Eduardo Tarazona-Santos

Federal University of Minas Gerais, Cidade de Minas, Minas Gerais, Brazil

Are you Eduardo Tarazona-Santos?

Claim your profile

Publications (42)174.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.
    Proceedings of the National Academy of Sciences 06/2015; 112(28). DOI:10.1073/pnas.1504447112 · 9.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MESTIFAR 2014 28-30 November 2014, Panama City, Panama The CEIBA consortium was created within the Ibero-American network of Pharmacogenetics (RIBEF) to study population pharmacogenetics. The current status of these initiatives and results of the MESTIFAR project were analyzed in Panama, 28-30 November 2014. The MESTIFAR project focused on studying CYPs genetic polymorphisms in populations of different ethnic origin. So far, more than 6000 healthy volunteers have been evaluated, making this one of the largest population pharmacogenomic studies worldwide. Three symposia were organized, 'Pharmacogenetics of indigenous and mestizos populations and its clinical implications', 'Methodological innovation in pharmacogenetics and its application in health', and 'General discussion and concluding remarks', about mechanisms and proposals for training, diffusion of pharmacogenetics for Spanish- and Portuguese-speaking health professionals, and 'bench to bedside' pilot projects.
    Pharmacogenomics 05/2015; DOI:10.2217/pgs.15.32 · 3.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: The frequency of CYP2D6 alleles, related to either a lack of or increased enzymatic activity, which may lead to poor metabolism (PM) or ultrarapid metabolism (UM), can vary across ethnic groups and hence across geographic regions. Areas covered: Worldwide original research papers on CYP2D6 allelic frequencies, metabolic phenotype frequencies measured with a probe drug, and/or genotype frequencies that studied > 50 healthy volunteers, were included in analyses to describe the distributions of alleles, phenotypes predicted from genotypes (predicted poor metabolizers [gPMs], predicted ultrarapid metabolizers [gUMs]) and metabolic phenotypes (mPMs, mUMs) across ethnic groups and geographic regions. The analysis included 44,572 individuals studied in 172 original research papers. Expert opinion: As of today, Africa and Asia are under-represented in this area relative to the total number of their inhabitants, so that further studies in these regions are warranted. The CYP2D6*4 allele frequency was higher in Caucasians, CYP2D6*10 in East Asians, CYP2D6*41 and duplication/multiplication of active alleles in Middle Easterns, CYP2D6*17 in Black Africans and CYP2D6*29 in African Americans, than in other ethnic groups. Overall, gPMs and mPMs are more frequent among Caucasians, and gUMs among Middle Easterns and Ethiopians. However, mUMs could not be evaluated because only two studies were found presenting this information. Further studies including mUMs are thus warranted. There is a correspondence between gPMs and mPMs, but the few studies of mUMs meant that their relationship with gUMs could not be demonstrated. Finally, evolutionary aspects of the CYP2D6 allele distribution appear to support the Great Human Expansion model.
    Expert Opinion on Drug Metabolism &amp Toxicology 11/2014; 10(11):1569-83. DOI:10.1517/17425255.2014.964204 · 2.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Archaeology reports millenary cultural contacts between Peruvian Coast-Andes and the Amazon Yunga, a rainforest transitional region between Andes and Lower Amazonia. To clarify the relationships between cultural and biological evolution of these populations, in particular between Amazon Yungas and Andeans, we used DNA-sequence data, a model-based Bayesian approach and several statistical validations to infer a set of demographic parameters.ResultsWe found that the genetic diversity of the Shimaa (an Amazon Yunga population) is a subset of that of Quechuas from Central-Andes. Using the Isolation-with-Migration population genetics model, we inferred that the Shimaa ancestors were a small subgroup that split less than 5300 years ago (after the development of complex societies) from an ancestral Andean population. After the split, the most plausible scenario compatible with our results is that the ancestors of Shimaas moved toward the Peruvian Amazon Yunga and incorporated the culture and language of some of their neighbors, but not a substantial amount of their genes. We validated our results using Approximate Bayesian Computations, posterior predictive tests and the analysis of pseudo-observed datasets.Conclusions We presented a case study in which model-based Bayesian approaches, combined with necessary statistical validations, shed light into the prehistoric demographic relationship between Andeans and a population from the Amazon Yunga. Our results offer a testable model for the peopling of this large transitional environmental region between the Andes and the Lower Amazonia. However, studies on larger samples and involving more populations of these regions are necessary to confirm if the predominant Andean biological origin of the Shimaas is the rule, and not the exception.
