Papers by Eduardo Gomez-Casado
International Journal of Modern Anthropology, 2016
Our aim is to study the HLA-A, -B, -C, -DRB1 and -DQB1 gene frequencies in the Chimila Amerindian... more Our aim is to study the HLA-A, -B, -C, -DRB1 and -DQB1 gene frequencies in the Chimila Amerindian (Colombia) ethnic group. Results are compared with other World populations in order to obtain information about Chimila and Amerindian Health promotion, Amerindian origins and America peopling. Written consent was obtained from Chimila subjects to be included in this study. Peripheral blood was drawn and HLA DNA genotyping was carried out by standard methods. Analyses of Chimila relatedness with other Amerindians and worldwide populations was performed with a standard NJ dendrogram and correspondence analyses methodology. Chimila HLA gene profile showed to be related to that of other Amerindians groups. New complete HLA extended haplotypes were obtained. Some of them are described for the first time. Also, specific genealogical comparisons were done between Chimila Amerindians and Pacific Islanders by using specific HLA alleles. Our conclusions are: 1) These new data and HLA extended ha...
Vaccines, 2020
Viral haemorrhagic septicaemia virus (VHSV) is one of the worst viral threats to fish farming. No... more Viral haemorrhagic septicaemia virus (VHSV) is one of the worst viral threats to fish farming. Non-virion (NV) gene-deleted VHSV (dNV-VHSV) has been postulated as an attenuated virus, because the absence of the NV gene leads to lower induced pathogenicity. However, little is known about the immune responses driven by dNV-VHSV and the wild-type (wt)-VHSV in the context of infection. Here, we obtained the immune transcriptome profiling in trout infected with dNV-VHSV and wt-VHSV and the pathways involved in immune responses. As general results, dNV-VHSV upregulated more trout immune genes than wt-VHSV (65.6% vs 45.7%, respectively), whereas wt-VHSV maintained more non-regulated genes than dNV-VHSV (45.7% vs 14.6%, respectively). The modulated pathways analysis (Gene-Set Enrichment Analysis, GSEA) showed that, when compared to wt-VHSV infected trout, the dNV-VHSV infected trout upregulated signalling pathways (n = 19) such as RIG-I (retinoic acid-inducible gene-I) like receptor signall...
PloS one, 2017
Kurds from Iraq (Dohuk and Erbil Area, North Iraq) have been analyzed for HLA genes. Their HLA ge... more Kurds from Iraq (Dohuk and Erbil Area, North Iraq) have been analyzed for HLA genes. Their HLA genetic profile has been compared with that of other Kurd groups from Iran and Tbilisi (Georgia, Caucasus) and also Worldwide populations. A total of 7,746 HLA chromosomes have been used. Genetic distances, NJ dendrograms and correspondence analyses have been carried out. Haplotype HLA-B*52-DRB1*15 is present in all three analyzed Kurd populations. HLA-A*02-B*51-DRB1*11 is present in Iraq and Georgia Kurds. Haplotypes common to Iran and Iraq Kurds are HLA DRB1*11-DQB1*03, HLA DRB1*03-DQB1*02 and others in a lower frequency. Our HLA study conclusions are that Kurds most probably belong to an ancient Mediterranean / Middle East / Caucasian genetic substratum and that present results and those previously obtained by us in Kurds may be useful for Medicine in future Kurd transplantation programs, HLA Epidemiology (HLA linked diseases) and Pharmacogenomics (HLA-associated drug side effects) and ...
Open Medicine Journal, 2016
Background:HLA autosomic genes are unique because they conform the most polymorphic human system.... more Background:HLA autosomic genes are unique because they conform the most polymorphic human system. Importance of this system is recognized in Medicine for Transplantation, Epidemiology (HLA and disease linkage), Pharmacogenomics (HLA linked to drug side effects) and for defining the origin of populations in both male and female lineages.Objectives:Studying HLA profile of a isolated Amerindian group from North Colombia (Wiwa) in order to draw conclusions about its Preventive Medicine, the genetic relationship with Worldwide populations and America peopling, since this last issue is hotly debated.Methodology:A total of 14,660 HLA chromosomes were included. Peripheral blood was obtained from volunteer blood donors belonging to Wiwa (also named Arsario) ethnic group. HLA-A, -B, -C, -DRB1 and -DQB1 genes were analyzed by standard methods. Wiwa Amerindians relationships with others were calculated by using Arlequin, Dispan and Vista software computer packages.Results:Extended HLA, -A, -B, ...
