title: Host genetic variants and gene expression patterns associated with Epstein-Barr virus copy number in lymphoblastoid cell lines.
abstract: 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.
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Division of Biological Anthropology, Department of Archaeology and Anthropology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Charlotte J
authors.initials: CJ
authors.lastname: Houldcroft
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Velislava
authors.initials: V
authors.lastname: Petrova
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Jimmy Z
authors.initials: JZ
authors.lastname: Liu
authors.affiliation: Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom.
authors.forename: Dan
authors.initials: D
authors.lastname: Frampton
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Anderson
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Astrid
authors.initials: A
authors.lastname: Gall
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Department of Infection, Division of Infection and Immunity, University College London, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002461:Cell Line, Transformed; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D018628:Gene Dosage; D005786:Gene Expression Regulation; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D059467:Transcriptome