Publications (28)53.98 Total impact
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Dataset: ijms-12-05815-s001
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Dataset: Genotypic data (STRUCTURE format) for the 46 AIM-INDELs in HGDP-CEPH diversity panel population samples from Africa, Europe, East Asia and Native America.
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Article: An overview of STRUCTURE: applications, parameter settings, and supporting software.
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ABSTRACT: Objectives: We present an up-to-date review of STRUCTURE software: one of the most widely used population analysis tools that allows researchers to assess patterns of genetic structure in a set of samples. STRUCTURE can identify subsets of the whole sample by detecting allele frequency differences within the data and can assign individuals to those sub-populations based on analysis of likelihoods. The review covers STRUCTURE's most commonly used ancestry and frequency models, plus an overview of the main applications of the software in human genetics including case-control association studies (CCAS), population genetics, and forensic analysis. The review is accompanied by supplementary material providing a step-by-step guide to running STRUCTURE. Methods: With reference to a worked example, we explore the effects of changing the principal analysis parameters on STRUCTURE results when analyzing a uniform set of human genetic data. Use of the supporting software: CLUMPP and distruct is detailed and we provide an overview and worked example of STRAT software, applicable to CCAS. Conclusion: The guide offers a simplified view of how STRUCTURE, CLUMPP, distruct, and STRAT can be applied to provide researchers with an informed choice of parameter settings and supporting software when analyzing their own genetic data.Frontiers in genetics. 01/2013; 4:98. -
Article: SNPs as Supplements in Simple Kinship Analysis or as Core Markers in Distant Pairwise Relationship Tests: When Do SNPs Add Value or Replace Well-Established and Powerful STR Tests?
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ABSTRACT: BACKGROUND: Genetic tests for kinship testing routinely reach likelihoods that provide virtual proof of the claimed relationship by typing microsatellites-commonly consisting of 12-15 standard forensic short tandem repeats (STRs). Single nucleotide polymorphisms (SNPs) have also been applied to kinship testing but these binary markers are required in greater numbers than multiple-allele STRs. However SNPs offer certain advantageous characteristics not found in STRs, including, much higher mutational stability, good performance typing highly degraded DNA, and the ability to be readily up-scaled to very high marker numbers reaching over a million loci. This article outlines kinship testing applications where SNPs markedly improve the genetic data obtained. In particular we explore the minimum number of SNPs that will be required to confirm pairwise relationship claims in deficient pedigrees that typify missing persons' identification or war grave investigations where commonly few surviving relatives are available for comparison and the DNA is highly degraded. METHODS: We describe the application of SNPs alongside STRs when incomplete profiles or allelic instability in STRs create ambiguous results, we review the use of high density SNP arrays when the relationship claim is very distant, and we outline simulations of kinship analyses with STRs supplemented with SNPs in order to estimate the practical limit of pairwise relationships that can be differentiated from random unrelated pairs from the same population. RESULTS: The minimum number of SNPs for robust statistical inference of parent-offspring relationships through to those of second cousins (S-3-3) is estimated for both simple, single multiplex SNP sets and for subsets of million-SNP arrays. CONCLUSIONS: There is considerable scope for resolving ambiguous STR results and for improving the statistical power of kinship analysis by adding small-scale SNP sets but where the pedigree is deficient the pairwise relationships must be relatively close. For more distant relationships it is possible to reduce chip-based SNP arrays from the million+ markers down to ∼7,000. However, such numbers indicate that current genotyping approaches will not be able to deliver sufficient data to resolve distant pairwise relationships from the limited DNA typical of the most challenging identification cases.Transfusion Medicine and Hemotherapy 06/2012; 39(3):202-210. · 1.16 Impact Factor -
Article: Differentiation of African components of ancestry to stratify groups in a case-control study of a Brazilian urban population.
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ABSTRACT: Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA <0.25 and >0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA <0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.Genetic Testing and Molecular Biomarkers 01/2012; 16(6):524-30. · 1.11 Impact Factor -
Article: Straightforward inference of ancestry and admixture proportions through ancestry-informative insertion deletion multiplexing.
