Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)

Abstract Preterm birth remains the leading identifiable risk factor for cerebral palsy (CP), a devastating form of motor impairment due to developmental brain injury occurring around the time of birth. We performed genome wide methylation and whole transcriptome analyses to elucidate the early patho...

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Autores principales:	An N. Massaro, Theo K. Bammler, James W. MacDonald, Krystle M. Perez, Bryan Comstock, Sandra E. Juul
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fcea0f7077dc4ee3b7e684612a03d384
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spelling	oai:doaj.org-article:fcea0f7077dc4ee3b7e684612a03d3842021-12-02T13:30:11ZWhole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)10.1038/s41598-021-84214-92045-2322https://doaj.org/article/fcea0f7077dc4ee3b7e684612a03d3842021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84214-9https://doaj.org/toc/2045-2322Abstract Preterm birth remains the leading identifiable risk factor for cerebral palsy (CP), a devastating form of motor impairment due to developmental brain injury occurring around the time of birth. We performed genome wide methylation and whole transcriptome analyses to elucidate the early pathogenesis of CP in extremely low gestational age neonates (ELGANs). We evaluated peripheral blood cell specimens collected during a randomized trial of erythropoietin for neuroprotection in the ELGAN (PENUT Trial, NCT# 01378273). DNA methylation data were generated from 94 PENUT subjects (n = 47 CP vs. n = 47 Control) on day 1 and 14 of life. Gene expression data were generated from a subset of 56 subjects. Only one differentially methylated region was identified for the day 1 to 14 change between CP versus no CP, without evidence for differential gene expression of the associated gene RNA Pseudouridine Synthase Domain Containing 2. iPathwayGuide meta-analyses identified a relevant upregulation of JAK1 expression in the setting of decreased methylation that was observed in control subjects but not CP subjects. Evaluation of whole transcriptome data identified several top pathways of potential clinical relevance including thermogenesis, ferroptossis, ribosomal activity and other neurodegenerative conditions that differentiated CP from controls.An N. MassaroTheo K. BammlerJames W. MacDonaldKrystle M. PerezBryan ComstockSandra E. JuulNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q An N. Massaro Theo K. Bammler James W. MacDonald Krystle M. Perez Bryan Comstock Sandra E. Juul Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)
description	Abstract Preterm birth remains the leading identifiable risk factor for cerebral palsy (CP), a devastating form of motor impairment due to developmental brain injury occurring around the time of birth. We performed genome wide methylation and whole transcriptome analyses to elucidate the early pathogenesis of CP in extremely low gestational age neonates (ELGANs). We evaluated peripheral blood cell specimens collected during a randomized trial of erythropoietin for neuroprotection in the ELGAN (PENUT Trial, NCT# 01378273). DNA methylation data were generated from 94 PENUT subjects (n = 47 CP vs. n = 47 Control) on day 1 and 14 of life. Gene expression data were generated from a subset of 56 subjects. Only one differentially methylated region was identified for the day 1 to 14 change between CP versus no CP, without evidence for differential gene expression of the associated gene RNA Pseudouridine Synthase Domain Containing 2. iPathwayGuide meta-analyses identified a relevant upregulation of JAK1 expression in the setting of decreased methylation that was observed in control subjects but not CP subjects. Evaluation of whole transcriptome data identified several top pathways of potential clinical relevance including thermogenesis, ferroptossis, ribosomal activity and other neurodegenerative conditions that differentiated CP from controls.
format	article
author	An N. Massaro Theo K. Bammler James W. MacDonald Krystle M. Perez Bryan Comstock Sandra E. Juul
author_facet	An N. Massaro Theo K. Bammler James W. MacDonald Krystle M. Perez Bryan Comstock Sandra E. Juul
author_sort	An N. Massaro
title	Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)
title_short	Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)
title_full	Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)
title_fullStr	Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)
title_full_unstemmed	Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)
title_sort	whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (cp) in extremely low gestational age neonates (elgan)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fcea0f7077dc4ee3b7e684612a03d384
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Whole genome methylation and transcriptome analyses to identify risk for cerebral palsy (CP) in extremely low gestational age neonates (ELGAN)

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