DNA methylation and chromosome instability in lymphoblastoid cell lines

Vilain, Armelle; Bernardino, Jacqueline; Gerbault-Seureau, M.; Vogt, Nicolas; Niveleau, Alain; Lefrançois, D.; Malfoy, Bernard; Dutrillaux, Bernard

doi:10.1159/000015641

Cited by 53 publications

(39 citation statements)

References 33 publications

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“…It is suggested that EBV may alter the DNA methylation status of some genes, 34 but it has not been well characterized how and to what extent the EBV alters DNA methylation status. To exclude the effect of EBV, we analyzed methylation status of PPIEL in leukocytes of this pair of discordant twins.…”

Section: Methodological Considerationsmentioning

confidence: 99%

Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins

et al. 2007

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To search DNA methylation difference between monozygotic twins discordant for bipolar disorder, we applied a comprehensive genome scan method, methylation-sensitive representational difference analysis (MS-RDA) to lymphoblastoid cells derived from the twins. MS-RDA isolated 10 DNA fragments derived from 5 0 region of known genes/ESTs. Among these 10 regions, four regions showed DNA methylation differences between bipolar twin and control co-twin confirmed by bisulfite sequencing. We performed a case-control study of DNA methylation status of these four regions by pyrosequencing. Two regions, upstream regions of spermine synthase (SMS) and peptidylprolyl isomerase E-like (PPIEL) (CN265253), showed aberrant DNA methylation status in bipolar disorder. SMS, a gene on X chromosome, showed significantly higher DNA methylation level in female patients with bipolar disorder compared with control females. However, there was no difference of mRNA expression. In PPIEL, DNA methylation level was significantly lower in patients with bipolar II disorder than in controls. The expression level of PPIEL was significantly higher in bipolar II disorder than in controls. We found strong inverse correlation between gene expression and DNA methylation levels of PPIEL. These results suggest that altered DNA methylation statuses of PPIEL might have some significance in pathophysiology of bipolar disorder.

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Section: Methodological Considerationsmentioning

confidence: 99%

Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins

et al. 2007

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“…However, EpsteinBarr virus that is used for transformation may alter the DNA methylation status of some genes. 80 Transposon may become active during cell culture, especially when the DNA methylation inhibitor, 5-aza-deoxycitidine (5-aza-dC), is applied. 81 In both cases, the possible effects of blood transfusion in utero might obscure the difference between twins.…”

Section: Methodological Considerations and Future Strategiesmentioning

confidence: 99%

Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders

et al. 2005

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Classical twin research focused on differentiating genetic factors from environmental factors by comparing the concordance rate between monozygotic (MZ) and dizygotic twins. On the other hand, recent twin research tries to identify genetic or epigenetic differences between MZ twins discordant for mental disorders. There are a number of reports of MZ twins discordant for genetic disorders caused by genetic or epigenetic differences of known pathogenic genes. In the case of mental disorder research, for which the causative gene has not been established yet, we are trying to identify the 'pathogenic gene' by comprehensive analysis of genetic or epigenetic difference between discordant MZ twins. To date, no compelling evidence suggesting such difference between MZ twins has been reported. However, if the genetic or epigenetic difference responsible for the discordant phenotype is found, it will have impact on the biology of mental disorder, in which few conclusive molecular genetic evidences have been obtained.

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“…40 In clinical settings, it is very difficult to obtain blood samples from bipolar patients who are not taking any drugs.…”

Section: Biomarkers Of Bipolar Disorder T Kato Et Almentioning

confidence: 99%

Gene expression analysis in lymphoblastoid cells as a potential biomarker of bipolar disorder

et al. 2011

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Although there is an urgent need for biological diagnosis of bipolar disorder (BD), there have been no established biomarkers. Gene expression analysis in lymphoblastoid cells (LCLs) would be a promising candidate for biomarkers. In this study, 17 candidate genes were measured in the LCLs of patients with BD. Using the data of the first set of samples (13 patients with bipolar I disorder and 21 controls), three genes, ANK3, RASGRP1 and POLG1, were selected by the logistic regression analysis with a stepwise method. Using the discriminant function generated by this analysis, the first sample was discriminated with the sensitivity of 76% and specificity of 85%. By applying the same function to the second sample set (18 patients with bipolar I and 37 controls), bipolar I disorder could be discriminated from the controls with the sensitivity of 44% and specificity of 81% (v 2 ¼3.97, P¼0.046). This study was the first to suggest a possible role of gene expression analysis of ANK3, RASGRP1 and POLG1 in the LCLs as potential biomarkers of BD.

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DNA methylation and chromosome instability in lymphoblastoid cell lines

Cited by 53 publications

References 33 publications

Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins

Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins

Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders

Gene expression analysis in lymphoblastoid cells as a potential biomarker of bipolar disorder

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