title: 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation.
abstract: 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.
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain Bioinformatics in Rare Diseases (BIER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain Functional Genomics Node, National Institute of Bioinformatics (INB), Valencia, Spain jdopazo@cipf.es gantinolo@us.es.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Amadoz
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain Bioinformatics in Rare Diseases (BIER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bleda
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Luz
authors.initials: L
authors.lastname: Garcia-Alonso
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain Bioinformatics in Rare Diseases (BIER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Alemán
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: García-García
authors.affiliation: Institut De Biologia Evolutiva, Consejo Superior de Investigaciones Científicas - Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rodriguez
authors.affiliation: Institut De Biologia Evolutiva, Consejo Superior de Investigaciones Científicas - Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Josephine T
authors.initials: JT
authors.lastname: Daub
authors.affiliation: Institut De Biologia Evolutiva, Consejo Superior de Investigaciones Científicas - Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Muntané
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rueda
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Vela-Boza
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Domingo
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Florido
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Arce
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/Consejo Superior de Investigaciones Científicas/University of Seville, Sevilla, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Sevilla, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Ruiz-Ferrer
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/Consejo Superior de Investigaciones Científicas/University of Seville, Sevilla, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Sevilla, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Méndez-Vidal
authors.affiliation: Research and Development, 454 Life Sciences, a Roche Company, Branford, CT, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Arnold
authors.affiliation: Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Spleiss
authors.affiliation: Roche Diagnostics SL, Sant Cugat del Vallès, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alvarez-Tejado
authors.affiliation: Departament of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain.
authors.forename: Arcadi
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Sevilla, Spain.
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/Consejo Superior de Investigaciones Científicas/University of Seville, Sevilla, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Sevilla, Spain.
authors.forename: Salud
authors.initials: S
authors.lastname: Borrego
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Santoyo-López
authors.affiliation: Medical Genome Project, Genomics and Bioinformatics Platform of Andalusia (GBPA), Sevilla, Spain Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocío/Consejo Superior de Investigaciones Científicas/University of Seville, Sevilla, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Sevilla, Spain jdopazo@cipf.es gantinolo@us.es.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Antiñolo
mesh_terms: D030561:Databases, Nucleic Acid; D004194:Disease / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D059472:Exome; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population / Q000379:methods; D006801:Humans; D020407:Internet; D000071185:Pharmacogenomic Testing; D011110:Polymorphism, Genetic; D013030:Spain / Q000453:epidemiology
keywords: disease variants; exome sequencing; pharmacogenomic variants.; population variability