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ABSTRACT: Ancestry-informative markers (AIMs) show high allele frequency divergence between different ancestral or geographically distant populations. These genetic markers are especially useful in inferring the likely ancestral origin of an individual or estimating the apportionment of ancestry components in admixed individuals or populations. The study of AIMs is of great interest in clinical genetics research, particularly to detect and correct for population substructure effects in case-control association studies, but also in population and forensic genetics studies. This work presents a set of 46 ancestry-informative insertion deletion polymorphisms selected to efficiently measure population admixture proportions of four different origins (African, European, East Asian and Native American). All markers are analyzed in short fragments (under 230 basepairs) through a single PCR followed by capillary electrophoresis (CE) allowing a very simple one tube PCR-to-CE approach. HGDP-CEPH diversity panel samples from the four groups, together with Oceanians, were genotyped to evaluate the efficiency of the assay in clustering populations from different continental origins and to establish reference databases. In addition, other populations from diverse geographic origins were tested using the HGDP-CEPH samples as reference data. The results revealed that the AIM-INDEL set developed is highly efficient at inferring the ancestry of individuals and provides good estimates of ancestry proportions at the population level. In conclusion, we have optimized the multiplexed genotyping of 46 AIM-INDELs in a simple and informative assay, enabling a more straightforward alternative to the commonly available AIM-SNP typing methods dependent on complex, multi-step protocols or implementation of large-scale genotyping technologies.PLoS ONE 01/2012; 7(1):e29684. · 4.09 Impact Factor -
Article: ENGINES: exploring single nucleotide variation in entire human genomes.
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ABSTRACT: Next generation ultra-sequencing technologies are starting to produce extensive quantities of data from entire human genome or exome sequences, and therefore new software is needed to present and analyse this vast amount of information. The 1000 Genomes project has recently released raw data for 629 complete genomes representing several human populations through their Phase I interim analysis and, although there are certain public tools available that allow exploration of these genomes, to date there is no tool that permits comprehensive population analysis of the variation catalogued by such data. We have developed a genetic variant site explorer able to retrieve data for Single Nucleotide Variation (SNVs), population by population, from entire genomes without compromising future scalability and agility. ENGINES (ENtire Genome INterface for Exploring SNVs) uses data from the 1000 Genomes Phase I to demonstrate its capacity to handle large amounts of genetic variation (>7.3 billion genotypes and 28 million SNVs), as well as deriving summary statistics of interest for medical and population genetics applications. The whole dataset is pre-processed and summarized into a data mart accessible through a web interface. The query system allows the combination and comparison of each available population sample, while searching by rs-number list, chromosome region, or genes of interest. Frequency and FST filters are available to further refine queries, while results can be visually compared with other large-scale Single Nucleotide Polymorphism (SNP) repositories such as HapMap or Perlegen. ENGINES is capable of accessing large-scale variation data repositories in a fast and comprehensive manner. It allows quick browsing of whole genome variation, while providing statistical information for each variant site such as allele frequency, heterozygosity or FST values for genetic differentiation. Access to the data mart generating scripts and to the web interface is granted from http://spsmart.cesga.es/engines.php.BMC Bioinformatics 01/2011; 12:105. · 2.75 Impact Factor -
Article: Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response.
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ABSTRACT: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot(®) and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (-71T>C) gene polymorphisms were identified by TaqMan(®) Real-time PCR. Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3-8.0, p < 0.05). SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.International Journal of Molecular Sciences 01/2011; 12(9):5815-27. · 2.60 Impact Factor -
Article: Forensic performance of insertion–deletion marker systems
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ABSTRACT: The ability to improve amplification and analysis of degraded DNA extracts has been a long-standing area of research in forensic genetics. One of the latest approaches is the single multiplex typing of insertion–deletions (InDels), short biallelic length polymorphisms. InDels share most of the properties of single nucleotide polymorphisms (SNPs) that makes them ideal markers for forensic analysis of degraded DNA. The short amplicon size ranges, high multiplexing capability, and low mutation rate make them an attractive complement to mini-STRs. In addition, as length polymorphism markers, InDels can be analyzed with the same simple end-labeled PCR primer methods as STRs, thus avoiding the multi-step protocols required of SNP typing single base extension assays, as well as providing a more direct relationship between input DNA and peak height ratios. InDel genotyping should be considered a serious candidate for incorporation into the forensic marker battery. In order to assess the utility of such assays to the forensic community we have conducted a thorough analysis of a set of U.S. population samples with a commercial Indel assay, a 30 marker multiplex ‘DIPplex’ produced by Qiagen.Forensic Science International Genetics Supplement Series 01/2011; 3(1):e443-e444. -
Article: Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women.
