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.
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: Brandon C McKinney; Chien-Wei Lin; Hyunjung Oh; George C Tseng; David A Lewis; Etienne Sibille Journal: Neuropsychopharmacology Date: 2015-04-16 Impact factor: 7.853
Authors: Jimmy L Huynh; Paras Garg; Tin Htwe Thin; Seungyeul Yoo; Ranjan Dutta; Bruce D Trapp; Vahram Haroutunian; Jun Zhu; Michael J Donovan; Andrew J Sharp; Patrizia Casaccia Journal: Nat Neurosci Date: 2013-11-24 Impact factor: 24.884
Authors: Gudrun E Moore; Miho Ishida; Charalambos Demetriou; Lara Al-Olabi; Lydia J Leon; Anna C Thomas; Sayeda Abu-Amero; Jennifer M Frost; Jaime L Stafford; Yao Chaoqun; Andrew J Duncan; Rachel Baigel; Marina Brimioulle; Isabel Iglesias-Platas; Sophia Apostolidou; Reena Aggarwal; John C Whittaker; Argyro Syngelaki; Kypros H Nicolaides; Lesley Regan; David Monk; Philip Stanier Journal: Philos Trans R Soc Lond B Biol Sci Date: 2015-03-05 Impact factor: 6.237
Authors: Conall M O'Seaghdha; Hongsheng Wu; Qiong Yang; Karen Kapur; Idris Guessous; Annie Mercier Zuber; Anna Köttgen; Candice Stoudmann; Alexander Teumer; Zoltán Kutalik; Massimo Mangino; Abbas Dehghan; Weihua Zhang; Gudny Eiriksdottir; Guo Li; Toshiko Tanaka; Laura Portas; Lorna M Lopez; Caroline Hayward; Kurt Lohman; Koichi Matsuda; Sandosh Padmanabhan; Dmitri Firsov; Rossella Sorice; Sheila Ulivi; A Catharina Brockhaus; Marcus E Kleber; Anubha Mahajan; Florian D Ernst; Vilmundur Gudnason; Lenore J Launer; Aurelien Mace; Eric Boerwinckle; Dan E Arking; Chizu Tanikawa; Yusuke Nakamura; Morris J Brown; Jean-Michel Gaspoz; Jean-Marc Theler; David S Siscovick; Bruce M Psaty; Sven Bergmann; Peter Vollenweider; Veronique Vitart; Alan F Wright; Tatijana Zemunik; Mladen Boban; Ivana Kolcic; Pau Navarro; Edward M Brown; Karol Estrada; Jingzhong Ding; Tamara B Harris; Stefania Bandinelli; Dena Hernandez; Andrew B Singleton; Giorgia Girotto; Daniela Ruggiero; Adamo Pio d'Adamo; Antonietta Robino; Thomas Meitinger; Christa Meisinger; Gail Davies; John M Starr; John C Chambers; Bernhard O Boehm; Bernhard R Winkelmann; Jie Huang; Federico Murgia; Sarah H Wild; Harry Campbell; Andrew P Morris; Oscar H Franco; Albert Hofman; Andre G Uitterlinden; Fernando Rivadeneira; Uwe Völker; Anke Hannemann; Reiner Biffar; Wolfgang Hoffmann; So-Youn Shin; Pierre Lescuyer; Hughes Henry; Claudia Schurmann; Patricia B Munroe; Paolo Gasparini; Nicola Pirastu; Marina Ciullo; Christian Gieger; Winfried März; Lars Lind; Tim D Spector; Albert V Smith; Igor Rudan; James F Wilson; Ozren Polasek; Ian J Deary; Mario Pirastu; Luigi Ferrucci; Yongmei Liu; Bryan Kestenbaum; Jaspal S Kooner; Jacqueline C M Witteman; Matthias Nauck; W H Linda Kao; Henri Wallaschofski; Olivier Bonny; Caroline S Fox; Murielle Bochud Journal: PLoS Genet Date: 2013-09-19 Impact factor: 5.917