Producción de ovino de carne en medio semiárido

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Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders

BACKGROUND: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with high heritability. Recent findings support a highly heterogeneous and complex genetic etiology including rare de novo and inherited mutations or chromosomal rearrangements as well as double or multiple hits. METHODS: We performed whole-exome sequencing (WES) and blood cell transcriptome by RNAseq in a subset of male patients with idiopathic ASD (n = 36) in order to identify causative genes, transcriptomic alterations, and susceptibility variants. RESULTS: We detected likely monogenic causes in seven cases: five de novo (SCN2A, MED13L, KCNV1, CUL3, and PTEN) and two inherited X-linked variants (MAOA and CDKL5). Transcriptomic analyses allowed the identification of intronic causative mutations missed by the usual filtering of WES and revealed functional consequences of some rare mutations. These included aberrant transcripts (PTEN, POLR3C), deregulated expression in 1.7% of mutated genes (that is, SEMA6B, MECP2, ANK3, CREBBP), allele-specific expression (FUS, MTOR, TAF1C), and non-sense-mediated decay (RIT1, ALG9). The analysis of rare inherited variants showed enrichment in relevant pathways such as the PI3K-Akt signaling and the axon guidance. CONCLUSIONS: Integrative analysis of WES and blood RNAseq data has proven to be an efficient strategy to identify likely monogenic forms of ASD (19% in our cohort), as well as additional rare inherited mutations that can contribute to ASD risk in a multifactorial manner. Blood transcriptomic data, besides validating 88% of expressed variants, allowed the identification of missed intronic mutations and revealed functional correlations of genetic variants, including changes in splicing, expression levels, and allelic expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13229-015-0017-0) contains supplementary material, which is available to authorized users

Clonal chromosomal mosaicism and loss of chromosome Y in men are risk factors for SARS-CoV-2 vulnerability in the elderly