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ABSTRACT: The post-partum period is a time of extreme vulnerability for a whole spectrum of psychiatric disorders. Delivery may be considered an important risk factor in genetically susceptible women. Five hundred and eight SNPs in 44 genes at candidate pathways putatively related to mood changes after delivery were genotyped in a multicenter cohort of 1804 women from Spain. Participants completed two scales at 2-3 days, 8 weeks, and 32 weeks post-partum, the Edinburgh Post-partum Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Those women who scored 9 or more on EPDS were evaluated for major depression using the Diagnostic Interview for Genetics Studies (DIGS) adapted for post-partum depression. Association with major depression was assessed using likelihood ratio tests under a codominant genotype model. Association with scale scores was tested using linear mixed models to take into account repeated measures over time. Two intronic SNPs, one at the serotonin transporter gene (SLC6A4) and another at dopa decarboxylase (DDC), were significantly associated to STAI anxiety scores after multiple testing correction (nominal P=0.0000513 and 0.000097, respectively). In addition, post hoc analysis at the unphased haplotype level using nominal significant SNPs revealed an association with a combination of three SNPs at protein kinase C, beta (PRKCB) with major depression, significant after multiple testing correction (nominal global P=0.0001596). In conclusion, we detected a role of SLC6A4 in mood changes after stressful events, and revealed new putative associations involving DDC and PRKCB. Therefore, these genes deserve further investigation to confirm these results.Journal of psychiatric research 08/2010; 44(11):717-24. · 3.72 Impact Factor -
Article: A new multiplex for human identification using insertion/deletion polymorphisms.
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ABSTRACT: Human identification is usually based on the study of STRs or SNPs depending on the particular characteristics of the investigation. However, other types of genetic variation such as insertion/deletion polymorphisms (indels) have considerable potential in the field of identification, since they can combine the desirable characteristics of both STRs and SNPs. In this study, a set of 38 non-coding bi-allelic autosomal indels reported to be polymorphic in African, European, and Asian populations were selected. We developed a sensitive genotyping assay, which is able to characterize all 38 bi-allelic markers using a single multiplex PCR and detected with standard CE analyzers. Amplicon length was designed to be shorter than 160 bp. Complete profiles were obtained using 0.3 ng of DNA, and full genotyping of degraded samples was possible in cases where standard STR typing had partially failed. A total of 306 individuals from Angola, Mozambique, Portugal, Macau, and Taiwan were studied and population data are presented. All indels were polymorphic in the three population groups studied and the random match probabilities of the set ranged in orders of magnitude from 10(-14) to 10(-15). Therefore, the indel-plex represents a valuable approach in human identification studies, especially in challenging DNA cases, as a more straightforward and efficient alternative to SNP typing.Electrophoresis 11/2009; 30(21):3682-90. · 3.30 Impact Factor -
Article: Viability of in-house datamarting approaches for population genetics analysis of SNP genotypes.
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ABSTRACT: Databases containing very large amounts of SNP (Single Nucleotide Polymorphism) data are now freely available for researchers interested in medical and/or population genetics applications. While many of these SNP repositories have implemented data retrieval tools for general-purpose mining, these alone cannot cover the broad spectrum of needs of most medical and population genetics studies. To address this limitation, we have built in-house customized data marts from the raw data provided by the largest public databases. In particular, for population genetics analysis based on genotypes we have built a set of data processing scripts that deal with raw data coming from the major SNP variation databases (e.g. HapMap, Perlegen), stripping them into single genotypes and then grouping them into populations, then merged with additional complementary descriptive information extracted from dbSNP. This allows not only in-house standardization and normalization of the genotyping data retrieved from different repositories, but also the calculation of statistical indices from simple allele frequency estimates to more elaborate genetic differentiation tests within populations, together with the ability to combine population samples from different databases. The present study demonstrates the viability of implementing scripts for handling extensive datasets of SNP genotypes with low computational costs, dealing with certain complex issues that arise from the divergent nature and configuration of the most popular SNP repositories. The information contained in these databases can also be enriched with additional information obtained from other complementary databases, in order to build a dedicated data mart. Updating the data structure is straightforward, as well as permitting easy implementation of new external data and the computation of supplementary statistical indices of interest.BMC Bioinformatics 02/2009; 10 Suppl 3:S5. · 2.75 Impact Factor -
Article: Ancestry analysis in the 11-M Madrid bomb attack investigation.