International Journal of Modern Anthropology, 2015
First Canary Islands (Spain) Inhabitants ("Guanches") origin has been much debated. Lately, it ha... more First Canary Islands (Spain) Inhabitants ("Guanches") origin has been much debated. Lately, it has come popular the simplistic theory that they came from North Africa. In the present paper, we conclude that not only North Africans but also Iberian/Atlantic Europeans (and possibly others) must have been first Canarians. Debate whether North Africans or Iberians were the first "Guanches" is artificial since Iberian Peninsula-North African genes flow in ancient times was abundant and Iberians share a great part of genetic profile with North Africans. New genetic (HLA) and linguistic data shown in the present paper is conjointly analyzed with early anthropological data; at least two "Guanches" anthropological types existed. In addition, a correct interpretation of R1b Y chromosome high frequency in Atlantic Europe (Ireland, British Isles, North Spain and Portugal), which is also found in Canary Islands (13.3%) supports that Atlantic/Europeans are among Canary Islands First Inhabitants. Present paper HLA genes partial data and presence of abundant old Iberian language scripts (which show an easy translation proposal by using Basque language) suggest that a present day dogma of a hypothetically North African single origin should be changed. Both Atlantic/Europeans and North Africans must have been in the origin of Canary Islands First Inhabitants.
International Journal of Modern Anthropology, 2015
Nineteen different new MHC-DMB complete cDNA sequences have been obtained in thirteen different i... more Nineteen different new MHC-DMB complete cDNA sequences have been obtained in thirteen different individuals belonging to the following primate species/families: Hylobates lar, Papio hamadryas, Macaca mulatta, Macaca fascicularis, Cercopithecus aethiops and Saguinus oedipus. Exonic allelism has been recorded all along the DM molecule domains and analyses of the critical residues in the conformation of the MHC-DR peptide-binding site were done; it was found an evolutionary pressure over the putative peptide-binding region of the DMB molecule that favours synonymous changes. These results are in contrast with the ones found in the MHC class I and class II genes, where non-synonymous DNA base substitutions are favoured The immunoreceptor inhibition motif Tyr230-X231-X232-Leu233 (ITIM) is invariantly present in all extant studied primates since 40 million years ago. It confirms the important function for this molecule, directing DR molecules towards the endosomal/ lysosomal class II compartment and sending inhibitory signals to cells in order to stop synthesis of unnecessary MHC-DR molecules. Some Macaca individuals DMB molecules (appear on Earth more than ten million years ago) dobear both short (without ITIM) and long cytoplasmic tails (with ITIM), similarly to what has been found in human individuals. These differences may have important functional implications. Other molecules, like NK-cell receptors and Fc receptors, bear this type of tyrosine-based inhibitory motifs in order to switch off specific cell functions. MHC-DMB variations occurring within each species suggest that their polymorphism may have an intraspecific evolution, since alleles of the same species cluster together, as it occurs in other MHC related genes (Bf, C4d). Other MHC class I and class II molecules, phylogenetic trees show a trans-species pattern of evolution. Finally, a cluster grouping human and gorilla DMB cDNA sequences is obtained using a dendrogram (for the MHC genes, i.e.: C4d trees); this is in contrast to others' results that obtain a human/chimpanzee cluster using different DNA sequences.
