The Genomic Ancestry of Individuals from Different Geographical Regions of Brazil Is More Uniform Than Expected

Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a “total ancestry” estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries - a phenomenon described and intended as the “whitening of Brazil” - is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations

<it>IL1B</it>, <it>IL4R</it>, <it>IL12RB1</it> and <it>TNF</it> gene polymorphisms are associated with <it>Plasmodium vivax</it> malaria in Brazil

Abstract Background Malaria is among the most prevalent parasitic diseases worldwide. In Brazil, malaria is concentrated in the northern region, where Plasmodium vivax accounts for 85% disease incidence. The role of genetic factors in host immune system conferring resistance/susceptibility against P. vivax infections is still poorly understood. Methods The present study investigates the influence of polymorphisms in 18 genes related to the immune system in patients with malaria caused by P. vivax. A total of 263 healthy individuals (control group) and 216 individuals infected by P. vivax (malaria group) were genotyped for 33 single nucleotide polymorphisms (SNPs) in IL1B, IL2, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, IL12RB1, SP110, TNF, TNFRSF1A, IFNG, IFNGR1, VDR, PTPN22 and P2X7 genes. All subjects were genotyped with 48 ancestry informative insertion-deletion polymorphisms to determine the proportion of African, European and Amerindian ancestry. Only 13 SNPs in 10 genes with differences lower than 20% between cases and controls in a Poisson Regression model with age as covariate were further investigated with a structured population association test. Results The IL1B gene -5839C > T and IL4R 1902A > G polymorphisms and IL12RB1 -1094A/-641C and TNF -1031 T/-863A/-857 T/-308 G/-238 G haplotypes were associated with malaria susceptibility after population structure correction (p = 0.04, p = 0.02, p = 0.01 and p = 0.01, respectively). Conclusion Plasmodium vivax malaria pathophysiology is still poorly understood. The present findings reinforce and increase our understanding about the role of the immune system in malaria susceptibility.</p

Influence of Genomic Ancestry on the Distribution of SLCO1B1, SLCO1B3 and ABCB1 Gene Polymorphisms among Brazilians

The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and SLCO1B3 genes varies largely among continental populations. This variation can lead to biases in pharmacogenetic studies conducted in admixed populations such as those from Brazil and other Latin American countries. The aim of this study was to evaluate the influence of self-reported colour, geographical origin and genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy adults from the north, north-east, south-east and south of Brazil were recruited for this investigation. The c.388A&gt;G (rs2306283), c.463C&gt;A (rs11045819) and c.521T&gt;C (rs4149056) SNPs in the SLCO1B1 gene and c.334T&gt;G (rs4149117) and c.699G&gt;A (rs7311358) SNPs in the SLCO1B3 gene were determined by Taqman 5'-nuclease assays. The ABCB1 c.1236C&gt;T (rs1128503), c.2677G&gt;T/A (rs2032582) and c.3435C&gt;T (rs1045642) polymorphisms were genotyped using a previously described single-base extension/termination method. The results showed that genotype and haplotype distributions are highly variable among populations of the same self-reported colour and geographical region. However, genomic ancestry showed that these associations are better explained by a continuous variable. The influence of ancestry on the distribution of alleles and haplotype frequencies was more evident in variants with large differences in allele frequencies between European and African populations. Design and interpretation of pharmacogenetic studies using these transporter genes should include genomic controls to avoid spurious conclusions based on improper matching of study cohorts from Brazilian populations and other highly admixed populations.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilFinanciadora de Estudos e Projetos (FINEP, Brazil)Financiadora de Estudos e Projetos (FINEP), Brazi