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ABSTRACT: The 11-M Madrid commuter train bombings of 2004 constituted the second biggest terrorist attack to occur in Europe after Lockerbie, while the subsequent investigation became the most complex and wide-ranging forensic case in Spain. Standard short tandem repeat (STR) profiling of 600 exhibits left certain key incriminatory samples unmatched to any of the apprehended suspects. A judicial order to perform analyses of unmatched samples to differentiate European and North African ancestry became a critical part of the investigation and was instigated to help refine the search for further suspects. Although mitochondrial DNA (mtDNA) and Y-chromosome markers routinely demonstrate informative geographic differentiation, the populations compared in this analysis were known to show a proportion of shared mtDNA and Y haplotypes as a result of recent gene-flow across the western Mediterranean, while any two loci can be unrepresentative of the ancestry of an individual as a whole. We based our principal analysis on a validated 34plex autosomal ancestry-informative-marker single nucleotide polymorphism (AIM-SNP) assay to make an assignment of ancestry for DNA from seven unmatched case samples including a handprint from a bag containing undetonated explosives together with personal items recovered from various locations in Madrid associated with the suspects. To assess marker informativeness before genotyping, we predicted the probable classification success for the 34plex assay with standard error estimators for a naïve Bayesian classifier using Moroccan and Spanish training sets (each n = 48). Once misclassification error was found to be sufficiently low, genotyping yielded seven near-complete profiles (33 of 34 AIM-SNPs) that in four cases gave probabilities providing a clear assignment of ancestry. One of the suspects predicted to be North African by AIM-SNP analysis of DNA from a toothbrush was identified late in the investigation as Algerian in origin. The results achieved illustrate the benefit of adding specialized marker sets to provide enhanced scope and power to an already highly effective system of DNA analysis for forensic identification.PLoS ONE 02/2009; 4(8):e6583. · 4.09 Impact Factor -
Article: pop.STR--An online population frequency browser for established and new forensic STRs
Forensic Science International Genetics Supplement Series 01/2009; 2(1):361-362. -
Article: SNP databases.
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ABSTRACT: Researchers interested in obtaining detailed information on SNPs now work in a golden age of online database availability: never has so much data and such a wealth of information been freely accessible for such a substantial proportion of the 18 million single nucleotide polymorphism (SNP) loci currently characterized in the human genome. This chapter describes the major SNP databases available for human genetics studies. Tools and strategies are outlined that can help researchers properly formulate a database query to be able to access the most appropriate information needed for their research aims, including medical or population genetics analysis--an approach that is getting increased attention given the expanding scale of online SNP data.Methods in molecular biology (Clifton, N.J.) 01/2009; 578:43-71. -
Article: SPSmart: adapting population based SNP genotype databases for fast and comprehensive web access.
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ABSTRACT: In the last five years large online resources of human variability have appeared, notably HapMap, Perlegen and the CEPH foundation. These databases of genotypes with population information act as catalogues of human diversity, and are widely used as reference sources for population genetics studies. Although many useful conclusions may be extracted by querying databases individually, the lack of flexibility for combining data from within and between each database does not allow the calculation of key population variability statistics. We have developed a novel tool for accessing and combining large-scale genomic databases of single nucleotide polymorphisms (SNPs) in widespread use in human population genetics: SPSmart (SNPs for Population Studies). A fast pipeline creates and maintains a data mart from the most commonly accessed databases of genotypes containing population information: data is mined, summarized into the standard statistical reference indices, and stored into a relational database that currently handles as many as 4 x 10(9) genotypes and that can be easily extended to new database initiatives. We have also built a web interface to the data mart that allows the browsing of underlying data indexed by population and the combining of populations, allowing intuitive and straightforward comparison of population groups. All the information served is optimized for web display, and most of the computations are already pre-processed in the data mart to speed up the data browsing and any computational treatment requested. In practice, SPSmart allows populations to be combined into user-defined groups, while multiple databases can be accessed and compared in a few simple steps from a single query. It performs the queries rapidly and gives straightforward graphical summaries of SNP population variability through visual inspection of allele frequencies outlined in standard pie-chart format. In addition, full numerical description of the data is output in statistical results panels that include common population genetics metrics such as heterozygosity, Fst and In.BMC Bioinformatics 11/2008; 9:428. · 2.75 Impact Factor -
Article: The SNPforID browser: an online tool for query and display of frequency data from the SNPforID project.
