Search

Your search keyword '"Cortón, Marta"' showing total 160 results
Start Over Author "Cortón, Marta"
160 results on '"Cortón, Marta"'

4. Comprehensive Genotyping and Phenotyping Analysis of GUCY2D-Associated Rod- and Cone-Dominated Dystrophies

Author

Rodilla, Cristina, Martín-Merida, Inmaculada, Blanco-Kelly, Fiona, Trujillo-Tiebas, María José, Avila-Fernandez, Almudena, Riveiro-Alvarez, Rosa, del Pozo-Valero, Marta, Perea-Romero, Irene, Swafiri, Saoud Tahsin, Zurita, Olga, Villaverde, Cristina, López, Miguel Ángel, Romero, Raquel, Iancu, Ionut Florin, Núñez-Moreno, Gonzalo, Jiménez-Rolando, Belén, Martin-Gutierrez, María Pilar, Carreño, Ester, Minguez, Pablo, García-Sandoval, Blanca, Ayuso, Carmen, and Corton, Marta

Published
2023
Full Text
View/download PDF

5. An evaluation of pipelines for DNA variant detection can guide a reanalysis protocol to increase the diagnostic ratio of genetic diseases

Author

Romero, Raquel, de la Fuente, Lorena, Del Pozo-Valero, Marta, Riveiro-Álvarez, Rosa, Trujillo-Tiebas, María José, Martín-Mérida, Inmaculada, Ávila-Fernández, Almudena, Iancu, Ionut-Florin, Perea-Romero, Irene, Núñez-Moreno, Gonzalo, Damián, Alejandra, Rodilla, Cristina, Almoguera, Berta, Cortón, Marta, Ayuso, Carmen, and Mínguez, Pablo

Published
2022
Full Text
View/download PDF

6. RPE65-related retinal dystrophy: Mutational and phenotypic spectrum in 45 affected patients

Author

Lopez-Rodriguez, Rosario, Lantero, Esther, Blanco-Kelly, Fiona, Avila-Fernandez, Almudena, Martin Merida, Inmaculada, del Pozo-Valero, Marta, Perea-Romero, Irene, Zurita, Olga, Jiménez-Rolando, Belén, Swafiri, Saoud Tahsin, Riveiro-Alvarez, Rosa, Trujillo-Tiebas, María José, Carreño Salas, Ester, García-Sandoval, Blanca, Corton, Marta, and Ayuso, Carmen

Published
2021
Full Text
View/download PDF

8. IL-6–based mortality prediction model for COVID-19: Validation and update in multicenter and second wave cohorts

Author

Utrero-Rico, Alberto, Ruiz-Hornillos, Javier, González-Cuadrado, Cecilia, Rita, Claudia Geraldine, Almoguera, Berta, Minguez, Pablo, Herrero-González, Antonio, Fernández-Ruiz, Mario, Carretero, Octavio, Taracido-Fernández, Juan Carlos, López-Rodriguez, Rosario, Corton, Marta, Aguado, José María, Villar, Luisa María, Ayuso-García, Carmen, Paz-Artal, Estela, and Laguna-Goya, Rocio

Published
2021
Full Text
View/download PDF

9. Genotype–Phenotype Correlations in a Spanish Cohort of 506 Families With Biallelic ABCA4 Pathogenic Variants

Author

Del Pozo-Valero, Marta, Riveiro-Alvarez, Rosa, Blanco-Kelly, Fiona, Aguirre-Lamban, Jana, Martin-Merida, Inmaculada, Iancu, Ionut-Florin, Swafiri, Saoud, Lorda-Sanchez, Isabel, Rodriguez-Pinilla, Elvira, Trujillo-Tiebas, Maria José, Jimenez-Rolando, Belen, Carreño, Ester, Mahillo-Fernandez, Ignacio, Rivolta, Carlo, Corton, Marta, Avila-Fernandez, Almudena, Garcia-Sandoval, Blanca, and Ayuso, Carmen

Published
2020
Full Text
View/download PDF

10. NHEJ-Mediated Repair of CRISPR-Cas9-Induced DNA Breaks Efficiently Corrects Mutations in HSPCs from Patients with Fanconi Anemia

Author

Román-Rodríguez, Francisco José, Ugalde, Laura, Álvarez, Lara, Díez, Begoña, Ramírez, María José, Risueño, Cristina, Cortón, Marta, Bogliolo, Massimo, Bernal, Sara, March, Francesca, Ayuso, Carmen, Hanenberg, Helmut, Sevilla, Julián, Rodríguez-Perales, Sandra, Torres-Ruiz, Raúl, Surrallés, Jordi, Bueren, Juan Antonio, and Río, Paula

Published
2019
Full Text
View/download PDF

13. Biallelic sequence and structural variants in RAX2 are a novel cause for autosomal recessive inherited retinal disease

Author

Van de Sompele, Stijn, Smith, Claire, Karali, Marianthi, Corton, Marta, Van Schil, Kristof, Peelman, Frank, Cherry, Timothy, Rosseel, Toon, Verdin, Hannah, Derolez, Julien, Van Laethem, Thalia, Khan, Kamron N., McKibbin, Martin, Toomes, Carmel, Ali, Manir, Torella, Annalaura, Testa, Francesco, Jimenez, Belen, Simonelli, Francesca, De Zaeytijd, Julie, Van den Ende, Jenneke, Leroy, Bart P., Coppieters, Frauke, Ayuso, Carmen, Inglehearn, Chris F., Banfi, Sandro, and De Baere, Elfride

Published
2019
Full Text
View/download PDF

14. Androgen receptor polyQ alleles and COVID‐19 severity in men: A replication study

Author

López Rodríguez, Rosario, Ruiz Hornillos, Javier, Cortón, Marta, Almoguera, Berta, Minguez, Pablo, Pérez Tomás, María Elena, Barreda Sánchez, María, Mancebo, Esther, Ondo, Lorena, Martínez Ramas, Andrea, Fernández Caballero, Lidia, Taracido Fernández, Juan Carlos, Herrero González, Antonio, Mahillo, Ignacio, Paz Artal, Estela, Guillén Navarro, Encarna, Ayuso García, María del Carmen Tomasa, and UAM. Departamento de Medicina

Subjects
Androgen receptor, Sex-related differences, Endocrinology, Reproductive Medicine, Medicina, Urology, Endocrinology, Diabetes and Metabolism, COVID-19, PolyQ polymorphism, Biomarker
Abstract

