Genome-wide methylation analysis in Silver–Russell syndrome, Temple syndrome, and Prader–Willi syndrome
| Autor: | Tomoko Fuke, Shinji Saitoh, Tsutomu Ogata, Masayo Kagami, Kazuhito Satou, Kenichiro Hata, Keiko Matsubara, Maki Fukami, Kazuhiko Nakabayashi, Nobuyuki Murakami, Kazuki Yamazawa, Kaori Hara-Isono |
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| Rok vydání: | 2020 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Temple syndrome Prader–Willi syndrome Nails Malformed Genome-wide methylation analysis Biology Genomic Imprinting Silver–Russell syndrome Intellectual Disability Genetics medicine Humans HumanMethylation450 BeadChip Molecular Biology Genetics (clinical) Genome Human Research nutritional and metabolic diseases High-Throughput Nucleotide Sequencing Methylation DNA Methylation medicine.disease Phenotype Human genetics Silver-Russell Syndrome Differentially methylated regions Thumb CpG site Case-Control Studies DNA methylation Hallux CpG Islands Human genome Prader-Willi Syndrome Imprinting disorders Genome-Wide Association Study Developmental Biology |
| Zdroj: | Clinical Epigenetics |
| ISSN: | 1868-7083 1868-7075 |
| Popis: | Background Imprinting disorders (IDs) show overlapping phenotypes, particularly in Silver–Russell syndrome (SRS), Temple syndrome (TS14), and Prader–Willi syndrome (PWS). These three IDs include fetal and postnatal growth failure, feeding difficulty, and muscular hypotonia as major clinical features. However, the mechanism that causes overlapping phenotypes has not been clarified. To investigate the presence or absence of methylation signatures associated with overlapping phenotypes, we performed genome-wide methylation analysis (GWMA). Results GWMA was carried out on 36 patients with three IDs (SRS [n = 16], TS14 [n = 7], PWS [n = 13]) and 11 child controls using HumanMethylation450 BeadChip including 475,000 CpG sites across the human genome. To reveal an aberrantly methylated region shared by SRS, TS14, and PWS groups, we compared genome-wide methylation data of the three groups with those of control subjects. All the identified regions were known as SRS-, TS14-, and PWS-related imprinting-associated differentially methylated regions (iDMRs), and there was no hypermethylated or hypomethylated region shared by different ID groups. To examine the methylation pattern shared by SRS, TS14, and PWS groups, we performed clustering analysis based on GWMA data. The result focusing on 620 probes at the 62 known iDMRs (except for SRS-, TS14-, and PWS-related iDMRs) classified patients into two categories: (1) category A, grossly normal methylation patterns mainly consisting of SRS group patients; and (2) category B, broad and mild hypermethylation patterns mainly consisting of TS14 and PWS group patients. However, we found no obvious relationship between these methylation patterns and phenotypes of patients. Conclusions GWMA in three IDs found no methylation signatures shared by SRS, TS14, and PWS groups. Although clustering analysis showed similar mild hypermethylation patterns in TS14 and PWS groups, further study is needed to clarify the effect of methylation patterns on the overlapping phenotypes. |
| Databáze: | OpenAIRE |
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