* SCOURGE Cohort Group Javier Abellan15,16; René Acosta-Isaac17; Jose María Aguado18,19,20,21; Carlos Aguilar22; Sergio Aguilera-Albesa23,24; Abdolah Ahmadi Sabbagh25; Jorge Alba26; Sergiu Albu27,28,29; Karla A.M. Alcalá-Gallardo30; Julia Alcoba-Florez31; Sergio Alcolea Batres32; Holmes Rafael AlgarinLara33,34; Virginia Almadana35; Kelliane A. Medeiros36,37; Julia Almeida38,39; Berta Almoguera40,3; María R. Alonso41; Nuria Alvarez41; Rodolfo Alvarez-Sala Walther32; Yady Álvarez-Benítez33,34; Felipe Álvarez-Navia42,43; Katiusse A. dos Santos44; Álvaro Andreu-Bernabeu45,20; Maria Rosa Antonijoan46; Eleno Martínez-Aquino47; Eunate Arana-Arri48,49; Carlos Aranda50,51; Celso Arango45,52,20; Carolina Araque53,54; Nathalia K. Araujo55; Ana C. Arcanjo56,57,58; Ana Arnaiz59,60; Francisco Arnalich Fernández61; María J. Arranz62; José Ramon Arribas Lopez61; Maria-Jesus Artiga63; Yubelly Avello-Malaver64; Carmen Ayuso40,3; Belén Ballina Martín25; Raúl C. BaptistaRosas65,66,67; Ana María Baldion64; Andrea Barranco-Díaz34; María Barreda- Sánchez68,69; Viviana Barrera-Penagos64; Moncef Belhassen-Garcia70,43; David Bernal-Bello71; Enrique Bernal68; Joao F. Bezerra72; Marcos A.C. Bezerra73; Natalia Blanca-López74; Rafael Blancas75; Lucía Boix-Palop76; Alberto Borobia77; Elsa Bravo78; María Brion79,80; Óscar Brochado-Kith81; Ramón Brugada82,83,80,84; Matilde Bustos85; Alfonso Cabello86; Alejandro Cáceres4,5; Juan J. Caceres-Agra87; Esther Calbo76; Enrique J. Calderón88,6,89; Shirley Camacho90; Francisco C. Ceballos81; Yolanda Cañadas51; Cristina Carbonell42,43; Servando Cardona-Huerta91; Maria Sanchez Carpintero50,51; Carlos Carpio Segura32; José Antonio Carrillo-Avila92; Marcela C. Campos56; Carlos Casasnovas93,94,3; Luis Castano48,95,3,96,97; Carlos F. Castaño50,51; Jose E. Castelao98; Aranzazu Castellano Candalija99; María A. Castillo90; Walter G. ChavesSantiago100,54; Sylena Chiquillo-Gómez33,34; Marco A. Cid-Lopez30; Oscar CienfuegosJimenez91; Rosa Conde-Vicente101; Gabriela C.R. Cunha102; M. Lourdes Cordero-Lorenzana103; Dolores Corella104,105; Almudena Corrales106,107; Jose L. Cortes-Sanchez91,108; Marta Corton40,3; Karla S.C. Souza109; Fabiola T.C. Silva56; Raquel Cruz8,3,9,10; Luisa Cuesta110; Nathali A.C. Tavares111; Maria C.C. Carvalho112; David Dalmau62,76; Raquel C.S. Dantas-Komatsu113; M. Teresa Darnaude114; Raimundo de Andrés115; Carmen de Juan116; Juan De la Cruz Troca117,118,6; Carmen de la Horra89; Ana B. de la Hoz48; Alba De Martino-Rodríguez119,120; Marina S. Cruz121; Julianna Lys de Sousa Alves Neri122; Victor del Campo-Pérez123; Juan Delgado-Cuesta124; Aranzazu Diaz de Bustamante114; Anderson Díaz-Pérez34; Beatriz Dietl76; Silvia Diz-de Almeida3,10; Manoella do Monte Alves125,126; Elena Domínguez-Garrido127; Lidia S. Rosa128; Andre D. Luchessi129; Jose Echave-Sustaeta130; Rocío Eiros131; César O. EncisoOlivera53,54; Gabriela Escudero132; Pedro Pablo España133; Gladys Mercedes Estigarribia Sanabria134; María Carmen Fariñas59,60,135; Ramón Fernández59,136; Lidia FernandezCaballero40,3; Ana Fernández-Cruz137; Silvia Fernández Ferrero25; Yolanda Fernández Martínez25; María J. Fernandez-Nestosa138; Uxía Fernández-Robelo139; Amanda FernándezRodríguez81; Marta Fernández-Sampedro59,135,60; Ruth Fernández40,3; Tania Fernández-Villa140; Carmen Fernéndez Capitán99; Antonio Augusto F. Carioca141; Patricia Flores-Pérez142; Lácides Fuenmayor-Hernández34; Marta Fuertes Núñez25; Victoria Fumadó143; Ignacio Gadea144; Lidia Gagliardi50,51; Manuela Gago-Domínguez13,9; Natalia Gallego11; Cristina Galoppo145; Ana García-Soidán146; Carlos Garcia Cerrada15,16; Aitor García-de-Vicuña48,95; Josefina GarciaGarcía68; Irene García-García77; Carmen García-Ibarbia59,135,60; Andrés C. García-Montero147; Leticia García50,51; Mercedes García50,51; María Carmen García Torrejón148,16; Inés García40,3; Elisa García-Vázquez68; Emiliano Garza-Frias91; Angela Gentile145; Belén Gil-Fournier149; Jéssica N.G. de Araújo150; Mario Gómez-Duque100,54; Javier Gómez-Arrue119,120; Luis Gómez Carrera32; María Gómez García151; Ángela Gómez Sacristán152; Juan R. González4,5,6,14; Anna González-Neira41; Beatriz González Álvarez119,120; Fernan Gonzalez Bernaldo de Quirós153; Rafaela González-Montelongo154; Javier González-Peñas45,20,52; Manuel Gonzalez-Sagrado101; Hugo Gonzalo Benito155; Oscar Gorgojo-Galindo156; Miguel Górgolas86; Florencia Guaragna145; Jessica G. Chaux54; Encarna Guillen-Navarro68,157,158,159; Beatriz Guillen-Guio106; Pablo Guisado-Vasco130; Luz D. Gutierrez-Castañeda160,54; Juan F. Gutiérrez-Bautista161; Sara HeiliFrades162; Rafael H. Jacomo163; Estefania Hernandez164; Cristina Hernández Moro25; Luis D. Hernandez-Ortega165,166; Guillermo Hernández-Pérez42; Rebeca Hernández-Vaquero167; Belen Herraez41; M. Teresa Herranz68; María Herrera50,51; María José Herrero168,169; Antonio HerreroGonzalez170; Juan P. Horcajada171,172,28,173; Natale Imaz-Ayo48; Maider IntxaustiUrrutibeaskoa174; Antonio Íñigo-Campos154; María Íñiguez175; Rubén Jara68; Ángel Jiménez50,51; Ignacio Jiménez-Alfaro176; Pilar Jiménez161; María A. Jimenez-Sousa81; Iolanda Jordan177,178,6; Rocío Laguna-Goya179,180; Daniel Laorden32; María Lasa-Lazaro179,180; María Claudia Lattig90,181; Ailen Lauriente145; Anabel Liger Borja182; Lucía Llanos183; Amparo López-Bernús42,43; Miguel It is made available under a CC-BY-NC-ND 4.0 International license . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. medRxiv preprint doi: https://doi.org/10.1101/2020.04.19.20071357; this version posted February 18, 2022. The copyright holder for this preprint López de Heredia3 ; Esther Lopez-Garcia117,118,6,184; Eduardo López Granados185,186,3; Rosario Lopez-Rodriguez40,3; Miguel A. López-Ruz187,188,189; Leonardo Lorente190; José M. LorenzoSalazar154; José E. Lozano191; María Lozano-Espinosa182; Ignacio Mahillo192,193,107; Esther Mancebo179,180; Carmen Mar133; Cristina Marcelo Calvo99; Alba Marcos-Delgado194; Miguel Marcos42,43; Alicia Marín Candon77; Pablo Mariscal Aguilar32; Laura Martin-Pedraza74; Marta Martin-Fernandez195; Caridad Martín-López182; José-Ángel Martín-Oterino42,43; María Dolores Martín196; Vicente Martín194,6; María M. Martín197; María Martín-Vicente81; Amalia Martinez198; Óscar Martínez-González75; Ricardo Martínez164; Pedro Martinez-Paz155; Covadonga M. DiazCaneja45,52,20; Oscar Martinez-Nieto64,181; Iciar Martinez-Lopez199,200; Michel F. MartinezResendez91; Silvia Martínez59,135; Juan José Martinez94,3; Angel Martinez-Perez201; Andrea Martínez-Ramas40,3; Violeta Martínez Robles25; Laura Marzal40,3; Juliana F. Mazzeu202,203,204; Francisco J. Medrano88,6,89; Xose M. Meijome205,206; Natalia Mejuto-Montero207; Ingrid Mendes3 ; Alice L. Duarte109; Ana Méndez-Echevarria208; Humberto Mendoza Charris78,34; Eleuterio Merayo Macías209; Fátima Mercadillo210; Arieh R. Mercado-Sesma165,166; Pablo Minguez40,3; Elena Molina-Roldán211; Antonio J J. Molina194; Juan José Montoya164; Susana M.T. Pinho36,212,213; Patricia Moreira-Escriche116; Xenia Morelos-Arnedo78,34; Rocío Moreno3 ; Victor Moreno Cuerda15,16; Antonio Moreno-Docón68; Junior Moreno-Escalante34; Alberto Moreno Fernández99; Patricia Muñoz García214,107,20; Pablo Neira145; Julian Nevado3,11,12; Israel NietoGañán146; Vivian N. Silbiger129; Rocio Nuñez- Torres41; Antònia Obrador-Hevia215,216; J. Gonzalo Ocejo-Vinyals59,135; Virginia Olivar145; Silviene F. Oliveira56,217,204,218; Lorena Ondo40,3; Alberto Orfao38,39; Eva Ortega-Paino63; Luis Ortega219; Rocio Ortiz-Lopez91; Fernando Ortiz-Flores59,135; José A. Oteo26,175; Manuel Pacheco164; Fredy Javier Pacheco-Miranda34; Irene Padilla Conejo25; Sonia Panadero-Fajardo92; Mara Parellada45,52,20; Roberto Pariente-Rodríguez146; Vicente Friaza6,89; Estela Paz-Artal179,180,220; Germán Peces-Barba221,107; Miguel S. Pedromingo Kus222; Celia Perales144; Ney P.C. Santos223; Genilson P. Guegel224; Perez Maria Jazmin145; Alexandra Perez82,80; Patricia Pérez-Matute175; César Pérez225; Gustavo Perez-de-Nanclares48,95; Felipe Pérez-García226,227; Patricia Perez228; Luis A. Pérez-Jurado1,2,3; M. Elena Pérez-Tomás68; Teresa Perucho229; Lisbeth A. Pichardo25; Adriana P. Ribeiro36,37,213; Mel·lina Pinsach-Abuin82,80; Luz Adriana Pinzón100,54; Jeane F.P. Medeiros230; Guillermo Pita41; Francesc Pla-Junca231,3; Laura Planas-Serra94,3; Ericka N. Pompa-Mera232; Gloria L. Porras-Hurtado164; Aurora Pujol94,3,233; María Eugenia Quevedo Chávez33,34; Maria Angeles Quijada46,234; Inés Quintela8 ; Soraya Ramiro León149; Pedro Rascado Sedes235; Joana F.R. Nunes56; Delia Recalde119,120; Emma Recio-Fernández175; Salvador Resino81; Renata R. Sousa213,236; Carlos S. RivadeneiraChamorro54; Diana Roa-Agudelo64; Montserrat Robelo Pardo235; Marianne R. Fernandes223,237; María A. Rodriguez-Hernandez85; Agustí Rodriguez-Palmero238,94; Emilio Rodríguez-Ruiz235,9; Marilyn Johanna Rodriguez54; Fernando Rodriguez-Artalejo117,118,6,184; Marena RodríguezFerrer34; Carlos Rodriguez-Gallego239,240; José A. Rodriguez-Garcia25; Belén Rodríguez Maya15; Antonio Rodriguez-Nicolas161; German Ezequiel Rodriguez Novoa145; Paula A. RodriguezUrrego64; Federico Rojo241,242; Andrea Romero-Coronado34; Rubén Morilla89,243; Filomeno Rondón García25; Antonio Rosales-Castillo244; Cladelis Rubio245; María Rubio Olivera50,51; Francisco Ruiz-Cabello161,188,246; Eva Ruiz-Casares229; Juan J. Ruiz-Cubillan59,135; Javier RuizHornillos247,51,248; Montserrat Ruiz94,3; Pablo Ryan249,250,251; Hector D. Salamanca53,54; Lorena Salazar-García90; Giorgina Gabriela Salgueiro Origlia 99; Anna Sangil76; Olga SánchezPernaute252; Pedro-Luis Sánchez131,43; Antonio J. Sánchez López253; Clara Sánchez-Pablo131; María Concepción Sánchez Prados32; Javier Sánchez Real25; Jorge Sánchez Redondo15,254; Cristina Sancho- Sainz174; Esther Sande255; Arnoldo Santos225; Agatha Schlüter94,3; Sonia Segovia231,256,257; Alex Serra-Llovich62; Fernando Sevil Puras22; Marta Sevilla Porras3,11; Miguel A. Sicolo258,259; Cristina Silván Fuentes3 ; Vitor M.S. Moraes260; Vanessa S. Souza102; Jordi SoléViolán261,107; José Manuel Soria201; Jose V. Sorlí104,105; Nayara S. Silva262; Juan Carlos Souto17; John J. Sprockel100,54; José Javier Suárez-Rama8 ; David A. Suarez-Zamora64; Xiana TaboadaFraga207; Eduardo Tamayo263,156; Alvaro Tamayo-Velasco264; Juan Carlos TaracidoFernandez170; Romero H.T. Vasconcelos111; Carlos Tellería119,120; Thássia M.T. Carratto260; Jair Antonio Tenorio Castaño3,11,12; Alejandro Teper145; Izabel M.T. Araujo109; Juan Torres-Macho265; Lilian Torres-Tobar266; Ronald P. Torres Gutiérrez222; Jesús Troya249; Miguel Urioste210; Juan Valencia-Ramos267; Agustín Valido35,268; Juan Pablo Vargas Gallo269,270; Belén Varón271; Tomas Vega272; Santiago Velasco-Quirce273; Valentina Vélez-Santamaría93,94; Virginia Víctor50,51; Julia Vidán Estévez25; Gabriela V. Silva109; Miriam Vieitez-Santiago59,135; Carlos Vilches274; Lavinia Villalobos25; Felipe Villar221; Judit Villar-Garcia275,276,277; Cristina Villaverde3,40; Pablo VillosladaBlanco175; Ana Virseda-Berdices81; Tatiana X. Costa278; Zuleima Yáñez34; Antonio Zapatero Gaviria279; Ruth Zarate280; Sandra Zazo241; Carlos Flores106,107,154; José A. Riancho59,60,135; Augusto Rojas-Martinez281; Pablo Lapunzina3,11,12; Ángel Carracedo3,8,9,10,13The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) has an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome events (CME) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (CME and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, CME and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people.The authors acknowledge support from the Catalan Department of Economy and Knowledge (SGR2017/1974, SGR2017/801) and the Spanish Ministry of Science “Programa de Excelencia María de Maeztu” (MDM-2014-0370) and “Centro de Excelencia Severo Ochoa” (CEX2018-000806-S), the Fondo Europeo de Desarrollo Regional, UE (RTI2018-100789-B-I00) and the Estonian Research Council (PUT1660). Authors also receive support from the Generalitat de Catalunya through the CERCA Program.N