Prehistoric Iberia, 2000
The high HLA (Human Leukocyte Antigens) polymorphism has been proven to be useful for singling ou... more The high HLA (Human Leukocyte Antigens) polymorphism has been proven to be useful for singling out individuals and populations. The discovery of new loci and the presently available DNA typing and sequencing of new alleles have dramatically increased the variety of HLA allelism (Tsuji et al. 1992). Certain HLA alleles are frequent only in specific populations (i.e., A36, A43 in African Americans) and the strong linkage disequilibrium between HLA neighboring loci demonstrates that certain combinations of contiguous alleles (HLA haplotypes) show a characteristic frequency or are distinctive in particular living populations (Imanishi et al. 1992a, b; Hors et al. 1997; Piazza et al. 1997). HLA is a unique tool for studying the origins of human groups, as the characteristic HLA allele frequencies of founder populations have not been completely lost with time in certain cases.
Applied Microbiology and Biotechnology, 2015
The non-virion (NV) protein of viral haemorrhagic septicaemia virus (VHSV), an economically impor... more The non-virion (NV) protein of viral haemorrhagic septicaemia virus (VHSV), an economically important fish novirhabdovirus, has been implicated in the interference of some host innate mechanisms (i.e. apoptosis) in vitro. This work aimed to characterise the immune-related transcriptome changes in rainbow trout induced by NV protein that have not yet been established in vivo. For that purpose, immunetargeted microarrays were used to analyse the transcriptomes from head kidney and spleen of rainbow trout (Oncorhynchus mykiss) after injection of recombinant NV (rNV). Results showed the extensive downregulation (and in some cases upregulation) of many innate and adaptive immune response genes not related previously to VHSV infection. The newly identified genes belonged to VHSV-induced genes (vigs), tumour necrosis factors, Toll-like receptors, antigen processing and presentation, immune co-stimulatory molecules, interleukins, macrophage chemotaxis, transcription factors, etc. Classification of differentially downregulated genes into rainbow trout immune pathways identified stat1 and jun/atf1 transcription factor genes as the most representative of the multipath gene targets of rNV. Altogether, these results contribute to define the role and effects of NV in trout by orchestrating an immunosuppression of the innate immune responses for favouring viral replication upon VHSV infection. Finally, these transcriptome results open up the possibility to find out new strategies against VHSV and better understand the interrelationships between some immune pathways in trout.
Major Histocompatibility Complex, 2000
The functions of the major histocompatibility complex-G (MHC-G) molecule are still unknown. The i... more The functions of the major histocompatibility complex-G (MHC-G) molecule are still unknown. The idea that this molecule may be involved in preventing the rejection of fetuses is suggested by only indirect evidence. In the present paper, we review the structure, in vitro function and tissue distribution of MHC-G genes and proteins in different primate species. From available data, we conclude the following. First, the nomenclature of MHC-G alleles needs to be revised. Rhesus monkey A/G gene cannot be orthologous to MHC-G because of a lack of structural similarity. Cotton-top tamarin G molecules (which are also structurally similar to E molecules) cannot be orthologous to classical class I molecules. Second, selective pressure to maintain a low degree of polymorphism appears to operate only at the peptide-binding region (PBR) of the MHC-G molecule. Thus, this observation contradicts the idea that the MHC-G leader peptide is the only functional part of the molecule, and suggests that G proteins may have an antigen presenting function to clonotypic T cell receptors besides the ability to interact with NK receptors. Third, MHC-G may also have a function in the thymus, because it is expressed in the thymic epithelium. MHC-G may be important for creating an appropriate T-cell repertoire. Fourth, the presence of HLA-G proteins in tumours and the specific absence of soluble HLA-G mRNA isoforms in the tissues taken from patients with autoimmune diseases suggest that MHC-G may have a role in the immune response and inflammation control.
