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Related Concept Videos

Restriction Enzymes01:11

Restriction Enzymes

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Restriction enzymes are bacterial enzymes used to cut DNA in a sequence-specific manner. To cleave DNA, they bind to specific palindromic sequences called restriction sites. Such palindromic DNA sequences or inverted repeats are commonly found in regions of functional significance, such as the origin of replication, gene operator sites, and regions containing transcription termination signals.
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
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Epigenetic Regulation01:46

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Related Experiment Video

Updated: Mar 12, 2026

Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution
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Epigenetic DNA Methylation Profiling with MSRE: A Quantitative NGS Approach Using a Parkinson's Disease Test Case.

Adam G Marsh1, Matthew T Cottrell2, Morton F Goldman3

  • 1Center for Bioinformatics and Computational Biology, Delaware Biotechnology Institute, University of DelawareNewark, DE, USA; Genome Profiling LLC, Helen F. Graham Cancer Center and Research Institute, Center for Translational Cancer ResearchNewark, DE USA; Marine Biosciences, School of Marine Science and Policy, University of DelawareLewes, DE, USA.

Frontiers in Genetics
|November 18, 2016
PubMed
Summary

This study introduces a new method for analyzing DNA methylation using next-generation sequencing and methyl-sensitive restriction enzymes. This approach successfully identified significant epigenetic differences in Parkinson's disease patients, highlighting potential diagnostic biomarkers.

Keywords:
DNA methylationParkinson's Diseaseblooddiagnosticsepigeneticslymphocytes

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Area of Science:

  • Epigenetics and Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Precision medicine increasingly relies on epigenetic signatures for diagnosis and prognosis.
  • High-throughput DNA methylation profiling is crucial for advancing precision medicine.
  • Current methodologies require enhancement for comprehensive epigenetic analysis.

Purpose of the Study:

  • To develop and validate a novel computational methodology for site-specific CpG methylation quantification.
  • To assess the utility of this method in identifying epigenetic differences between Parkinson's disease patients and healthy controls.
  • To explore the functional relevance of identified methylation changes in neurodegeneration.

Main Methods:

  • Utilized methyl-sensitive restriction enzymes (MSRE) with next-generation sequencing (NGS) data.
  • Developed an integrated bioinformatics pipeline for raw NGS metric analysis.
  • Applied a statistical discrimination platform to compare DNA methylation profiles.
  • Introduced a methylation load calculation for assessing gene and pathway impacts.

Main Results:

  • Successfully quantified and compared CpG methylation in Parkinson's disease blood serum versus healthy controls.
  • Identified 1008 statistically significant differentially methylated CpG sites (p < 0.0025).
  • Highlighted FGF3, FGF8, HTT, KMTA5, MIR8073, and YWHAG as key differentially methylated genes relevant to Parkinson's disease and neurodegeneration.

Conclusions:

  • The novel MSRE-NGS method provides high-throughput DNA methylation profiling with high statistical discrimination.
  • Epigenetic signatures, specifically DNA methylation patterns, can differentiate Parkinson's disease patients.
  • This methodology holds promise for developing precision diagnostics for neurodegenerative diseases and understanding cellular dysfunction.