Exploring the unique function of imprinting control centers in the PWS/AS-responsible region: finding from array-based methylation analysis in cases with variously sized microdeletions.
15q11–13
Angelman syndrome
Deletion
Genome-wide methylation study
Prader-Willi syndrome
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
28 02 2019
28 02 2019
Historique:
received:
28
12
2018
accepted:
14
02
2019
entrez:
2
3
2019
pubmed:
2
3
2019
medline:
22
1
2020
Statut:
epublish
Résumé
Human 15q11-13 is responsible for Prader-Willi syndrome (PWS) and Angelman syndrome (AS) and includes several imprinted genes together with bipartite elements named AS-IC (imprinting center) and PWS-IC. These concertedly confer allele specificity on 15q11-13. Here, we report DNA methylation status of 15q11-13 and other autosomal imprinted differentially methylated regions (iDMRs) in cases with various deletions within the PWS/AS-responsible region. We performed array-based methylation analysis and examined the methylation status of CpG sites in 15q11-13 and in 71 iDMRs in six cases with various microdeletions, eight cases with conventional deletions within 15q11-13, and healthy controls. We detected 89 CpGs in 15q11-13 showing significant methylation changes in our cases. Of them, 14 CpGs in the SNORD116s cluster presented slight hypomethylation in the PWS cases and hypermethylation in the AS cases. No iDMRs at regions other than 15q11-13 showed abnormal methylation. We identified CpG sites and regions in which methylation status is regulated by AS-IC and PWS-IC. This result indicated that each IC had unique functions and coordinately regulated the DNA methylation of respective alleles. In addition, only aberrant methylation at iDMRs in 15q11-13 leads to the development of the phenotypes in our cases.
Sections du résumé
BACKGROUND
Human 15q11-13 is responsible for Prader-Willi syndrome (PWS) and Angelman syndrome (AS) and includes several imprinted genes together with bipartite elements named AS-IC (imprinting center) and PWS-IC. These concertedly confer allele specificity on 15q11-13. Here, we report DNA methylation status of 15q11-13 and other autosomal imprinted differentially methylated regions (iDMRs) in cases with various deletions within the PWS/AS-responsible region.
METHODS
We performed array-based methylation analysis and examined the methylation status of CpG sites in 15q11-13 and in 71 iDMRs in six cases with various microdeletions, eight cases with conventional deletions within 15q11-13, and healthy controls.
RESULTS
We detected 89 CpGs in 15q11-13 showing significant methylation changes in our cases. Of them, 14 CpGs in the SNORD116s cluster presented slight hypomethylation in the PWS cases and hypermethylation in the AS cases. No iDMRs at regions other than 15q11-13 showed abnormal methylation.
CONCLUSIONS
We identified CpG sites and regions in which methylation status is regulated by AS-IC and PWS-IC. This result indicated that each IC had unique functions and coordinately regulated the DNA methylation of respective alleles. In addition, only aberrant methylation at iDMRs in 15q11-13 leads to the development of the phenotypes in our cases.
Identifiants
pubmed: 30819260
doi: 10.1186/s13148-019-0633-1
pii: 10.1186/s13148-019-0633-1
pmc: PMC6396496
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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