| Summary: | It is now known that at least 80% of the human genome is composed of non-coding DNA which has a biochemical activity and is involved in a wide range of activities and mechanisms. Among these, epigenetic modifications, cis-trans gene expression regulation, transcription factor binding sequences, are the most studied. Non-coding DNA is often characterised by a polymorphic and repetitive nature and it is composed of a high density of GC nucleotides. These polymorphic and repetitive regions within the population may represent either protective elements or risk factors, based on population studies in various diseases, for several conditions and at the same time have the power to shape our behaviours or wellbeing. The compositions of transcription factor binding sites (BSs) and epigenetic factors at these regions act in concert with external and environmental factors to modify gene function and gene expression. This combined effect of environmental and genetic factors capable of influence people's wellbeing or disease risk is known as Gene - Environment Interaction (GxE) and it is a key feature that allows us to adapt to our surrounding. The data presented in this thesis will try to address some of the well characterised polymorphic variants associated with Central Nervous System (CNS) conditions, such as the Monoamine oxidase A (MAOA) gene, and I will show how they can modify gene expression in response to environmental stimuli. We also report two regulatory regions in the CACNA1C (Calcium Voltage-Gated Channel Subunit Alpha1 C) gene, strongly associated to schizophrenia by GWAS (Genome-Wide Association Study) investigations. Finally I will also report a novel polymorphic microsatellite in the promoter region of the gene that has been defined 'the master regulator' of transcription, the RE1-Silencing Transcription factor (REST) gene, that strongly suggests an association with Alzheimer's disease. Therefore I demonstrate a similarity in mechanisms and in the activity of these repeat elements in the promoter regions of three key genes for CNS behaviour and illustrate the potential power of these elements as transcriptional regulatory DNA regions.
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