Houldcroft Charlotte J, Petrova Velislava, Liu Jimmy Z, Frampton Dan, Anderson Carl A, Gall Astrid, Kellam Paul
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.
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
PLoS One. 2014 Oct 7;9(10):e108384. doi: 10.1371/journal.pone.0108384. eCollection 2014.
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.
淋巴母细胞系（LCLs）常用于分子遗传学领域，为国际人类基因组单体型图计划（HapMap）和千人基因组计划提供DNA，用于测试化疗药物，并为许多关于基因表达的群体遗传学研究提供基础。将人类B细胞转化为LCLs的过程需要爱泼斯坦-巴尔病毒（EBV）的存在，这是一种双链DNA病毒，它通过B细胞永生化，在LCLs的每个细胞中以可变拷贝数维持一种游离病毒基因组。先前的研究报道，EBV会改变宿主基因表达，且EBV拷贝数可能受宿主遗传控制。我们对LCLs中的EBV基因组拷贝数进行了全基因组关联研究，发现该表型具有高度遗传性，尽管没有单个单核苷酸多态性（SNP）与EBV拷贝数达到显著关联。两个宿主基因（CXCL16和AGL）的表达呈正相关，而ADARB2的表达与EBV拷贝数呈负相关，且不依赖于基因型。这项研究显示了EBV拷贝数与LCLs基因表达谱之间的关联，并表明在未来关于LCLs宿主基因表达的研究中，应将EBV拷贝数视为一个协变量。