Distribution of <i>CYP2D6</i> Alleles and Phenotypes in the Brazilian Population

<div><p>Abstract</p><p>The CYP2D6 enzyme is one of the most important members of the cytochrome P450 superfamily. This enzyme metabolizes approximately 25% of currently prescribed medications. The <i>CYP2D6</i> gene presents a high allele heterogeneity that determines great inter-individual variation. The aim of this study was to evaluate the variability of <i>CYP2D6</i> alleles, genotypes and predicted phenotypes in Brazilians. Eleven single nucleotide polymorphisms and <i>CYP2D6</i> duplications/multiplications were genotyped by TaqMan assays in 1020 individuals from North, Northeast, South, and Southeast Brazil. Eighteen <i>CYP2D6</i> alleles were identified in the Brazilian population. The <i>CYP2D6*1</i> and <i>CYP2D6*2</i> alleles were the most frequent and widely distributed in different geographical regions of Brazil. The highest number of <i>CYPD6</i> alleles observed was six and the frequency of individuals with more than two copies ranged from 6.3% (in Southern Brazil) to 10.2% (Northern Brazil). The analysis of molecular variance showed that <i>CYP2D6</i> is homogeneously distributed across different Brazilian regions and most of the differences can be attributed to inter-individual differences. The most frequent predicted metabolic status was EM (83.5%). Overall 2.5% and 3.7% of Brazilians were PMs and UMs respectively. Genomic ancestry proportions differ only in the prevalence of intermediate metabolizers. The IM predicted phenotype is associated with a higher proportion of African ancestry and a lower proportion of European ancestry in Brazilians. PM and UM classes did not vary among regions and/or ancestry proportions therefore unique <i>CYP2D6</i> testing guidelines for Brazilians are possible and could potentially avoid ineffective or adverse events outcomes due to drug prescriptions.</p></div

Insights into the evolutionary history of the most skilled tool-handling platyrrhini monkey: Sapajus libidinosus from the Serra da Capivara National Park

Abstract Sapajus libidinosus members of the Pedra Furada group, living in the Serra da Capivara National Park, use stone tools in a wider variety of behaviors than any other living animal, except humans. To rescue the evolutionary history of the Caatinga S. libidinosus and identify factors that may have contributed to the emergence and maintenance of their tool-use culture, we conducted fieldwork seasons to obtain biological samples of these capuchin monkeys. UsingCYTBsequences, we show a discrete but constant population growth from the beginning of the Holocene to the present, overlapping the emergence of the Caatinga biome. Our habitat suitability reconstruction reports the presence of plants whose hard fruits, seeds, or roots are processed by capuchins using tools. TheS. libidinosusindividuals in the Caatingawere capable of dynamically developing and maintaining their autochthonous culture thanks to: a) cognitive capacity to generate and execute innovation under selective pressure; b) tolerance favoring learning and cultural inheritance; c) an unknown genetic repertoire that underpins the adaptive traits; d) a high degree of terrestriality; e) presence and abundance of natural resources, which makes some places “hot spots” for innovation, and cultural diversification within a relatively short time

Pairwise F_ST (95% Confidence Interval) among Brazilian regions and grouped according to color.

<p>Pairwise F_ST (95% Confidence Interval) among Brazilian regions and grouped according to color.</p

Genetic ancestry (mean ± standard deviation) proportions according to CYP2D6 phenotypes.

a<p>P-value for the Kruskal-Wallis One-Way ANOVA.</p>b<p>Significantly higher mean in the pairwise comparisons. FDR adjusted p-values for the IM×PM, IM×EM, and IM×UM comparisons are, respectively: 0.0014, 0.011, and 0.048.</p>c<p>Significantly higher mean in the pairwise comparisons with EM and UM phenotypes. FDR adjusted p-values for the IM×EM, and IM×UM comparisons are, respectively: 0.018, 0.027.</p><p>Genetic ancestry (mean ± standard deviation) proportions according to CYP2D6 phenotypes.</p

CYP2D6 predicted phenotype frequencies according to self-reported color and geographical region.

a<p>Not Determined.</p><p>The Multinomial Log-Linear analysis: self-reported skin color is not associated with the predicted phenotype (p = 0.089); region is not associated with the predicted phenotype (p = 0.467).</p><p>CYP2D6 predicted phenotype frequencies according to self-reported color and geographical region.</p

Copy number variation of the <i>CYP2D6</i> in the Brazilian population.

<p>Copy number variation of the <i>CYP2D6</i> in the Brazilian population.</p