RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex-specific effects / Daniel S. TYLEE in Autism Research, 10-3 (March 2017)  

Public ISBD [article]  inAutism Research > 10-3 (March 2017) . - p.439-455 Titre : RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex-specific effects Type de document : Texte imprimé et/ou numérique Auteurs : Daniel S. TYLEE, Auteur ; Alfred J. ESPINOZA, Auteur ; Jonathan L. HESS, Auteur ; Muhammad A. TAHIR, Auteur ; Sarah Y. MCCOY, Auteur ; Joshua K. RIM, Auteur ; Totadri DHIMAL, Auteur ; Ori S. COHEN, Auteur ; Stephen J. GLATT, Auteur Article en page(s) : p.439-455 Langues : Anglais (eng) Mots-clés : RNA sequencing  transcriptome  lymphoblastoid  autism spectrum disorder  sex-differences  biomarker Index. décimale : PER Périodiques Résumé : Genome-wide expression studies of samples derived from individuals with autism spectrum disorder (ASD) and their unaffected siblings have been widely used to shed light on transcriptomic differences associated with this condition. Females have historically been under-represented in ASD genomic studies. Emerging evidence from studies of structural genetic variants and peripheral biomarkers suggest that sex-differences may exist in the biological correlates of ASD. Relatively few studies have explicitly examined whether sex-differences exist in the transcriptomic signature of ASD. The present study quantified genome-wide expression values by performing RNA sequencing on transformed lymphoblastoid cell lines and identified transcripts differentially expressed between same-sex, proximal-aged sibling pairs. We found that performing separate analyses for each sex improved our ability to detect ASD-related transcriptomic differences; we observed a larger number of dysregulated genes within our smaller set of female samples (n?=?12 sibling pairs), as compared with the set of male samples (n?=?24 sibling pairs), with small, but statistically significant overlap between the sexes. Permutation-based gene-set analyses and weighted gene co-expression network analyses also supported the idea that the transcriptomic signature of ASD may differ between males and females. We discuss our findings in the context of the relevant literature, underscoring the need for future ASD studies to explicitly account for differences between the sexes. En ligne : http://dx.doi.org/10.1002/aur.1679 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304 [article] RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex-specific effects [Texte imprimé et/ou numérique] / Daniel S. TYLEE, Auteur ; Alfred J. ESPINOZA, Auteur ; Jonathan L. HESS, Auteur ; Muhammad A. TAHIR, Auteur ; Sarah Y. MCCOY, Auteur ; Joshua K. RIM, Auteur ; Totadri DHIMAL, Auteur ; Ori S. COHEN, Auteur ; Stephen J. GLATT, Auteur . - p.439-455. Langues : Anglais (eng) in Autism Research > 10-3 (March 2017) . - p.439-455 Mots-clés : RNA sequencing  transcriptome  lymphoblastoid  autism spectrum disorder  sex-differences  biomarker Index. décimale : PER Périodiques Résumé : Genome-wide expression studies of samples derived from individuals with autism spectrum disorder (ASD) and their unaffected siblings have been widely used to shed light on transcriptomic differences associated with this condition. Females have historically been under-represented in ASD genomic studies. Emerging evidence from studies of structural genetic variants and peripheral biomarkers suggest that sex-differences may exist in the biological correlates of ASD. Relatively few studies have explicitly examined whether sex-differences exist in the transcriptomic signature of ASD. The present study quantified genome-wide expression values by performing RNA sequencing on transformed lymphoblastoid cell lines and identified transcripts differentially expressed between same-sex, proximal-aged sibling pairs. We found that performing separate analyses for each sex improved our ability to detect ASD-related transcriptomic differences; we observed a larger number of dysregulated genes within our smaller set of female samples (n?=?12 sibling pairs), as compared with the set of male samples (n?=?24 sibling pairs), with small, but statistically significant overlap between the sexes. Permutation-based gene-set analyses and weighted gene co-expression network analyses also supported the idea that the transcriptomic signature of ASD may differ between males and females. We discuss our findings in the context of the relevant literature, underscoring the need for future ASD studies to explicitly account for differences between the sexes. En ligne : http://dx.doi.org/10.1002/aur.1679 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304

SLC9A9 Co-expression modules in autism-associated brain regions / Jameson PATAK in Autism Research, 10-3 (March 2017)  

Public ISBD [article]  inAutism Research > 10-3 (March 2017) . - p.414-429 Titre : SLC9A9 Co-expression modules in autism-associated brain regions Type de document : Texte imprimé et/ou numérique Auteurs : Jameson PATAK, Auteur ; Jonathan L. HESS, Auteur ; Yanli ZHANG-JAMES, Auteur ; Stephen J. GLATT, Auteur ; Stephen V. FARAONE, Auteur Article en page(s) : p.414-429 Langues : Anglais (eng) Mots-clés : SLC9A9  weighted gene co-expression network analysis  Autism spectrum disorder  endosomal pathway  transcriptome Index. décimale : PER Périodiques Résumé : SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism-associated brain regions throughout development. We conducted a weighted gene co-expression network analysis on RNA-seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD-associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD-associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co-immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. En ligne : http://dx.doi.org/10.1002/aur.1670 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304 [article] SLC9A9 Co-expression modules in autism-associated brain regions [Texte imprimé et/ou numérique] / Jameson PATAK, Auteur ; Jonathan L. HESS, Auteur ; Yanli ZHANG-JAMES, Auteur ; Stephen J. GLATT, Auteur ; Stephen V. FARAONE, Auteur . - p.414-429. Langues : Anglais (eng) in Autism Research > 10-3 (March 2017) . - p.414-429 Mots-clés : SLC9A9  weighted gene co-expression network analysis  Autism spectrum disorder  endosomal pathway  transcriptome Index. décimale : PER Périodiques Résumé : SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism-associated brain regions throughout development. We conducted a weighted gene co-expression network analysis on RNA-seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD-associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD-associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co-immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. En ligne : http://dx.doi.org/10.1002/aur.1670 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=304

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