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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression analysis of Pea3 overexpression in SH-SY5Y cell line

ABSTRACT: Investigation of whole genome gene expression level changes in SH-SY5Y cells transfected Pea3-VP16 cells compared to pCDNA3 transfected cells as a control.

ORGANISM(S): Homo sapiens

SUBMITTER: Basak Kandemir

PROVIDER: E-MTAB-5324 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Analysis of Elk-1-VP16 overexpression in SH-SY5Y cell line

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Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy

Project description:Autism is present in 1% of the population, yet treatments are extremely limited. We identified homozygous inactivating mutations in the BCKDK gene in families presenting with autism and epilepsy. The encoded branched chain ketoacid dehydrogenase kinase protein is responsible for phosphorylation-mediated inactivation of the E1-alpha subunit of branched chain ketoacid dehydrogenase, itself mutated in Maple Syrup Urine Disease (MSUD). Patients with homozygous BCKDK mutations display reductions in BCKDK mRNA and protein, E1-alpha phosphorylation and serum branched chain amino acids (BCAAs). Bckdk knockout mice show abnormal brain amino acids profiles and neurobehavioral defects, which are largely corrected by dietary BCAA supplementation. Thus autism presenting with epilepsy due to BCKDK mutations represent a new and potentially treatable disease. A 51 chip study that includes both human and mouse samples to investigate the expression changes that result in a mutation or knockout of the BCKDK gene. Starting with human fibroblasts from three affecteds and two controls, cells were converted into IPSs, then NPCs, and finally Neurons. Each of these cell types were used to view the expression changes between a cells with a BCKDK mutation versus controls. Finally, a mouse knockout was performed to verify consistency of the expression pattern differences between the BCKCK knockout and wild-type. Samples are labeled as Affected if the sample came from a patient with a BCKDK mutation and WildType otherwise. Samples were usually replicated once.

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