Dataset Information

Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome.

ABSTRACT:

Purpose

Recent studies have identified multilocus imprinting disturbances (MLIDs) in a subset of patients with imprinting diseases (IDs) caused by epimutations. We examined MLIDs in patients with Temple syndrome (TS14) and Kagami-Ogata syndrome (KOS14).

Methods

We studied four TS14 patients (patients 1-4) and five KOS14 patients (patients 5-9) with epimutations. We performed HumanMethylation450 BeadChip (HM450k) analysis for 43 differentially methylated regions (DMRs) (753 CpG sites) and pyrosequencing for 12 DMRs (62 CpG sites) using leukocyte genomic DNA (Leu-gDNA) of patients 1-9, and performed HM450k analysis for 43 DMRs (a slightly different set of 753 CpG sites) using buccal cell gDNA (Buc-gDNA) of patients 1, 3, and 4. We also performed mutation analysis for six causative and candidate genes for MLIDs and quantitative expression analysis using immortalized lymphocytes in MLID-positive patients.

Results

Methylation analysis showed hypermethylated ZDBF2-DMR and ZNF597/NAA60-DMR, hypomethylated ZNF597-DMR in both Leu-gDNA and Buc-gDNA, and hypomethylated PPIEL-DMR in Buc-gDNA of patient 1, and hypermethylated GNAS-A/B-DMR in Leu-gDNA of patient 3. No mutations were detected in the six genes for MLIDs. Expression patterns of ZDBF2, ZNF597, and GNAS-A/B were consistent with the identified MLIDs.

Conclusion

This study indicates the presence of MLIDs in TS14 patients but not in KOS14 patients.Genet Med 19 4, 476-482.

SUBMITTER: Kagami M

PROVIDER: S-EPMC5392596 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome.

Kagami Masayo M Matsubara Keiko K Nakabayashi Kazuhiko K Nakamura Akie A Sano Shinichiro S Okamura Kohji K Hata Kenichiro K Fukami Maki M Ogata Tsutomu T

Genetics in medicine : official journal of the American College of Medical Genetics 20160915 4

<h4>Purpose</h4>Recent studies have identified multilocus imprinting disturbances (MLIDs) in a subset of patients with imprinting diseases (IDs) caused by epimutations. We examined MLIDs in patients with Temple syndrome (TS14) and Kagami-Ogata syndrome (KOS14).<h4>Methods</h4>We studied four TS14 patients (patients 1-4) and five KOS14 patients (patients 5-9) with epimutations. We performed HumanMethylation450 BeadChip (HM450k) analysis for 43 differentially methylated regions (DMRs) (753 CpG sit ...[more]

PMID: 27632690

Similar Datasets

Project description:5-hydroxymethylcytosine (5hmC), converted from 5-methylcytosine (5mC) by Tet enzymes, has recently drawn attention as the ‘sixth base’ of DNA since it is considered to be an intermediate of the demethylation pathway. Nonetheless, it remains to be addressed how 5hmC is linked to the development of human imprinting disorders. In this regard, conventional bisulfite (BS) treatment is unable to differentiate 5hmC from 5mC. It is thus hypothesized that BS conversion-derived ‘hypermethylation’ at imprinting control regions (ICRs), which may cause human imprinting disorders, would in fact be attributable to excessively increased levels of 5hmC as well as 5mC. To test this hypothesis, we applied the newly developed oxidative BS (oxBS) treatment to detect 5hmC in blood samples from Kagami-Ogata syndrome (KOS14) patients caused by perturbed expression of clustered imprinted genes on 14q32.2 resulting from the hypermethylation of ICRs at this locus, IG-DMR and MEG3-DMR. oxBS with pyrosequencing and cloning-based sequencing revealed that there were few amounts of 5hmC at the hypermethylated IG-DMR in blood samples from KOS14 patients. oxBS with genome-wide methylation array analysis demonstrated that global levels of 5hmC were very low with similar distribution patterns in blood samples from KOS14 patients and normal controls. We also confirmed the presence of a large amount of 5hmC in the brain sample from a normal control. 5hmC is not a major component in abnormally hypermethylated ICRs or at a global level, at least in blood from KOS14 patients. As the brain sample contained a large amount of 5hmC, the neural tissues of KOS14 patients are promising candidates for analysis in elucidating the role of 5hmC in the neurodevelopmental context. We generated illumina 450k DNA methylation data for BS or oxBS converted samples of three KOS14 blood samples, one control pooled blood sample and one control brain sample with two technical replicates for each sample.

Dataset Information

Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome.

Purpose

Methods

Results

Conclusion

Publications

Genome-wide multilocus imprinting disturbance analysis in Temple syndrome and Kagami-Ogata syndrome.

Similar Datasets

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