Background: Ample evidence indicates a sex-related difference in severity of COVID19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID-19 severity. Objective: To test the association between the androgen receptor polyQ polymorphism and COVID-19 severity in a large cohort of COVID-19 male patients. Materials and methods: This study included 1136 male patients infected with SARSCoV-2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short ( 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation (COVID-19 Research Call; COV20/00181) co-financed by European Development Regional Fund (FEDER, A way to achieve Europe); Estrella de Levante (E G-N); Colabora Mujer (E G-N); Instituto de Salud Carlos III (Centro de Investigación en Red de Enfermedades Raras, CIBERer); IIS-Fundación Jiménez Díaz-UAM Chair in Genomic Medicine; Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation (Miguel Servet Contract Number: CP17/00006 and Juan Rodes Contract Number: JR17/00020) co-financied by European Regional Development Fund (FEDER); CEGEN-PRB3-ISCIII is funded by ISCIII and ERDF, Grant Number: PT17/0019

Published
2022
Full Text
View/download PDF

15. SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations

Author

Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Agencia Estatal de Investigación (España), Comunidad de Madrid, Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), Ministerio de Economía y Competitividad (España), Martínez-González, Brenda [0000-0002-4482-5181], Soria, María Eugenia [0000-0002-4719-3351], Lobo-Vega, Rebeca [0000-0002-4882-6763], Mínguez, Pablo [0000-0003-4099-9421], Llorens, Carlos [0000-0003-1402-4743], Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Cortón, Marta [0000-0003-0087-1626], García-Crespo, Carlos [0000-0001-6561-5389], Durán-Pastor, Antoni [0000-0002-4248-0554], Delgado, Soledad [0000-0003-4868-3712], López-Galíndez, Cecilio [0000-0002-2324-9584], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Salar-Vidal, Llanos [0000-0002-3052-0176], Esteban, Jaime [0000-0002-8971-3167], Ayuso, Carmen [0000-0002-9242-7065], Verdaguer, Núria [0000-0001-8826-7129], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Somovilla, Pilar, Durán-Pastor, Antoni, Gallego, Isabel, Ávila, Ana Isabel de, Delgado, Soledad, Morán, Federico, López-Galíndez, Cecilio, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban-Muñoz, Mario, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, Perales, Celia, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Agencia Estatal de Investigación (España), Comunidad de Madrid, Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), Ministerio de Economía y Competitividad (España), Martínez-González, Brenda [0000-0002-4482-5181], Soria, María Eugenia [0000-0002-4719-3351], Lobo-Vega, Rebeca [0000-0002-4882-6763], Mínguez, Pablo [0000-0003-4099-9421], Llorens, Carlos [0000-0003-1402-4743], Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Cortón, Marta [0000-0003-0087-1626], García-Crespo, Carlos [0000-0001-6561-5389], Durán-Pastor, Antoni [0000-0002-4248-0554], Delgado, Soledad [0000-0003-4868-3712], López-Galíndez, Cecilio [0000-0002-2324-9584], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Salar-Vidal, Llanos [0000-0002-3052-0176], Esteban, Jaime [0000-0002-8971-3167], Ayuso, Carmen [0000-0002-9242-7065], Verdaguer, Núria [0000-0001-8826-7129], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Somovilla, Pilar, Durán-Pastor, Antoni, Gallego, Isabel, Ávila, Ana Isabel de, Delgado, Soledad, Morán, Federico, López-Galíndez, Cecilio, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban-Muñoz, Mario, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, and Perales, Celia

Abstract

Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50- to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussed.

Published
2022

17. Exome Sequencing Extends the Phenotypic Spectrum for ABHD12 Mutations: From Syndromic to Nonsyndromic Retinal Degeneration

Author

Nishiguchi, Koji M., Avila-Fernandez, Almudena, van Huet, Ramon A.C., Corton, Marta, Pérez-Carro, Raquel, Martín-Garrido, Esther, López-Molina, María Isabel, Blanco-Kelly, Fiona, Hoefsloot, Lies H., van Zelst-Stams, Wendy A., García-Ruiz, Pedro J., del Val, Javier, Di Gioia, Silvio Alessandro, Klevering, B. Jeroen, van de Warrenburg, Bart P.C., Vazquez, Carlos, Cremers, Frans P.M., García-Sandoval, Blanca, Hoyng, Carel B., Collin, Rob W.J., Rivolta, Carlo, and Ayuso, Carmen

Published
2014
Full Text
View/download PDF

19. SARS-CoV-2 mutant spectra reveal differences between COVID-19 severity categories

Author

Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruíz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Somovilla, Pilar, Durán-Pastor, Antoni, Gallego, Isabel, Ávila, Ana Isabel de, Delgado, Soledad, Morán, Federico, López-Galíndez, Cecilio, Gómez, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban-Muñoz, Mario, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, Perales, Celia, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, European Commission, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), and Ministerio de Economía y Competitividad (España)

Abstract

Trabajo presentado en el XVI Congreso Nacional de Virología, celebrado en Málaga (España) del 06 al 09 de septiembre de 2022., RNA virus populations are composed of complex mixtures of genomes that are termed mutant spectra. SARS-CoV-2 replicates as a viral quasispecies, and mutations that are detected at low frequencies in a host can be dominant in subsequent variants. We have studied mutant spectrum complexities of SARS-CoV-2 populations derived from thirty nasopharyngeal swabs of patients infected during the first wave (April 2020) in the Hospital Universitario Fundación Jiménez Díaz. The patients were classified according to the COVID-19 severity in mild (non-hospitalized), moderate (hospitalized) and exitus (hospitalized with ICU admission and who passed away due to COVID-19). Using ultra-deep sequencing technologies (MiSeq, Illumina), we have examined four amplicons of the nsp12 (polymerase)-coding region and two amplicons of the spike-coding region. Ultra-deep sequencing data were analyzed with different cut-off frequency for mutation detection. Average number of different point mutations, mutations per haplotype and several diversity indices were significantly higher in SARS-CoV-2 isolated from patients who developed mild disease. A feature that we noted in the SARS-CoV-2 mutant spectra from diagnostic samples is the remarkable absence of mutations at intermediate frequencies, and an overwhelming abundance of mutations at frequencies lower than 10%. Thus, the decrease of the cut-off frequency for mutation detection from 0.5% to 0.1% revealed an increasement (50- to 100 fold) in the number of different mutations. The significantly higher frequency of mutations in virus from patients displaying mild than moderate or severe disease was maintained with the 0.1% cut- off frequency. To evaluate whether the frequency repertoire of amino acid substitutions differed between SARS-CoV-2 and the well characterized hepatitis C virus (HCV), we performed a comparative study of mutant spectra from infected patients using the same bioinformatics pipelines. HCV did not show the deficit of intermediate frequency substitutions that was observed with SARS-CoV-2. This difference was maintained when two functionally equivalent proteins, the corresponding viral polymerases, were compared. In conclusion, SARS-CoV-2 mutant spectra are rich reservoirs of mutants, whose complexity is not uniform among clinical isolates. Virus from patients who developed mild disease may be a source of new variants that may acquire epidemiological relevance., This work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and In-novation (COVID-19 Research Call COV20/00181), and co-financed by European Development Regional Fund ‘A way to achieve Europe’. The work was also supported by grants CSIC-COV19-014 from Consejo Superior de Investigaciones Científicas (CSIC), project 525/C/2021 from Fundació La Marató de TV3, PID2020-113888RB-I00 from Ministerio de Ciencia e Innovación, BFU2017-91384-EXP from Ministerio de Ciencia, Innovación y Universidades (MCIU), PI18/00210 and PI21/00139 from Instituto de Salud Carlos III, and S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). C.P., M.C., and P.M. are supported by the Miguel Servet programme of the Instituto de Salud Carlos III (CPII19/00001, CPII17/00006, and CP16/00116, respectively) co-financed by the European Regional Development Fund (ERDF). CIBERehd (Centro de Investi-gación en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). B.M.-G. is supported by predoctoral contract PFIS FI19/00119 from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo) cofinanced by Fondo Social Europeo (FSE). R.L.-V. is supported by predoctoral contract PEJD-2019-PRE/BMD-16414 from Comunidad de Madrid. C.G.-C. is sup-ported by predoctoral contract PRE2018-083422 from MCIU. BS was supported by a predoctoral research fellowship (Doctorados Industriales, DI-17-09134) from Spanish MINECO.

