267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
| Autor: | Salud Borrego, Javier Santoyo-Lopez, Alicia Vela-Boza, Marta Bleda, Olivia Spleiss, Luz Garcia-Alonso, Joaquín Dopazo, Francisco García-García, Pablo Arce, Macarena Ruiz-Ferrer, Alicia Amadoz, Juan Antonio Rodríguez, Antonio Rueda, Guillermo Antiñolo, Josephine T. Daub, Arcadi Navarro, Cristina Méndez-Vidal, Miguel Álvarez-Tejado, Gerard Muntané, Javier Florido, Alejandro Alemán, Francisco J. López-Domingo, Todd E. Arnold, Shomi S. Bhattacharya |
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| Přispěvatelé: | Centro de Investigación Biomédica en Red Enfermedades Raras (España), Instituto de Salud Carlos III, Generalitat Valenciana, European Commission, Fundació La Marató de TV3, Generalitat de Catalunya, Ministerio de Economía y Competitividad (España), Junta de Andalucía, Universidad de Sevilla. Departamento de Cirugía, Ministerio de Economía y Competitividad (MINECO). España |
| Rok vydání: | 2016 |
| Předmět: |
Exome sequencing
0301 basic medicine disease variants Population Drug Resistance Genome-wide association study Biology Pharmacogenomic Variants Population variability 03 medical and health sciences Gene Frequency Genetic variation Genetics Humans Disease Exome Genetic Predisposition to Disease Allele education Molecular Biology Allele frequency Discoveries Ecology Evolution Behavior and Systematics Internet education.field_of_study Polymorphism Genetic Disease variants Genetic Variation pharmacogenomic variants Pharmacogenomic Testing Genetics Population Farmacogenòmica 030104 developmental biology Spain population variability Pharmacogenomic variants Databases Nucleic Acid exome sequencing Common disease-common variant |
| Zdroj: | MOLECULAR BIOLOGY AND EVOLUTION r-CIPF: Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Centro de Investigación Principe Felipe (CIPF) Digital.CSIC. Repositorio Institucional del CSIC instname r-FISABIO. Repositorio Institucional de Producción Científica r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) Molecular Biology and Evolution Recercat. Dipósit de la Recerca de Catalunya idUS. Depósito de Investigación de la Universidad de Sevilla |
| ISSN: | 0737-4038 1537-1719 |
| Popis: | Dopazo, Joaquín et al. Recent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalog of local variability motivated the whole-exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one-third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including ~10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes, and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies to distinguish real disease associations from population-specific polymorphisms. © 2016 The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. The MGP is a joint initiative between the Consejería de Salud de la Junta de Andalucía and Roche, supported by the “Programa Nacional de Proyectos de investigación Aplicada,” I+D+i 2008, “Subprograma de actuaciones Científicas y Tecnológicas en Parques Científicos y Tecnológicos” (ACTEPARQ 2009), and European Regional Development Funds (ERDF). This work is also supported by grants BIO2014-57291-R and BFU2012-38236 from the Spanish Ministry of Economy and Competitiveness and “Plataforma de Recursos Biomoleculares y Bioinformáticos” PT 13/0001/0030 from the ISCIII, both cofunded with ERDF; grants PI1102923 and PI1001290 from the Fondo de Investigación Sanitaria, PROMETEOII/2014/025 from the Generalitat Valenciana (GVA-FEDER), FP7-PEOPLE-2012-ITN MLPM2012 318861 from the EU FP7, Fundació la Marató TV3 [20133134], and by Direcció General de Recerca, Generalitat de Catalunya (2014SGR1311). The CIBER de Enfermedades Raras is an Instituto de Salud Carlos III initiative. |
| Databáze: | OpenAIRE |
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