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CpG Methylation

Definition

Addition of a methyl group to cytosine in a CpG dinucleotide. Methylation at age-associated CpGs increases or decreases with chronological age in a predictable pattern that forensic age-estimation clocks exploit.

Chemical change
Methyl group added to cytosine in a CpG dinucleotide
Age relationship
Methylation level rises or falls predictably with chronological age
Application
Forensic DNA methylation age-estimation clocks
Related markers
miRNA, HIrisPlex-S phenotyping

Common questions

Why does age-related CpG methylation work as a forensic age estimator?+

Certain CpG sites accumulate or lose methylation at a fairly consistent rate across a person's life, so measuring methylation at a panel of these sites and comparing it to population-calibrated models lets an examiner predict a donor's approximate chronological age from a biological stain without needing a reference sample.

How accurate is DNA methylation age estimation compared to traditional age indicators like bone or dental development?+

Methylation clocks in adults typically achieve error margins of several years rather than the tight windows possible with skeletal or dental development in juveniles, so they are most useful in adult cold cases or unidentified remains where morphological age indicators are unavailable or already fused.

Related terms

Bisulphite Conversion
A chemical treatment that deaminates unmethylated cytosines to uracil, converting them to thymine upon PCR amplification; methylated cytosines are protected. Allows methylation...
Cell-Free DNA (cfDNA)
Short DNA fragments (~166 bp) circulating extracellularly in body fluids, shed from apoptotic and necrotic cells. In plasma, predominantly hematopoietic; in pregnancy,...
ELOVL2 Clock
A forensic age-estimation system based on bisulphite pyrosequencing of 5 CpG sites in the ELOVL2 gene promoter; validated in multiple independent European...
EPIC Array (Illumina)
The Infinium MethylationEPIC v2.0 microarray measuring methylation beta values at approximately 935,000 CpG sites genome-wide; the current standard instrument for multi-CpG age-clock...
EpiTYPER
Agena Bioscience (formerly Sequenom) reagent system for quantitative methylation analysis via bisulphite PCR and MALDI-TOF mass spectrometry; used for multi-CpG methylation profiling...
HIrisPlex-S
A 41-SNP externally visible characteristics (EVC) panel for simultaneous prediction of eye, hair, and skin colour, developed at Erasmus MC Rotterdam by...
Horvath 353-CpG Clock
A pan-tissue epigenetic age clock built on the methylation values of 353 CpG sites from the Illumina 450K array; developed by Steve...
MiRNA (microRNA)
A small non-coding RNA (21-23 nt) that regulates gene expression post-transcriptionally. Different tissues and body fluids express different miRNA sets; forensic miRNA...

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