TY - JOUR T1 - CIBERER: Spanish National Network for Research on Rare Diseases: a highly productive collaborative initiative. JF - Clin Genet Y1 - 2022 A1 - Luque, Juan A1 - Mendes, Ingrid A1 - Gómez, Beatriz A1 - Morte, Beatriz A1 - de Heredia, Miguel López A1 - Herreras, Enrique A1 - Corrochano, Virginia A1 - Bueren, Juan A1 - Gallano, Pia A1 - Artuch, Rafael A1 - Fillat, Cristina A1 - Pérez-Jurado, Luis A A1 - Montoliu, Lluis A1 - Carracedo, Ángel A1 - Millán, José M A1 - Webb, Susan M A1 - Palau, Francesc A1 - Lapunzina, Pablo AB -

CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on Rare Diseases currently consists of 75 research groups belonging to universities, research centers and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical and cellular research of rare diseases. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this paper, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions towards the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to rare disease research. This article is protected by copyright. All rights reserved.

ER - TY - JOUR T1 - Novel genes and sex differences in COVID-19 severity. JF - Hum Mol Genet Y1 - 2022 A1 - Cruz, Raquel A1 - Almeida, Silvia Diz-de A1 - Heredia, Miguel López A1 - Quintela, Inés A1 - Ceballos, Francisco C A1 - Pita, Guillermo A1 - Lorenzo-Salazar, José M A1 - González-Montelongo, Rafaela A1 - Gago-Domínguez, Manuela A1 - Porras, Marta Sevilla A1 - Castaño, Jair Antonio Tenorio A1 - Nevado, Julián A1 - Aguado, Jose María A1 - Aguilar, Carlos A1 - Aguilera-Albesa, Sergio A1 - Almadana, Virginia A1 - Almoguera, Berta A1 - Alvarez, Nuria A1 - Andreu-Bernabeu, Álvaro A1 - Arana-Arri, Eunate A1 - Arango, Celso A1 - Arranz, María J A1 - Artiga, Maria-Jesus A1 - Baptista-Rosas, Raúl C A1 - Barreda-Sánchez, María A1 - Belhassen-Garcia, Moncef A1 - Bezerra, Joao F A1 - Bezerra, Marcos A C A1 - Boix-Palop, Lucía A1 - Brión, Maria A1 - Brugada, Ramón A1 - Bustos, Matilde A1 - Calderón, Enrique J A1 - Carbonell, Cristina A1 - Castano, Luis A1 - Castelao, Jose E A1 - Conde-Vicente, Rosa A1 - Cordero-Lorenzana, M Lourdes A1 - Cortes-Sanchez, Jose L A1 - Corton, Marta A1 - Darnaude, M Teresa A1 - De Martino-Rodríguez, Alba A1 - Campo-Pérez, Victor A1 - Bustamante, Aranzazu Diaz A1 - Domínguez-Garrido, Elena A1 - Luchessi, André D A1 - Eirós, Rocío A1 - Sanabria, Gladys Mercedes Estigarribia A1 - Fariñas, María Carmen A1 - Fernández-Robelo, Uxía A1 - Fernández-Rodríguez, Amanda A1 - Fernández-Villa, Tania A1 - Gil-Fournier, Belén A1 - Gómez-Arrue, Javier A1 - Álvarez, Beatriz González A1 - Quirós, Fernan Gonzalez Bernaldo A1 - González-Peñas, Javier A1 - Gutiérrez-Bautista, Juan F A1 - Herrero, María José A1 - Herrero-Gonzalez, Antonio A1 - Jimenez-Sousa, María A A1 - Lattig, María Claudia A1 - Borja, Anabel Liger A1 - Lopez-Rodriguez, Rosario A1 - Mancebo, Esther A1 - Martín-López, Caridad A1 - Martín, Vicente A1 - Martinez-Nieto, Oscar A1 - Martinez-Lopez, Iciar A1 - Martinez-Resendez, Michel F A1 - Martinez-Perez, Ángel A1 - Mazzeu, Juliana A A1 - Macías, Eleuterio Merayo A1 - Minguez, Pablo A1 - Cuerda, Victor Moreno A1 - Silbiger, Vivian N A1 - Oliveira, Silviene F A1 - Ortega-Paino, Eva A1 - Parellada, Mara A1 - Paz-Artal, Estela A1 - Santos, Ney P C A1 - Pérez-Matute, Patricia A1 - Perez, Patricia A1 - Pérez-Tomás, M Elena A1 - Perucho, Teresa A1 - Pinsach-Abuin, Mel Lina A1 - Pompa-Mera, Ericka N A1 - Porras-Hurtado, Gloria L A1 - Pujol, Aurora A1 - León, Soraya Ramiro A1 - Resino, Salvador A1 - Fernandes, Marianne R A1 - Rodríguez-Ruiz, Emilio A1 - Rodriguez-Artalejo, Fernando A1 - Rodriguez-Garcia, José A A1 - Ruiz-Cabello, Francisco A1 - Ruiz-Hornillos, Javier A1 - Ryan, Pablo A1 - Soria, José Manuel A1 - Souto, Juan Carlos A1 - Tamayo, Eduardo A1 - Tamayo-Velasco, Alvaro A1 - Taracido-Fernandez, Juan Carlos A1 - Teper, Alejandro A1 - Torres-Tobar, Lilian A1 - Urioste, Miguel A1 - Valencia-Ramos, Juan A1 - Yáñez, Zuleima A1 - Zarate, Ruth A1 - Nakanishi, Tomoko A1 - Pigazzini, Sara A1 - Degenhardt, Frauke A1 - Butler-Laporte, Guillaume A1 - Maya-Miles, Douglas A1 - Bujanda, Luis A1 - Bouysran, Youssef A1 - Palom, Adriana A1 - Ellinghaus, David A1 - Martínez-Bueno, Manuel A1 - Rolker, Selina A1 - Amitrano, Sara A1 - Roade, Luisa A1 - Fava, Francesca A1 - Spinner, Christoph D A1 - Prati, Daniele A1 - Bernardo, David A1 - García, Federico A1 - Darcis, Gilles A1 - Fernández-Cadenas, Israel A1 - Holter, Jan Cato A1 - Banales, Jesus M A1 - Frithiof, Robert A1 - Duga, Stefano A1 - Asselta, Rosanna A1 - Pereira, Alexandre C A1 - Romero-Gómez, Manuel A1 - Nafría-Jiménez, Beatriz A1 - Hov, Johannes R A1 - Migeotte, Isabelle A1 - Renieri, Alessandra A1 - Planas, Anna M A1 - Ludwig, Kerstin U A1 - Buti, Maria A1 - Rahmouni, Souad A1 - Alarcón-Riquelme, Marta E A1 - Schulte, Eva C A1 - Franke, Andre A1 - Karlsen, Tom H A1 - Valenti, Luca A1 - Zeberg, Hugo A1 - Richards, Brent A1 - Ganna, Andrea A1 - Boada, Mercè A1 - Rojas, Itziar A1 - Ruiz, Agustín A1 - Sánchez, Pascual A1 - Real, Luis Miguel A1 - Guillén-Navarro, Encarna A1 - Ayuso, Carmen A1 - González-Neira, Anna A1 - Riancho, José A A1 - Rojas-Martinez, Augusto A1 - Flores, Carlos A1 - Lapunzina, Pablo A1 - Carracedo, Ángel AB -