Cellular and Molecular Life Sciences (CMLS), 1999
HLA-E and-G genes show a restricted poly-may reach the cell surface and inhibit the lysis by NK c... more HLA-E and-G genes show a restricted poly-may reach the cell surface and inhibit the lysis by NK cells. Most findings are consistent with the hypothesis morphism encoding for molecules whose variability is limited at the peptide binding site. Fourteen alleles that that HLA-E and-G proteins may be tolerogenic give rise to only three productive proteins for HLA-G molecules at either the T-cell receptor (TcR) (inflammation, graft rejection) or NK level, switching off cells (*0101, *0103 and *0104) and five alleles with three different proteins for HLA-E (*0101, *0102 and *0103) which usually attack foreign (including foetus) or self (autoimmune) antigens. A low HLA-E and-G polymor-have been described. Expression of these molecules is low and found in many tissues for HLA-E; HLA-G phism is observed in humans, and their allele frequencies protein is expressed in extravillous trophoblast cells and are mostly homogeneous in the populations tested so far. Many studies to detect these alleles are now being thymic epithelium. Molecular studies have shown how performed in isolated populations and also in preg-HLA-G and HLA-E bind to natural killer (NK) cells immunoglobulin and lectin-type inhibitory receptors. nancy-associated pathologies. In the present paper, stan-HLA-E may act as a sentinel of the cell; if classical class dard and detailed techniques to detect HLA-E and-G DNA polymorphism are reported and discussed. I and HLA-G are being expressed, HLA-E molecules
Frontiers in Immunology, 2016
Three different immunoglobulin (Ig) isotypes can be found in teleost fish, IgM, IgD, and the tele... more Three different immunoglobulin (Ig) isotypes can be found in teleost fish, IgM, IgD, and the teleost-specific IgT. IgM is considered to have a systemic activity, and IgT is attributed a mucosal role, similar to mammalian IgA. In this study, the complete sequence of gilthead sea bream IgM and IgT in their membrane (m) and soluble (s) forms are described for the first time in a perciform fish. Their constitutive gene expression is analyzed in different tissues, and their regulation upon viral, bacterial, parasitic, mucosal vaccination and dietary challenges are studied. GCB IgM and IgT have the prototypical structure when compared to other fish Igs. The constitutive expression of sIgM was the highest overall in all tissues, whereas mIgT expression was highest in mucosal tissues, such as gills and intestine. IgM and IgT were differentially regulated upon infection. IgT was highly upregulated locally upon infection with the intestinal parasite Enteromyxum leei or systemically after Nodavirus infection. Long-term intestinal parasitic infections increased the serum titer of both isotypes. Mucosal vaccination against Photobacterium damselae subsp. piscicida finely regulated the Ig response inducing a systemic increase of IgM titers in serum and a local IgT response in skin mucus when animals were exposed to the pathogen by bath challenge. Interestingly, plant-based diets inhibit IgT upregulation upon intestinal parasitic challenge, which was related to a worse disease outcome. All these results corroborate the mucosal role of IgT and emphasize the importance of a finely tuned regulation of Ig isotypes upon infection, which could be of special interest in vaccination studies.
Human immunology, 2018
America First Inhabitants population (Amerindians, Na Dene and Eskimos) underwent a drastic popul... more America First Inhabitants population (Amerindians, Na Dene and Eskimos) underwent a drastic population reduction and gene exchange after Europeans and Africans arrival after 1492 AD. Barranquilla population may be a good model to study present day population admixture in South America. HLA-A, -B and -DRB1 DNA typing has been performed in 188 unrelated individuals originated in the area and speak Spanish language; they showed apparent European/African and mixed characters. HLA genetic European/African features were found and only 1.85% Amerindian one. This contrasts with neighboring Cuban population where 10% HLA Amerindian characters appear.
Description of New American Carduelis/Spinus Bird Species in La Paz (Bolivia): C./S. lapazensis, 2020
Introduction: South American siskins (Genus Carduelis/Spinus) are the outcome of regional evoluti... more Introduction: South American siskins (Genus Carduelis/Spinus) are the outcome of regional evolutionary radiation from an extant (or other extinct) species: C. notata, a North America siskin, which thrives in Mexico subtropical areas and is parental of one of the three described North American siskin radiations. Methods: Speciation and/or subspeciation of this South American siskin radiation have probably occurred during Pleistocene Epoch. In the present paper, a new species/subspecies akin to C./S. atrata is described by genetic and phenotypic parameters: this new species/subspecies was previously considered a subspecies of C./S. xanthogastra, which thrives further North and is separated about 1,762 km, 1,094 miles, from this described subspecies, Carduelis/ Spinus xanthogastra stejnegeri. Results: Our genetic study using mt cyt b, phenotypic and behavior observations show that this putative C./S. xanthogastra subspecies is either a different species or a C./S.atrata subspecies; we have proposed a provisional name for this finch, C./S. lapazensis, instead of C./S. x. stejnegeri. Conclusion: Species definition is movable and controversial, and it is uncertain in South American siskins, which all show a close genetic and phenotypical relationship, which may be still immersed in speciation processes since Pleistocene Epoch.
