Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Brennan, Eoin; Ehrich, Mathias; Brazil, Derek P.; Crean, John; Murphy, Madeline; Sadlier, Denise; Martin, Finian; Godson, Catherine; McKnight, Amy Jayne; Boom, Dirk van den; Maxwell, Alexander P.; Savage, David A.

doi:10.4161/epi.4.3.8793

Cited by 33 publications

(33 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The largest differences in methylation profile were localized in areas of low CpG density. 28 This is consistent with our finding that, compared to other cell types, the lowest methylation levels measured by LUMA were seen in LCL, and the levels of LUMA measured in LCL were not correlated with any of the other cell types (Gran, MN and WBC). We did not observe lower methylation levels for the three repetitive elements which contain much of the CpG methylation in LCL.…”

Section: Resultssupporting

confidence: 82%

“…Combined measures of Alu methylation profiles in WBC and LCL. 28 However, a subset of genes (~8%) had regions that were differentially methylated in the two sources. The largest differences in methylation profile were localized in areas of low CpG density.…”

Section: Resultsmentioning

confidence: 99%

“…There is concern about the utility of LCL as a resource for methylation studies as it may be likely that through the transformation process to extend the replication capacity of the cells, global DNA methylation levels may decrease. 28 A study comparing DNA methylation profiles between WBC and EBV-transformed LCL from the same individuals found that the majority of genes have similar 3 H]-methyl acceptance assay and concluded that the two assays had good and DNA methylation status of specific sequences has also been found to be correlated with neutrophil count, suggesting different cell types have alternative ways to regulate expression of their genome. 30 While such evidence supports the presence of differential methylation patterns in different blood cell subsets, it cannot readily explain some of our results, such as why MN DNA methylation correlates so closely with WBC methylation.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Global methylation profiles in DNA from different blood cell types

et al. 2011

View full text Add to dashboard Cite

Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Global methylation profiles in DNA from different blood cell types

et al. 2011

View full text Add to dashboard Cite

“…[1][2][3][4] Although LCL DNA has been used to investigate associations between methylation markers and phenotypes, 5 it is less clear whether it is equally suitable for methylation investigations. [6][7][8] A number of targeted studies indicate that EBV transformation affects the methylation pattern, 9,10 and a recent study comparing DNA from primary B-lymphocytes and their corresponding LCLs, using 427 000 markers mainly located in CpG-rich regions, has shown that gene regulation is changed during EBV transformation. 6 Other studies using similar protocols to investigate CpG-rich regions have shown that the correlations between the methylation patterns in DNA from WB and LCL are high (r40.9).…”

Section: Introductionmentioning

confidence: 99%

Methylome-wide comparison of human genomic DNA extracted from whole blood and from EBV-transformed lymphocyte cell lines

et al. 2012

View full text Add to dashboard Cite

DNA from Epstein-Barr virus-transformed lymphocyte cell lines (LCLs) has proven useful for studies of genetic sequence polymorphisms. Whether LCL DNA is suitable for methylation studies is less clear. We conduct a genome-wide methylation investigation using an array set with 45 million probes to investigate the methylome of LCL DNA and technical duplicates of WB DNA from the same 10 individuals. We focus specifically on methylation sites that show variation between individuals and, therefore, are potentially useful as biomarkers. The sample correlations for the methylation variable probes ranged from 0.69 to 0.78 for the WB duplicates and from 0.27 to 0.72 for WB vs LCL. To compare the pattern of the methylation signals, we grouped adjacent probes based on their inter-correlations. These analyses showed B29 000 and B14 000 blocks in WB and LCL, respectively. Merely 31% of the methylated regions detected in WB were detectable in LCLs. Furthermore, we observed significant differences in mean difference between WB and LCL as compared with duplicates of WB (P-value ¼2.2Â10 À16 ). Our study shows that there are substantial differences in the DNA methylation patterns between LCL and WB. Thus, LCL DNA should not be used as a proxy for WB DNA in methylome-wide studies. European Journal of Human Genetics (2012) 20, 953-955; doi:10.1038/ejhg.2012 published online 29 February 2012 Keywords: DNA methylation; methylome; inter-individual variation; biomarkers INTRODUCTIONIt is common to extract DNA from Epstein-Barr virus (EBV)-transformed lymphocyte cell lines (LCLs). This provides an almost unlimited amount of DNA, which has proven very useful for studies of genetic sequence polymorphisms. [1][2][3][4] Although LCL DNA has been used to investigate associations between methylation markers and phenotypes, 5 it is less clear whether it is equally suitable for methylation investigations. [6][7][8] A number of targeted studies indicate that EBV transformation affects the methylation pattern, 9,10 and a recent study comparing DNA from primary B-lymphocytes and their corresponding LCLs, using 427 000 markers mainly located in CpG-rich regions, has shown that gene regulation is changed during EBV transformation. 6 Other studies using similar protocols to investigate CpG-rich regions have shown that the correlations between the methylation patterns in DNA from WB and LCL are high (r40.9). 7,8 In this article, we focus specifically on methylation sites that show variation between individuals and, therefore, are potentially useful as biomarkers in disease studies. As such sites may not be in CpG-rich regions, 11 we use a genome-wide (tiling array) approach, which is not limited to pre-selected regions of interest. Similar approaches have been used to study the methylome of, for example, human brain samples 12 and Arabidopsis. 13 In total, we investigate 45 million probes per sample in 30 methylomes from 10 individuals. To identify the sites that reliably measure inter-individual variation in methylation in WB, we use technical dupl...

show abstract

“…21,22 The identification of DNA methylation marks in cell models of DN, which if replicated in diabetic individuals with nephropathy, could be useful biomarkers and localize gene targets for novel therapies.…”

Section: Discussionmentioning

confidence: 99%