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5 results on '"Avila‐Fernandez, Almudena"'

1. A crowdsourcing database for the copy-number variation of the spanish population

Author

López-López, Daniel, Roldán, Gema, Fernández-Rueda, Jose L., Bostelmann, Gerrit, Carmona, Rosario, Aquino, Virginia, Perez-Florido, Javier, Ortuño, Francisco, Pita, Guillermo, Núñez-Torres, Rocío, González-Neira, Anna, Alonso, Angel, Salgado-Garrido, Josefa, Pasalodos-Sanchez, Sara, Ayuso, Carmen, Minguez, Pablo, Avila-Fernandez, Almudena, Corton, Marta, Artuch, Rafael, Borrego, Salud, Antiñolo, Guillermo, Carracedo, Angel, Amigo, Jorge, Castaño, Luis Antonio, Tejada, Isabel, Delmiro, Aitor, Espinos, Carmina, Grinberg, Daniel, Guillén, Encarnación, Lapunzina, Pablo, Lopez-Escámez, Jose Antonio, Gallego-Martinez, Alvaro, Martí, Ramón, Rovira, Eulalia, Millán, José Mª, Moreno, Miguel Angel, Morin, Matías, Moreno-Galdó, Antonio, Fernández-Cancio, Mónica, Morte, Beatriz, Mulero, Victoriano, García, Diana, Nunes, Virginia, Palau, Francesc, Perez, Belén, Jurado, Luis Pérez, Perona, Rosario, Pujol, Aurora, Ramos, Feliciano, Lopez, Esther, Ribes, Antonia, Rosell, Jordi, Surrallés, Jordi, Peña-Chilet, María, Dopazo, Joaquin, Universidad Pública de Navarra. Departamento de Ciencias de la Salud, and Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila

Subjects
Copy-number variation, Espanya -- Població, Drug Discovery, Genetics, Molecular Medicine, Proveïment participatiu, Espanya -- Estadístiques, Molecular Biology, Spanish population
Abstract

Background Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants. Results Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/. Conclusion SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database.

