Theses and dissertations

This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students. 

Displaying 1 - 2 of 2
Filtering by

Clear all filters

133149-Thumbnail Image.png

The Genomics of Cancer Resistance in Long-Lived Vesper Bats

Description
Bats (order Chiroptera) are the longest lived mammals for their size, with particularly extreme longevity evolving in the family Vespertilionidae, or vesper bats. Because of this, researchers have proposed using bats to study ageing and cancer suppression. Here, we study gene duplications across mammalian genomes and show that, similar to…

Bats (order Chiroptera) are the longest lived mammals for their size, with particularly extreme longevity evolving in the family Vespertilionidae, or vesper bats. Because of this, researchers have proposed using bats to study ageing and cancer suppression. Here, we study gene duplications across mammalian genomes and show that, similar to previous findings in elephants, bats have experienced duplications of the tumor suppressor gene TP53, including five genomic copies in the genome of the little brown bat (Myotis lucifugus) and two copies in Brandt's bat (Myotis brandtii). These species can live 37 and 41 years, respectively, despite having an adult body mass of only ~7 grams. We use evolutionary genetics and next generation sequencing approaches to show that positive selection has acted on the TP53 locus across bats, and two recently duplicated TP53 gene copies in the little brown bat are both highly conserved and expressed, suggesting they are functional. We also report an extraordinary genomic copy number expansion of the tumor suppressor gene FBXO31 in the common ancestor of vesper bats which accelerated in the Myotis lineage, leading to 34\u201457 copies and the expression of 20 functional FBXO31 homologs in Brandt's bat. As FBXO31 directs the degradation of MDM2, which is a negative regulator of TP53, we suggest that increased expression of both FBXO31 and TP53 may be related to an enhanced DNA-damage response to genotoxic stress brought on by long lifespans and rapid metabolic rates in bats.
ContributorsSchneider-Utaka, Aika Kunigunda (Author) / Maley, Carlo (Thesis director) / Wilson Sayres, Melissa (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
135515-Thumbnail Image.png

A network analysis of SNP-SNP associations in the antigen presentation pathway of hepatocellular carcinoma using extended pathways of distinction analysis

Description
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has been shown to have genetic factors that contribute to cancer susceptibility. These genetic factors can be studied using Genome-Wide association studies (GWAS), which allow for the assessment of associations between specific biologic markers. Through GWAS, associations can…

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has been shown to have genetic factors that contribute to cancer susceptibility. These genetic factors can be studied using Genome-Wide association studies (GWAS), which allow for the assessment of associations between specific biologic markers. Through GWAS, associations can be analyzed to identify genetic components that contribute to the onset of HCC. This study uses an extended version of Pathways of Distinction analysis (PoDA) to identify the subset of SNPs within the Antigen Presentation and Processing Pathway that distinguish cases from controls. Further analysis was performed to explore SNP-SNP association differences between HCC cases and controls using R-squared values and p-values. Three SNPs show significant inter-SNP associations in both HCC cases and controls. Additionally, 4 SNPs showed significant SNP-SNP associations exclusively in the control data set, possibly suggesting that control pathways have a greater degree of genetic regulation and robustness that is lost in carcinogenesis. This result suggests that these SNP associations may contribute to HCC susceptibility.
ContributorsAghili, Ardesher Joshua (Author) / Buetow, Kenneth (Thesis director) / Wilson Sayres, Melissa (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05