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Integrated genome-wide Alu methylation and transcriptome profiling analyses reveal novel epigenetic regulatory networks associated with autism spectrum disorder / T. SAELIW in Molecular Autism, 9 (2018)
[article]
Titre : Integrated genome-wide Alu methylation and transcriptome profiling analyses reveal novel epigenetic regulatory networks associated with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : T. SAELIW, Auteur ; C. TANGSUWANSRI, Auteur ; S. THONGKORN, Auteur ; W. CHONCHAIYA, Auteur ; K. SUPHAPEETIPORN, Auteur ; A. MUTIRANGURA, Auteur ; T. TENCOMNAO, Auteur ; V. W. HU, Auteur ; T. SARACHANA, Auteur Article en page(s) : 27p. Langues : Anglais (eng) Mots-clés : Alu Elements Autism Spectrum Disorder/genetics Case-Control Studies Cells, Cultured DNA Methylation Epigenesis, Genetic Female Gene Regulatory Networks Genome, Human Humans Male Transcriptome Autism spectrum disorder Epigenetic regulation Gene expression profiles Lymphoblastoid cell lines Neuroinflammation Retrotransposon Sex bias Subgrouping Index. décimale : PER Périodiques Résumé : Background: Alu elements are a group of repetitive elements that can influence gene expression through CpG residues and transcription factor binding. Altered gene expression and methylation profiles have been reported in various tissues and cell lines from individuals with autism spectrum disorder (ASD). However, the role of Alu elements in ASD remains unclear. We thus investigated whether Alu elements are associated with altered gene expression profiles in ASD. Methods: We obtained five blood-based gene expression profiles from the Gene Expression Omnibus database and human Alu-inserted gene lists from the TranspoGene database. Differentially expressed genes (DEGs) in ASD were identified from each study and overlapped with the human Alu-inserted genes. The biological functions and networks of Alu-inserted DEGs were then predicted by Ingenuity Pathway Analysis (IPA). A combined bisulfite restriction analysis of lymphoblastoid cell lines (LCLs) derived from 36 ASD and 20 sex- and age-matched unaffected individuals was performed to assess the global DNA methylation levels within Alu elements, and the Alu expression levels were determined by quantitative RT-PCR. Results: In ASD blood or blood-derived cells, 320 Alu-inserted genes were reproducibly differentially expressed. Biological function and pathway analysis showed that these genes were significantly associated with neurodevelopmental disorders and neurological functions involved in ASD etiology. Interestingly, estrogen receptor and androgen signaling pathways implicated in the sex bias of ASD, as well as IL-6 signaling and neuroinflammation signaling pathways, were also highlighted. Alu methylation was not significantly different between the ASD and sex- and age-matched control groups. However, significantly altered Alu methylation patterns were observed in ASD cases sub-grouped based on Autism Diagnostic Interview-Revised scores compared with matched controls. Quantitative RT-PCR analysis of Alu expression also showed significant differences between ASD subgroups. Interestingly, Alu expression was correlated with methylation status in one phenotypic ASD subgroup. Conclusion: Alu methylation and expression were altered in LCLs from ASD subgroups. Our findings highlight the association of Alu elements with gene dysregulation in ASD blood samples and warrant further investigation. Moreover, the classification of ASD individuals into subgroups based on phenotypes may be beneficial and could provide insights into the still unknown etiology and the underlying mechanisms of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0213-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 27p.[article] Integrated genome-wide Alu methylation and transcriptome profiling analyses reveal novel epigenetic regulatory networks associated with autism spectrum disorder [Texte imprimé et/ou numérique] / T. SAELIW, Auteur ; C. TANGSUWANSRI, Auteur ; S. THONGKORN, Auteur ; W. CHONCHAIYA, Auteur ; K. SUPHAPEETIPORN, Auteur ; A. MUTIRANGURA, Auteur ; T. TENCOMNAO, Auteur ; V. W. HU, Auteur ; T. SARACHANA, Auteur . - 27p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 27p.
Mots-clés : Alu Elements Autism Spectrum Disorder/genetics Case-Control Studies Cells, Cultured DNA Methylation Epigenesis, Genetic Female Gene Regulatory Networks Genome, Human Humans Male Transcriptome Autism spectrum disorder Epigenetic regulation Gene expression profiles Lymphoblastoid cell lines Neuroinflammation Retrotransposon Sex bias Subgrouping Index. décimale : PER Périodiques Résumé : Background: Alu elements are a group of repetitive elements that can influence gene expression through CpG residues and transcription factor binding. Altered gene expression and methylation profiles have been reported in various tissues and cell lines from individuals with autism spectrum disorder (ASD). However, the role of Alu elements in ASD remains unclear. We thus investigated whether Alu elements are associated with altered gene expression profiles in ASD. Methods: We obtained five blood-based gene expression profiles from the Gene Expression Omnibus database and human Alu-inserted gene lists from the TranspoGene database. Differentially expressed genes (DEGs) in ASD were identified from each study and overlapped with the human Alu-inserted genes. The biological functions and networks of Alu-inserted DEGs were then predicted by Ingenuity Pathway Analysis (IPA). A combined bisulfite restriction analysis of lymphoblastoid cell lines (LCLs) derived from 36 ASD and 20 sex- and age-matched unaffected individuals was performed to assess the global DNA methylation levels within Alu elements, and the Alu expression levels were determined by quantitative RT-PCR. Results: In ASD blood or blood-derived cells, 320 Alu-inserted genes were reproducibly differentially expressed. Biological function and pathway analysis showed that these genes were significantly associated with neurodevelopmental disorders and neurological functions involved in ASD etiology. Interestingly, estrogen receptor and androgen signaling pathways implicated in the sex bias of ASD, as well as IL-6 signaling and neuroinflammation