Published
2023

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

Author

Peña-Chilet, María, Roldán Gema, Perez-Florido, Javier, Ortuño, Francisco M., Carmona, Rosario, Aquino, Virginia, Lopez-Lopez, Daniel, Loucera, Carlos, Fernandez-Rueda, Jose L., Gallego, Asunción, García-García, Francisco, González-Neira, Anna, Pita, Guillermo, Núñez-Torres, Rocío, Santoyo-López, Javier, Ayuso, Carmen, Minguez, Pablo, Avila-Fernandez, Almudena, Corton, Marta, Moreno-Pelayo, Miguel Ángel, Morin, Matías, Gallego-Martinez, Alvaro, Lopez-Escamez, Jose A., Borrego, Salud, Antiñolo, Guillermo, Amigo, Jorge, Salgado-Garrido, Josefa, Pasalodos-Sanchez, Sara, Morte, Beatriz, The Spanish Exome Crowdsourcing Consortium, Carracedo Álvarez, Ángel, Alonso, Ángel, Dopazo, Joaquín, Grinberg Vaisman, Daniel Raúl, [Peña-Chilet,M, Roldán,G, Perez-Florido,J, Ortuño,FM, Carmona,R, Aquino,V, Lopez-Lopez,D, Loucera,C, Fernandez-Rueda,JL, Dopazo,J] Clinical Bioinformatics Area, Fundacion Progreso y Salud (FPS), Hospital Virgen del Rocío, Sevilla, Spain. [Peña-Chilet,M, Dopazo,J] Bioinformatics in Rare Diseases (BiER), Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Sevilla, Spain. [Peña-Chilet,M, Dopazo,J] Computational Systems Medicine group, Institute of Biomedicine of Seville (IBIS) Hospital Virgen del Rocío, Sevilla, Spain. [Perez-Florido,J, Dopazo,J] Functional Genomics Node, FPS/ELIXIR-ES, Hospital Virgen del Rocío, Sevilla, Spain. [Gallego,A] Sistemas Genomicos, Paterna, Valencia, Spain. [García-Garcia,F] Unidad de Bioinformatica y Bioestadística, Centro de Investigacion Príncipe Felipe (CIPF), Valencia, Spain. [González-Neira,A, Pita,G, Núñez-Torres,R] Human Genotyping Unit–Centro Nacional de Genotipado (CEGEN), Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Santoyo-López,J] Edinburgh Genomics, The University of Edinburgh, Edinburgh, UK. [Ayuso,C, Minguez,P, Avila-Fernandez,A, Corton,M] Department of Genetics, Instituto de Investigacion Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), Madrid, Spain. [Minguez,P] Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. [Moreno-Pelayo,MÁ, Morin,M] Servicio de Genetica, Ramón y Cajal Institute of Health Research (IRYCIS) and Biomedical Network Research Centre on Rare Diseases (CIBERER), Madrid, Spain, [Gallego-Martinez,A, Lopez-Escamez,JA] Otology & Neurotology Group CTS 495, Department of Genomic Medicine, Centre for Genomics and Oncological Research (GENYO), Pfizer University of Granada, Granada, Spain. [Gallego-Martinez,A, Lopez-Escamez,JA] Department of Otolaryngology, Instituto de Investigacion Biosanitaria, IBS. GRANADA, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain. [Borrego,S, Antiñolo,G] Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville (IBIS), University Hospital Virgen del Rocío /CSIC/University of Seville, Seville, Spain. [Borrego,S, Antiñolo,G] Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain. [Amigo,J, Carracedo,Á] Fundacion Pública Galega de Medicina Xenómica, SERGAS, IDIS, Santiago de Compostela, Spain. [Salgado-Garrido,J, Pasalodos-Sanchez,S, Alonso,Á] Navarrabiomed-IdiSNA, Complejo Hospitalario de Navarra, Universidad Publica de Navarra (UPNA), IdiSNA (Navarra Institute for Health Research), Pamplona, Navarra, Spain. [Morte,B] Undiagnosed Rare Diseases Programme (ENoD). Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. [Carracedo,Á] Grupo de Medicina Xenomica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), CIMUS, Universidade de Santiago de Compostela, Santiago de Compostela, España., Spanish Ministry of Economy and Competitiveness [SAF2017-88908-R, PT17/0009/0006 to J.D., PI19/00321 and CIBERER ACCI-06/07/0036 to C.A., PI14-948, PI17-1659 and CIBERER ACCI-06/07/0036 to M.A.M.P.], Regional Government of Madrid, RAREGenomics CM [B2017/BMD-3721 to C.A. and B2017/BMD3721 to M.A.M.P.], all co-funded with European Regional Development Funds (ERDF) as well as EU H2020-INFRADEV-1-2015-1 ELIXIR-EXCELERATE [676559], University Chair UAM-IIS-FJD of Genomic Medicine and the Ramon Areces Foundation also supported this work. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [SAF2017-88908-R]., Ministerio de Economía, Industria y Competitividad (España), Comunidad de Madrid, European Commission, Fundación Ramón Areces, Ministerio de Economía y Competitividad (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), and Universidad Autónoma de Madrid

Subjects
Genetics, population, Població, AcademicSubjects/SCI00010, computer.software_genre, Bases de dades, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Gene Frequency, Genética de poblaciones, Databases, Genetic, Database Issue, Exome, Precision Medicine, 0303 health sciences, education.field_of_study, Database, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genetics, Population [Medical Subject Headings], Chromosome Mapping, Genomics, Bases de datos genéticas, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome, Human [Medical Subject Headings], 3. Good health, Databases, genetic, Information Science::Information Science::Data Collection::Crowdsourcing [Medical Subject Headings], Crowdsourcing, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Chromosome Mapping::Physical Chromosome Mapping [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], Participación colectiva, Population, Proveïment participatiu, Biology, Variación genética, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Exome [Medical Subject Headings], Genètica de poblacions humanes, 03 medical and health sciences, Databases, Information Science::Information Science::Information Storage and Retrieval::Databases as Topic::Databases, Factual::Databases, Genetic [Medical Subject Headings], Genetic variation, Genetics, Humans, Genetic variability, Espanya, education, Allele frequency, Alleles, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], 030304 developmental biology, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Internet, Genoma humà -- Espanya, business.industry, Genome, Human, Genetic Variation, Human population genetics, Gene frequency, Frecuencia génica, Genetics, Population, Spain, Personalized medicine, business, Phenomena and Processes::Genetic Phenomena::Gene Frequency [Medical Subject Headings], computer, 030217 neurology & neurosurgery, Imputation (genetics), Software
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 variabilityworldwide. CSVS is also part of the GA4GH Beacon network., Spanish Ministry of Economy and Competitiveness SAF2017-88908-R PT17/0009/0006 PI19/00321 CIBERER ACCI-06/07/0036 PI14-948 PI171659, Regional Government of Madrid, RAREGenomicsCM B2017/BMD3721 B2017/BMD-3721, European Union (EU), European Union (EU) 676559, University Chair UAM-IIS-FJD of Genomic Medicine, Ramon Areces Foundation

