267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation

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,...

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Detalles Bibliográficos
Autores: Dopazo, Joaquín, Amadoz, Alicia, Bleda, Marta, Garcia Alonso, Luz, Daub, Josephine T., Antiñolo Gil, Guillermo, Bhattacharya, Shomi S.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/63711
Acceso en línea:http://hdl.handle.net/11441/63711
https://doi.org/10.1093/molbev/msw005
Access Level:acceso abierto
Palabra clave:Population variability
Exome sequencing
Disease variants
Pharmacogenomic variants
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spelling 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic VariationDopazo, JoaquínAmadoz, AliciaBleda, MartaGarcia Alonso, LuzDaub, Josephine T.Antiñolo Gil, GuillermoBhattacharya, Shomi S.Population variabilityExome sequencingDisease variantsPharmacogenomic variantsRecent 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.España, MINECO BIO2014-57291-R BFU2012-38236Oxford University PressCirugíaMinisterio de Economía y Competitividad (MINECO). España2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/11441/63711https://doi.org/10.1093/molbev/msw005reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésMolecular Biology and Evolution, 33 (5), 1205-1218.info:eu-repo/grantAgreement/MINECO/BIO2014-57291-R/info:eu-repo/grantAgreement/MINECO/BFU2012-38236/http://dx.doi.org/10.1093/molbev/msw005info:eu-repo/semantics/openAccessoai:idus.us.es:11441/637112026-06-17T12:51:07Z
dc.title.none.fl_str_mv 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
title 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
spellingShingle 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
Dopazo, Joaquín
Population variability
Exome sequencing
Disease variants
Pharmacogenomic variants
title_short 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
title_full 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
title_fullStr 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
title_full_unstemmed 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
title_sort 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation
dc.creator.none.fl_str_mv Dopazo, Joaquín
Amadoz, Alicia
Bleda, Marta
Garcia Alonso, Luz
Daub, Josephine T.
Antiñolo Gil, Guillermo
Bhattacharya, Shomi S.
author Dopazo, Joaquín
author_facet Dopazo, Joaquín
Amadoz, Alicia
Bleda, Marta
Garcia Alonso, Luz
Daub, Josephine T.
Antiñolo Gil, Guillermo
Bhattacharya, Shomi S.
author_role author
author2 Amadoz, Alicia
Bleda, Marta
Garcia Alonso, Luz
Daub, Josephine T.
Antiñolo Gil, Guillermo
Bhattacharya, Shomi S.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Cirugía
Ministerio de Economía y Competitividad (MINECO). España
dc.subject.none.fl_str_mv Population variability
Exome sequencing
Disease variants
Pharmacogenomic variants
topic Population variability
Exome sequencing
Disease variants
Pharmacogenomic variants
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11441/63711
https://doi.org/10.1093/molbev/msw005
url http://hdl.handle.net/11441/63711
https://doi.org/10.1093/molbev/msw005
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Molecular Biology and Evolution, 33 (5), 1205-1218.
info:eu-repo/grantAgreement/MINECO/BIO2014-57291-R/
info:eu-repo/grantAgreement/MINECO/BFU2012-38236/
http://dx.doi.org/10.1093/molbev/msw005
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
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