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- All Subjects: Genetics
- Creators: School of Life Sciences
Description
The use of genetic management in conservation has sparked much debate around the ethical and environmental impacts of the plans. A case study on the conservation of leopard frogs in Arizona was analyzed to better understand the benefits and issues surrounding genetic management plans. The first part of the case focuses on the recent management plan for Chiricahua Leopard Frogs implemented by the Arizona Game and Fish Department. The goal of the plan is to better understand the genetic dynamics of the established Chiricahua Leopard Frog populations to develop a more effective management plan. The second part of the case focuses on the Arizona Game and Fish Department’s management of the Northern Leopard Frog. There was little success with the initial breed and release program of the native species, however a nonnative subspecies of Northern Leopard Frog was able to establish a thriving population. This case study exemplifies the many complications with genetic management plans and the importance of careful assessment of options when deciding on a genetic management plan. Despite the complexity of genetic management plans, it is an important method to consider when discussing the conservation of a species.
ContributorsTurpen, Alexa (Author) / Murphree, Julie (Thesis director) / Collins, James (Thesis director) / Owens, Audrey (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / College of Integrative Sciences and Arts (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2024-05
Description
Cancer is a disease in which abnormal cells divide uncontrollably and destroy body tissue, and currently plagues today’s world. Carcinomas are cancers derived from epithelial cells and include breast and prostate cancer. Breast cancer is a type of carcinoma that forms in breast tissue cells. The tumor cells can be further categorized after testing the cells for the presence of certain molecules. Hormone receptor positive breast cancer includes the tumor cells with receptors that respond to the steroid hormones, estrogen and progesterone, or the peptide hormone, HER2. These forms of cancer respond well to chemotherapy and endocrine therapy. On the other hand, triple negative breast cancer (TNBC) is characterized by the lack of hormone receptor expression and tends to have a worse prognosis in women. Prostate cancer forms in the cells of the prostate gland and has been attributed to mutations in androgen receptor ligand specificity. In a subset of triple negative breast cancer, genetic expression profiling has found a luminal androgen receptor that is dependent on androgen signaling. TNBC has also been found to respond well to enzalutamide, a an androgen receptor inhibitor. As the gene of the androgen receptor, AR, is located on the X chromosome and expressed in a variety of tissues, the responsiveness of TNBC to androgen receptor inhibition could be due to the differential usage of isoforms - different gene mRNA transcripts that produce different proteins. Thus, this study analyzed differential gene expression and differential isoform usage between TNBC cancers – that do and do not express the androgen receptor – and prostate cancer in order to better understand the underlying mechanism behind the effectiveness of androgen receptor inhibition in TNBC. Through the analysis of differential gene expression between the TNBC AR+ and AR- conditions, it was found that seven genes are significantly differentially expressed between the two types of tissues. Genes of significance are AR and EN1, which was found to be a potential prognostic marker in a subtype of TNBC. While some genes are differentially expressed between the TNBC AR+ and AR- tissues, the differences in isoform expression between the two tissues do not reflect the difference in gene expression. We discovered 11 genes that exhibited significant isoform switching between AR+ and AR- TNBC and have been found to contribute to cancer characteristics. The genes CLIC1 and RGS5 have been found to help the rapid, uncontrolled growth of cancer cells. HSD11B2, IRAK1, and COL1Al have been found to contribute to general cancer characteristics and metastasis in breast cancer. PSMA7 has been found to play a role in androgen receptor activation. Finally, SIDT1 and GLYATL1 are both associated with breast and prostate cancers. Overall, through the analysis of differential isoform usage between AR+ and AR- samples, we uncovered differences that were not detected by a gene level differential expression analysis. Thus, future work will focus on analyzing differential gene and isoform expression across all types of breast cancer and prostate cancer to better understand the responsiveness of TNBC to androgen receptor inhibition.
