Genetics meets DNA methylation in rare diseases

Area of Science:

• Epigenetics
• Human Genetics
• Molecular Biology

Background:

• Epigenetic alterations are key in complex diseases, but mechanisms are hard to study.
• Monogenic disorders affecting epigenetic factors provide models for understanding complex traits.
• Advances in genome-wide approaches identify hereditary disorders linked to epigenetic mark defects.

Purpose of the Study:

• To review how mutations in epigenetic machinery genes alter DNA methylation landscapes.
• To explore the link between monogenic epigenetic disorders and complex human diseases.
• To highlight the potential of studying rare diseases for understanding genome function.

Main Methods:

• Review of literature focusing on monogenic diseases affecting DNA methylation.
• Analysis of genome-wide studies identifying epigenetic alterations in patients.
• Examination of mutations in DNA methyltransferases, chromatin modifiers, and transcription factors.

Main Results:

• Mutations in epigenetic factors can lead to genome-wide DNA methylation alterations.
• These alterations can stem directly from DNA methyltransferase defects or indirectly from chromatin changes.
• Identification of an increasing number of hereditary disorders linked to epigenetic establishment or perpetuation defects.

Conclusions:

• Understanding rare epigenetic disorders enhances knowledge of human DNA methylation genetics.
• Investigating these perturbations offers insights into the etiology of complex human diseases.
• Studying epigenetic machinery defects is crucial for advancing our comprehension of genome function and disease.