Genome-wide DNA methylome profiling to differentiate monozygotic twins.

Area of Science:

• Forensic Science
• Epigenetics
• Genetics

Background:

• Short tandem repeat (STR) profiling is standard for individual identification but fails to distinguish monozygotic (MZ) twins due to identical genomic DNA.
• DNA methylation, an epigenetic modification, exhibits variable patterns even between MZ twins, making it a potential tool for differentiating them.
• Epigenetic patterns are influenced by environmental factors and age, with distinct DNA methylation profiles observed among different types of MZ twins (dichorionic-diamniotic, monochorionic-diamniotic, monochorionic-monoamniotic).

Purpose of the Study:

• To compare DNA methylation profiles among the three types of MZ twins.
• To identify common DNA methylation markers capable of differentiating MZ twins.
• To validate these markers for forensic applications.

Main Methods:

• Collected cord blood samples from 54 pairs of MZ twins.
• Analyzed DNA methylation profiles using the Human MethylationEPIC v2.0 platform.
• Validated selected CpG site combinations in independent cohorts (118 British and 47 Korean MZ twin pairs) and using pyrosequencing.

Main Results:

• Differences in DNA methylation among MZ twin types were observed primarily in immune-related regions.
• Differentially methylated genes in monochorionic twins were enriched in cytokine and interleukin signaling pathways.
• Differentially methylated genes in dichorionic twins were enriched in synaptic and neuronal system pathways.

Conclusions:

• Selected combinations of CpG sites effectively differentiate MZ twins.
• These methylation differences, observed at birth, appear to persist throughout life.
• These DNA methylation markers hold promise for forensic identification in cases involving MZ twins.