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Access Type
WSU Access
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Molecular Biology and Genetics
First Advisor
Jun Li
Abstract
Peripheral nerves are composed of various cell types that are highly regulated to form anatomical features during the early development. These characteristics enable acquisition of an optimal conduction velocity (CV). Therefore, CV changes mark specific stages of nerve development. This study aimed to examine the developmental changes in peripheral nerves at critical time points determined by CV in rat nerves. Transcriptome analysis of peripheral nerve tissues from 20-day-old animals, exhibiting the fastest increment in CV, and 70-day-old animals, displaying CV at its plateau, revealed genes crucial for nerve development. These genes are predominantly involved in immune pathways, extracellular matrix, and collagen organization. Protein-protein network analysis of differentially expressed genes demonstrated significant interactions with genes associated with various peripheral neuropathies, emphasizing the importance of these genes in peripheral nerve function. Preliminary analysis of spatial transcriptome from these peripheral nerve tissues identified genes enriched in specific cell populations and offered insights into spatio-temporal transcriptome changes during peripheral nervous development. Functional and behavioral assessments of patients with peripheral neuropathies revealed a strong correlation between physical functions and disease severity. Genetic burden score calculated from variants in the genes identified through the transcriptome study exhibited a significant correlation with disease severity, highlighting the contribution of genetic background on these identified genes to peripheral neuropathies. Taken together, this study advances our understanding in genetic regulation of peripheral nerve development, and their relevance to the peripheral nerve diseases.
Recommended Citation
Saba, Sadaf, "Genetic Determinants Of Peripheral Neuropathies" (2023). Wayne State University Dissertations. 3863.
https://digitalcommons.wayne.edu/oa_dissertations/3863