عنوان

شناسایی مسیرهای مولکولی درگیر در بیماری ناتوانی‌ذهنی در خانواده ای با جهش در ژنCDK ۹ با استفاده از تکنیکseq- RNA

Around 1-3 of world population have been affected by Intellectual disability (ID), a neurodevelopmental disorder with a high level of genetic and clinical heterogeneity. Although intellectual disability is a clinically important disorder, the etiology and pathogenesis are poorly understood. Transcriptome profiling is a very important tool for understanding how genetic variants alter cell expression. Detecting differentially expressed genes and isoforms, specifying the functional consequence of known and novel variants and linking between genetic changes and phenotype are some of the countless applications of RNA-Seq. In the current study, we applied whole blood transcriptome analysis using RNA-seq to identify biological and molecular pathways underlying ID disease in a consanguineous family with a mutation in CDK9 transcription factor. Overall, 972 differentially expressed genes (q value <0.01 and fold change> 1.5) were identified between CDK9 mutant patients and controls, of these 972 genes, 459 genes downregulated and 513 genes upregulated in patients. Based on detailed gene ontology analysis, the most significant pathways dysregulated in patients were gene expression, structural constituent of ribosome and RNA binding, histone modification, tyrosine protein kinase, small GTPase signal transduction, and actin cytoskeleton. The findings reported here provides new insights into the molecular pathways underlying intellectual disability and highlight the importance of these transcription factors in neuronal functions. Key words: Intellectual disability, Transcriptomics, Molecular pathways, Gene expression, RNA-seq, CDK9

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