Browsing by Subject "RNA-Seq"
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(2023)Depression and anxiety are the two most common mental disorders worldwide, and especially common among women of reproductive age. Hence, they are also common problems among pregnant women. Maternal depression and anxiety not only compromise the mother’s quality of life during pregnancy but increase the risk of perinatal complications and poor child neurodevelopment. The biological mechanisms that underpin this transmission remain largely unknown. The placenta, a transient fetal organ functioning as an interface between the mother and the fetus, plays a pivotal role, as the placenta transmits all environmental cues to the fetus. This thesis aims to investigate differential gene expression in the first-trimester chorionic villi and birth placenta samples from women with depression and/or anxiety and healthy controls. Samples are collected and processed as a part of the InTraUterine sampling in early pregnancy (ITU) study and both chorionic villus samples (CVS) collected during the early pregnancy and delivery placenta samples were studied. I defined three different phenotypes based on (i) maternal depression and anxiety disorder diagnosis, (ii) antidepressant and anxiolytic medication purchases, or (iii) self-reported depressive and anxiety symptoms during pregnancy. Genome-wide analysis of differential gene expression was conducted with DESeq2 R-package and further gene set enrichment analysis was performed with a web-based platform FUMA. When comparing mothers with depressive and anxiety symptoms to asymptotic controls, but not those with or without diagnoses or medication purchases, I found 478 genes differentially expressed. In the enrichment analysis these genes related to immune response and inflammation, such as leukocyte and T cell activation, defense response, and cytokine production. Together these results indicate that maternal depressive and anxiety symptoms during pregnancy change the immune system functions in the placenta which may partly explain the adverse effects of maternal depression and anxiety on the developing fetus. These findings may afford a target for timely targeted interventions to prevent perinatal complications and the transmission of maternal depression and anxiety to the next generation.
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(2024)The TTN gene is composed of 364 exons (363 coding) and encodes for titin, the largest protein in nature. Pathogenic TTN variants result in a wide spectrum of skeletal muscle and cardiac disorders known as Titinopathies. These differ in inheritance patterns, onset age, disease course and severity. The biological mechanisms underlying disease-causing variants specific to titinopathy patients are still elusive. Investigating gene signatures causing the biological pathomechanisms is crucial for understanding genotype-phenotype corelations. RNA-sequencing emerges as a valuable technique for analysing transcriptomic data and exploring gene expression profiles of patient and control samples. To elucidate common pathomechanisms in titinopathies, including adult tibial muscular dystrophy (TMD) due to heterozygous FINmaj variant, and biallelic recessive titinopathies, an extensive differential gene expression (DGE) analysis was conducted using three RNA cohorts from human muscle biopsies. The cohorts involved two polyA enriched and one rRNA depleted batch-corrected cohort. Human DGE analysis identified 265 commonly upregulated genes and 147 commonly downregulated genes in the titinopathy cohorts. A significant downregulation of TTN expression levels was observed in one of the cohorts. To validate and understand the biological significance of these findings, data from a mouse model was incorporated with homozygous Ttn FINmaj variants. Common genes among all cohorts accounted for the structural integrity of the extracellular matrix. This study indicates the pathomechanisms for a skeletal muscle pathology and discusses the future steps in efficiently performing RNA-Seq for titinopathies.
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