title: A novel approach identifies new differentially methylated regions (DMRs) associated with imprinted genes.
abstract: Imprinted genes are critical for normal human growth and neurodevelopment. They are characterized by differentially methylated regions (DMRs) of DNA that confer parent of origin-specific transcription. We developed a new strategy to identify imprinted gene-associated DMRs. Using genome-wide methylation profiling of sodium bisulfite modified DNA from normal human tissues of biparental origin, candidate DMRs were identified by selecting CpGs with methylation levels consistent with putative allelic differential methylation. In parallel, the methylation profiles of tissues of uniparental origin, i.e., paternally-derived androgenetic complete hydatidiform moles (AnCHMs), and maternally-derived mature cystic ovarian teratoma (MCT), were examined and then used to identify CpGs with parent of origin-specific DNA methylation. With this approach, we found known DMRs associated with imprinted genomic regions as well as new DMRs for known imprinted genes, NAP1L5 and ZNF597, and novel candidate imprinted genes. The paternally methylated DMR for one candidate, AXL, a receptor tyrosine kinase, was also validated in experiments with mouse embryos that demonstrated Axl was expressed preferentially from the maternal allele in a DNA methylation-dependent manner.
authors.affiliation: Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Choufani
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Shapiro
authors.forename: Martha
authors.initials: M
authors.lastname: Susiarjo
authors.forename: Darci T
authors.initials: DT
authors.lastname: Butcher
authors.forename: Daria
authors.initials: D
authors.lastname: Grafodatskaya
authors.forename: Youliang
authors.initials: Y
authors.lastname: Lou
authors.forename: Jose C
authors.initials: JC
authors.lastname: Ferreira
authors.forename: Dalila
authors.initials: D
authors.lastname: Pinto
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Philippe
authors.initials: P
authors.lastname: Coullin
authors.forename: Isabella
authors.initials: I
authors.lastname: Caniggia
authors.forename: Joseph
authors.initials: J
authors.lastname: Beyene
authors.forename: Rima
authors.initials: R
authors.lastname: Slim
authors.forename: Marisa S
authors.initials: MS
authors.lastname: Bartolomei
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D019175:DNA Methylation; D004622:Embryo, Mammalian; D005260:Female; D014644:Genetic Variation; D016678:Genome; D018392:Genomic Imprinting; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000378:metabolism; D051379:Mice; D046228:Microarray Analysis / Q000379:methods; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D013447:Sulfites / Q000737:chemistry; D013724:Teratoma / Q000235:genetics / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D013447:Sulfites; D004247:DNA; D020794:Receptor Protein-Tyrosine Kinases; C009279:sodium bisulfite; D000094963:Axl Receptor Tyrosine Kinase