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Updated: Oct 24, 2025
Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Patients with PWS and related syndromes display differentially methylated regions involved in neurodevelopmental and
Juliette Salles1,2,3,4, Sanaa Eddiry5, Emmanuelle Lacassagne5
1Université de Toulouse, Toulouse, France. Juliette.salles@hotmail.fr.
Insights
Prader-Willi syndrome (PWS) involves epigenetic changes affecting genes like SNORD116 and MAGEL2. These modifications correlate with distinct PWS phenotypes, impacting neurodevelopment and metabolism.
Area of Science:
- Genetics
- Epigenetics
- Neurodevelopmental Disorders
Background:
- Prader-Willi syndrome (PWS) is a rare genetic disorder linked to chromosome 15q11-q13 gene expression.
- Neurodevelopmental disorders often arise from gene expression imbalances affecting neuronal development.
- Epigenetic modifications play a crucial role in these disorders, but specific epigenetic comparisons in PWS are underexplored.
Purpose of the Study:
- Investigate epigenetic modifications in Prader-Willi syndrome (PWS) and related disorders.
- Compare epigenetic changes associated with SNORD116 and MAGEL2 gene inactivation in PWS.
- Analyze genome-wide methylation patterns to understand PWS pathogenesis.
Main Methods:
- Genome-wide methylation analysis (GWAS) was performed on blood samples from PWS patients and controls.
- Seven PWS patients with deletions, SNORD116 microdeletion, or MAGEL2 mutation were analyzed.
- Two control infants with unconfirmed genetic disease suspicion were included for comparison.
Main Results:
- Over 29,000 differentially methylated cytosines and 5,000 regions (DMRs) were identified in PWS patients.
- PWS-associated DMRs linked to neurodevelopmental, endocrine, and social/addictive pathways.
- SNORD116 deletions correlated with metabolic and nervous system gene DMRs; MAGEL2 mutations with macromolecule biosynthesis genes.
Conclusions:
- Prader-Willi syndrome exhibits distinct epigenetic modifications related to SNORD116 and MAGEL2 mutations.
- These epigenetic differences are relevant to the varying clinical phenotypes observed in PWS.
- Epigenetic analysis provides insights into the molecular mechanisms underlying PWS and related conditions.
Background:
Prader-Willi syndrome is a rare genetic neurodevelopmental disorder caused by a paternal deficiency of maternally imprinted gene expression located in the chromosome 15q11-q13 region. Previous studies have demonstrated that several classes of neurodevelopmental disorders can be attributed to either over- or under-expression of specific genes that may lead to impairments in neuronal generation, differentiation, maturation and growth. Epigenetic changes that modify gene expression have been highlighted in these disorders. One recent study focused on epigenetic analysis and compared patients with PWS with patients with other imprinting disorders. No study, however, has yet focused on epigenetics in patients with PWS specifically by comparing the mutations associated with this syndrome.
Objective:
This study investigated the epigenetic modifications in patients with PWS and patients with PWS-related disorders caused by inactivation of two genes of the PWS chromosomal region, SNORD116 and MAGEL2. Our approach also aimed to compare the epigenetic modifications in PWS and PWS-related disorders.
Methods:
We compared genome-wide methylation analysis (GWAS) in seven blood samples from patients with PWS phenotype (five with deletions of the PWS locus, one with a microdeletion of SNORD116 and one with a frameshift mutation of MAGEL2 presenting with Schaaf-Yang syndrome), as well as two control patients. Controls were infants that had been studied for suspicion of genetic diseases that was not confirmed by the genetic analysis and the clinical follow-up.
Results:
The analysis identified 29,234 differentially methylated cytosines, corresponding to 5,308 differentially methylated regions (DMRs), which matched with 2,280 genes. The DMRs in patients with PWS were associated with neurodevelopmental pathways, endocrine dysfunction and social and addictive processes consistent with the key features of the PWS phenotype. In addition, the separate analysis for the SNORD116 and MAGEL2 deletions revealed that the DMRs associated with the SNORD116 microdeletion were found in genes implicated in metabolic pathways and nervous system development, whereas MAGEL2 mutations mostly concerned genes involved in macromolecule biosynthesis.
Conclusion:
The PWS is associated with epigenetic modifications with differences in SNORD116 and MAGEL2 mutations, which seem to be relevant to the different associated phenotypes.
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