Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Biology

Supervisor

Shiva M. Singh

Abstract

The incidence of cognitive impairments, including age-associated spatial learning impairment (ASLI), has risen dramatically in past decades due to increasing human longevity. To better understand the genes and gene networks involved in ASLI, data from a number of past gene expression microarray studies in rats are integrated and used to perform a meta- and network analysis. Results from the data selection and preprocessing steps show that for effective downstream analysis to take place both batch effects and outlier samples must be properly removed. The meta-analysis undertaken in this research has identified significant differentially expressed genes across both age and ASLI in rats. Knowledge based gene network analysis shows that these genes affect many key functions and pathways in aged compared to young rats. The resulting changes might manifest as various neurodegenerative diseases/disorders or syndromic memory impairments at old age. Other changes might result in altered synaptic plasticity, thereby leading to normal, non-syndromic learning impairments such as ASLI.

Next, I employ the weighted gene co-expression network analysis (WGCNA) on the datasets. I identify several reproducible network modules each highly significant with genes functioning in specific biological functional categories. It identifies a “learning and memory” specific module containing many potential key ASLI hub genes. Functions of these ASLI hub genes link a different set of mechanisms to learning and memory formation, which meta-analysis was unable to detect. This study generates some new hypotheses related to the new candidate genes and networks in ASLI, which could be investigated through future research.


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