ContributorsDeshpande, Anagha J (Author) / Wilson-Sayres, Melissa (Thesis director) / Buetow, Kenneth (Committee member) / Natri, Heini (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Small cell carcinoma of the ovary (SCCOHT) is a rare ovarian cancer affecting young women and characterized by mutation in SMARCA4 and silencing of SMARCA2, two tumor suppressors that function as ATPases in the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. SCCOHT patients face a 5-year survival rate of only 26%, but recently we have identified sensitivity of SCCOHT models to a natural product, triptolide. This study aims to ascertain the mechanism of action of triptolide. Previous SCCOHT epigenetic drug research has shown that some drugs reverse SMARCA2 epigenetic silencing to inhibit tumor growth, therefore it is hypothesized that triptolide acts the same and restores SWI/SNF function. Cells treated with triptolide have no change in SMARCA2 expression, suggesting that re-expression of epigenetically silenced tumor suppressor gene does not underlie its mechanism of action. Growth rates following triptolide treatment were observed in the presence and absence of SMARCA4, but no difference in sensitivity was observed. Thus, it is not likely that triptolide acts by restoring SWI/SNF. Others have observed that triptolide acts on xeroderma pigmentosa type B protein (XPB), a component of super-enhancers, which are DNA regions with high levels of transcription that regulate genes responsible for cell identity and oncogenes driving tumorigenesis. Both SCCOHT-1 and BIN67 cell lines treated with triptolide displayed lower expression of the super-enhancer associated MYC oncogene compared to untreated cells, supporting the theory that triptolide could be inhibiting super-enhancers regulating oncogenes.. A western blot confirmed reduced protein levels of RNA polymerase II and bromodomain 4 (BRD4), two essential components found at high levels at super-enhancers, in BIN67 cells treated with triptolide. ChIP-sequencing of Histone H3 Lysine-27 Acetylation (H3K27ac) marks in BIN67 and SCCOHT-1 cell lines identified super-enhancers in SCCOHT using tools CREAM and ROSE, which were mapped to neighboring genes associated genes and compared with the COSMIC database to identify oncogenes, of which the top 11 were examined by qRT-PCR to ascertain whether triptolide reduces their expression. It has been found that 6 out of 11 of the oncogenes examined (SALL4, MYC, SGK1, HIST1H3B, HMGA2, and CALR) decreased in expression when treated with triptolide. Thus, there is reason to believe that triptolide’s mechanism of action is via inhibition of super-enhancers that regulate oncogene expression.
ContributorsViloria, Nicolle Angela (Author) / Lake, Douglas (Thesis director) / Hendricks, William (Committee member) / Lang, Jessica (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Immediate early genes (IEGs) are rapidly activated in response to an environmental stimulus, and most code for transcription factors that mediate processes of synaptic plasticity, learning, and memory. EGR3, an immediate early gene transcription factor, is a mediator of biological processes that are disrupted in patients with schizophrenia (SCZ). A microarray experiment conducted by our lab revealed that Egr3 also regulates genes involved in DNA damage response. A recent study revealed that physiological neuronal activity results in the formation of DNA double-stranded breaks (DSBs) in the promoters of IEGs. Additionally, they showed that these DSBs are essential for inducing the expression of IEGs, and failure to repair these DSBs results in the persistent expression of IEGs. We hypothesize that Egr3 plays a role in repairing activity- induced DNA DSBs, and mice lacking Egr3 should have an abnormal accumulation of these DSBs. Before proceeding with that experiment, we conducted a preliminary investigation to determine if electroconvulsive stimulation (ECS) is a reliable method of inducing activity- dependent DNA damage, and to measure this DNA damage in three subregions of the hippocampus: CA1, CA3, and dentate gyrus (DG). We asked the question, are levels of DNA DSBs different between these hippocampal subregions in animals at baseline and following electroconvulsive stimulation (ECS)? To answer this question, we quantified γ-H2AX, a biomarker of DNA DSBs, in the hippocampal subregions of wildtype mice. Due to technical errors and small sample size, we were unable to substantiate our preliminary findings. Despite these shortcomings, our experimental design can be modified in future studies that investigate the role of Egr3 in activity-induced DNA damage repair.
