Antonio Salas

University of Santiago de Compostela, Santiago, Galicia, Spain

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Publications (342)1706.51 Total impact

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    ABSTRACT: We have analyzed the specific male genetic component of 226 Bolivians recruited in five different regions (“departments”), La Paz, Cochabamba, Pando, Beni, and Santa Cruz. To evaluate the effect of geography on the distribution of genetic variability, the samples were also grouped into three main eco-geographical regions, namely, Andean, Sub-Andean, and Llanos. All the individuals were genotyped for 17 Y-STR and 32 Y-SNP markers. The average Y-chromosome Native American component in Bolivians is 28%, and it is mainly represented by haplogroup Q1a3a, while the average Y-chromosome European ancestry is 65%, and it is mainly represented by haplogroup R1b1-P25. The data indicate that there exists significant population sub-division in the country in terms of continental ancestry. Thus, the partition of ancestries in Llanos, Sub-Andean, and Andean regions is as follows (respectively): (i) Native American ancestry: 47%, 7%, and 19%, (ii) European ancestry: 46%, 86%, and 75%, and (iii) African ancestry: 7%, 7%, and 6%. The population sub-structure in the country is also well mirrored when inferred from an AMOVA analysis, indicating that among-population variance in the country reaches 9.74–11.15%. This suggests the convenience of using regional datasets for forensic applications in Bolivia, instead of using a global and single country database. By comparing the Y-chromosome patterns with those previously reported on the same individuals on autosomal SNPs and mitochondrial DNA (mtDNA), it becomes clear that Bolivians show a strong gender-bias.
    Forensic Science International: Genetics. 11/2014;
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    ABSTRACT: Certain mitochondrial DNA (mtDNA) variants and haplogroups have been found to be associated with neurological disorders. Several studies have suggested that mtDNA variation could have an etiologic role in these disorders by affecting the ATP production on high-energy demanding organs, such as the brain. We have analyzed 15 mtDNA SNPs (mtSNPs) in five cohorts of cases presenting Alzheimer disease (AD), Parkinson disease (PD), and migraine, and in controls, to evaluate the role mtDNA variation in disease risk. Association tests were undertaken both for mtSNPs and mitochondrial haplogroups. No significant association was detected for any mtSNP or haplogroup in AD and PD cohorts. Two mtSNPs were associated with one migraine cohort after correcting for multiple tests, namely, T4216C and G13708A and haplogroup J (FDR q-value = 0.02; Santiago's cohort). However, this association was not confirmed in a second replication migraine series. A review of the literature reveals the existence of inconsistent findings and methodological shortcomings affecting a large proportion of mtDNA association studies on AD, PD, and migraine. A detailed inspection of the literature highlights the need for performing more rigorous methodological and statistical standards in mtDNA genetic association studies aimed to avoid false positive results of association between mtDNA variants and neurological diseases. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2014; · 3.23 Impact Factor
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    ABSTRACT: The origin of the Etruscan civilization (Etruria, Central Italy) is a long-standing subject of debate among scholars from different disciplines. The bulk of the information has been reconstructed from ancient texts and archaeological findings and, in the last few years, through the analysis of uniparental genetic markers.
    PLoS ONE 09/2014; 9(9):e105920. · 3.53 Impact Factor
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    ABSTRACT: A large body of genetic research has focused on the potential role that mitochondrial DNA (mtDNA) variants might play on the predisposition to common and complex (multi-factorial) diseases. It has been argued however that many of these studies could be inconclusive due to artifacts related to genotyping errors or inadequate design.
    BMC Cancer 09/2014; 14(1):659. · 3.33 Impact Factor
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    ABSTRACT: It has been reported that certain genetic factors involved in schizophrenia could be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that mtDNA mutations and/or variants would be present in schizophrenia patients and may be related to schizophrenia characteristics and mitochondrial function. This study was performed in three steps: (1) identification of pathogenic mutations and variants in 14 schizophrenia patients with an apparent maternal inheritance of the disease by sequencing the entire mtDNA; (2) case-control association study of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in 495 patients and 615 controls, and (3) analyses of the associated variants according to the clinical, psychopathological, and neuropsychological characteristics and according to the oxidative and enzymatic activities of the mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations in the 14 sequenced patients. Two known variants were nominally associated with schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does not play a major role in schizophrenia, as it was not associated with clinical, psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C p.Ile195Thr variant did not result in differences in the oxidative and enzymatic functions of the mitochondrial respiratory chain. The patients with apparent maternal inheritance of schizophrenia did not exhibit any mutations in their mtDNA. The variants nominally associated with schizophrenia in the present study were not related either to phenotypic characteristics or to mitochondrial function. We did not find evidence pointing to a role for mtDNA sequence variation in schizophrenia. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2014; · 3.23 Impact Factor
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    ABSTRACT: The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the question of human identification. Previous recommendations published in 2000 addressed the analysis and interpretation of mitochondrial DNA (mtDNA) in forensic casework. While the foundations set forth in the earlier recommendations still apply, new approaches to the quality control, alignment and nomenclature of mitochondrial sequences, as well as the establishment of mtDNA reference population databases, have been developed. Here, we describe these developments and discuss their application to both mtDNA casework and mtDNA reference population databasing applications. While the generation of mtDNA for forensic casework has always been guided by specific standards, it is now well-established that data of the same quality are required for the mtDNA reference population data used to assess the statistical weight of the evidence. As a result, we introduce guidelines regarding sequence generation, as well as quality control measures based on the known worldwide mtDNA phylogeny, that can be applied to ensure the highest quality population data possible. For both casework and reference population databasing applications, the alignment and nomenclature of haplotypes is revised here and the phylogenetic alignment proffered as acceptable standard. In addition, the interpretation of heteroplasmy in the forensic context is updated, and the utility of alignment-free database searches for unbiased probability estimates is highlighted. Finally, we discuss statistical issues and define minimal standards for mtDNA database searches.
    Forensic science international. Genetics. 07/2014; 13C:134-142.
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    ABSTRACT: OBJECTIVE: Pancreatic acinar cell maturation is dependent on the activity of the pancreas transcription factor 1 (PTF1) complex. Induction of pancreatitis leads to MAP kinase activation and transient suppression of the acinar differentiation programme. We investigated the role of MAP kinase-interacting kinase 1 (Mnk1) in mouse exocrine pancreas development and in the response to secretagogue-induced pancreatitis. DESIGN: Mnk1 expression was analysed using immunohistochemistry, RT-qPCR and western blotting. Ptf1a binding to Mnk1 was assessed by chromatin immunoprecipitation and qPCR. Acute pancreatitis was induced in wild type and Mnk1-/- mice by 7 h intraperitoneal injections of caerulein. In vitro amylase secretion and trypsinogen activation were assessed using freshly isolated acinar cells. In vivo secretion was quantified by secretin-stimulated MRI. RESULTS: Mnk1 is expressed at the highest levels in pancreatic acinar cells and is a direct PTF1 target. Mnk1 is activated upon induction of pancreatitis and is indispensable for eIF4E phosphorylation. The pancreas of Mnk1-/- mice is histologically normal. Digestive enzyme content is significantly increased and c-Myc and Ccnd1 levels are reduced in Mnk1-/- mice. Upon induction of acute pancreatitis, Mnk1-/- mice show impaired eIF4E phosphorylation, activation of c-Myc and downregulation of zymogen content. Acinar cells show defective relocalisation of digestive enzymes, polarity defects and impaired secretory response in vitro and in vivo. CONCLUSIONS: Mnk1 is a novel pancreatic acinar cell-specific stress response kinase that regulates digestive enzyme abundance and eIF4E phosphorylation. It is required for the physiological secretory response of acinar cells and for the homeostatic response to caerulein administration during acute pancreatitis.
    Gut 07/2014; · 10.73 Impact Factor
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    ABSTRACT: We carried out an admixture analysis of a sample comprising 1,019 individuals from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry Informative Markers (AIMs) to estimate the admixture proportions. We also characterized a number of haplogroup diagnostic markers in the mtDNA and Y-chromosome in order to evaluate admixture using uniparental markers. Finally, we analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation. In the total sample, the average European, African and Native American contributions as estimated from autosomal AIMs were 72%, 20% and 8%, respectively. The Eastern provinces of Cuba showed relatively higher African and Native American contributions than the Western provinces. In particular, the highest proportion of African ancestry was observed in the provinces of Guantánamo (40%) and Santiago de Cuba (39%), and the highest proportion of Native American ancestry in Granma (15%), Holguín (12%) and Las Tunas (12%). We found evidence of substantial population stratification in the current Cuban population, emphasizing the need to control for the effects of population stratification in association studies including individuals from Cuba. The results of the analyses of uniparental markers were concordant with those observed in the autosomes. These geographic patterns in admixture proportions are fully consistent with historical and archaeological information. Additionally, we identified a sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side, and higher Native American and African contributions from the maternal side. This sex-biased contribution was particularly evident for Native American ancestry. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 are strongly associated with melanin levels in the sample.
    PLoS Genetics 07/2014; 10(7):e1004488. · 8.52 Impact Factor
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    ABSTRACT: There is a growing interest among geneticists in developing panels of Ancestry Informative Markers (AIMs) aimed at measuring the biogeographical ancestry of individual genomes. The efficiency of these panels is commonly tested empirically by contrasting self-reported ancestry with the ancestry estimated from these panels.
    BMC genomics. 06/2014; 15(1):543.
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    ABSTRACT: Mitochondrial common variants (mtSNPs) and the haplogroups defined by them have been inconsistently correlated with increased prostate cancer risk. Here we aimed to investigate the influence of the mitochondrial genetic background on prostate cancer. A total of 15 single-nucleotide polymorphisms (SNPs) representing the common European branches of the mtDNA phylogeny were analyzed in a cohort of 620 Spanish prostate cancer patients and 616 matched population-based controls. Association tests were computed on mtSNPs and haplogroups. None of the evaluated mtSNPs or haplogroups were statistically associated with prostate cancer risk in our Spanish cohort. We show that previous association findings do not rest on solid grounds given that all of them (i) were based on underpowered studies, (ii) did not control for population stratification, (iii) lacked replication/confirmation cohorts, and (iv) and did not control for multiple test corrections. Taken together, a critical reassessment of the previous literature and the results obtained in the present study suggest that mtDNA common European variants are not correlated with increases in the risk for prostate cancer.Journal of Human Genetics advance online publication, 5 June 2014; doi:10.1038/jhg.2014.46.
    Journal of human genetics. 06/2014;
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    ABSTRACT: In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend towards smaller genetic distances resulting from larger numbers of markers became apparent.
    Forensic Science International: Genetics 04/2014; 12:12-23. · 3.86 Impact Factor
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    ABSTRACT: Mitochondrial DNA common variants have been reported to be associated with the development of radiation-induced toxicity. Using a large cohort of patients, we aimed to validate these findings by investigating the potential role of common European mitochondrial DNA SNPs (mtSNPs) to the development of radio-toxicity. Overall acute and late toxicity data were assessed in a cohort of 606 prostate cancer patients by means of Standardized Total Average Toxicity (STAT) score. We carried out association tests between radiation toxicity and a selection of 15 mtSNPs (and the haplogroups defined by them). Statistically significant association between mtSNPs and haplogroups with toxicity could not be validated in our Spanish cohort. The present study suggests that the mtDNA common variants analyzed are not associated with clinically relevant increases in risk of overall radiation-induced toxicity in prostate cancer patients.
    Radiotherapy and Oncology 04/2014; · 4.52 Impact Factor
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    ABSTRACT: In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend towards smaller genetic distances resulting from larger numbers of markers became apparent.
    Forensic Science International: Genetics 01/2014; · 3.86 Impact Factor
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    ABSTRACT: Background and purpose Mitochondrial DNA common variants have been reported to be associated with the development of radiation-induced toxicity. Using a large cohort of patients, we aimed to validate these findings by investigating the potential role of common European mitochondrial DNA SNPs (mtSNPs) to the development of radio-toxicity. Material and methods Overall acute and late toxicity data were assessed in a cohort of 606 prostate cancer patients by means of Standardized Total Average Toxicity (STAT) score. We carried out association tests between radiation toxicity and a selection of 15 mtSNPs (and the haplogroups defined by them). Results Statistically significant association between mtSNPs and haplogroups with toxicity could not be validated in our Spanish cohort. Conclusions The present study suggests that the mtDNA common variants analyzed are not associated with clinically relevant increases in risk of overall radiation-induced toxicity in prostate cancer patients.
    Radiotherapy and Oncology. 01/2014;
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    ABSTRACT: An increase in CD3+TCRγδ+ and a decrease in CD3- intraepithelial lymphocytes (IEL) is a characteristic flow cytometric pattern of celiac disease (CD) with atrophy. The aim was to evaluate the usefulness of both CD IEL cytometric pattern and anti-TG2 IgA subepithelial deposit analysis (CD IF pattern) for diagnosing lymphocytic enteritis due to CD.
    PLoS ONE 01/2014; 9(7):e101249. · 3.53 Impact Factor
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    ABSTRACT: Analysis of ancient DNA can reveal historical events that are difficult to discern through study of present-day individuals. To investigate European population history around the time of the agricultural transition, we sequenced complete genomes from a ~7,500 year old early farmer from the Linearbandkeramik (LBK) culture from Stuttgart in Germany and an ~8,000 year old hunter-gatherer from the Loschbour rock shelter in Luxembourg. We also generated data from seven ~8,000 year old hunter-gatherers from Motala in Sweden. We compared these genomes and published ancient DNA to new data from 2,196 samples from 185 diverse populations to show that at least three ancestral groups contributed to present-day Europeans. The first are Ancient North Eurasians (ANE), who are more closely related to Upper Paleolithic Siberians than to any present-day population. The second are West European Hunter-Gatherers (WHG), related to the Loschbour individual, who contributed to all Europeans but not to Near Easterners. The third are Early European Farmers (EEF), related to the Stuttgart individual, who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model the deep relationships of these populations and show that about ~44% of the ancestry of EEF derived from a basal Eurasian lineage that split prior to the separation of other non-Africans.
    Nature. 12/2013; 513(7518).
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    ABSTRACT: The African ethnicity of New World slaves was highly significant for the transmission of African social, cultural and religious beliefs and practices. This study employs the mitochondrial DNA (mtDNA) analysis of present-day Jamaicans in order to assess the ethnic origins of their enslaved female ancestors (males, including white overseers and masters, do not contribute to mtDNA). The evidence suggests that the Gold Coast was the largest single source of Jamaican slaves who arrived, remained and survived in Jamaica. While this finding fits with some historical evidence, it refines the data contained within the Voyages: Transatlantic Slave Trade Database, which indicates that the Bight of Biafra provided the most enslaved Africans to Jamaica.
    Slavery & Abolition 09/2013; 34(3).
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    ABSTRACT: We have genotyped 46 Ancestry Informative Markers (AIMs) in two of the most populated areas in Bolivia, namely, La Paz (Andean region; n=105), and Chuquisaca (Sub-Andean region; n=73). Using different analytical tools, we inferred admixture proportions of these two American communities by comparing the genetic profiles with those publicly available from the CEPH (Centre d'Etude du Polymorphisme Humain) panel representing three main continental groups (Africa, Europe, and America). By way of simulations, we first evaluated the minimum sample size needed in order to obtain accurate estimates of ancestry proportions. The results indicated that sample sizes above 30 individuals could be large enough to estimate main continental ancestry proportions using the 46 AIMs panel. With the exception of a few individuals, the results also indicated that Bolivians showed a predominantly Native American ancestry with variable levels of European admixture. The proportions of ancestry were statistically different in La Paz and Chuquisaca: the Native American component was 86% and 77% (Mann-Whitney U-test: un-adjusted P-value=2.1×10(-5)), while the European ancestry was 13% and 21% (Mann-Whitney U-test: un-adjusted P-value=3.6×10(-5)), respectively. The African ancestry in Bolivians captured by the AIMs analyzed in the present study was below 2%. The inferred ancestry of Bolivians fits well with previous studies undertaken on haplotype data, indicating a major proportion of Native American lineages. The genetic differences observed in these two groups suggest that forensic genetic analysis should be better performed based on local databases built in the main Bolivian areas.
    Forensic Science International: Genetics 09/2013; 7(5):537-42. · 3.86 Impact Factor
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    ABSTRACT: To assess the aetiological role of Helicobacter pylori (H. pylori) infection in adult patients with iron-refractory or iron-dependent anaemia of previously unknown origin. Consecutive patients with chronic iron-deficient anaemia (IDA) with H. pylori infection and a negative standard work-up were prospectively evaluated. All of them had either iron refractoriness or iron dependency. Response to H. pylori eradication was assessed at 6 and 12 mo from follow-up. H. pylori infection was considered to be the cause of the anaemia when a complete anaemia resolution without iron supplements was observed after eradication. H. pylori was eradicated in 88 of the 89 patients. In the non-eradicated patient the four eradicating regimens failed. There were violations of protocol in 4 patients, for whom it was not possible to ascertain the cause of the anaemia. Thus, 84 H. pylori eradicated patients (10 men; 74 women) were available to assess the effect of eradication on IDA. H. pylori infection was considered to be the aetiology of IDA in 32 patients (38.1%; 95%CI: 28.4%-48.8%). This was more frequent in men/postmenopausal women than in premenopausal women (75% vs 23.3%; P < 0.0001) with an OR of 9.8 (95%CI: 3.3-29.6). In these patients, anaemia resolution occurred in the first follow-up visit at 6 mo, and no anaemia or iron deficiency relapse was observed after a mean follow-up of 21 ± 2 mo. Gastric H. pylori infection is a frequent cause of iron-refractory or iron-dependent anaemia of previously unknown origin in adult patients.
    World Journal of Gastroenterology 07/2013; 19(26):4166-71. · 2.55 Impact Factor

Publication Stats

8k Citations
1,706.51 Total Impact Points

Institutions

  • 1997–2014
    • University of Santiago de Compostela
      • • Department of Pathological Anatomy and Forensic Sciences
      • • Instituto de Medicina Legal
      Santiago, Galicia, Spain
  • 1993–2014
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain
  • 2013
    • Centro Nacional de Investigaciones Oncológicas
      • Molecular Pathology Programme
      Madrid, Madrid, Spain
  • 2012
    • University of California, San Francisco
      San Francisco, California, United States
    • Instituto Nacional de Toxicología y Ciencias Forenses
      Madrid, Madrid, Spain
    • Catholic University of the Sacred Heart
      • Institute of Legal Medicine and Insurance
      Milano, Lombardy, Italy
  • 2011–2012
    • University of São Paulo
      San Paulo, São Paulo, Brazil
    • Kunming Institute of Zoology CAS
      • State Key Laboratory of Genetic Resources and Evolution
      Kunming, Yunnan, China
    • Norwegian University of Life Sciences (UMB)
      • Department of Chemistry, Biotechnology and Food Science (IKBM)
      Ås, Akershus Fylke, Norway
  • 2006–2012
    • Medizinische Universität Innsbruck
      • Univ.-Klinik für Innere Medizin I (Stoffwechselerkrankungen, Pulmologie, Infektiologie, Endokrinologie, Rheumatologie und Angiologie)
      Innsbruck, Tyrol, Austria
    • Conselleria de Sanidade
      La Corogne, Galicia, Spain
  • 2005–2012
    • University of Hamburg
      • Department of Mathematics
      Hamburg, Hamburg, Germany
  • 2002–2012
    • Instituto De Medicina Legal
      La Habana, Ciudad de La Habana, Cuba
    • University of Zulia
      • Faculty of Medicine
      Maracaibo, Estado Zulia, Venezuela
  • 2008–2011
    • Fundación Favaloro
      Buenos Aires, Buenos Aires F.D., Argentina
  • 2005–2010
    • University of Porto
      • • Instituto de Patologia e Imunologia Molecular da Universidade do Porto
      • • Institute of Molecular Pathology and Immunology (IPATIMUP)
      Porto, Distrito do Porto, Portugal
  • 2009
    • Institute of Evolutionary Biology
      Barcino, Catalonia, Spain
  • 2008–2009
    • University of Pavia
      • Department of Biology and Biotechnology "Lazzaro Spallanzani"
      Pavia, Lombardy, Italy
  • 2004–2008
    • University Pompeu Fabra
      • Department of Experimental and Health Sciences
      Barcino, Catalonia, Spain
    • University of Oslo
      • • Institute of Medical Informatics (IMI)
      • • Department of Mathematics
      Oslo, Oslo, Norway
    • University of Huddersfield
      • Department of Chemical and Biological Sciences
      Huddersfield, England, United Kingdom
  • 2007
    • Complejo Hospitalario Universitario a Coruña (CHUAC)
      La Corogne, Galicia, Spain
  • 1989–2007
    • University Hospital Vall d'Hebron
      • • Digestive System Research Unit
      • • Department of Digestive System
      • • Department of Pathology
      Barcino, Catalonia, Spain
  • 1990–2005
    • Autonomous University of Barcelona
      • • Faculty of Medicine
      • • Department of Medicine
      Cerdanyola del Vallès, Catalonia, Spain
  • 2003
    • University of Valencia
      Valenza, Valencia, Spain
    • Instituto Nacional de Medicina Legal y Ciencias Forenses (Colombia)
      Μπογκοτά, Bogota D.C., Colombia
  • 2001
    • University of Antioquia
      • Instituto de Biología
      Santa Fe de Antioquia, Antioquia, Colombia
  • 1999
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 1991–1997
    • Hospital Son Dureta
      Palma, Balearic Islands, Spain