Molecular Epidemiology in Amerindians of the Brazilian Amazon Reveals New Genetic Variants in DNA Repair Genes

Abstract

Native American populations from the Brazilian Amazon have a low genetic diversity and a different genetic profile when compared to people from other continents. Despite this, few studies have been conducted in this group, and there is no description of their genetic data in the various currently existent international databases. The characterization of the genomic profile of a population not only has an impact in studies of population genetics, but also helps to advance diagnostic and therapeutic response studies, leading to the optimization of clinical applicability. Genetic variations in DNA repair genes have been associated with the modulation of susceptibility to various pathologies, as well as in their prognosis and therapy. This is the first study to investigate DNA repair genes in Amerindians from the Brazilian Amazon region. We investigated 13 important DNA repair genes in the exome of 63 Native Americans, comparing our results with those found in 5 continental populations, whose data are available in the Genome Aggregation Database. Our results showed that 57 variants already described in literature were differentially distributed in the Amerindian populations in relation to the continental populations, 7 of which have significant clinical relevance. In addition, 9 new variants were described, suggesting that they are unique to these populations. Our study reinforces the understanding that the Amazonian Native American population presents a unique genetic profile, and our findings may collaborate with the creation of public policies that optimize the quality of life of these groups as well as the Brazilian population, which presents a high degree of interethnic mixing with Amerindian groups.

Effect of American genomic ancestry on severe toxicities in children with acute lymphoblastic leukemia in the Amazon region

“…Thus, the correlation of Amerindian ancestry with the severe toxicities observed may potentially result from specific gene variants within this ethnic group found in mixed populations. Other studies investigating the exomes of indigenous people have already demonstrated the existence of novel variants in other genes important for pharmacogenetics, which further supports our hypothesis [29][30][31].…”

Molecular Profile of Variants in CDH1, TP53, PSCA, PRKAA1, and TTN Genes Related to Gastric Cancer Susceptibility in Amazonian Indigenous Populations

“…Despite being a highly type of neoplastic study, only rare studies have been conducted in populations genetically heterogeneous or in original people, and an even smaller portion of the Brazilian indigenous population [ 8 ]. In this way, it is extremely valid to analyze the genetic profile of this original population of the Brazilian Amazon, in order to investigate genetic variants already elucidated in the world literature, as well as unknown or unscreened variants that may be associated with the development of Gastric Cancer.…”