Published
2020

3. A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice.

Author

Sanchez-Alcudia, Rocio, Garcia-Hoyos, Maria, Lopez-Martinez, Miguel Angel, Sanchez-Bolivar, Noelia, Zurita, Olga, Gimenez, Ascension, Villaverde, Cristina, Rodrigues-Jacy da Silva, Luciana, Corton, Marta, Perez-Carro, Raquel, Torriano, Simona, Kalatzis, Vasiliki, Rivolta, Carlo, Avila-Fernandez, Almudena, Lorda, Isabel, Trujillo-Tiebas, Maria J., Garcia-Sandoval, Blanca, Lopez-Molina, Maria Isabel, Blanco-Kelly, Fiona, and Riveiro-Alvarez, Rosa

Subjects
CHOROIDEREMIA, GENETICS of retinal degeneration, GENETIC mutation, GENETIC code, GERANYLGERANYLTRANSFERASES, EYE diseases, PATIENTS
Abstract

Choroideremia (CHM) is a rare X-linked disease leading to progressive retinal degeneration resulting in blindness. The disorder is caused by mutations in the CHM gene encoding REP-1 protein, an essential component of the Rab geranylgeranyltransferase (GGTase) complex. In the present study, we evaluated a multi-technique analysis algorithm to describe the mutational spectrum identified in a large cohort of cases and further correlate CHM variants with phenotypic characteristics and biochemical defects of choroideremia patients. Molecular genetic testing led to the characterization of 36 out of 45 unrelated CHM families (80%), allowing the clinical reclassification of four CHM families. Haplotype reconstruction showed independent origins for the recurrent p.Arg293* and p.Lys178Argfs*5 mutations, suggesting the presence of hotspots in CHM, as well as the identification of two different unrelated events involving exon 9 deletion. No certain genotype-phenotype correlation could be established. Furthermore, all the patients´ fibroblasts analyzed presented significantly increased levels of unprenylated Rabs proteins compared to control cells; however, this was not related to the genotype. This research demonstrates the major potential of the algorithm proposed for diagnosis. Our data enhance the importance of establish a differential diagnosis with other retinal dystrophies, supporting the idea of an underestimated prevalence of choroideremia. Moreover, they suggested that the severity of the disorder cannot be exclusively explained by the genotype. [ABSTRACT FROM AUTHOR]

Published
2016
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4. Dominant Retinitis Pigmentosa, p.Gly56Arg Mutation in NR2E3: Phenotype in a Large Cohort of 24 Cases.

