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...
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2024-10-01
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| 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 |
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| 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 |
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| 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 |
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