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41

A Novel Approach Identifies New Differentially Methylated Regions (DMRs) Associated with Imprinted Genes


ABSTRACT: Imprinted genes are critical for normal human growth and neurodevelopment. We developed a strategy to identify new DNA differentially methylated regions (DMRs), a hallmark of imprinted genes. Using genome-wide methylation profiling, candidate DMRs were selected by identifying CpGs with putative allelic differential methylation in normal biparental tissues. In parallel, we looked for parent of origin-specific DNA methylation patterns in paternally derived human androgenetic complete hydatidiform mole (AnCHM), and maternally derived mature cystic ovarian teratoma (MCT). Using this approach, we found known DMRs associated with imprinted genomic regions as well as new DMRs for known imprinted genes, NAP1L5 and ZNF597. Most importantly, novel candidate imprinted genes were identified. The paternally methylated DMR for one candidate, AXL, a receptor tyrosine kinase, was validated by methylation analyses in humans. Further validation in mouse embryos showed that Axl was expressed preferentially from the maternal allele in a DNA methylation–dependent manner. Overall design: We have analyzed 3 androgenetic complete hydatidiform mole (AnCHM), 16 white blood cell (WBC), 1 mature cystic ovarian teratoma (MCT), 5 placenta, and 1 lymphoblastoid cell line paternal UPD4 sample

INSTRUMENT(S): Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2)

ORGANISM(S): Homo sapiens  

SUBMITTER: Rosanna Weksberg 

PROVIDER: GSE22091 | GEO | 2011-01-26

SECONDARY ACCESSION(S): PRJNA128825

REPOSITORIES: GEO

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