Genetic factors affecting EBV copy number in lymphoblastoid cell lines derived from the 1000 Genome Project samples

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  • dc.contributor.author Mandage, Rajendra, 1984-ca
  • dc.contributor.author Telford, Marco, 1984-ca
  • dc.contributor.author Rodríguez, Juan Antonioca
  • dc.contributor.author Farré, Xavierca
  • dc.contributor.author Layouni, Hafidca
  • dc.contributor.author Marigorta, Urko M.ca
  • dc.contributor.author Cundiff, Caitlinca
  • dc.contributor.author Heredia Genestar, José María, 1985-ca
  • dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-ca
  • dc.contributor.author Santpere Baró, Gabriel, 1981-ca
  • dc.date.accessioned 2017-11-06T17:40:26Z
  • dc.date.available 2017-11-06T17:40:26Z
  • dc.date.issued 2017
  • dc.description.abstract Epstein-Barr virus (EBV), human herpes virus 4, has been classically associated with infectious mononucleosis, multiple sclerosis and several types of cancers. Many of these diseases show marked geographical differences in prevalence, which points to underlying genetic and/or environmental factors. Those factors may include a different susceptibility to EBV infection and viral copy number among human populations. Since EBV is commonly used to transform B-cells into lymphoblastoid cell lines (LCLs) we hypothesize that differences in EBV copy number among individual LCLs may reflect differential susceptibility to EBV infection. To test this hypothesis, we retrieved whole-genome sequenced EBV-mapping reads from 1,753 LCL samples derived from 19 populations worldwide that were sequenced within the context of the 1000 Genomes Project. An in silico methodology was developed to estimate the number of EBV copy number in LCLs and validated these estimations by real-time PCR. After experimentally confirming that EBV relative copy number remains stable over cell passages, we performed a genome wide association analysis (GWAS) to try detecting genetic variants of the host that may be associated with EBV copy number. Our GWAS has yielded several genomic regions suggestively associated with the number of EBV genomes per cell in LCLs, unraveling promising candidate genes such as CAND1, a known inhibitor of EBV replication. While this GWAS does not unequivocally establish the degree to which genetic makeup of individuals determine viral levels within their derived LCLs, for which a larger sample size will be needed, it potentially highlighted human genes affecting EBV-related processes, which constitute interesting candidates to follow up in the context of EBV related pathologies
  • dc.description.sponsorship This work was supported by Instituto de Salud Carlos III (ES) (RD07/0060); Spanish Government Grants (BFU2012-38236); Departament d'Innovació, Universitats I Empresa, Generalitat de Catalunya (2014SGR1311); Instituto de Salud Carlos III (PT13/0001/0026); FEDER (Fondo Europeo de Desarrollo Regional)/FSE (Fondo Social Europeo).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Mandage R, Telford M, Rodríguez JA, Farré X, Layouni H, Marigorta UM, [et al]. Genetic factors affecting EBV copy number in lymphoblastoid cell lines derived from the 1000 Genome Project samples. PLoS One. 2017 Jun 27;12(6):e0179446. DOI: 10.1371/journal.pone.0179446
  • dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0179446
  • dc.identifier.issn 1932-6203
  • dc.identifier.uri http://hdl.handle.net/10230/33152
  • dc.language.iso eng
  • dc.publisher Public Library of Science (PLoS)ca
  • dc.relation.ispartof PLoS One. 2017 Jun 27;12(6):e0179446
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-38236
  • dc.rights © 2017 Mandage et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Cell Line, Tumor
  • dc.subject.keyword Computer Simulation
  • dc.subject.keyword DNA Copy Number Variations
  • dc.subject.keyword DNA, Viral/genetics
  • dc.subject.keyword Herpesvirus 4, Human/genetics
  • dc.subject.keyword Polymorphism, Single Nucleotide
  • dc.title Genetic factors affecting EBV copy number in lymphoblastoid cell lines derived from the 1000 Genome Project samplesca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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Articles (Departament de Medicina i Ciències de la Vida)
Articles (Center for Genomic Regulation (CRG))