首页 | 本学科首页   官方微博 | 高级检索  
   检索      


EBV transformation and cell culturing destabilizes DNA methylation in human lymphoblastoid cell lines
Authors:D Grafodatskaya  S Choufani  JC Ferreira  DT Butcher  Y Lou  C Zhao  SW Scherer  R Weksberg
Institution:1. Program in Genetic and Genomic Biology, Hospital for Sick Children Research Institute, 101 College street, Toronto, Ontario, Canada M5G 1L7;2. The Centre for Applied Genomics, The Hospital for Sick Children, 101 College street, Toronto, Ontario, Canada M5G 1L7;3. Division of Clinical and Metabolic Genetics, Hospital for Sick Children, 525 University Avenue, Toronto, Ontario, Canada M5G 2L3
Abstract:Recent research suggests that epigenetic alterations involving DNA methylation can be causative for neurodevelopmental, growth and metabolic disorders. Although lymphoblastoid cell lines have been an invaluable resource for the study of both genetic and epigenetic disorders, the impact of EBV transformation, cell culturing and freezing on epigenetic patterns is unknown. We compared genome-wide DNA methylation patterns of four white blood cell samples, four low-passage lymphoblastoid cell lines pre and post freezing and four high-passage lymphobastoid cell lines, using two microarray platforms: Illumina HumanMethylation27 platform containing 27,578 CpG sites and Agilent Human CpG island Array containing 27,800 CpG islands. Comparison of genome-wide methylation profiles between white blood cells and lymphoblastoid cell lines demonstrated methylation alterations in lymphoblastoid cell lines occurring at random genomic locations. These changes were more profound in high-passage cells. Freezing at low-passages did not have a significant effect on DNA methylation. Methylation changes were observed in several imprinted differentially methylated regions, including DIRAS3, NNAT, H19, MEG3, NDN and MKRN3, but not in known imprinting centers. Our results suggest that lymphoblastoid cell lines should be used with caution for the identification of disease-associated DNA methylation changes or for discovery of new imprinted genes, as the methylation patterns seen in these cell lines may not always be representative of DNA methylation present in the original B-lymphocytes of the patient.
Keywords:
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号