A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation

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dc.contributor.author El Maarri, Osman
dc.contributor.author Kareta, Micheal S.
dc.contributor.author Mikeska, Thomas
dc.contributor.author Becker, Tim
dc.contributor.author Diaz-Lacava, Amalia
dc.contributor.author Junen, Judith
dc.contributor.author Nusgen, Nicole
dc.contributor.author Behne, Frank
dc.contributor.author Wienker, Thomas
dc.contributor.author Waha, Andreas
dc.date.accessioned 2017-09-14T08:44:15Z
dc.date.available 2017-09-14T08:44:15Z
dc.date.copyright 2009 en_US
dc.date.issued 2017-09-14
dc.identifier.issn 1460-2083 en_US
dc.identifier.uri http://hdl.handle.net/10725/6184
dc.description.abstract Causes underlying inter-individual variations in DNA methylation profiles among normal healthy populations are not thoroughly understood. To investigate the contribution of genetic variation in DNA methyltransferase (DNMT) genes to such epigenetic variation, we performed a systematic search for polymorphisms in all known human DNMT genes [ DNMT1 , DNMT3A , DNMT3B , DNMT3L and DNMT2 (TRDMT1 )] in 192 healthy males and females. One hundred and eleven different polymorphisms were detected. Of these, 24 were located in coding regions and 10 resulted in an amino acid change that may affect the corresponding DNMT protein structure or function. Association analysis between all major polymorphisms (frequency > 1%) and quantitative DNA methylation profiles did not return significant results after correction for multiple testing. Polymorphisms leading to an amino acid change were further investigated for changes in global DNA methylation by differential methylation hybridization. This analysis revealed that a rare change at DNMT3L (R271Q) was associated with significant DNA hypomethylation. Biochemical characterization confirmed that DNMT3L R271Q is impaired in its ability to stimulate de novo DNA methylation by DNMT3A. Methylated DNA immunoprecipitation based analysis using CpG island microarrays revealed that the hypomethylation in this sample preferentially clustered to subtelomeric genomic regions with affected loci corresponding to a subset of repetitive CpG islands with low predicted promoter potential located outside of genes. en_US
dc.language.iso en en_US
dc.title A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201508713 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Human Molecular Genetics en_US
dc.journal.volume 18 en_US
dc.journal.issue 10 en_US
dc.article.pages 1755-1768 en_US
dc.keywords Amino acids en_US
dc.keywords Polymorphism en_US
dc.keywords Cpg islands en_US
dc.keywords DNA en_US
dc.keywords DNA methylation en_US
dc.keywords DNA modification methylases en_US
dc.keywords Genes en_US
dc.keywords Genome en_US
dc.keywords Methylation en_US
dc.keywords Single nucleotide polymorphism en_US
dc.keywords DNA hypomethylation en_US
dc.keywords Dnmt3a gene en_US
dc.identifier.doi https://doi.org/10.1093/hmg/ddp088 en_US
dc.identifier.ctation El-Maarri, O., Kareta, M. S., Mikeska, T., Becker, T., Diaz-Lacava, A., Junen, J., ... & Oldenburg, J. (2009). A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. Human molecular genetics, 18(10), 1755-1768. en_US
dc.author.email osman.elmaarri@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://academic.oup.com/hmg/article/18/10/1755/2355994/A-systematic-search-for-DNA-methyltransferase en_US
dc.author.affiliation Lebanese American University en_US

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