Characterization of DNA Polymerase Genes in Amazonian Amerindian Populations

Amanda Cohen-Paes; Angélica Leite de Alcântara; Elisa de Souza Menezes; Fabiano Cordeiro Moreira; Marianne Rodrigues Fernandes; João Farias Guerreiro; Ândrea Ribeiro-Dos-Santos; Sidney Emanuel Batista Dos Santos; Ney Pereira Carneiro Dos Santos

doi:10.3390/genes14010053

Characterization of DNA Polymerase Genes in Amazonian Amerindian Populations

Genes (Basel). 2022 Dec 24;14(1):53. doi: 10.3390/genes14010053.

Affiliations

¹ Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém 66073-000, PA, Brazil.
² Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, PA, Brazil.

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.

Keywords: Brazilian population; DNA polymerase genes; Indigenous; continental populations; genetic variants.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brazil / epidemiology
DNA-Binding Proteins
DNA-Directed DNA Polymerase* / genetics
Gene Frequency / genetics
Humans
Quality of Life*

Substances

DNA-Directed DNA Polymerase
REV3L protein, human
DNA-Binding Proteins

Grants and funding

We acknowledge funding from UFPA (Universidade Federal do Pará), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), and PROPESP—UFPA (Pró-Reitoria de Pesquisa e Pós-Graduação da Universidade Federal do Pará). Ney Santos is supported by CNPq/Produtividade (CNPQ 309999/2021-9). This work is part of the Rede de Pesquisa em Genômica Populacional Humana (Biocomputacional-Protocol No. 3381/2013/CAPES), FAPESPA (Amazon Foundation for the Support of Studies and Research) and Pro-rector of Research and Post-graduation (Propesp) of the Federal University of Pará.