    BMC Evolutionary Biology 09/2014; 14(1):174. DOI:10.1186/s12862-014-0174-3 · 3.41 Impact Factor
  • L C Schmidt · A C V Cabral · M A Faria · F Monken · E Tarazona-Santos · M L Martins
    [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated the efficacy of noninvasive fetal Rhesus D (RHD) genotyping from maternal plasma in a highly admixed population. Fifty-five blood samples from RhD-negative pregnant women from Brazil were processed for extraction of cell-free plasma DNA. Real-time PCR was performed to amplify segments of exons 5 and 7 from the RHD gene, as well as for detection of the SRY gene to confirm the presence of fetal DNA. Fetal genotyping results were compared with the RhD phenotype determined from newborn cord blood samples obtained at birth. Thirty-two samples were RHD-positive, 18 were RHD-negative and 5 were inconclusive due to amplification of only one RHD exon. In 43 samples, the fetal RHD genotype was compared to the neonatal RhD phenotype, and only one result was discordant, due to false-negative serology. There was one false SRY genotyping negative result. We conclude that noninvasive fetal RHD genotyping from maternal blood provides accurate results and suggests its viability as a clinical tool for the management of RhD-negative pregnant women in an admixed population.
    Genetics and molecular research: GMR 01/2014; 13(1):799-805. DOI:10.4238/2014.February.7.1 · 0.85 Impact Factor
  • Forensic Science International: Genetics 08/2013; 9. DOI:10.1016/j.fsigen.2013.08.002 · 3.20 Impact Factor
  • Source
    Clinical Therapeutics 08/2013; 35(8):e65. DOI:10.1016/j.clinthera.2013.07.191 · 2.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox and p67-phox (encoded by NCF4, NCF1 and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. Based on a resequencing analysis of ∼35 kb of CYBB, CYBA, NCF2 and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, non-phagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.
    Molecular Biology and Evolution 07/2013; DOI:10.1093/molbev/mst119 · 14.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The relationship between the "individualism-collectivism" and the serotonin trans-porter functional polymorphism (5-HTTLPR), suggested in the previous reports, was tested in Native South Amerindian populations. A total of 170 individuals from 21 populations were genotyped for the 5-HTTLPR alleles. For comparative purposes, these populations were classified as individualistic (recent history of hunter–gathering) or collectivistic (agriculturalists). These two groups showed an almost identical S allele frequency (75 and 76%, respectively). The analysis of molecular variance showed no structural differences between them. Behavioral typologies like those sug-gested by JY Chiao and KD Blizinsky (Proc R Soc B 277 (2010) 529–537) are always a simplification of complex phenomena and should be regarded with caution. In addition, classification of a whole nation in the individu-alist/collectivist dichotomy is controversial. The focus on modes of subsistence in preindustrial societies, as was tested here, may be a good alternative although the postulated association between the 5-HTTLPR S allele and the collectivist societies was not confirmed. Am J Phys Anthropol 000:000–000, 2013. V C 2013 Wiley Periodicals, Inc.
    American Journal of Physical Anthropology 07/2013; DOI:10.1002/ajpa.22286 · 2.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Interindividual differences in response to drug treatments are mainly caused by differences in drug metabolism, in which cytochrome P450 (CYP450) enzymes are involved. Genetic polymorphisms of these enzymes have a key role in this variability. However, environmental factors, endogenous metabolism and disease states also have a great influence on the actual drug metabolism rate (metabolic phenotype). Consequently, the genotype does not always correlate with the actual drug hydroxylation phenotype. In this sense, in vivo phenotyping strategies represent an alternative to evaluate the interindividual variability in drug metabolism. Therefore, the 'cocktail' approach is considered as an advantageous strategy to obtain actual and reliable information on several CYP activities in just one experiment. As reviewed, phenotyping studies on Latin-American populations, which comprise about 400 million people, are scarce, and only selective phenotyping methods were applied. Therefore, a novel cocktail approach is here proposed as a phenotyping tool to evaluate the relationship between genotype and phenotype of major CYP enzymes in Hispanic populations. This determination will allow adaptation of drug therapies to these populations and consequently to benefit from the application of pharmacogenetics in the reduction of drug adverse effects and in the improvement of therapeutic responses.
    Drug metabolism and drug interactions 06/2013; 28(3):1-12. DOI:10.1515/dmdi-2013-0020
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group.
    PLoS ONE 08/2012; 7(8):e41200. DOI:10.1371/journal.pone.0041200 · 3.23 Impact Factor
  • Source
    Maira R Rodrigues · Wagner Cs Magalhaes · Moara Machado · Eduardo Tarazona-Santos
    [Show abstract] [Hide abstract]
    ABSTRACT: BackgroundIn bioinformatics, it is important to build extensible and low-maintenance systems that are able to deal with the new tools and data formats that are constantly being developed. The traditional and simplest implementation of pipelines involves hardcoding the execution steps into programs or scripts. This approach can lead to problems when a pipeline is expanding because the incorporation of new tools is often error prone and time consuming. Current approaches to pipeline development such as workflow management systems focus on analysis tasks that are systematically repeated without significant changes in their course of execution, such as genome annotation. However, more dynamism on the pipeline composition is necessary when each execution requires a different combination of steps.ResultsWe propose a graph-based approach to implement extensible and low-maintenance pipelines that is suitable for pipeline applications with multiple functionalities that require different combinations of steps in each execution. Here pipelines are composed automatically by compiling a specialised set of tools on demand, depending on the functionality required, instead of specifying every sequence of tools in advance. We represent the connectivity of pipeline components with a directed graph in which components are the graph edges, their inputs and outputs are the graph nodes, and the paths through the graph are pipelines. To that end, we developed special data structures and a pipeline system algorithm. We demonstrate the applicability of our approach by implementing a format conversion pipeline for the fields of population genetics and genetic epidemiology, but our approach is also helpful in other fields where the use of multiple software is necessary to perform comprehensive analyses, such as gene expression and proteomics analyses. The project code, documentation and the Java executables are available under an open source license at http://code.google.com/p/dynamic-pipeline. The system has been tested on Linux and Windows platforms.ConclusionsOur graph-based approach enables the automatic creation of pipelines by compiling a specialised set of tools on demand, depending on the functionality required. It also allows the implementation of extensible and low-maintenance pipelines and contributes towards consolidating openness and collaboration in bioinformatics systems. It is targeted at pipeline developers and is suited for implementing applications with sequential execution steps and combined functionalities. In the format conversion application, the automatic combination of conversion tools increased both the number of possible conversions available to the user and the extensibility of the system to allow for future updates with new file formats.