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

ER - TY - JOUR T1 - CSVS, a crowdsourcing database of the Spanish population genetic variability. JF - Nucleic Acids Res Y1 - 2021 A1 - Peña-Chilet, Maria A1 - Roldán, Gema A1 - Perez-Florido, Javier A1 - Ortuno, Francisco M A1 - Carmona, Rosario A1 - Aquino, Virginia A1 - López-López, Daniel A1 - Loucera, Carlos A1 - Fernandez-Rueda, Jose L A1 - Gallego, Asunción A1 - Garcia-Garcia, Francisco A1 - González-Neira, Anna A1 - Pita, Guillermo A1 - Núñez-Torres, Rocío A1 - Santoyo-López, Javier A1 - Ayuso, Carmen A1 - Minguez, Pablo A1 - Avila-Fernandez, Almudena A1 - Corton, Marta A1 - Moreno-Pelayo, Miguel Ángel A1 - Morin, Matías A1 - Gallego-Martinez, Alvaro A1 - Lopez-Escamez, Jose A A1 - Borrego, Salud A1 - Antiňolo, Guillermo A1 - Amigo, Jorge A1 - Salgado-Garrido, Josefa A1 - Pasalodos-Sanchez, Sara A1 - Morte, Beatriz A1 - Carracedo, Ángel A1 - Alonso, Ángel A1 - Dopazo, Joaquin KW - Alleles KW - Chromosome Mapping KW - Crowdsourcing KW - Databases, Genetic KW - Exome KW - Gene Frequency KW - Genetic Variation KW - Genetics, Population KW - Genome, Human KW - Genomics KW - Humans KW - Internet KW - Precision Medicine KW - Software KW - Spain AB -