ContributorsKhoshaba, Rami Samuel (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Committee member) / Marballi, Ketan (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
In most bird species, females disperse prior to their first breeding attempt, while males remain close to the place they were hatched for their entire lives (Greenwood and Harvey (1982)). Explanations for such female bias in natal dispersal have focused on the potential benefits that males derive from knowing the local environment to establish territories, while females search for suitable mates (Greenwood (1980)). However, the variables shaping dispersal decisions appear more complex (Mabry et al. (2013), Végvári et al. (2018)). There are a number of different variables that could act as a driving force behind dispersal including the social mating system, food competition, inbreeding avoidance, predation, and others. Here, we investigate whether females are the dispersing sex in great-tailed grackles, which have a mating system where the males hold territories and the females choose which territory to place their nest in (Johnson et al. (2000)). We used genetic approaches to identify sex biases in the propensity to disperse. In the experiment, we found that the male grackles were less related to each other while the female grackles were more related to each other. Building on that, the average distance between closely related individuals of the male group was longer than the average distance of closely related females. But, the mantel correlograms for the males and females both lack a consistent trend. Overall, the results indicated suggest that the males are the dispersing sex while the females are potentially philopatric and that the average dispersal distance for the grackle is greater than 2000 meters, the size of the sampling range used in the experiment. These results will inform our long-term study on the relationship between behavioral flexibility and rapid geographic range expansion by elucidating which individuals are likely to experience similar conditions across their lives, and which are likely to face new conditions when they become breeders.
ContributorsSevchik, August L (Author) / Langergraber, Kevin (Thesis director) / Logan, Corina (Committee member) / College of Integrative Sciences and Arts (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Damage to DNA can affect the genes it encodes; if this damage is not repaired, abnormal proteins may be produced and cellular functions may be disturbed. DNA damage has been implicated in the initiation and progression of a variety of diseases. Conversely, DNA damage has also been discovered to contribute to beneficial biological processes. Madabhushi and colleagues (2015) determined that activity-dependent DNA double strand breaks (DSBs) in the promoter region of immediate early genes (IEGs) induced their expression. EGR3 is an IEG transcription factor which regulates the expression of growth factors and synaptic plasticity-associated genes. In a previously conducted microarray experiment, it was revealed that EGR3 regulates the expression of genes associated with DNA repair such as Cenpa and Nr4a2. These findings inspired us to investigate if EGR3 affects DNA repair in vivo. Before conducting this experiment, we sought to standardize and optimize a method of inducing DNA damage in the hippocampus. Electroconvulsive stimulation (ECS) is utilized to induce neuronal activity. Since neuronal activity leads to the formation of DNA DSBs, we theorized that ECS could be used to induce DNA DSBs in the hippocampus. We predicted that mice that receive ECS would have more DNA DSBs than those that receive the sham treatment. Gamma H2AX, a biomarker for DNA damage, was utilized to quantify DNA DSBs. Gamma H2AX expression in the dentate gyrus, CA1 and CA3 regions of the hippocampus was compared between mice that received the sham treatment and mice that received ECS. Mice that received ECS were sacrificed either 1 or 2 hours post-administration, constituting treatment conditions of 1 hr post-ECS and 2 hrs post-ECS. Our results suggest that ECS has a statistically significant effect exclusively in the CA1 region of the hippocampus. However, our analyses may have been limited due to sample size. A power analysis was conducted, and the results suggest that a sample size of n=4 mice will be sufficient to detect significant differences across treatments in all three regions of the hippocampus. Ultimately, future studies with an increased sample size will need to be conducted to conclusively assess the use of ECS to induce DNA damage within the hippocampus.
ContributorsAden, Aisha Abubakar (Author) / Newbern, Jason (Thesis director) / Gallitano, Amelia (Thesis director) / Marballi, Ketan (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
In vitro gametogenesis (IVG) research has been growing in countries like Japan, US, and China after the development of stem cell research and other scientific advancements as well as because of the perception of infertility as a domestic and international problem. IVG research’s progress has been deliberated internationally, with discussion of questions, challenges, and possibilities that have arisen and may arise in the future as the technology is adopted by different countries. The first section introduces the meaning of IVG, explains the importance of review by scientists and citizens for IVG, and describes a rise in infertility reported in multiple developed countries that could be addressed by IVG. The second section discusses IVG’s applications and implications using 5 ethical categories articulated by Obama’s Presidential Commission for the Study of Bioethical Issues: Public Beneficence, Responsible Stewardship, Intellectual Freedom and Responsibility, Democratic Deliberation, and Justice and Fairness. These five ethical principles were intended for analysis of emerging technologies, and IVG is an emerging technology with possible integration into clinical settings. Among the principles, it seemed that a major weak point of inquiry concerns LGBT+ and disability inclusion, especially of gender dysphoric and transgender people who may experience higher rates of infertility and have a harder time conceiving due to a mix of discrimination, gender dysphoria, and infertility due to hormone replacement therapy (HRT) treatment or gender/sex reassignment surgeries (GRSs/SRSs) that may impair or remove reproductive body parts. A number of other ethical considerations arise about this technology.