Published
2022

20. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Author

Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Fundación Banco Santander, Agencia Estatal de Investigación (España), Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Cortón, Marta [0000-0003-0087-1626], Martínez-González, Brenda [0000-0002-4482-5181], Lobo-Vega, Rebeca [0000-0002-4882-6763], Vázquez-Sirvent, Lucía [0000-0002-0396-7781], Mínguez, Pablo [0000-0003-4099-9421], Macías-Valcayo, Alicia [0000-0003-3879-0493], Esteban, Jaime [0000-0002-8971-3167], Gadea, Ignacio [0000-0003-4684-7816], Ayuso, Carmen [0000-0002-9242-7065], Perales, Celia [000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, Perales, Celia, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Fundación Banco Santander, Agencia Estatal de Investigación (España), Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Cortón, Marta [0000-0003-0087-1626], Martínez-González, Brenda [0000-0002-4482-5181], Lobo-Vega, Rebeca [0000-0002-4882-6763], Vázquez-Sirvent, Lucía [0000-0002-0396-7781], Mínguez, Pablo [0000-0003-4099-9421], Macías-Valcayo, Alicia [0000-0003-3879-0493], Esteban, Jaime [0000-0002-8971-3167], Gadea, Ignacio [0000-0003-4684-7816], Ayuso, Carmen [0000-0002-9242-7065], Perales, Celia [000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, and Perales, Celia

Abstract

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work was to determine a possible association between viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or death. Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab. Here we report a statistically significant association between viral load and disease severity, a high viral load being associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

Published
2021

22. Outcome of ABCA4 Disease-Associated Alleles in Autosomal Recessive Retinal Dystrophies: Retrospective Analysis in 420 Spanish Families

Author

Riveiro-Alvarez, Rosa, Lopez-Martinez, Miguel-Angel, Zernant, Jana, Aguirre-Lamban, Jana, Cantalapiedra, Diego, Avila-Fernandez, Almudena, Gimenez, Ascension, Lopez-Molina, Maria-Isabel, Garcia-Sandoval, Blanca, Blanco-Kelly, Fiona, Corton, Marta, Tatu, Sorina, Fernandez-San Jose, Patricia, Trujillo-Tiebas, Maria-Jose, Ramos, Carmen, Allikmets, Rando, and Ayuso, Carmen

Published
2013
Full Text
View/download PDF

24. Aggregated Genomic Data as Cohort-Specific Allelic Frequencies can Boost Variants and Genes Prioritization in Non-Solved Cases of Inherited Retinal Dystrophies

Author

Iancu, Ionut-Florin, primary, Perea-Romero, Irene, additional, Núñez-Moreno, Gonzalo, additional, de la Fuente, Lorena, additional, Romero, Raquel, additional, Ávila-Fernandez, Almudena, additional, Trujillo-Tiebas, María José, additional, Riveiro-Álvarez, Rosa, additional, Almoguera, Berta, additional, Martín-Mérida, Inmaculada, additional, Del Pozo-Valero, Marta, additional, Damián-Verde, Alejandra, additional, Cortón, Marta, additional, Ayuso, Carmen, additional, and Minguez, Pablo, additional

Published
2022
Full Text
View/download PDF

25. SARS-CoV-2 Mutant Spectra at Different Depth Levels Reveal an Overwhelming Abundance of Low Frequency Mutations

Author

Martínez-González, Brenda, primary, Soria, María Eugenia, additional, Vázquez-Sirvent, Lucía, additional, Ferrer-Orta, Cristina, additional, Lobo-Vega, Rebeca, additional, Mínguez, Pablo, additional, de la Fuente, Lorena, additional, Llorens, Carlos, additional, Soriano, Beatriz, additional, Ramos-Ruíz, Ricardo, additional, Cortón, Marta, additional, López-Rodríguez, Rosario, additional, García-Crespo, Carlos, additional, Somovilla, Pilar, additional, Durán-Pastor, Antoni, additional, Gallego, Isabel, additional, de Ávila, Ana Isabel, additional, Delgado, Soledad, additional, Morán, Federico, additional, López-Galíndez, Cecilio, additional, Gómez, Jordi, additional, Enjuanes, Luis, additional, Salar-Vidal, Llanos, additional, Esteban-Muñoz, Mario, additional, Esteban, Jaime, additional, Fernández-Roblas, Ricardo, additional, Gadea, Ignacio, additional, Ayuso, Carmen, additional, Ruíz-Hornillos, Javier, additional, Verdaguer, Nuria, additional, Domingo, Esteban, additional, and Perales, Celia, additional

Published
2022
Full Text
View/download PDF

26. Genetic variants near TIMP3 and high-density lipoprotein—associated loci influence susceptibility to age-related macular degeneration

