degree of genetic similarity between AMR and IND populations, the genomic profiles of these countries indicate considerable heterogeneity in terms of Amerindian ancestry contribution, resulting from the different historical aspects of their formation and their degree of genetic admixture, which may explain the differences found in the BRCA1 and BRCA2 gene variants [ 10 , 47 , 48 , 49 ].…”

“…The genetic ancestry was obtained through a panel of 64 informative ancestry markers (IAM), as described by Ramos et al 2016 [ 9 ]. Additional information about this population can be found in [ 10 ].…”

“…The bioinformatic analysis was performed as previously described in Rodrigues and colleagues [ 10 ].…”

Association between the TPMT*3C (rs1142345) Polymorphism and the Risk of Death in the Treatment of Acute Lymphoblastic Leukemia in Children from the Brazilian Amazon Region

“…A number of studies have concluded that the differential mortality rates in Hispanics with ALL are related to a genetic predisposition linked to the Native American ancestry of these populations [ 10 , 11 , 12 , 13 , 14 ]. In fact, many of the genetic variants associated with the toxicity and relapses in the treatment of ALL have been found more frequently in Native American populations or in populations with a high degree of miscegenation involving this ethnic group [ 15 , 16 , 17 , 18 ].…”