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Host genetic variants and gene expression patterns associated with Epstein-Barr virus copy number in lymphoblastoid cell lines

Title: Host genetic variants and gene expression patterns associated with Epstein-Barr virus copy number in lymphoblastoid cell lines
Authors: Houldcroft, CJ
Petrova, V
Liu, JZ
Frampton, D
Anderson, CA
Gall, A
Kellam, P
Item Type: Journal Article
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.
Issue Date: 7-Oct-2014
Date of Acceptance: 20-Aug-2014
URI: http://hdl.handle.net/10044/1/69568
DOI: https://dx.doi.org/10.1371/journal.pone.0108384
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS ONE
Volume: 9
Issue: 10
Copyright Statement: © 2014 Houldcroft 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.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GENOME-WIDE ASSOCIATION
IN-VIVO
HODGKIN LYMPHOMA
B-CELL
SUSCEPTIBILITY
DIFFERENTIATION
DETERMINANTS
POLYMORPHISM
INFECTION
GENOTYPES
B-Lymphocytes
Cell Line, Transformed
Epstein-Barr Virus Infections
Gene Dosage
Gene Expression Regulation
Genetic Variation
Genome-Wide Association Study
Herpesvirus 4, Human
Humans
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Transcriptome
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: e108384
Online Publication Date: 2014-10-07
Appears in Collections:Department of Medicine



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