1. Transcribed B lymphocyte genes and multiple sclerosis risk genes are underrepresented in Epstein–Barr Virus hypomethylated regions
- Author
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Sanjay Swaminathan, Grant P Parnell, Graeme J. Stewart, Lawrence T C Ong, Ali Afrasiabi, and David R. Booth
- Subjects
0301 basic medicine ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Multiple Sclerosis ,Cellular differentiation ,Lymphocyte ,Immunology ,Bisulfite sequencing ,Single-nucleotide polymorphism ,Biology ,medicine.disease_cause ,Article ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Genetics ,medicine ,Humans ,Promoter Regions, Genetic ,Gene ,Genetics (clinical) ,B-Lymphocytes ,B cells ,DNA methylation ,Methylation ,Epstein–Barr virus ,030104 developmental biology ,medicine.anatomical_structure ,030217 neurology & neurosurgery - Abstract
Epstein–Barr Virus (EBV) infection appears to be necessary for the development of Multiple Sclerosis (MS), although the specific mechanisms are unknown. More than 200 single-nucleotide polymorphisms (SNPs) are known to be associated with the risk of developing MS. About a quarter of these are also highly associated with proximal gene expression in B cells infected with EBV (lymphoblastoid cell lines—LCLs). The DNA of LCLs is hypomethylated compared with both uninfected and activated B cells. Since methylation can affect gene expression, and so cell differentiation and immune evasion, we hypothesised that EBV-driven hypomethylation may affect the interaction between EBV infection and MS. We interrogated an existing dataset comprising three individuals with whole-genome bisulfite sequencing data from EBV transformed B cells and CD40L-activated B cells. DNA methylation surrounding MS risk SNPs associated with gene expression in LCLs (LCLeQTL) was less likely to be hypomethylated than randomly selected chromosomal regions. Differential methylation was independent of genomic features such as promoter regions, but genes preferentially expressed in EBV-infected B cells, including the LCLeQTL genes, were underrepresented in the hypomethylated regions. Our data does not indicate MS genetic risk is affected by EBV hypomethylation.
- Published
- 2019