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• W2028033268 abstract "Common genetic variation and rare mutations in genes encoding calcium channel subunits have pleiotropic effects on risk for multiple neuropsychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. To gain further mechanistic insights by extending previous gene expression data, we constructed co-expression networks in Timothy syndrome (TS), a monogenic condition with high penetrance for ASD, caused by mutations in the L-type calcium channel, Cav1.2. To identify patient-specific alterations in transcriptome organization, we conducted a genome-wide weighted co-expression network analysis (WGCNA) on neural progenitors and neurons from multiple lines of induced pluripotent stem cells (iPSC) derived from normal and TS (G406R in CACNA1C) individuals. We employed transcription factor binding site enrichment analysis to assess whether TS associated co-expression changes reflect calcium-dependent co-regulation. We identified reproducible developmental and activity-dependent gene co-expression modules conserved in patient and control cell lines. By comparing cell lines from case and control subjects, we also identified co-expression modules reflecting distinct aspects of TS, including intellectual disability and ASD-related phenotypes. Moreover, by integrating co-expression with transcription factor binding analysis, we showed the TS-associated transcriptional changes were predicted to be co-regulated by calcium-dependent transcriptional regulators, including NFAT, MEF2, CREB, and FOXO, thus providing a mechanism by which altered Ca2+ signaling in TS patients leads to the observed molecular dysregulation. We applied WGCNA to construct co-expression networks related to neural development and depolarization in iPSC-derived neural cells from TS and control individuals for the first time. These analyses illustrate how a systems biology approach based on gene networks can yield insights into the molecular mechanisms of neural development and function, and provide clues as to the functional impact of the downstream effects of Ca2+ signaling dysregulation on transcription." @default.
• W2028033268 created "2016-06-24" @default.
• W2028033268 creator A5000192581 @default.
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• W2028033268 creator A5091758919 @default.
• W2028033268 date "2014-10-01" @default.
• W2028033268 modified "2023-10-18" @default.
• W2028033268 title "Alteration in basal and depolarization induced transcriptional network in iPSC derived neurons from Timothy syndrome" @default.
• W2028033268 cites W1544691147 @default.
• W2028033268 cites W1546952499 @default.
• W2028033268 cites W1569503463 @default.
• W2028033268 cites W1585306115 @default.
• W2028033268 cites W1964617200 @default.
• W2028033268 cites W1966327575 @default.
• W2028033268 cites W1967232661 @default.
• W2028033268 cites W1967463041 @default.
• W2028033268 cites W1974033269 @default.
• W2028033268 cites W1977756287 @default.
• W2028033268 cites W1986145335 @default.
• W2028033268 cites W1988670106 @default.
• W2028033268 cites W1989119979 @default.
• W2028033268 cites W1991085184 @default.
• W2028033268 cites W1993205491 @default.
• W2028033268 cites W1993237244 @default.
• W2028033268 cites W1994109113 @default.
• W2028033268 cites W1995647101 @default.
• W2028033268 cites W2000931014 @default.
• W2028033268 cites W2004922458 @default.
• W2028033268 cites W2006948906 @default.
• W2028033268 cites W2007180149 @default.
• W2028033268 cites W2007300748 @default.
• W2028033268 cites W2011389660 @default.
• W2028033268 cites W2011747578 @default.
• W2028033268 cites W2014764883 @default.
• W2028033268 cites W2014787267 @default.
• W2028033268 cites W2022689242 @default.
• W2028033268 cites W2030803511 @default.
• W2028033268 cites W2033572023 @default.
• W2028033268 cites W2033613660 @default.
• W2028033268 cites W2033877733 @default.
• W2028033268 cites W2034998738 @default.
• W2028033268 cites W2037094652 @default.
• W2028033268 cites W2040030455 @default.
• W2028033268 cites W2042625441 @default.
• W2028033268 cites W2043567981 @default.
• W2028033268 cites W2052661726 @default.
• W2028033268 cites W2052827796 @default.
• W2028033268 cites W2057932313 @default.
• W2028033268 cites W2059144308 @default.
• W2028033268 cites W2059743066 @default.
• W2028033268 cites W2060337750 @default.
• W2028033268 cites W2060705109 @default.
• W2028033268 cites W2061173712 @default.
• W2028033268 cites W2061725286 @default.
• W2028033268 cites W2061971803 @default.
• W2028033268 cites W2064959296 @default.
• W2028033268 cites W2066057252 @default.
• W2028033268 cites W2067110557 @default.
• W2028033268 cites W2068412840 @default.
• W2028033268 cites W2071598557 @default.
• W2028033268 cites W2073580835 @default.
• W2028033268 cites W2081038787 @default.
• W2028033268 cites W2082023836 @default.
• W2028033268 cites W2084778633 @default.
• W2028033268 cites W2088359631 @default.
• W2028033268 cites W2089424629 @default.
• W2028033268 cites W2098023402 @default.
• W2028033268 cites W2109807917 @default.
• W2028033268 cites W2112680288 @default.
• W2028033268 cites W2112906768 @default.
• W2028033268 cites W2116631863 @default.
• W2028033268 cites W2123490534 @default.
• W2028033268 cites W2124432707 @default.
• W2028033268 cites W2132082846 @default.
• W2028033268 cites W2133850147 @default.
• W2028033268 cites W2135030836 @default.
• W2028033268 cites W2138773108 @default.
• W2028033268 cites W2139695427 @default.
• W2028033268 cites W2139852368 @default.
• W2028033268 cites W2145748421 @default.
• W2028033268 cites W2152717615 @default.
• W2028033268 cites W2156081018 @default.
• W2028033268 cites W2160616996 @default.
• W2028033268 cites W2161888326 @default.
• W2028033268 cites W2161926708 @default.
• W2028033268 cites W2166898290 @default.
• W2028033268 cites W2167884902 @default.
• W2028033268 cites W2170070762 @default.
• W2028033268 cites W2171854303 @default.
• W2028033268 cites W2259938310 @default.
• W2028033268 cites W2301131921 @default.
• W2028033268 cites W31058257 @default.
• W2028033268 cites W4230102805 @default.
• W2028033268 doi "https://doi.org/10.1186/s13073-014-0075-5" @default.
• W2028033268 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4213483" @default.

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