Author

Blanco-Kelly, Fiona, García Hoyos, María, Lopez Martinez, Miguel Angel, Lopez-Molina, Maria Isabel, Riveiro-Alvarez, Rosa, Fernandez-San Jose, Patricia, Avila-Fernandez, Almudena, Corton, Marta, Millan, Jose M., García Sandoval, Blanca, and Ayuso, Carmen

Subjects
RETINITIS pigmentosa, GENETIC mutation, PHENOTYPES, HAPLOTYPES, COHORT analysis, PATIENTS
Abstract

Importance: This research is the single largest NR2E3 genotype-phenotype correlation study performed to date in autosomal dominant Retinitis Pigmentosa. Objective: The aim of this study is to analyse the frequency of the p.Gly56Arg mutation in NR2E3 for the largest cohort of autosomal dominant Retinitis Pigmentosa patients to date and its associated phenotype. Patients and Methods: A cohort of 201 unrelated Spanish families affected by autosomal dominant Retinitis Pigmentosa. The p.Gly56Arg mutation in the NR2E3 (NM_014249.2) gene was analysed in 201 families. In the 24 cases where the mutation had been detected, a haplotype analysis linked to the p.Gly56Arg families was performed, using four extragenic polymorphic markers D15S967, D15S1050, D15S204 and D15S188. Phenotype study included presence and age of onset of night blindness, visual field loss and cataracts; and an ophthalmoscopic examination after pupillary dilation and electroretinogram for the 24 cases. Results: Seven of the 201 analyzed families were positive for the p.Gly56Arg, leading to a prevalence of 3.5%. Clinical data were available for 24 subjects. Night blindness was the first noticeable symptom (mean 15.9 years). Visual field loss onset was variable (23.3 ± 11.9 years). Loss of visual acuity appeared late in the disease´s evolution. Most of the patients with cataracts (50%) presented it from the third decade of life. Fundus changes showed inter and intrafamiliar variability, but most of the patients showed typical RP changes and it was common to find macular affectation (47.4%). Electroretinogram was impaired from the beginning of the disease. Two families shared a common haplotype. Additionally, all patients shared a 104Kb region between D15S1050 and the NR2E3 gene. Conclusions: This study highlights the importance of p.Gly56Arg in the NR2E3 gene as a common mutation associated with adRP, and provides new clues to its phenotype, which can allow for a better clinical management and genetic counselling of patients and their families. [ABSTRACT FROM AUTHOR]

Published
2016
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5. Identification of an RP1 Prevalent Founder Mutation and Related Phenotype in Spanish Patients with Early-Onset Autosomal Recessive Retinitis

Author

Avila-Fernandez, Almudena, Corton, Marta, Nishiguchi, Koji M., Muñoz-Sanz, Nelida, Benavides-Mori, Belen, Blanco-Kelly, Fiona, Riveiro-Alvarez, Rosa, Garcia-Sandoval, Blanca, Rivolta, Carlo, and Ayuso, Carmen

Subjects
*RETINITIS pigmentosa, *GENETIC disorders, *RETINAL degeneration, *HOMOZYGOSITY, *GENETIC mutation, *HAPLOTYPES, *VISUAL acuity, *OPTICAL coherence tomography, *GENETICS, *PATIENTS
Abstract

Objective: To identify the genetic causes underlying early-onset autosomal recessive retinitis pigmentosa (arRP) in the Spanish population and describe the associated phenotype. Design: Case series. Participants: A total of 244 unrelated families affected by early-onset arRP. Methods: Homozygosity mapping or exome sequencing analysis was performed in 3 families segregating arRP. A mutational screening was performed in 241 additional unrelated families for the p.Ser452Stop mutation. Haplotype analysis also was conducted. Individuals who were homozygotes, double heterozygotes, or carriers of mutations in RP1 underwent an ophthalmic evaluation to establish a genotype–phenotype correlation. Main Outcome Measures: DNA sequence variants, homozygous regions, haplotypes, best-corrected visual acuity, visual field assessments, electroretinogram responses, and optical coherence tomography images. Results: Four novel mutations in RP1 were identified. The new mutation p.Ser542Stop was present in 11 of 244 (4.5%) of the studied families. All chromosomes harboring this mutation shared the same haplotype. All patients presented a common phenotype with an early age of onset and a prompt macular degeneration, whereas the heterozygote carriers did not show any signs of retinitis pigmentosa (RP). Conclusions: p.Ser542Stop is a single founder mutation and the most prevalent described mutation in the Spanish population. It causes early-onset RP with a rapid macular degeneration and is responsible for 4.5% of all cases. Our data suggest that the implication of RP1 in arRP may be underestimated. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Published
2012
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