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variability worldwide. CSVS is also part of the GA4GH Beacon network. CSVS can be accessed at: http://csvs.babelomics.org/.

VL - 49 IS - D1 U1 - https://www.ncbi.nlm.nih.gov/pubmed/32990755?dopt=Abstract ER - TY - JOUR T1 - Schuurs–Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review JF - Genes Y1 - 2021 A1 - Tenorio-Castaño, Jair A1 - Morte, Beatriz A1 - Nevado, Julián A1 - Martínez-Glez, Víctor A1 - Santos-Simarro, Fernando A1 - García-Miñaur, Sixto A1 - Palomares-Bralo, María A1 - Pacio-Míguez, Marta A1 - Gómez, Beatriz A1 - Arias, Pedro A1 - Alcochea, Alba A1 - Carrión, Juan A1 - Arias, Patricia A1 - Almoguera, Berta A1 - López-Grondona, Fermina A1 - Lorda-Sanchez, Isabel A1 - Galán-Gómez, Enrique A1 - Valenzuela, Irene A1 - Méndez Perez, María A1 - Cuscó, Ivón A1 - Barros, Francisco A1 - Pié, Juan A1 - Ramos, Sergio A1 - Ramos, Feliciano A1 - Kuechler, Alma A1 - Tizzano, Eduardo A1 - Ayuso, Carmen A1 - Kaiser, Frank A1 - Pérez-Jurado, Luis A1 - Carracedo, Ángel A1 - Lapunzina, Pablo VL - 12 UR - https://www.mdpi.com/2073-4425/12/5/738https://www.mdpi.com/2073-4425/12/5/738/pdf IS - 5 JO - Genes ER - TY - JOUR T1 - Progress in pharmacogenetics: consortiums and new strategies. JF - Drug Metab Pers Ther Y1 - 2016 A1 - Maroñas, Olalla A1 - Latorre, Ana A1 - Dopazo, Joaquin A1 - Pirmohamed, Munir A1 - Rodríguez-Antona, Cristina A1 - Siest, Gérard A1 - Carracedo, Ángel A1 - LLerena, Adrián KW - Cooperative Behavior KW - Genome-Wide Association Study KW - High-Throughput Screening Assays KW - Humans KW - Patient Care Team KW - pharmacogenetics KW - Polymorphism, Single Nucleotide KW - Precision Medicine AB -

Pharmacogenetics (PGx), as a field dedicated to achieving the goal of personalized medicine (PM), is devoted to the study of genes involved in inter-individual response to drugs. Due to its nature, PGx requires access to large samples; therefore, in order to progress, the formation of collaborative consortia seems to be crucial. Some examples of this collective effort are the European Society of Pharmacogenomics and personalized Therapy and the Ibero-American network of Pharmacogenetics. As an emerging field, one of the major challenges that PGx faces is translating their discoveries from research bench to bedside. The development of genomic high-throughput technologies is generating a revolution and offers the possibility of producing vast amounts of genome-wide single nucleotide polymorphisms for each patient. Moreover, there is a need of identifying and replicating associations of new biomarkers, and, in addition, a greater effort must be invested in developing regulatory organizations to accomplish a correct standardization. In this review, we outline the current progress in PGx using examples to highlight both the importance of polymorphisms and the research strategies for their detection. These concepts need to be applied together with a proper dissemination of knowledge to improve clinician and patient understanding, in a multidisciplinary team-based approach.