Author

Chen, Wei, Stambolian, Dwight, Edwards, Albert O., Branham, Kari E., Othman, Mohammad, Jakobsdottir, Johanna, Tosakulwong, Nirubol, Pericak-Vance, Margaret A., Campochiaro, Peter A., Klein, Michael L., Tan, Perciliz L., Conley, Yvette P., Kanda, Atsuhiro, Kopplin, Laura, Li, Yanming, Augustaitis, Katherine J., Karoukis, Athanasios J., Scott, William K., Agarwal, Anita, Kovach, Jaclyn L., Schwartz, Stephen G., Postel, Eric A., Brooks, Matthew, Baratz, Keith H., Brown, William L., Brucker, Alexander J., Orlin, Anton, Brown, Gary, Ho, Allen, Regillo, Carl, Donoso, Larry, Tian, Lifeng, Kaderli, Brian, Hadley, Dexter, Hagstrom, Stephanie A., Peachey, Neal S., Klein, Ronald, Klein, Barbara E. K., Gotoh, Norimoto, Yamashiro, Kenji, Ferris,, Frederick, Fagerness, Jesen A., Reynolds, Robyn, Farrer, Lindsay A., Kim, Ivana K., Miller, Joan W., Cortón, Marta, Carracedo, Angel, Sanchez-Salorio, Manuel, Pugh, Elizabeth W., Doheny, Kimberly F., Brion, Maria, DeAngelis, Margaret M., Weeks, Daniel E., Zack, Donald J., Chew, Emily Y., Heckenlively, John R., Yoshimura, Nagahisa, Iyengar, Sudha K., Francis, Peter J., Katsanis, Nicholas, Seddon, Johanna M., Haines, Jonathan L., Gorin, Michael B., Abecasis, Gonçalo R., Swaroop, Anand, and Keating, Mark T.