    BMC Bioinformatics 07/2012; 13(1):163. DOI:10.1186/1471-2105-13-163 · 2.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Large-scale genomics initiatives such as the HapMap project and the 1000-genomes rely on powerful bioinformatics support to assist data production and analysis. Contrastingly, few bioinformatics platforms oriented to smaller research groups exist to store, handle, share, and integrate data from different sources, as well as to assist these scientists to perform their analyses efficiently. We developed such a bioinformatics platform, DIVERGENOME, to assist population genetics and genetic epidemiology studies performed by small- to medium-sized research groups. The platform is composed of two integrated components, a relational database (DIVERGENOMEdb), and a set of tools to convert data formats as required by popular software in population genetics and genetic epidemiology (DIVERGENOMEtools). In DIVERGENOMEdb, information on genotypes, polymorphism, laboratory protocols, individuals, populations, and phenotypes is organized in projects. These can be queried according to permissions. Here, we validated DIVERGENOME through a use case regarding the analysis of SLC2A4 genetic diversity in human populations. DIVERGENOME, with its intuitive Web interface and automatic data loading capability, facilitates its use by individuals without bioinformatics background, allowing complex queries to be easily interrogated and straightforward data format conversions (not available in similar platforms). DIVERGENOME is open source, freely available, and can be accessed online (pggenetica.icb.ufmg.br/divergenome) or hosted locally.
    Genetic Epidemiology 05/2012; 36(4):360-7. DOI:10.1002/gepi.21629 · 2.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Elucidating the pattern of genetic diversity for non-European populations is necessary to make the benefits of human genetics research available to individuals from these groups. In the era of large human genomic initiatives, Native American populations have been neglected, in particular, the Quechua, the largest South Amerindian group settled along the Andes. We characterized the genetic diversity of a Quechua population in a global setting, using autosomal noncoding sequences (nine unlinked loci for a total of 16 kb), 351 unlinked SNPs and 678 microsatellites and tested predictions of the model of the evolution of Native Americans proposed by (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485-1496). European admixture is <5% and African ancestry is barely detectable in the studied population. The largest genetic distances were between African versus Quechua or Melanesian populations, which is concordant with the African origin of modern humans and the fact that South America was the last part of the world to be peopled. The diversity in the Quechua population is comparable with that of Eurasian populations, and the allele frequency spectrum based on resequencing data does not reflect a reduction in the proportion of rare alleles. Thus, the Quechua population is a large reservoir of common and rare genetic variants of South Amerindians. These results are consistent with and complement our evolutionary model of South Amerindians (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 1485-1496), proposed based on Y-chromosome data, which predicts high genomic diversity due to the high level of gene flow between Andean populations and their long-term effective population size.
    American Journal of Physical Anthropology 03/2012; 147(3):443-51. DOI:10.1002/ajpa.22013 · 2.51 Impact Factor
  • Source
    Blood 10/2011; 118(16):4493-5; author reply 4495. DOI:10.1182/blood-2011-06-361915 · 10.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Information on one Ecuadorian and three Peruvian Amerindian populations for 11 autosomal short tandem repeat (STR) loci is presented and incorporated in analyses that includes 26 other Native groups spread all over South America. Although in comparison with other studies we used a reduced number of markers, the number of populations included in our analyses is currently unmatched by any genome-wide dataset. The genetic polymorphisms indicate a clear division of the populations into three broad geographical areas: Andes, Amazonia, and the Southeast, which includes the Chaco and southern Brazil. The data also show good agreement with proposed hypotheses of splitting and dispersion of major language groups over the last 3,000 years. Therefore, relevant aspects of Native American history can be traced using as few as 11 STR autosomal markers coupled with a broad geographic distribution of sampled populations.
    American Journal of Physical Anthropology 07/2011; 145(3):371-81. DOI:10.1002/ajpa.21505 · 2.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region.