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ABSTRACT: The SNPforID browser is a web-based tool for the query and visualization of the SNP allele frequency data generated by the SNPforID consortium ( http://www.snpforid.org/ ). From this project, validated panels of single nucleotide polymorphisms (SNPs) for a variety of forensic applications have been generated with the browser concentrating on the single-tube identification SNP set comprising 52 markers. A web interface allows the visitor to review the allele frequencies of the studied markers from all the available populations used by SNPforID to validate global SNP variability. The interface has been designed to offer the useful facility of combining populations into appropriate geographic groups for visual comparison of populations individually or amongst user-defined groupings and with equivalent HapMap data.Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 06/2008; 122(5):435-40. · 2.59 Impact Factor -
Article: Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia.
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ABSTRACT: Relationships between gender, age-of-onset of schizophrenia and reproductive age strongly suggest a key role for gonadal hormones, and more specifically for estrogens, in the etiology of the illness. Also, estrogens act as neural growth and trophic factors influencing neuron and glial cells in many areas of the central nervous system. Therefore, we investigated the association between schizophrenia and 4 genes related to estrogen metabolism. These genes are ESR1 (estrogen receptor 1), ESR2 (estrogen receptor 2), APOE (apolipoprotein E) and COMT (catechol-O-methyltransferase). The expression of APOE and COMT, which contain estrogen response elements, have been demonstrated to be regulated by the estrogen receptors. In this current association study, we examined 59 single nucleotide polymorphisms (SNPs) located in the ESR1 (26), ESR2 (14), APOE (7) and COMT (12) loci. Allele frequencies were evaluated in the schizophrenia (n=585)-control (n=615) sample and no association was found with any of the four genes. In conclusion, our data suggest that the four analyzed genes do not play an important role in susceptibility to schizophrenia.Schizophrenia Research 04/2008; 100(1-3):308-15. · 4.75 Impact Factor -
Article: Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction.
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ABSTRACT: Recent reports indicate that DAO, DAOA, DTNBP1, NRG1 and RGS4 are some of the most-replicated genes implicated in susceptibility to schizophrenia. Also, the functions of these genes could converge in a common pathway of glutamate metabolism. The aim of this study was to evaluate if each of these genes, or their interaction, was associated with schizophrenia. A case-control study was conducted in 589 Spanish patients having a diagnosis of schizophrenia, and compared with 617 equivalent control subjects. Several single nucleotide polymorphisms (SNPs) in each gene were determined in all individuals. SNP and haplotype frequencies were compared between cases and controls. The interaction between different SNPs at the same, or at different gene, loci was analyzed by the multifactor dimensionality reduction (MDR) method. We found a new schizophrenia risk and protective haplotypes in intron VII of DTNBP1; one of the most important candidate genes for this disorder, to-date. However, no association was found between DAO, DAOA, NRG1 and RGS4 and schizophrenia. The hypothesis that gene-gene interaction in these five genes could increase the risk for the disorder was not confirmed in the present study. In summary, these results may provide further support for an association between the dysbindin gene (DTNBP1) and schizophrenia, but not between the disease and DAO, DAOA, NRG1 and RGS4 or with the interaction of these genes. In the light of recent data, these results need to be interpreted with caution and future analyses with dense genetic maps are awaited.Journal of Psychiatric Research 04/2008; 42(4):278-88. · 4.66 Impact Factor -
Conference Proceeding: Viability of in-house datamarting approaches for population genetics analysis of snp genotypes.
Proceeding of the 2nd International Workshop on Data and Text Mining in Bioinformatics, DTMBIO 2008, Napa Valley, California, USA, October 30, 2008; 01/2008
Top co-authors
Top Journals
Institutions
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2011–2012
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University of São Paulo
São Paulo, Estado de Sao Paulo, Brazil
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2009–2012
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University of Porto
- Institute of Molecular Pathology and Immunology (IPATIMUP)
Porto, Distrito do Porto, Portugal
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2005–2012
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Universidad de Santiago de Compostela
- • Servicio de Genética Forense
- • Grupo de Medicina Genómica
Santiago de Compostela, Galicia, Spain
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