VL - 31 IS - 1 U1 - https://www.ncbi.nlm.nih.gov/pubmed/26913460?dopt=Abstract ER - TY - JOUR T1 - Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome. JF - Clin Chim Acta Y1 - 2013 A1 - Silbiger, Vivian N A1 - Luchessi, André D A1 - Hirata, Rosário D C A1 - Lima-Neto, Lídio G A1 - Cavichioli, Débora A1 - Carracedo, Ángel A1 - Brión, Maria A1 - Dopazo, Joaquin A1 - Garcia-Garcia, Francisco A1 - Dos Santos, Elizabete S A1 - Ramos, Rui F A1 - Sampaio, Marcelo F A1 - Armaganijan, Dikran A1 - Sousa, Amanda G M R A1 - Hirata, Mario H KW - Acute Coronary Syndrome KW - Acute-Phase Proteins KW - Adult KW - biomarkers KW - Blood Cells KW - Early Diagnosis KW - gene expression KW - Gene Expression Profiling KW - Humans KW - Male KW - Middle Aged KW - Oligonucleotide Array Sequence Analysis KW - RNA, Messenger KW - Transcriptome AB -

BACKGROUND: Genome-wide expression analysis using microarrays has been used as a research strategy to discovery new biomarkers and candidate genes for a number of diseases. We aim to find new biomarkers for the prediction of acute coronary syndrome (ACS) with a differentially expressed mRNA profiling approach using whole genomic expression analysis in a peripheral blood cell model from patients with early ACS.

METHODS AND RESULTS: This study was carried out in two phases. On phase 1 a restricted clinical criteria (ACS-Ph1, n=9 and CG-Ph1, n=6) was used in order to select potential mRNA biomarkers candidates. A subsequent phase 2 study was performed using selected phase 1 markers analyzed by RT-qPCR using a larger and independent casuistic (ACS-Ph2, n=74 and CG-Ph2, n=41). A total of 549 genes were found to be differentially expressed in the first 48 h after the ACS-Ph1. Technical and biological validation further confirmed that ALOX15, AREG, BCL2A1, BCL2L1, CA1, COX7B, ECHDC3, IL18R1, IRS2, KCNE1, MMP9, MYL4 and TREML4, are differentially expressed in both phases of this study.

CONCLUSIONS: Transcriptomic analysis by microarray technology demonstrated differential expression during a 48 h time course suggesting a potential use of some of these genes as biomarkers for very early stages of ACS, as well as for monitoring early cardiac ischemic recovery.

VL - 421 U1 - https://www.ncbi.nlm.nih.gov/pubmed/23535507?dopt=Abstract ER - TY - JOUR T1 - Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome: Transcriptional profiling of acute coronary syndrome. JF - Clinica chimica acta; international journal of clinical chemistry Y1 - 2013 A1 - Silbiger, Vivian N A1 - Luchessi, André D A1 - Hirata, Rosário D C A1 - Lima-Neto, Lídio G A1 - Cavichioli, Débora A1 - Carracedo, Ángel A1 - Brión, Maria A1 - Joaquín Dopazo A1 - Garcia-Garcia, Francisco A1 - Dos Santos, Elizabete S A1 - Ramos, Rui F A1 - Sampaio, Marcelo F A1 - Armaganijan, Dikran A1 - Sousa, Amanda G M R A1 - Hirata, Mario H AB - {BACKGROUND: Genome-wide expression analysis using microarrays has been used as a research strategy to discovery new biomarkers and candidate genes for a number of diseases. We aim to find new biomarkers for the prediction of acute coronary syndrome (ACS) with a differentially expressed mRNA profiling approach using whole genomic expression analysis in a peripheral blood cell model from patients with early ACS. METHODS AND RESULTS: This study was carried out in two phases. On phase 1 a restricted clinical criteria (ACS-Ph1 ER - TY - CONF T1 - Peripheral blood cells transcriptome to study new biomarkers for myocardial infarction follow up Y1 - 2009 A1 - Silbiger, Vivian A1 - Luchessi, André A1 - Hirata, Rosario A1 - Carracedo, Ángel A1 - Brión, Maria A1 - Lima Neto, Lidio A1 - P. Pastorelli, C A1 - Dopazo, Joaquin A1 - Montaner, David A1 - Garcia, F A1 - P. Sampaio, M A1 - P. Pereira, M A1 - S. Santos, E A1 - Armaganijan, Dikran A1 - Hirata, Mario ER -