signaling pathways, were also highlighted. Alu methylation was not significantly different between the ASD and sex- and age-matched control groups. However, significantly altered Alu methylation patterns were observed in ASD cases sub-grouped based on Autism Diagnostic Interview-Revised scores compared with matched controls. Quantitative RT-PCR analysis of Alu expression also showed significant differences between ASD subgroups. Interestingly, Alu expression was correlated with methylation status in one phenotypic ASD subgroup. Conclusion: Alu methylation and expression were altered in LCLs from ASD subgroups. Our findings highlight the association of Alu elements with gene dysregulation in ASD blood samples and warrant further investigation. Moreover, the classification of ASD individuals into subgroups based on phenotypes may be beneficial and could provide insights into the still unknown etiology and the underlying mechanisms of ASD. En ligne : https://dx.doi.org/10.1186/s13229-018-0213-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 Placental methylome analysis from a prospective autism study / D. I. SCHROEDER in Molecular Autism, 7 (2016)
[article]
Titre : Placental methylome analysis from a prospective autism study Type de document : Texte imprimé et/ou numérique Auteurs : D. I. SCHROEDER, Auteur ; Rebecca J. SCHMIDT, Auteur ; F. K. CRARY-DOOLEY, Auteur ; Cheryl K. WALKER, Auteur ; S. OZONOFF, Auteur ; Daniel J. TANCREDI, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; J. M. LASALLE, Auteur Article en page(s) : 51p. Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis/genetics Biomarkers/metabolism Child, Preschool DNA Methylation Early Diagnosis Enhancer Elements, Genetic Epigenesis, Genetic Female Genome, Human Genome-Wide Association Study High-Throughput Nucleotide Sequencing Humans Infant, Newborn Intercellular Signaling Peptides and Proteins/genetics/metabolism Male Membrane Proteins/genetics/metabolism Placenta/metabolism Pregnancy Biomarkers DNA methylation Epigenetics Genomics Methylome Placenta Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders that are behaviorally diagnosed in early childhood. Most ASD cases likely arise from a complex mixture of genetic and environmental factors, an interface where the epigenetic marks of DNA methylation may be useful as risk biomarkers. The placenta is a potentially useful surrogate tissue characterized by a methylation pattern of partially methylated domains (PMDs) and highly methylated domains (HMDs) reflective of methylation patterns observed in the early embryo. METHODS: In this study, we investigated human term placentas from the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) prospective study by whole genome bisulfite sequencing. We also examined the utility of PMD/HMDs in detecting methylation differences consistent with ASD diagnosis at age three. RESULTS: We found that while human placental methylomes have highly reproducible PMD and HMD locations, there is a greater variation between individuals in methylation levels over PMDs than HMDs due to both sampling and individual variability. In a comparison of methylation differences in placental samples from 24 ASD and 23 typically developing (TD) children, a HMD containing a putative fetal brain enhancer near DLL1 was found to reach genome-wide significance and was validated for significantly higher methylation in ASD by pyrosequencing. CONCLUSIONS: These results suggest that the placenta could be an informative surrogate tissue for predictive ASD biomarkers in high-risk families. En ligne : http://dx.doi.org/10.1186/s13229-016-0114-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329
in Molecular Autism > 7 (2016) . - 51p.[article] Placental methylome analysis from a prospective autism study [Texte imprimé et/ou numérique] / D. I. SCHROEDER, Auteur ; Rebecca J. SCHMIDT, Auteur ; F. K. CRARY-DOOLEY, Auteur ; Cheryl K. WALKER, Auteur ; S. OZONOFF, Auteur ; Daniel J. TANCREDI, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; J. M. LASALLE, Auteur . - 51p.
Langues : Anglais (eng)
in Molecular Autism > 7 (2016) . - 51p.
Mots-clés : Autism Spectrum Disorder/diagnosis/genetics Biomarkers/metabolism Child, Preschool DNA Methylation Early Diagnosis Enhancer Elements, Genetic Epigenesis, Genetic Female Genome, Human Genome-Wide Association Study High-Throughput Nucleotide Sequencing Humans Infant, Newborn Intercellular Signaling Peptides and Proteins/genetics/metabolism Male Membrane Proteins/genetics/metabolism Placenta/metabolism Pregnancy Biomarkers DNA methylation Epigenetics Genomics Methylome Placenta Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are increasingly prevalent neurodevelopmental disorders that are behaviorally diagnosed in early childhood. Most ASD cases likely arise from a complex mixture of genetic and environmental factors, an interface where the epigenetic marks of DNA methylation may be useful as risk biomarkers. The placenta is a potentially useful surrogate tissue characterized by a methylation pattern of partially methylated domains (PMDs) and highly methylated domains (HMDs) reflective of methylation patterns observed in the early embryo. METHODS: In this study, we investigated human term placentas from the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) prospective study by whole genome bisulfite sequencing. We also examined the utility of PMD/HMDs in detecting methylation differences consistent with ASD diagnosis at age three. RESULTS: We found that while human placental methylomes have highly reproducible PMD and HMD locations, there is a greater variation between individuals in methylation levels over PMDs than HMDs due to both sampling and individual variability. In a comparison of methylation differences in placental samples from 24 ASD and 23 typically developing (TD) children, a HMD containing a putative fetal brain enhancer near DLL1 was found to reach genome-wide significance and was validated for significantly higher methylation in ASD by pyrosequencing. CONCLUSIONS: These results suggest that the placenta could be an informative surrogate tissue for predictive ASD biomarkers in high-risk families. En ligne : http://dx.doi.org/10.1186/s13229-016-0114-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329