Equivalent DNA methylation variation between monozygotic co-twins and unrelated individuals reveals universal epigenetic inter-individual dissimilarity.
Clustered protocadherins
DNA methylation
Epigenetic drift
Epigenetics
Inter-individual variation
Metastable epialleles
Monozygotic twin discordance
Monozygotic twins
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
05 01 2021
05 01 2021
Historique:
received:
16
12
2019
accepted:
07
12
2020
entrez:
6
1
2021
pubmed:
7
1
2021
medline:
1
12
2021
Statut:
epublish
Résumé
Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such as the environment or aging. Particularly for young and healthy monozygotic twins, DNA methylation divergence, if any, may be restricted to stochastic processes occurring post-twinning during embryonic development and early life. However, to what extent such stochastic mechanisms can systematically provide a stable source of inter-individual epigenetic variation remains uncertain until now. We enriched for inter-individual stochastic variation by using an equivalence testing-based statistical approach on whole blood methylation microarray data from healthy adolescent monozygotic twins. As a result, we identified 333 CpGs displaying similarly large methylation variation between monozygotic co-twins and unrelated individuals. Although their methylation variation surpasses measurement error and is stable in a short timescale, susceptibility to aging is apparent in the long term. Additionally, 46% of these CpGs were replicated in adipose tissue. The identified sites are significantly enriched at the clustered protocadherin loci, known for stochastic methylation in developing neurons. We also confirmed an enrichment in monozygotic twin DNA methylation discordance at these loci in whole genome bisulfite sequencing data from blood and adipose tissue. We have isolated a component of stochastic methylation variation, distinct from genetic influence, measurement error, and epigenetic drift. Biomarkers enriched in this component may serve in the future as the basis for universal epigenetic fingerprinting, relevant for instance in the discrimination of monozygotic twin individuals in forensic applications, currently impossible with standard DNA profiling.
Sections du résumé
BACKGROUND
Although the genomes of monozygotic twins are practically identical, their methylomes may evolve divergently throughout their lifetime as a consequence of factors such as the environment or aging. Particularly for young and healthy monozygotic twins, DNA methylation divergence, if any, may be restricted to stochastic processes occurring post-twinning during embryonic development and early life. However, to what extent such stochastic mechanisms can systematically provide a stable source of inter-individual epigenetic variation remains uncertain until now.
RESULTS
We enriched for inter-individual stochastic variation by using an equivalence testing-based statistical approach on whole blood methylation microarray data from healthy adolescent monozygotic twins. As a result, we identified 333 CpGs displaying similarly large methylation variation between monozygotic co-twins and unrelated individuals. Although their methylation variation surpasses measurement error and is stable in a short timescale, susceptibility to aging is apparent in the long term. Additionally, 46% of these CpGs were replicated in adipose tissue. The identified sites are significantly enriched at the clustered protocadherin loci, known for stochastic methylation in developing neurons. We also confirmed an enrichment in monozygotic twin DNA methylation discordance at these loci in whole genome bisulfite sequencing data from blood and adipose tissue.
CONCLUSIONS
We have isolated a component of stochastic methylation variation, distinct from genetic influence, measurement error, and epigenetic drift. Biomarkers enriched in this component may serve in the future as the basis for universal epigenetic fingerprinting, relevant for instance in the discrimination of monozygotic twin individuals in forensic applications, currently impossible with standard DNA profiling.
Identifiants
pubmed: 33402197
doi: 10.1186/s13059-020-02223-9
pii: 10.1186/s13059-020-02223-9
pmc: PMC7786996
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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