Host genetic variants and gene expression patterns associated with Epstein-Barr virus copy number in lymphoblastoid cell lines
Lymphoblastoid cell lines (LCLs) are commonly used in molecular genetics, supplying DNA for the HapMap and 1000 Genomes Projects, used to test chemotherapeutic agents, and informing the basis of a number of population genetics studies of gene expression. The process of transforming human B cells int...
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| creator | Houldcroft, Charlotte J Petrova, Velislava Liu, Jimmy Z Frampton, Dan Anderson, Carl A Gall, Astrid Kellam, Paul |
| description | Lymphoblastoid cell lines (LCLs) are commonly used in molecular genetics, supplying DNA for the HapMap and 1000 Genomes Projects, used to test chemotherapeutic agents, and informing the basis of a number of population genetics studies of gene expression. The process of transforming human B cells into LCLs requires the presence of Epstein-Barr virus (EBV), a double-stranded DNA virus which through B-cell immortalisation maintains an episomal virus genome in every cell of an LCL at variable copy numbers. Previous studies have reported that EBV alters host-gene expression and EBV copy number may be under host genetic control. We performed a genome-wide association study of EBV genome copy number in LCLs and found the phenotype to be highly heritable, although no individual SNPs achieved a significant association with EBV copy number. The expression of two host genes (CXCL16 and AGL) was positively correlated and expression of ADARB2 was negatively correlated with EBV copy number in a genotype-independent manner. This study shows an association between EBV copy number and the gene expression profile of LCLs, and suggests that EBV copy number should be considered as a covariate in future studies of host gene expression in LCLs. |
| doi_str_mv | 10.1371/journal.pone.0108384 |
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The process of transforming human B cells into LCLs requires the presence of Epstein-Barr virus (EBV), a double-stranded DNA virus which through B-cell immortalisation maintains an episomal virus genome in every cell of an LCL at variable copy numbers. Previous studies have reported that EBV alters host-gene expression and EBV copy number may be under host genetic control. We performed a genome-wide association study of EBV genome copy number in LCLs and found the phenotype to be highly heritable, although no individual SNPs achieved a significant association with EBV copy number. The expression of two host genes (CXCL16 and AGL) was positively correlated and expression of ADARB2 was negatively correlated with EBV copy number in a genotype-independent manner. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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The process of transforming human B cells into LCLs requires the presence of Epstein-Barr virus (EBV), a double-stranded DNA virus which through B-cell immortalisation maintains an episomal virus genome in every cell of an LCL at variable copy numbers. Previous studies have reported that EBV alters host-gene expression and EBV copy number may be under host genetic control. We performed a genome-wide association study of EBV genome copy number in LCLs and found the phenotype to be highly heritable, although no individual SNPs achieved a significant association with EBV copy number. The expression of two host genes (CXCL16 and AGL) was positively correlated and expression of ADARB2 was negatively correlated with EBV copy number in a genotype-independent manner. This study shows an association between EBV copy number and the gene expression profile of LCLs, and suggests that EBV copy number should be considered as a covariate in future studies of host gene expression in LCLs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25290448</pmid><doi>10.1371/journal.pone.0108384</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | B cells B-Lymphocytes - metabolism B-Lymphocytes - pathology B-Lymphocytes - virology Biology and life sciences Biotechnology Blood diseases Cell Line, Transformed Chemotherapy College campuses Copy number CXCL16 protein Cytokines Cytomegalovirus Deoxyribonucleic acid Disease DNA Epstein-Barr virus Epstein-Barr Virus Infections - genetics Epstein-Barr Virus Infections - immunology Epstein-Barr Virus Infections - virology Gene Dosage Gene expression Gene Expression Regulation Genes Genetic aspects Genetic control Genetic diversity Genetic research Genetic variance Genetic Variation Genetics Genome-wide association studies Genome-Wide Association Study Genomes Genomics Genotypes Herpesvirus 4, Human - genetics Herpesvirus 4, Human - immunology Humans Infections Lymphoblastoid cell lines Lymphocytes B Lymphoma Medicine and Health Sciences Phenotypes Polymorphism, Single Nucleotide Population genetics Population studies Quantitative Trait Loci Research and Analysis Methods Single nucleotide polymorphisms Single-nucleotide polymorphism Studies Transcriptome Viruses |
| title | Host genetic variants and gene expression patterns associated with Epstein-Barr virus copy number in lymphoblastoid cell lines |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T04%3A03%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Host%20genetic%20variants%20and%20gene%20expression%20patterns%20associated%20with%20Epstein-Barr%20virus%20copy%20number%20in%20lymphoblastoid%20cell%20lines&rft.jtitle=PloS%20one&rft.au=Houldcroft,%20Charlotte%20J&rft.date=2014-10-07&rft.volume=9&rft.issue=10&rft.spage=e108384&rft.pages=e108384-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0108384&rft_dat=%3Cgale_plos_%3EA418708157%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1609101152&rft_id=info:pmid/25290448&rft_galeid=A418708157&rft_doaj_id=oai_doaj_org_article_c75620679ee645e0937996230d767a5f&rfr_iscdi=true |