Clinical utility of chromosomal microarray analysis in invasive prenatal diagnosis

Novel methodologies for detection of chromosomal abnormalities have been made available in the recent years but their clinical utility in prenatal settings is still unknown. We have conducted a comparative study of currently available methodologies for detection of chromosomal abnormalities after invasive prenatal sampling. A multicentric collection of a 1-year series of fetal samples with indication for prenatal invasive sampling was simultaneously evaluated using three screening methodologies: (1) karyotype and quantitative fluorescent polymerase chain reaction (QF-PCR), (2) two panels of multiplex ligation-dependent probe amplification (MLPA), and (3) chromosomal microarray-based analysis (CMA) with a targeted BAC microarray. A total of 900 pregnant women provided informed consent to participate (94% acceptance rate). Technical performance was excellent for karyotype, QF-PCR, and CMA (~1% failure rate), but relatively poor for MLPA (10% failure). Mean turn-around time (TAT) was 7 days for CMA or MLPA, 25 for karyotype, and two for QF-PCR, with similar combined costs for the different approaches. A total of 57 clinically significant chromosomal aberrations were found (6.3%), with CMA yielding the highest detection rate (32% above other methods). The identification of variants of uncertain clinical significance by CMA (17, 1.9%) tripled that of karyotype and MLPA, but most alterations could be classified as likely benign after proving they all were inherited. High acceptability, significantly higher detection rate and lower TAT, could justify the higher cost of CMA and favor targeted CMA as the best method for detection of chromosomal abnormalities in at-risk pregnancies after invasive prenatal sampling

Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850). A significant proportion of ASD cases display biochemical alterations suggestive of mitochondrial dysfunction and several studies have reported that mutations in the mitochondrial DNA (mtDNA) molecule could be involved in the disease phenotype.</p> <p>Methods</p> <p>We analysed a cohort of 148 patients with idiopathic ASD for a number of mutations proposed in the literature as pathogenic in ASD. We also carried out a case control association study for the most common European haplogroups (hgs) and their diagnostic single nucleotide polymorphisms (SNPs) by comparing cases with 753 healthy and ethnically matched controls.</p> <p>Results</p> <p>We did not find statistical support for an association between mtDNA mutations or polymorphisms and ASD.</p> <p>Conclusions</p> <p>Our results are compatible with the idea that mtDNA mutations are not a relevant cause of ASD and the frequent observation of concomitant mitochondrial dysfunction and ASD could be due to nuclear factors influencing mitochondrion functions or to a more complex interplay between the nucleus and the mitochondrion/mtDNA.</p

The RD-Connect Genome-Phenome Analysis Platform: Accelerating diagnosis, research, and gene discovery for rare diseases.

Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative

13 páginas,1 figura, 3 tablas, 1 apéndice. Se extraen los autores pertenecientes a The CIBERER network que trabajan en Centros del CSIC del Appendix ACIBER (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 (RDs) 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 RDs. 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 article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research.This study has been funded by Instituto de Salud Carlos III (ISCIII) and Spanish Ministry of Science and InnovationPeer reviewe

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.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 (RDs) 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 RDs. 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 article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research