Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning

Background/Objectives: Human identical twins are born at a rate of 3–4 per 1000 live births. Many other mammals also occasionally produce monozygotic twins, referred to as sporadic polyembryony. The underlying mechanisms are unknown. Through epigenome-wide association studies (EWAS), we identified a...

Full description

Saved in:
Bibliographic Details
Main Authors: Jenny van Dongen, Charles E. Breeze, Twinning Genetics Consortium
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Epigenomes
Subjects:
Online Access:https://www.mdpi.com/2075-4655/8/4/37
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850241695076057088
author Jenny van Dongen
Charles E. Breeze
Twinning Genetics Consortium
author_facet Jenny van Dongen
Charles E. Breeze
Twinning Genetics Consortium
author_sort Jenny van Dongen
collection DOAJ
description Background/Objectives: Human identical twins are born at a rate of 3–4 per 1000 live births. Many other mammals also occasionally produce monozygotic twins, referred to as sporadic polyembryony. The underlying mechanisms are unknown. Through epigenome-wide association studies (EWAS), we identified a robust DNA methylation signature in somatic tissues from human monozygotic (MZ) twins, comprising 834 differentially methylated positions (MZ-DMPs). The results point to a connection between monozygotic twinning and early genome programming and enable new angles to study monozygotic twinning. Methods: The mammalian methylation array (MMA) measures 38,608 CpGs focusing on regions that are well-conserved across many mammalian species, allowing for pan-mammalian comparative epigenomic studies. Here, we successfully map human MZ-DMPs to probes of the mammalian methylation array across 157 mammalian genomes. Results: As expected, based on the modest probe overlap between Illumina 450k/EPIC and mammalian methylation array probes, only a subset of MZ-DMPs reside in conserved regions covered by the mammalian methylation array. These include probes mapping to <i>NPAS3</i>, <i>KLHL35</i>, <i>CASZ1</i>, and <i>ATP2B2</i>. Re-analysis restricting the original EWAS in humans to conserved MMA regions yielded additional MZ-DMPs, suggesting that more loci may be detected by application of the mammalian array to monozygotic twins. Conclusions: In conclusion, the mammalian methylation array may prove to be a promising platform to study whether a shared DNA methylation signature of sporadic polyembryony exists across diverse mammalian species. This may potentially point to shared underlying mechanisms.
format Article
id doaj-art-3e16899ca18747f1965d2997cd445a0b
institution OA Journals
issn 2075-4655
language English
publishDate 2024-10-01
publisher MDPI AG
record_format Article
series Epigenomes
spelling doaj-art-3e16899ca18747f1965d2997cd445a0b2025-08-20T02:00:33ZengMDPI AGEpigenomes2075-46552024-10-01843710.3390/epigenomes8040037Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic TwinningJenny van Dongen0Charles E. Breeze1Twinning Genetics ConsortiumDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081 BT Amsterdam, The NetherlandsUCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UKBackground/Objectives: Human identical twins are born at a rate of 3–4 per 1000 live births. Many other mammals also occasionally produce monozygotic twins, referred to as sporadic polyembryony. The underlying mechanisms are unknown. Through epigenome-wide association studies (EWAS), we identified a robust DNA methylation signature in somatic tissues from human monozygotic (MZ) twins, comprising 834 differentially methylated positions (MZ-DMPs). The results point to a connection between monozygotic twinning and early genome programming and enable new angles to study monozygotic twinning. Methods: The mammalian methylation array (MMA) measures 38,608 CpGs focusing on regions that are well-conserved across many mammalian species, allowing for pan-mammalian comparative epigenomic studies. Here, we successfully map human MZ-DMPs to probes of the mammalian methylation array across 157 mammalian genomes. Results: As expected, based on the modest probe overlap between Illumina 450k/EPIC and mammalian methylation array probes, only a subset of MZ-DMPs reside in conserved regions covered by the mammalian methylation array. These include probes mapping to <i>NPAS3</i>, <i>KLHL35</i>, <i>CASZ1</i>, and <i>ATP2B2</i>. Re-analysis restricting the original EWAS in humans to conserved MMA regions yielded additional MZ-DMPs, suggesting that more loci may be detected by application of the mammalian array to monozygotic twins. Conclusions: In conclusion, the mammalian methylation array may prove to be a promising platform to study whether a shared DNA methylation signature of sporadic polyembryony exists across diverse mammalian species. This may potentially point to shared underlying mechanisms.https://www.mdpi.com/2075-4655/8/4/37identical twinsepigeneticsgeneticsclonal speciescomparative epigenomics
spellingShingle Jenny van Dongen
Charles E. Breeze
Twinning Genetics Consortium
Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning
Epigenomes
identical twins
epigenetics
genetics
clonal species
comparative epigenomics
title Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning
title_full Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning
title_fullStr Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning
title_full_unstemmed Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning
title_short Examining the Utility of the Mammalian Methylation Array for Pan-Mammalian Analysis of Monozygotic Twinning
title_sort examining the utility of the mammalian methylation array for pan mammalian analysis of monozygotic twinning
topic identical twins
epigenetics
genetics
clonal species
comparative epigenomics
url https://www.mdpi.com/2075-4655/8/4/37
work_keys_str_mv AT jennyvandongen examiningtheutilityofthemammalianmethylationarrayforpanmammaliananalysisofmonozygotictwinning
AT charlesebreeze examiningtheutilityofthemammalianmethylationarrayforpanmammaliananalysisofmonozygotictwinning
AT twinninggeneticsconsortium examiningtheutilityofthemammalianmethylationarrayforpanmammaliananalysisofmonozygotictwinning