Introduction: Genus Carduelis (Fringillidae family) includes goldfinches, siskins, redpolls, gree... more Introduction: Genus Carduelis (Fringillidae family) includes goldfinches, siskins, redpolls, greenfinches and crossbills. Many of the species classified within this genus and other related genera have been grouped by using molecular systematics and the mitochondrial cytochrome b (mt cyt b) gene. According to this, the Eurasian siskin (C. spinus) is the only one extant direct ancestor of several North American finches; North American / South American radiations may have been originated by Eurasian siskin (or extinct relative). In the present work, we aim to perform a study of transpecies and transcontinental analyses of MHC (Major Histocompatibility Complex) Class I alleles in several genus Carduelis / Spinus species in order to draw evolutionary conclusions in several wild bird species belonging to the genus Carduelis / Spinus. Materials and Methods: Blood was taken from worldwide wild bird species. Passerine phylogeny was done after analysing mtDNA with Maximun Likelihood and Bayesian dendrograms. Major histocompatibility complex alleles were obtained by standard DNA cloning and sequencing. Results: We found two matches between MHC-I DNA alleles from different South American siskins at DNA level. Also, it was observed that the Eurasian siskin shares a protein with pine siskin and another with three South American siskins. Eight South American siskins species also share the same MHC protein. In addition, studied songbirds MHC class I intron 2 is longer than that of Gallus gallus. Conclusion: We have drawn the following conclusions: 1) We present the first direct evidence that " Minimal Essential MHC " does not exist for birds; one of its main definition characters, i.e.: small intron size does not hold for songbirds. 2) We also report that MHC genes transpecies evolution exist in birds by showing also for the first time that worldwide bird species keep the same MHC protein and DNA alleles. 3) New evidences on MHC alleles conservation from Eurasian Carduelis spinus (most ancient) to South American siskins (most recent) during million years support that Eurasian siskin is the parental species for American Genus Carduelis
First Canary Islands (Spain) Inhabitants (" Guanches ") origin has been much debated. Lately, it ... more First Canary Islands (Spain) Inhabitants (" Guanches ") origin has been much debated. Lately, it has come popular the simplistic theory that they came from North Africa. In the present paper, we conclude that not only North Africans but also Iberian/Atlantic Europeans (and possibly others) must have been first Canarians. Debate whether North Africans or Iberians were the first " Guanches " is artificial since Iberian Peninsula-North African genes flow in ancient times was abundant and Iberians share a great part of genetic profile with North Africans. New genetic (HLA) and linguistic data shown in the present paper is conjointly analyzed with early anthropological data; at least two " Guanches " anthropological types existed. In addition, a correct interpretation of R1b Y chromosome high frequency in Atlantic Europe (Ireland, British Isles, North Spain and Portugal), which is also found in Canary Islands (13.3%) supports that Atlantic/Europeans are among Canary Islands First Inhabitants. Present paper HLA genes partial data and presence of abundant old Iberian language scripts (which show an easy translation proposal by using Basque language) suggest that a present day dogma of a hypothetically North African single origin should be changed. Both Atlantic/Europeans and North Africans must have been in the origin of Canary Islands First Inhabitants.
