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Alternative Promoter Usage using Transcription Start Sites in Patients with Alzheimer’s Disease

Description
Alzheimer’s Disease (AD) is one of the most common forms of dementia and a major cause of disability and dependency in older patients worldwide.Although there has been a lot of research done in the field of gene expression and possible drivers of AD, there has not been enough investigation into…

Alzheimer’s Disease (AD) is one of the most common forms of dementia and a major cause of disability and dependency in older patients worldwide.Although there has been a lot of research done in the field of gene expression and possible drivers of AD, there has not been enough investigation into transcription start site and alternative promoter usage of AD. With relatively small genomes, species have evolved mechanisms for diversifying their transcriptome, which is the set of messenger mRNA transcripts produced in a given cell. While the most well-known mechanism of diversification is alternative splicing, another mechanism that has been less explored is alternative promoter (AP) usage, which generates different transcripts by selecting different transcription start sites (TSSs) upstream of a gene. More importantly, AP usage can bring about different coding sequences, which can in some cases lead to changes within the N-termini of the cognate proteins. Alternative promoter usage has the potential to regulate processes like alternative splicing, tissue specificity, regional specificity and subcellular specificity of gene expression and gene activation during development. In this study a customized pipeline for STRIPE-seq generated data was applied to AD and control data set and the first AD promoter atlas was generated. This atlas was used to generate list of genes with differentially used TSRs and biological pathways they are involved in. Finally, a consensus cluster set was created to investigate alternative promoter usage in AD patients and alternative promoter usage was shown in Alzheimer’s Disease related genes such as APOE and MAPT.
ContributorsStampar, Mojca (Author) / Lee, Heewook (Thesis advisor) / Raborn, Randolph T (Committee member) / Mastroeni, Diego (Committee member) / Arizona State University (Publisher)
Created2022