    Human Mutation 07/2011; 32(7):743-50. DOI:10.1002/humu.21491 · 5.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Targeted re-sequencing is one of the most powerful and widely used strategies for population genetics studies because it allows an unbiased screening for variation that is suitable for a wide variety of organisms. Examples of studies that require re-sequencing data are evolutionary inferences, epidemiological studies designed to capture rare polymorphisms responsible for complex traits and screenings for mutations in families and small populations with high incidences of specific genetic diseases. Despite the advent of next-generation sequencing technologies, Sanger sequencing is still the most popular approach in population genetics studies because of the widespread availability of automatic sequencers based on capillary electrophoresis and because it is still less prone to sequencing errors, which is critical in population genetics studies. Two popular software applications for re-sequencing studies are Phred-Phrap-Consed-Polyphred, which performs base calling, alignment, graphical edition and genotype calling and DNAsp, which performs a set of population genetics analyses. These independent tools are the start and end points of basic analyses. In between the use of these tools, there is a set of basic but error-prone tasks to be performed with re-sequencing data. In order to assist with these intermediate tasks, we developed a pipeline that facilitates data handling typical of re-sequencing studies. Our pipeline: (1) consolidates different outputs produced by distinct Phred-Phrap-Consed contigs sharing a reference sequence; (2) checks for genotyping inconsistencies; (3) reformats genotyping data produced by Polyphred into a matrix of genotypes with individuals as rows and segregating sites as columns; (4) prepares input files for haplotype inferences using the popular software PHASE; and (5) handles PHASE output files that contain only polymorphic sites to reconstruct the inferred haplotypes including polymorphic and monomorphic sites as required by population genetics software for re-sequencing data such as DNAsp. We tested the pipeline in re-sequencing studies of haploid and diploid data in humans, plants, animals and microorganisms and observed that it allowed a substantial decrease in the time required for sequencing analyses, as well as being a more controlled process that eliminates several classes of error that may occur when handling datasets. The pipeline is also useful for investigators using other tools for sequencing and population genetics analyses.
    02/2011; 2(1):3. DOI:10.1186/2041-2223-2-3
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil. Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection. GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity. Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population.
    PLoS ONE 01/2011; 6(1):e16123. DOI:10.1371/journal.pone.0016123 · 3.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Plasmodium vivax malaria is a major public health challenge in Latin America, Asia and Oceania, with 130-435 million clinical cases per year worldwide. Invasion of host blood cells by P. vivax mainly depends on a type I membrane protein called Duffy binding protein (PvDBP). The erythrocyte-binding motif of PvDBP is a 170 amino-acid stretch located in its cysteine-rich region II (PvDBPII), which is the most variable segment of the protein. To test whether diversifying natural selection has shaped the nucleotide diversity of PvDBPII in Brazilian populations, this region was sequenced in 122 isolates from six different geographic areas. A Bayesian method was applied to test for the action of natural selection under a population genetic model that incorporates recombination. The analysis was integrated with a structural model of PvDBPII, and T- and B-cell epitopes were localized on the 3-D structure. The results suggest that: (i) recombination plays an important role in determining the haplotype structure of PvDBPII, and (ii) PvDBPII appears to contain neutrally evolving codons as well as codons evolving under natural selection. Diversifying selection preferentially acts on sites identified as epitopes, particularly on amino acid residues 417, 419, and 424, which show strong linkage disequilibrium. This study shows that some polymorphisms of PvDBPII are present near the erythrocyte-binding domain and might serve to elude antibodies that inhibit cell invasion. Therefore, these polymorphisms should be taken into account when designing vaccines aimed at eliciting antibodies to inhibit erythrocyte invasion.
    Malaria Journal 11/2010; 9(1):334. DOI:10.1186/1475-2875-9-334 · 3.49 Impact Factor

Publication Stats

620 Citations
174.41 Total Impact Points

Institutions

  • 2006–2014
    • Federal University of Minas Gerais
      • • Departamento de Biologia Geral
      • • Departamento de Bioquímica e Imunologia
      Cidade de Minas, Minas Gerais, Brazil
  • 2006–2013
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 2005
    • University of Maryland, College Park
      • Department of Biology
      CGS, Maryland, United States
  • 1998–2003
    • University of Bologna
      • • Department of Pharmacy and Biotechnology FaBiT
      • • Department of Experimental Evolutionary Biology BES
      Bolonia, Emilia-Romagna, Italy