Browsing by Author "Dicks, Laetitia"
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- ItemInvestigating differential expression in PTSD patients versus controls: An RNA-Seq study(Stellenbosch : Stellenbosch University, 2017-12) Dicks, Laetitia; Hemmings, Sian M. J.; Seedat, Soraya; Dashti, M Jalali Sefid; Stellenbosch University. Faculty of Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.ENGLISH ABSTRACT: Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric disorder underpinned by complex, multi-factorial interactions including genetic and environmental factors. To date, most genetic studies have focused on specific candidate genes involved in PTSD and therefore lack a holistic view of the disorder. In this study, we aimed to utilise RNA-Seq to investigate molecular mechanisms and possible blood bio-signatures in South African PTSD patients. Whole blood gene expression levels of South African mixed ancestry ethnicity (Coloured) individuals were compared between PTSD diagnosed (N = 19) and trauma-exposed control (N = 29) individuals. RNA from whole blood from each participant was subjected to RNA-Seq using the Illumina HiSeq 4000 platform at a sequencing depth of 50 million paired-end reads. Differentially expressed genes (p-value < 0.05) were further prioritized based on their involvement in disease phenotype, function, pathways and known gene/protein interactions using the semantic model of disease in BioOntological Relationship Graph (BORG) database. Furthermore, co-expression analysis of the prioritized candidate genes were carried out to investigate co-regulated differentially expressed gene sets between each groups. A total of 556 differentially expressed genes were identified, of which 196 (21 up- and 175 downregulated) genes were identified as being possibly biologically relevant. Co-expression analysis revealed a network of four highly co-expressed, upregulated genes and a large co-expression network consisting of 36 downregulated genes. The four co-expressed upregulated genes (RPL6, RPS6, RPS3A and EEF1B2) and six highly connected co-expressed downregulated genes (DHX9, BCLAF1, THRAP3, EIF4G1, HSPA4 and MCL1) were identified as potentially relevant gene candidates contributing to the pathology of PTSD. In conclusion, we were able to identify putative blood transcriptomic response in PTSD patients’ vs trauma-exposed controls. Additionally, a set of differentially expressed genes, possibly associated with molecular functions/mechanisms of PTSD were determined. These preliminary findings provide novel insight in underlying genetic expression of PTSD in South African population. Future transcriptomic studies using larger sample size will be instrumental in validating our findings, and should include miRNA profiling to identify a more robust signature of potential blood based biomarkers.