title: Epigenetic state and expression of imprinted genes in umbilical cord correlates with growth parameters in human pregnancy.
abstract: BACKGROUND
  Genomic imprinting is a process causing genes to be expressed according to parental origin. Imprinting acts to coordinate fetal and prenatal growth, as well as control postnatal adaptations. Studies on human imprinting are confounded by tissue availability, sampling variability and limitations posed by tissue-specific expression and cellular heterogeneity within tissues. The human umbilical cord is an easily available, embryonic-derived fetal tissue with the potential to overcome many of these limitations.
  
  
  METHODS
  In a sensitive, gene-specific quantitative expression analysis, we show for the first time robust imprinted gene expression combined with methylation analysis in cords isolated from Asian Chinese full-term births.
  
  
  RESULTS
  Linear regression analyses revealed an inverse correlation between expression of pleckstrin homology-like domain, family A, member 2 (PHLDA2) with birth weight (BW). Furthermore, we observed significant down-regulation of the paternally expressed gene 10 (PEG10) in low BW babies compared to optimum BW babies. This change in PEG10 gene expression was accompanied by concomitant methylation alterations at the PEG10 promoter.
  
  
  CONCLUSIONS
  These data are the first to demonstrate relative expression of an imprinted gene associated with epigenetic changes in non-syndromic fetal growth restriction in babies. They show that perturbed expression in compromised fetal growth may be associated with in utero modulation of the epigenetic state at the imprinting control regions and implicate specific imprinted genes as new biomarkers of fetal growth.
authors.affiliation: Department of Growth Development and Metabolism, Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A-STAR), Singapore, Singapore.
authors.forename: Ai Lin
authors.initials: AL
authors.lastname: Lim
authors.forename: Shilen
authors.initials: S
authors.lastname: Ng
authors.forename: Suet Ching Pamela
authors.initials: SC
authors.lastname: Leow
authors.forename: Robin
authors.initials: R
authors.lastname: Choo
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Ito
authors.forename: Yiong Huak
authors.initials: YH
authors.lastname: Chan
authors.forename: Siew Kheng
authors.initials: SK
authors.lastname: Goh
authors.forename: Emilia
authors.initials: E
authors.lastname: Tng
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kwek
authors.forename: Yap Seng
authors.initials: YS
authors.lastname: Chong
authors.forename: Peter D
authors.initials: PD
authors.lastname: Gluckman
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
mesh_terms: D051017:Apoptosis Regulatory Proteins; D001724:Birth Weight / Q000235:genetics*; D002681:China; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development / Q000235:genetics; D005333:Fetus / Q000378:metabolism; D015870:Gene Expression; D056726:Genetic Association Studies; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D014470:Umbilical Cord / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C432965:PEG10 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; C109277:TSSC3 protein