Published
2010

27. Supplementary files of the article 'Novel genes and sex differences in COVID-19 severity' [Dataset]

Author

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

Published
2022

28. Novel genes and sex differences in COVID-19 severity

Author

Instituto de Salud Carlos III, European Commission, Fundación Amancio Ortega, Banco Santander, Estrella de Levante, Colabora Mujer, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Cruz Modino, Raquel de la, Diz-de Almeida, Silvia, López de Heredia, Miguel, Quintela, Inés, Ceballos, Francisco C., Pita, Guillermo, Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Gago-Dominguez, Manuela, Sevilla Porras, Marta, Tenorio Castaño, Jair Antonio, Carbonell, Cristina, Migeotte, Isabelle, Renieri, Alessandra, Aguilera-Albesa, Sergio, Planas, Anna M., Ludwig, Kerstin U., Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Tamayo-Velasco, Álvaro, Franke, Andre, Castaño, Luis, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Almadana Pacheco, Virginia, Richards, Brent, Ganna, Andrea, Boada, Mercè, Rojas, Itziar de, Gil-Fournier, Belén, Ruiz, Agustín, Sánchez-Juan, Pascual, Castelao, Jose E., Real, Luis Miguel, SCOURGE Cohort Group, HOSTAGE Cohort Group, GRA@CE Cohort Group, Almoguera, Berta, Guillen-Navarro, Encarna, Ayuso, Carmen, Gómez-Arrue, Javier, González-Neira, Anna, Riancho, José A., Rojas-Martinez, Augusto, Conde-Vicente, Rosa, Flores, Carlos, Lapunzina, Pablo, Carracedo, Ángel, Álvarez, Nuria, Andreu-Bernabeu, Álvaro, Arana-Arri, Eunate, González Álvarez, Beatriz, Arango, Celso, Arranz, Maria J., Artiga, María Jesús, Baptista-Rosas, Raúl C., Cordero-Lorenzana, M. Lourdes, Barreda-Sánchez, María, Belhassen-García, Moncef, Bezerra, Joao F., Bezerra, Marcos A. C., Boix-Palop, Lucía, Gonzalez Bernaldo de Quirós, Fernán, Briones, María, Brugada, Ramón, Bustos, Matilde, Cortés-Sánchez, José L., Cortón, Marta, Darnaude, M. Teresa, Martino-Rodríguez, Alba de, Tamayo, Eduardo, Campo-Pérez, Víctor de, Diaz de Bustamante, Aranzazu, González-Peñas, Javier, Domínguez-Garrido, Elena, Luchessi, Andre D., Eiros, Rocío, Estigarribia Sanabria, Gladys Mercedes, Fariñas, María del Carmen, Fernández-Robelo, Uxía, Fernández-Rodríguez, Amanda, Fernández-Villa, Tania, Gutiérrez-Bautista, Juan F., Herrero, María José, Herrero-Gonzalez, Antonio, Jiménez-Sousa, María A., Aguado, José María, Lattig, María Claudia, Taracido-Fernandez, Juan Carlos, Liger Borja, Anabel, López-Rodríguez, Rosario, Mancebo, Esther, Martín-López, Caridad, Martín, Vicente, Martínez-Nieto, Oscar, Martinez-López, Icíar, Martinez-Resendez, Michel F., Amitrano, Sara, Martínez-Pérez, Àngel, Mazzeu, Juliana F, Teper, Alejandro, Merayo Macías, Eleuterio, Mínguez, Pablo, Moreno Cuerda, Víctor, Silbiger, Vivian N., Oliveira, Silviene F., Ortega-Paino, Eva, Parellada, Mara, Roade, Luisa, Paz-Artal, Estela, Santos, Ney P. C., Pérez-Matute, Patricia, Torres-Tobar, Lilian, Pérez Ramírez, Patricia, Pérez-Tomás, M. Elena, Perucho, Teresa, Pinsach-Abuin, Mel Lina, Pompa-Mera, Ericka N., Porras-Hurtado, Gloria L., Fava, Francesca, Pujol, Aurora, Ramiro León, Soraya, Resino, Salvador, Fernandes, Marianne R., Urioste, Miguel, Rodríguez-Ruiz, Emilio, Rodríguez-Artalejo, Fernando, Rodríguez-García, José A, Ruiz Cabello, Francisco, Ruiz-Hornillos, Javier, Spinner, Christoph D., Ryan, Pablo, Soria, José Manuel, Souto, Juan Carlos, Valencia-Ramos, Juan, Yáñez, Zuleima, Zarate, Ruth, Nakanishi, Tomoko, Nevado, Julian, Pigazzini, Sara, Degenhardt, Frauke, Prati, Daniele, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Bujanda, Luis, Bouysran, Youssef, Palom, Adriana, Ellinghaus, David, Martínez-Bueno, Manuel, Rolker, Selina, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Calderón, Enrique J., Holter, Jan Cato, Aguilar, Carlos, Banales, Jesús M., Frithiof, Robert, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre C., Romero-Gómez, Manuel, Nafría-Jiménez, Beatriz, Hov, Johannes R., Instituto de Salud Carlos III, European Commission, Fundación Amancio Ortega, Banco Santander, Estrella de Levante, Colabora Mujer, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Cruz Modino, Raquel de la, Diz-de Almeida, Silvia, López de Heredia, Miguel, Quintela, Inés, Ceballos, Francisco C., Pita, Guillermo, Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Gago-Dominguez, Manuela, Sevilla Porras, Marta, Tenorio Castaño, Jair Antonio, Carbonell, Cristina, Migeotte, Isabelle, Renieri, Alessandra, Aguilera-Albesa, Sergio, Planas, Anna M., Ludwig, Kerstin U., Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Tamayo-Velasco, Álvaro, Franke, Andre, Castaño, Luis, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Almadana Pacheco, Virginia, Richards, Brent, Ganna, Andrea, Boada, Mercè, Rojas, Itziar de, Gil-Fournier, Belén, Ruiz, Agustín, Sánchez-Juan, Pascual, Castelao, Jose E., Real, Luis Miguel, SCOURGE Cohort Group, HOSTAGE Cohort Group, GRA@CE Cohort Group, Almoguera, Berta, Guillen-Navarro, Encarna, Ayuso, Carmen, Gómez-Arrue, Javier, González-Neira, Anna, Riancho, José A., Rojas-Martinez, Augusto, Conde-Vicente, Rosa, Flores, Carlos, Lapunzina, Pablo, Carracedo, Ángel, Álvarez, Nuria, Andreu-Bernabeu, Álvaro, Arana-Arri, Eunate, González Álvarez, Beatriz, Arango, Celso, Arranz, Maria J., Artiga, María Jesús, Baptista-Rosas, Raúl C., Cordero-Lorenzana, M. Lourdes, Barreda-Sánchez, María, Belhassen-García, Moncef, Bezerra, Joao F., Bezerra, Marcos A. C., Boix-Palop, Lucía, Gonzalez Bernaldo de Quirós, Fernán, Briones, María, Brugada, Ramón, Bustos, Matilde, Cortés-Sánchez, José L., Cortón, Marta, Darnaude, M. Teresa, Martino-Rodríguez, Alba de, Tamayo, Eduardo, Campo-Pérez, Víctor de, Diaz de Bustamante, Aranzazu, González-Peñas, Javier, Domínguez-Garrido, Elena, Luchessi, Andre D., Eiros, Rocío, Estigarribia Sanabria, Gladys Mercedes, Fariñas, María del Carmen, Fernández-Robelo, Uxía, Fernández-Rodríguez, Amanda, Fernández-Villa, Tania, Gutiérrez-Bautista, Juan F., Herrero, María José, Herrero-Gonzalez, Antonio, Jiménez-Sousa, María A., Aguado, José María, Lattig, María Claudia, Taracido-Fernandez, Juan Carlos, Liger Borja, Anabel, López-Rodríguez, Rosario, Mancebo, Esther, Martín-López, Caridad, Martín, Vicente, Martínez-Nieto, Oscar, Martinez-López, Icíar, Martinez-Resendez, Michel F., Amitrano, Sara, Martínez-Pérez, Àngel, Mazzeu, Juliana F, Teper, Alejandro, Merayo Macías, Eleuterio, Mínguez, Pablo, Moreno Cuerda, Víctor, Silbiger, Vivian N., Oliveira, Silviene F., Ortega-Paino, Eva, Parellada, Mara, Roade, Luisa, Paz-Artal, Estela, Santos, Ney P. C., Pérez-Matute, Patricia, Torres-Tobar, Lilian, Pérez Ramírez, Patricia, Pérez-Tomás, M. Elena, Perucho, Teresa, Pinsach-Abuin, Mel Lina, Pompa-Mera, Ericka N., Porras-Hurtado, Gloria L., Fava, Francesca, Pujol, Aurora, Ramiro León, Soraya, Resino, Salvador, Fernandes, Marianne R., Urioste, Miguel, Rodríguez-Ruiz, Emilio, Rodríguez-Artalejo, Fernando, Rodríguez-García, José A, Ruiz Cabello, Francisco, Ruiz-Hornillos, Javier, Spinner, Christoph D., Ryan, Pablo, Soria, José Manuel, Souto, Juan Carlos, Valencia-Ramos, Juan, Yáñez, Zuleima, Zarate, Ruth, Nakanishi, Tomoko, Nevado, Julian, Pigazzini, Sara, Degenhardt, Frauke, Prati, Daniele, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Bujanda, Luis, Bouysran, Youssef, Palom, Adriana, Ellinghaus, David, Martínez-Bueno, Manuel, Rolker, Selina, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Calderón, Enrique J., Holter, Jan Cato, Aguilar, Carlos, Banales, Jesús M., Frithiof, Robert, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre C., Romero-Gómez, Manuel, Nafría-Jiménez, Beatriz, and Hov, Johannes R.

Abstract

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (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 < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). 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 = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). 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.

Published
2022

29. SARS-CoV-2 mutant spectra reveal differences between COVID-19 severity categories

Author

Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, European Commission, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), Ministerio de Economía y Competitividad (España), Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Somovilla, Pilar, Durán-Pastor, Antoni, Gallego, Isabel, Ávila, Ana Isabel de, Delgado, Soledad, Morán, Federico, López-Galíndez, Cecilio, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban-Muñoz, Mario, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, Perales, Celia, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, European Commission, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), Ministerio de Economía y Competitividad (España), Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Somovilla, Pilar, Durán-Pastor, Antoni, Gallego, Isabel, Ávila, Ana Isabel de, Delgado, Soledad, Morán, Federico, López-Galíndez, Cecilio, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban-Muñoz, Mario, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, and Perales, Celia