ContributorsVillarreal, Lance Edward (Author) / Maienschein, Jane (Thesis director) / Ellison, Karin (Committee member) / Wilson-Rawls, Jeanne (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The study of macaque monkeys harbors advancements in the field of biomedical research. It is imperative to understand the genetic composition of different species of macaques to assess their accuracy as non-human primate (NHP) models for disease detection and treatment assessments. We sought to characterize the hybridization and admixture of the Southeast Asian macaques using single nucleotide polymorphism markers and analyzing the populations on the mainland and the island. Using AMOVA tests and STRUCTURE analysis, we determined that there are three distinct populations: Macaca mulatta, M. fascicularis fascicularis, and M. f. aurea. Furthermore, the island species holds an isolated population of M. f. aurea that demonstrate high inbreeding and genetic uniqueness compared to the mainland species. Findings from this study confirm that NHP models may need to be modified or updated according to changing allelic frequencies and genetic drift.
ContributorsFalak, Asiya (Author) / Kanthaswamy, Sreetharan (Thesis director) / Oldt, Robert (Committee member) / Barrett, The Honors College (Contributor) / Computer Science and Engineering Program (Contributor) / School of Life Sciences (Contributor)
Created2022-05
Description
The Founders lab is a year-long program that gives its students an opportunity to participate in a unique team-based, experiential Barrett honors thesis project to design and apply marketing and sales strategies, as well as business and financial models to create and launch a new business. Initially, our team focused on creating a product that would provide those who have received basic genetic testing from services such as 23andMe with nutrition, exercise, and health/wellness educational resources. Over time, we transitioned our focus to creating a community forum that would also provide those resources to people who had not received basic genetic testing, but were still interested in accessing educational resources about the specific conditions that basic genetic testing services provide reports for. To accomplish this, we have produced a website that allows users to post content and interact with each other.
ContributorsChapman, Isabelle (Author) / Umana Fleck, David (Co-author) / Niu, Hardy (Co-author) / Byrne, Jared (Thesis director) / Lee, Christopher (Committee member) / Balven, Rachel (Committee member) / Barrett, The Honors College (Contributor) / Division of Teacher Preparation (Contributor) / School of Life Sciences (Contributor)
Created2022-05
Description
Tissue regeneration is a complex process that activates both developmental and metabolic signaling pathways (Kashio & Miura, 2020). The wing imaginal disc in Drosophila melanogaster has been invaluable in discerning what pathways are activated during tissue regeneration, which is typically done by genetically or physically wounding the wing disc and using fluorescent markers to track different signals. However, despite its importance in other regeneration contexts (Tafesh-Edwards & Eleftherianos, 2020), immune signaling has not been well studied in this tissue. Furthermore, what we do know about tissue regeneration and immune signaling is specific to apoptotic cellular death, less is known about other types of cellular death, such as necrotic cellular death and the consequent signaling systems that result from necrosis. Drosophila have an open immune system and only possess innate immunity (Pastor-Pareja et al., 2008), making them an ideal model to study hemocyte involvement in tissue regeneration. Hemocytes are equivalent to blood cells in vertebrates, and are involved in immunological response (Kurucz et al., 2003). In this work, we observed hemocyte accumulation during injury-induced regeneration. Cellular damage was induced using a genetic ablation system known as DUAL Control, with hemipterous CA and GluR1 used to induce apoptotic and necrotic cell death respectfully. We have discovered that while hemocytes are recruited to the wing disc upon both apoptotic and necrotic injury, necrotic tissue has more hemocytes adhered than apoptotic tissue. The difference in adherence could be due to basement membrane integrity being damaged more severely in necrotic discs than apoptotic discs. Our results show that hemocytes are attracted to wing discs that have undergone necrotic damage, indicating that the immune system plays some sort of role in necrotic cellular death. Though the immune response to different types of tissue damage in Drosophila is much simpler than in vertebrate models, there are many similarities between the two, and could lead to research involving human immune signaling as it pertains to regeneration.
ContributorsZustra, Ayla (Author) / Harris, Robin (Thesis director) / Gile, Gillian (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05