Non-virion (NV) protein is essential for an efficient replication increasing the pathogenicity of... more Non-virion (NV) protein is essential for an efficient replication increasing the pathogenicity of the Salmonid novirhabdovirus (formerly IHNV), Piscine novirhabdovirus (formerly VHSV), and Hirame novirhabdovirus (HIRV). The interferon system, apoptosis, and other immune-related genes are modulated by NV to finally induce a deficient antiviral state in the cell. However, little is known about the VHSV NV regions involved in function and location. Here, eight different NV 07.71 fragments and eleven NV 07.71 mutants derived from the region between the two first α-helices have been studied in order to establish the mx and il8 transcript levels in ZF4 cells and the subcellular location. As a result, we determined that the N-terminal part of NV preserves the same ability as the wild-type (wt) NV in mx/il8 modulation and it also shares the subcellular location. Among NV mutants, some induced mx upregulation (N34A, C35A, D38A, and S40A) but maintained the il8 levels stable when compared to wt-NV in ZF4. Four NV mutants (D28A, N31A, L33A, and F37A) were not affected by the mutation and showed mx and il8 transcript levels similar to wt-NV. Surprisingly, mutants D36A, R39A, and D41A induced a stronger downregulation of both mx and il8 transcript levels than wt-NV, suggesting that a more stable structure and an improved interaction with ligands could be achieved through these mutations. Amino acids at positions 36 and 39 are conserved among known VHSV NV proteins whereas at position 41 two different amino acids have been described. To date, no natural NV proteins with alanine at positions 36, 39, and 41 have been found. In addition, wt-NV, all NV mutants, and one N-terminal NV fragment were located at cytoplasm with a characteristic pattern, which might support that cytoplasm is the site for interaction with candidate ligands such as PPM1Bb. Taken together, the data presented in this work indicated that NV function relies on the first part of the molecule and is dependent on tertiary structure rather than on the linear one. This study could lead to a better knowledge of VHSV escape from fish antiviral mechanisms as well as to future studies on immune targets.
International Journal of Modern Anthropology, 2015
Nineteen different new MHC-DMB complete cDNA sequences have been obtained in thirteen different i... more Nineteen different new MHC-DMB complete cDNA sequences have been obtained in thirteen different individuals belonging to the following primate species/families: Hylobates lar, Papio hamadryas, Macaca mulatta, Macaca fascicularis, Cercopithecus aethiops and Saguinus oedipus. Exonic allelism has been recorded all along the DM molecule domains and analyses of the critical residues in the conformation of the MHC-DR peptide-binding site were done; it was found an evolutionary pressure over the putative peptide-binding region of the DMB molecule that favours synonymous changes. These results are in contrast with the ones found in the MHC class I and class II genes, where non-synonymous DNA base substitutions are favoured The immunoreceptor inhibition motif Tyr230-X231-X232-Leu233 (ITIM) is invariantly present in all extant studied primates since 40 million years ago. It confirms the important function for this molecule, directing DR molecules towards the endosomal/ lysosomal class II compartment and sending inhibitory signals to cells in order to stop synthesis of unnecessary MHC-DR molecules. Some Macaca individuals DMB molecules (appear on Earth more than ten million years ago) dobear both short (without ITIM) and long cytoplasmic tails (with ITIM), similarly to what has been found in human individuals. These differences may have important functional implications. Other molecules, like NK-cell receptors and Fc receptors, bear this type of tyrosine-based inhibitory motifs in order to switch off specific cell functions. MHC-DMB variations occurring within each species suggest that their polymorphism may have an intraspecific evolution, since alleles of the same species cluster together, as it occurs in other MHC related genes (Bf, C4d). Other MHC class I and class II molecules, phylogenetic trees show a trans-species pattern of evolution. Finally, a cluster grouping human and gorilla DMB cDNA sequences is obtained using a dendrogram (for the MHC genes, i.e.: C4d trees); this is in contrast to others' results that obtain a human/chimpanzee cluster using different DNA sequences.
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porque su ayuda ha resultado indispensable en la selección de individuos y recopilación de muestr... more porque su ayuda ha resultado indispensable en la selección de individuos y recopilación de muestras para su estudio.
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Papers by Eduardo Gomez-Casado