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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Differential methylation is associated with non-syndromic cleft lip and palate and contributes to penetrance effects

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Alvizi, Lucas ; Ke, Xiayi ; Brito, Luciano Abreu ; Seselgyte, Rimante ; Moore, Gudrun E. ; Stanier, Philip ; Passos-Bueno, Maria Rita
Total Authors: 7
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, MAY 26 2017.
Web of Science Citations: 25

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. (AU)

FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC