IADR Abstract Archives
The role of the epigenome in dental development
Objectives:
There is growing evidence that developmental tooth anomalies share common genetic influences. Phenotypic discordance in monozygous (MZ) co-twins traditionally indicates the influence of the environment. Epigenetic modifications may also play a role. DNA methylation, one of a range of epigenetic processes, is fundamental for embryological development. The aim of this study was to determine whether differential DNA methylation is associated with differential expression of dental anomalies.
Methods:
The population was sourced from a cohort of young (6-10 years) Australian twins with available buccal DNA and relevant metadata. The control group comprised 10 MZ pairs with no agenesis/supernumeraries. The first test group comprised 14 MZ pairs discordant for agenesis. The second test group comprised 6 MZ pairs discordant for supernumerary teeth. Equal numbers of male and female pairs were selected. DNA samples were subjected to genome-wide methylation analysis using the Illumina450 microarray. Despite modest degradation, all samples yielded methylation data. Observed discordance was greater for twins also discordant for supernumerary teeth, which became the focus for subsequent analyses. Following quality control and data cleaning, data were analysed in R using Bioconductor packages. Limma was used to detect differentially methylated probes (DMPs) and bumphunter to find differentially methylated regions (DMRs). Gene ontology analysis was performed using missMethyl.
Results: Approximately 13,000 statistically significant (adjusted p-value < 0.05) DMPs were detected, of which ~9000 showed an absolute difference in mean methylation (deltabeta) between control and supernumerary groups >10%. We detected 175 DMRs with a false discovery rate <0.05. Gene ontology analysis found most DMPs were at or near genes associated with inter-cellular communication. Many of the DMPs and DMRs detected in our study were located in gene promotors and enhancers.
Conclusions:
Whilst analysis is ongoing, this is the first study to suggest that epigenetic factors may play a role in early dental development.
There is growing evidence that developmental tooth anomalies share common genetic influences. Phenotypic discordance in monozygous (MZ) co-twins traditionally indicates the influence of the environment. Epigenetic modifications may also play a role. DNA methylation, one of a range of epigenetic processes, is fundamental for embryological development. The aim of this study was to determine whether differential DNA methylation is associated with differential expression of dental anomalies.
Methods:
The population was sourced from a cohort of young (6-10 years) Australian twins with available buccal DNA and relevant metadata. The control group comprised 10 MZ pairs with no agenesis/supernumeraries. The first test group comprised 14 MZ pairs discordant for agenesis. The second test group comprised 6 MZ pairs discordant for supernumerary teeth. Equal numbers of male and female pairs were selected. DNA samples were subjected to genome-wide methylation analysis using the Illumina450 microarray. Despite modest degradation, all samples yielded methylation data. Observed discordance was greater for twins also discordant for supernumerary teeth, which became the focus for subsequent analyses. Following quality control and data cleaning, data were analysed in R using Bioconductor packages. Limma was used to detect differentially methylated probes (DMPs) and bumphunter to find differentially methylated regions (DMRs). Gene ontology analysis was performed using missMethyl.
Results: Approximately 13,000 statistically significant (adjusted p-value < 0.05) DMPs were detected, of which ~9000 showed an absolute difference in mean methylation (deltabeta) between control and supernumerary groups >10%. We detected 175 DMRs with a false discovery rate <0.05. Gene ontology analysis found most DMPs were at or near genes associated with inter-cellular communication. Many of the DMPs and DMRs detected in our study were located in gene promotors and enhancers.
Conclusions:
Whilst analysis is ongoing, this is the first study to suggest that epigenetic factors may play a role in early dental development.