Characterization of DNA Polymerase Genes in Amazonian Amerindian Populations

Abstract

Due to their continuing geographic isolation, the Amerindian populations of the Brazilian Amazon present a different genetic profile when compared to other continental populations. Few studies have investigated genetic variants present in these populations, especially in the context of next-generation sequencing. Knowledge of the molecular profile of a population is one of the bases for inferences about human evolutionary history, in addition, it has the ability to assist in the validation of molecular biomarkers of susceptibility to complex and rare diseases, and in the improvement of specific precision medicine protocols applied to these populations and to populations with high Amerindian ancestry, such as Brazilians. DNA polymerases play essential roles in DNA replication, repair, recombination, or damage repair, and their influence on various clinical phenotypes has been demonstrated in the specialized literature. Thus, the aim of this study is to characterize the molecular profile of POLA1, POLE, POLG, POLQ, and REV3L genes in Amerindian populations from the Brazilian Amazon, comparing these findings with genomic data from five continental populations described in the gnomAD database, and with data from the Brazilian population described in ABraOM. We performed the whole exome sequencing (WES) of 63 Indigenous individuals. Our study described for the first time the allele frequency of 45 variants already described in the other continental populations, but never before described in the investigated Amerindian populations. Our results also describe eight unique variants of the investigated Amerindians populations, with predictions of moderate, modifier and high clinical impact. Our findings demonstrate the unique genetic profile of the Indigenous population of the Brazilian Amazon, reinforcing the need for further studies on these populations, and may contribute to the creation of public policies that optimize not only the quality of life of this population, but also of the Brazilian population.

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

“…Numerous studies have illustrated that Native American populations exhibit a distinct pattern of variability within the immune system. With regard to our finding of a correlation between Amerindian ancestry and severe infectious toxicity, we can explain it by the fact that Amazonian Amerindians have, throughout their generations, intermarried and have undergone drastic population reductions, which has a direct impact on the diversity of the immune response [ 26 – 28 ].…”

Molecular Profile of Important Genes for Radiogenomics in the Amazon Indigenous Population

“…However, the physical and geographic isolation of these peoples contributes to a gap in epidemiologic and genetic information. Therefore, knowledge of their molecular profile may be of importance to indigenous populations, as well as those intermixed with them [63].…”