Abstract

RNA virus populations are composed of complex mixtures of genomes that are termed mutant spectra. SARS-CoV-2 replicates as a viral quasispecies, and mutations that are detected at low frequencies in a host can be dominant in subsequent variants. We have studied mutant spectrum complexities of SARS-CoV-2 populations derived from thirty nasopharyngeal swabs of patients infected during the first wave (April 2020) in the Hospital Universitario Fundación Jiménez Díaz. The patients were classified according to the COVID-19 severity in mild (non-hospitalized), moderate (hospitalized) and exitus (hospitalized with ICU admission and who passed away due to COVID-19). Using ultra-deep sequencing technologies (MiSeq, Illumina), we have examined four amplicons of the nsp12 (polymerase)-coding region and two amplicons of the spike-coding region. Ultra-deep sequencing data were analyzed with different cut-off frequency for mutation detection. Average number of different point mutations, mutations per haplotype and several diversity indices were significantly higher in SARS-CoV-2 isolated from patients who developed mild disease. A feature that we noted in the SARS-CoV-2 mutant spectra from diagnostic samples is the remarkable absence of mutations at intermediate frequencies, and an overwhelming abundance of mutations at frequencies lower than 10%. Thus, the decrease of the cut-off frequency for mutation detection from 0.5% to 0.1% revealed an increasement (50- to 100 fold) in the number of different mutations. The significantly higher frequency of mutations in virus from patients displaying mild than moderate or severe disease was maintained with the 0.1% cut- off frequency. To evaluate whether the frequency repertoire of amino acid substitutions differed between SARS-CoV-2 and the well characterized hepatitis C virus (HCV), we performed a comparative study of mutant spectra from infected patients using the same bioinformatics pipelines. HCV did not show the deficit of intermediat

Published
2022

30. SARS-CoV-2 Point Mutation and Deletion Spectra and Their Association with Different Disease Outcomes

Author

Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Esteban, Jaime [0000-0002-8971-3167], Verdaguer, Núria [0000-0001-8826-7129], Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Gallego, Isabel, Ávila, Ana Isabel de, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, Perales, Celia, Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Esteban, Jaime [0000-0002-8971-3167], Verdaguer, Núria [0000-0001-8826-7129], Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Gallego, Isabel, Ávila, Ana Isabel de, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, and Perales, Celia

Abstract

Mutant spectra of RNA viruses are important to understand viral pathogenesis and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultradeep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)-coding regions of 30 nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low-frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype, and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three-dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19.

Published
2022

31. SARS-CoV-2 Point Mutation and Deletion Spectra, and Their Association with Different Disease Outcome

Author

Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), Ministerio de Economía y Competitividad (España), Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Esteban, Jaime [0000-0002-8971-3167], Verdaguer, Núria [0000-0001-8826-7129], Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Gallego, Isabel, Ávila, Ana Isabel de, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, Perales, Celia, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Fundació La Marató de TV3, Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Ramón Areces, Banco Santander, Ministerio de Sanidad y Consumo (España), Ministerio de Economía y Competitividad (España), Ramos-Ruiz, Ricardo [0000-0002-6331-9786], Enjuanes Sánchez, Luis [0000-0002-0854-0226], Esteban, Jaime [0000-0002-8971-3167], Verdaguer, Núria [0000-0001-8826-7129], Domingo, Esteban [0000-0002-0573-1676], Perales, Celia [0000-0003-1618-1937], Martínez-González, Brenda, Soria, María Eugenia, Vázquez-Sirvent, Lucía, Ferrer-Orta, Cristina, Lobo-Vega, Rebeca, Mínguez, Pablo, Fuente, Lorena de la, Llorens, Carlos, Soriano, Beatriz, Ramos-Ruiz, Ricardo, Cortón, Marta, López-Rodríguez, Rosario, García-Crespo, Carlos, Gallego, Isabel, Ávila, Ana Isabel de, Gómez-Castilla, Jordi, Enjuanes Sánchez, Luis, Salar-Vidal, Llanos, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ayuso, Carmen, Ruíz-Hornillos, Javier, Verdaguer, Núria, Domingo, Esteban, and Perales, Celia

Abstract

Mutant spectra of RNA viruses are important to understand viral pathogenesis, and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultra-deep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)-coding regions of thirty nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19.

Published
2022

32. SARS-CoV-2 Point Mutation and Deletion Spectra and Their Association with Different Disease Outcomes

Author

Martínez-González, Brenda, primary, Soria, María Eugenia, additional, Vázquez-Sirvent, Lucía, additional, Ferrer-Orta, Cristina, additional, Lobo-Vega, Rebeca, additional, Mínguez, Pablo, additional, de la Fuente, Lorena, additional, Llorens, Carlos, additional, Soriano, Beatriz, additional, Ramos, Ricardo, additional, Cortón, Marta, additional, López-Rodríguez, Rosario, additional, García-Crespo, Carlos, additional, Gallego, Isabel, additional, de Ávila, Ana Isabel, additional, Gómez, Jordi, additional, Enjuanes, Luis, additional, Salar-Vidal, Llanos, additional, Esteban, Jaime, additional, Fernandez-Roblas, Ricardo, additional, Gadea, Ignacio, additional, Ayuso, Carmen, additional, Ruíz-Hornillos, Javier, additional, Verdaguer, Nuria, additional, Domingo, Esteban, additional, and Perales, Celia, additional

Published
2022
Full Text
View/download PDF

34. Fine Breakpoint Mapping by Genome Sequencing Reveals the First Large X Inversion Disrupting the NHS Gene in a Patient with Syndromic Cataracts

Author

Damián, Alejandra, primary, Ionescu, Raluca Oancea, additional, Rodríguez de Alba, Marta, additional, Tamayo, Alejandra, additional, Trujillo-Tiebas, María José, additional, Cotarelo-Pérez, María Carmen, additional, Pérez Rodríguez, Olga, additional, Villaverde, Cristina, additional, de la Fuente, Lorena, additional, Romero, Raquel, additional, Núñez-Moreno, Gonzalo, additional, Mínguez, Pablo, additional, Ayuso, Carmen, additional, and Cortón, Marta, additional

Published
2021
Full Text
View/download PDF

36. Androgen receptor polyQ alleles and COVID‐19 severity in men: A replication study.

Author

López‐Rodríguez, Rosario, Ruiz‐Hornillos, Javier, Cortón, Marta, Almoguera, Berta, Minguez, Pablo, Pérez‐Tomás, María Elena, Barreda‐Sánchez, María, Mancebo, Esther, Ondo, Lorena, Martínez‐Ramas, Andrea, Fernández‐Caballero, Lidia, Taracido‐Fernández, Juan Carlos, Herrero‐González, Antonio, Mahillo, Ignacio, Paz‐Artal, Estela, Guillén‐Navarro, Encarna, and Ayuso, Carmen

Subjects
ANDROGEN receptors, COVID-19, ALLELES, LOGISTIC regression analysis
Abstract

Background: Ample evidence indicates a sex‐related difference in severity of COVID‐19, with less favorable outcomes observed in men. Genetic factors have been proposed as candidates to explain this difference. The polyglutamine (polyQ) polymorphism in the androgen receptor gene has been recently described as a genetic biomarker of COVID‐19 severity. Objective: To test the association between the androgen receptor polyQ polymorphism and COVID‐19 severity in a large cohort of COVID‐19 male patients. Materials and methods: This study included 1136 male patients infected with SARS‐CoV‐2 as confirmed by positive PCR. Patients were retrospectively and prospectively enrolled from March to November 2020. Patients were classified according to their severity into three categories: oligosymptomatic, hospitalized and severe patients requiring ventilatory support. The number of CAG repeats (polyQ polymorphism) at the androgen receptor was obtained by PCR and patients were classified as either short (<23 repeats) or long (≥23 repeats) allele carriers. The association between polyQ alleles (short or long) and COVID‐19 severity was assessed by Chi‐squared (Chi2) and logistic regression analysis. Results: The mean number of polyQ CAG repeats was 22 (±3). Patients were classified as oligosymptomatic (15.5%), hospitalized (63.2%), and severe patients (21.3%) requiring substantial respiratory support. PolyQ alleles distribution did not show significant differences between severity classes in our cohort (Chi2 test p > 0.05). Similar results were observed after adjusting by known risk factors such as age, comorbidities, and ethnicity (multivariate logistic regression analysis). Discussion: Androgen sensitivity may be a critical factor in COVID‐19 disease severity. However, we did not find an association between the polyQ polymorphism and the COVID‐19 severity. Additional studies are needed to clarify the mechanism underlying the association between androgens and COVID‐19 outcome. Conclusions: The results obtained in our study do not support the role of this polymorphism as biomarker of COVID‐19 severity. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

37. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Author

Soria, María Eugenia, primary, Cortón, Marta, additional, Martínez-González, Brenda, additional, Lobo-Vega, Rebeca, additional, Vázquez-Sirvent, Lucía, additional, López-Rodríguez, Rosario, additional, Almoguera, Berta, additional, Mahillo, Ignacio, additional, Mínguez, Pablo, additional, Herrero, Antonio, additional, Taracido, Juan Carlos, additional, Macías-Valcayo, Alicia, additional, Esteban, Jaime, additional, Fernandez-Roblas, Ricardo, additional, Gadea, Ignacio, additional, Ruíz-Hornillos, Javier, additional, Ayuso, Carmen, additional, and Perales, Celia, additional

Published
2021
Full Text
View/download PDF

38. Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment

Author

García-García, Gema, Sanchez-Navarro, Iker, Aller, Elena, Jaijo, Teresa, Fuster-Garcia, Carla, Rodríguez-Munoz, Ana, Vallejo, Elena, Tellería, Juan José, Vázquez, Selma, Beltrán, Sergi, Derdak, Sophia, Zurita, Olga, Villaverde-Montero, Cristina, Ávila-Fernández, Almudena, Cortón, Marta, Blanco-Kelly, Fiona, Hakonarson, Hakon, Millán, José M., Instituto de Salud Carlos III, Fundación ONCE, and Children’s Hospital of Philadelphia

Abstract

[Purpose]: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. [Methods]: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing. [Results]: The study allowed us to detect likely pathogenic variants in PEX6, a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf–blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism. [Conclusions]: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness–blindness association., This work was financially supported by grants of the Institute of Health Carlos III (ISCIII /FEDER), (Ref.: PI13/00638 PI16/00415, PI16/00539 and CIBER-ER 06/07/0036; Biobank FJD (RD09/0076/00101),); Fundación ONCE (Ref.: 2015/0398) ONCE & Fundaluce, Sponsored Chair IIS-FJD, UAM of Genomics Medicine. CNAG's 2013 call “300 exomes to elucidate rare diseases.” Institutional Development Fund at CAG from The Children’s Hospital of Philadelphia. CFG, ISN and MCP are recipients of fellowshipsfrom the ISCIII (Ref.: IFI14/00021; Sara Borrell CD13–00085 and Miguel Servet CPII17_00006 respectively). Carmen Ayuso (CAyuso@fjd.es) and José M. Millán (millan_jos@gva.es) are co-corresponding authors of this work

Published
2020

39. CSVS, a crowdsourcing database of the Spanish population genetic variability

Author

Ministerio de Economía y Competitividad (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Comunidad de Madrid, European Commission, Universidad Autónoma de Madrid, Fundación Ramón Areces, Peña-Chilet, María, Roldán, Gema, Pérez-Florido, Javier, Ortuño, Francisco M., Carmona, Rosario, Aquino, Virginia, López-López, Daniel, Loucera, Carlos, Fernández-Rueda, José L., Gallego, Asunción, García-García, Francisco, González-Neira, Anna, Pita, Guillermo, Núñez-Torres, Rocío, Santoyo-López, Javier, Ayuso, Carmen, Mínguez, Pablo, Ávila-Fernández, Almudena, Cortón, Marta, Moreno-Pelayo, Miguel Ángel, Morin, Matías, Gallego-Martinez, Álvaro, López-Escamez, José A., Borrego, Salud, Antiñolo, Guillermo, Amigo, Jorge, Salgado-Garrido, Josefa, Pasalodos-Sánchez, Sara, Morte, Beatriz, Spanish Exome Crowdsourcing Consortium, Carracedo, Ángel, Alonso, Ángel, Dopazo, Joaquín, Ministerio de Economía y Competitividad (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Comunidad de Madrid, European Commission, Universidad Autónoma de Madrid, Fundación Ramón Areces, Peña-Chilet, María, Roldán, Gema, Pérez-Florido, Javier, Ortuño, Francisco M., Carmona, Rosario, Aquino, Virginia, López-López, Daniel, Loucera, Carlos, Fernández-Rueda, José L., Gallego, Asunción, García-García, Francisco, González-Neira, Anna, Pita, Guillermo, Núñez-Torres, Rocío, Santoyo-López, Javier, Ayuso, Carmen, Mínguez, Pablo, Ávila-Fernández, Almudena, Cortón, Marta, Moreno-Pelayo, Miguel Ángel, Morin, Matías, Gallego-Martinez, Álvaro, López-Escamez, José A., Borrego, Salud, Antiñolo, Guillermo, Amigo, Jorge, Salgado-Garrido, Josefa, Pasalodos-Sánchez, Sara, Morte, Beatriz, Spanish Exome Crowdsourcing Consortium, Carracedo, Ángel, Alonso, Ángel, and Dopazo, Joaquín

Abstract

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/.

Published
2021

40. Author Correction: Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Author

Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Comunidad de Madrid, European Commission, ONCE, Fundación Ramón Areces, Fundación Conchita Rábago de Jiménez Díaz, Perea-Romero, Irene, Gordo, Gema, Iancu, Ionut F., Pozo-Valero, Marta del, Almoguera, Berta, Blanco-Kelly, Fiona, Carreño, Ester, Jiménez-Rolando, Belén, López-Rodríguez, Rosario, Lorda-Sánchez, Isabel, Martín Mérida, Inmaculada, Pérez de Ayala, Lucía, Riveiro-Álvarez, Rosa, Rodríguez-Pinilla, Elvira, Tahsin-Swafiri, Saoud, Trujillo-Tiebas, María J., García-Sandoval, Blanca, Mínguez, Pablo, Ávila-Fernández, Almudena, Cortón, Marta, Ayuso, Carmen, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Comunidad de Madrid, European Commission, ONCE, Fundación Ramón Areces, Fundación Conchita Rábago de Jiménez Díaz, Perea-Romero, Irene, Gordo, Gema, Iancu, Ionut F., Pozo-Valero, Marta del, Almoguera, Berta, Blanco-Kelly, Fiona, Carreño, Ester, Jiménez-Rolando, Belén, López-Rodríguez, Rosario, Lorda-Sánchez, Isabel, Martín Mérida, Inmaculada, Pérez de Ayala, Lucía, Riveiro-Álvarez, Rosa, Rodríguez-Pinilla, Elvira, Tahsin-Swafiri, Saoud, Trujillo-Tiebas, María J., García-Sandoval, Blanca, Mínguez, Pablo, Ávila-Fernández, Almudena, Cortón, Marta, and Ayuso, Carmen

Abstract

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.

Published
2021

41. Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Author

Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Comunidad de Madrid, European Commission, ONCE, Fundación Ramón Areces, Fundación Conchita Rábago de Jiménez Díaz, Perea-Romero, Irene, Gordo, Gema, Iancu, Ionut F., Pozo-Valero, Marta del, Almoguera, Berta, Blanco-Kelly, Fiona, Carreño, Ester, Jiménez-Rolando, Belén, López-Rodríguez, Rosario, Lorda-Sánchez, Isabel, Martín Mérida, Inmaculada, Pérez de Ayala, Lucía, Riveiro-Álvarez, Rosa, Rodríguez-Pinilla, Elvira, Tahsin-Swafiri, Saoud, Trujillo-Tiebas, María J., García-Sandoval, Blanca, Mínguez, Pablo, Ávila-Fernández, Almudena, Cortón, Marta, Ayuso, Carmen, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Comunidad de Madrid, European Commission, ONCE, Fundación Ramón Areces, Fundación Conchita Rábago de Jiménez Díaz, Perea-Romero, Irene, Gordo, Gema, Iancu, Ionut F., Pozo-Valero, Marta del, Almoguera, Berta, Blanco-Kelly, Fiona, Carreño, Ester, Jiménez-Rolando, Belén, López-Rodríguez, Rosario, Lorda-Sánchez, Isabel, Martín Mérida, Inmaculada, Pérez de Ayala, Lucía, Riveiro-Álvarez, Rosa, Rodríguez-Pinilla, Elvira, Tahsin-Swafiri, Saoud, Trujillo-Tiebas, María J., García-Sandoval, Blanca, Mínguez, Pablo, Ávila-Fernández, Almudena, Cortón, Marta, and Ayuso, Carmen

Abstract

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.

Published
2021

43. Gene Correction Recovers Phagocytosis in Retinal Pigment Epithelium Derived from Retinitis Pigmentosa-Human-Induced Pluripotent Stem Cells

Author

Artero-Castro, Ana, primary, Long, Kathleen, additional, Bassett, Andrew, additional, Ávila-Fernandez, Almudena, additional, Cortón, Marta, additional, Vidal-Puig, Antonio, additional, Jendelova, Pavla, additional, Rodriguez-Jimenez, Francisco, additional, Clemente, Eleonora, additional, Ayuso, Carmen, additional, and Erceg, Slaven, additional

Published
2021
Full Text
View/download PDF

45. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Author

Soria, María Eugenia, primary, Cortón, Marta, additional, Martínez-González, Brenda, additional, Lobo-Vega, Rebeca, additional, Vázquez-Sirvent, Lucía, additional, López-Rodríguez, Rosario, additional, Almoguera, Berta, additional, Mahillo, Ignacio, additional, Mínguez, Pablo, additional, Herrero, Antonio, additional, Taracido, Juan Carlos, additional, Macías-Valcayo, Alicia, additional, Esteban, Jaime, additional, Fernandez-Roblas, Ricardo, additional, Gadea, Ignacio, additional, Ruíz-Hornillos, Javier, additional, Ayuso, Carmen, additional, and Perales, Celia, additional

Published
2020
Full Text
View/download PDF

48. Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment

Author

Instituto de Salud Carlos III, Fundación ONCE, Children’s Hospital of Philadelphia, García-García, Gema, Sanchez-Navarro, Iker, Aller, Elena, Jaijo, Teresa, Fuster-Garcia, Carla, Rodríguez-Munoz, Ana, Vallejo, Elena, Tellería, Juan José, Vázquez, Selma, Beltrán, Sergi, Derdak, Sophia, Zurita, Olga, Villaverde-Montero, Cristina, Ávila-Fernández, Almudena, Cortón, Marta, Blanco-Kelly, Fiona, Hakonarson, Hakon, Millán, José M., Instituto de Salud Carlos III, Fundación ONCE, Children’s Hospital of Philadelphia, García-García, Gema, Sanchez-Navarro, Iker, Aller, Elena, Jaijo, Teresa, Fuster-Garcia, Carla, Rodríguez-Munoz, Ana, Vallejo, Elena, Tellería, Juan José, Vázquez, Selma, Beltrán, Sergi, Derdak, Sophia, Zurita, Olga, Villaverde-Montero, Cristina, Ávila-Fernández, Almudena, Cortón, Marta, Blanco-Kelly, Fiona, Hakonarson, Hakon, and Millán, José M.

Abstract

[Purpose]: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. [Methods]: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing. [Results]: The study allowed us to detect likely pathogenic variants in PEX6, a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf–blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism. [Conclusions]: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness–blindness association.

Published
2020

49. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Author

Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Lobo-Vega, Rebeca [0000-0002-4882-6763], Perales, Celia [0000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, Perales, Celia, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Lobo-Vega, Rebeca [0000-0002-4882-6763], Perales, Celia [0000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, and Perales, Celia

Abstract

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work is to determine a possible association between the viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we have clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or exitus. Here we report a statistically significant correlation between viral load and disease severity, being high viral load associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity, and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce the viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results