Alvizi, L;
Ke, X;
Brito, LA;
Seselgyte, R;
Moore, GE;
Stanier, P;
Passos-Bueno, MR;
(2017)
Differential methylation is associated with non-syndromic cleft lip and palate and contributes to penetrance effects.
Scientific Reports
, 7
, Article 244. 10.1038/s41598-017-02721-0.
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Abstract
Non-syndromic cleft lip and/or palate (NSCLP) is a common congenital malformation with a multifactorial model of inheritance. Although several at-risk alleles have been identified, they do not completely explain the high heritability. We postulate that epigenetic factors as DNA methylation might contribute to this missing heritability. Using a Methylome-wide association study in a Brazilian cohort (67 NSCLP, 59 controls), we found 578 methylation variable positions (MVPs) that were significantly associated with NSCLP. MVPs were enriched in regulatory and active regions of the genome and in pathways already implicated in craniofacial development. In an independent UK cohort (171 NSCLP, 177 controls), we replicated 4 out of 11 tested MVPs. We demonstrated a significant positive correlation between blood and lip tissue DNA methylation, indicating blood as a suitable tissue for NSCLP methylation studies. Next, we quantified CDH1 promoter methylation levels in CDH1 mutation-positive families, including penetrants, non-penetrants or non-carriers for NSCLP. We found methylation levels to be significantly higher in the penetrant individuals. Taken together, our results demonstrated the association of methylation at specific genomic locations as contributing factors to both non-familial and familial NSCLP and altered DNA methylation may be a second hit contributing to penetrance.
| Type: | Article |
|---|---|
| Title: | Differential methylation is associated with non-syndromic cleft lip and palate and contributes to penetrance effects |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-017-02721-0 |
| Publisher version: | http://dx.doi.org/10.1038/s41598-017-02721-0 |
| Additional information: | © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, EPIGENOME-WIDE ASSOCIATION, ISOLATED OROFACIAL CLEFTS, DNA METHYLATION, CRANIOFACIAL DEVELOPMENT, ALCOHOL-CONSUMPTION, EPIGENETIC CHANGES, CDH1 PROMOTER, ORAL CLEFTS, IN-UTERO, RISK |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1553221 |
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