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- All Subjects: Genetics
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
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
Abstract
Purpose—Use a framework of genetic knowledge to investigate the association between the genotypes of various genes with phenotypes, specifically the traits of elite athletes, in order to establish a personal opinion on their relevance to athletic performance.
Methods—Assemble and analyze selected published scientific studies on genotype and athletic performance and lastly to formulate a personal opinion on the value of genetic testing of athletes. ACTN3, ACE, MSTN, and apoE were the genes selected for analyses.
Results—Two genes, ACTN3 and ACE, showed a significant relationship of genotype to phenotypic traits related to athletic performance. ApoE did not demonstrate a phenotypic association with athletic performance, however it showed a correlation with injury susceptibility leading to traumatic brain injury (TBI). MSTN did not show a phenotypic association with athletic performance.
Conclusion—When considering the multifactorial nature of athletics, each sport must be investigated individually due to the different individual requirements. ACTN3 and ACE are the most widely studied genes, therefore, considerable data on their relevance to athletic performance was easily obtained and supported a relationship between genotype and athletic performance.
Purpose—Use a framework of genetic knowledge to investigate the association between the genotypes of various genes with phenotypes, specifically the traits of elite athletes, in order to establish a personal opinion on their relevance to athletic performance.
Methods—Assemble and analyze selected published scientific studies on genotype and athletic performance and lastly to formulate a personal opinion on the value of genetic testing of athletes. ACTN3, ACE, MSTN, and apoE were the genes selected for analyses.
Results—Two genes, ACTN3 and ACE, showed a significant relationship of genotype to phenotypic traits related to athletic performance. ApoE did not demonstrate a phenotypic association with athletic performance, however it showed a correlation with injury susceptibility leading to traumatic brain injury (TBI). MSTN did not show a phenotypic association with athletic performance.
Conclusion—When considering the multifactorial nature of athletics, each sport must be investigated individually due to the different individual requirements. ACTN3 and ACE are the most widely studied genes, therefore, considerable data on their relevance to athletic performance was easily obtained and supported a relationship between genotype and athletic performance.
ContributorsMinto, Jordan Taylor- Lloyd (Author) / Steele, Kelly (Thesis director) / Penton, C. Ryan (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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
Small Cell Carcinoma of the Ovary Hypercalcemic Type (SCCOHT) is a rare and highly aggressive ovarian cancer that affects children and young women at a mean age of 24 years. Most SCCOHT patients are diagnosed at an advanced stage and do not respond to chemotherapy. As a result, more than 75% of patients succumb to their disease within 1-2 years. To provide insights into the biological, diagnostic, and therapeutic vulnerabilities of this deadly cancer, a comprehensive characterization of 22 SCCOHT cases and 2 SCCOHT cell lines using microarray and next-generation sequencing technologies was performed. Following histological examination, tumor DNA and RNA were extracted and used for array comparative genomic hybridization and gene expression microarray analyses. In agreement with previous reports, SCCOHT presented consistently diploid profiles with few copy number aberrations. Gene expression analysis showed SCCOHT tumors have a unique gene expression profile unlike that of most common epithelial ovarian carcinomas. Dysregulated cell cycle control, DNA repair, DNA damage-response, nucleosome assembly, neurogenesis and nervous system development were all characteristic of SCCOHT tumors. Sequencing of DNA from SCCOHT patients and cell lines revealed germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 79% (19/24) of SCCOHT patients in addition to SMARCA4 protein loss in 84% (16/19) of SCCOHT tumors, but in only 0.4% (2/485) of other primary ovarian tumors. Ongoing studies are now focusing on identifying treatments for SCCOHT based on therapeutic vulnerabilities conferred by ubiquitous inactivating mutations in SMARCA4 in addition to gene and protein expression data. Our characterization of the molecular landscape of SCCOHT and the breakthrough identification of inactivating SMARCA4 mutations in almost all cases of SCCOHT offers the first significant insight into the molecular pathogenesis of this disease. The loss of SMARCA4 protein is a highly sensitive and specific marker of the disease, highlighting its potential role as a diagnostic marker, and offers the opportunity for genetic testing of family members at risk. Outstanding questions remain about the role of SMARCA4 loss in the biology, histogenesis, diagnosis, and treatment of SCCOHT.
ContributorsRamos, Pilar (Author) / Anderson, Karen (Thesis advisor) / Trent, Jeffrey (Committee member) / Kusumi, Kenro (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2014
Description
Intervertebral Disc Degeneration (IVDD) is a complex phenomenon characterizing the desiccation and structural compromise of the primary joint in the human spine. The intervertebral disc (IVD) serves to connect vertebral bodies, cushion shock, and allow for flexion and extension of the vertebral column. Often presenting in the 4th or 5th decades of life as low back pain, this disease was originally believed to be the result of natural “wear and tear” coupled with repetitive mechanical insult, and as such most studies focus on patients between 40 and 50 years of age. Research over the past two decades, however, has demonstrated that environmental factors have only a modest effect on disc degeneration, with genetic influences playing a much more substantial role. Extensive research has focused on this process, though definitive risk factors and a clear pathophysiology have proven elusive. The aim of this study was to assemble a cohort of patients exhibiting definitive signs of degeneration who were well below the average age of presentation, with minimal or no exposure to suspected environmental risk factors and to conduct a targeted genome analysis in an attempt to elucidate a common genetic component. Through whole genome sequencing and analysis, the results corroborated findings in a previous study, as well as demonstrated a potential connection and influence between mutations found in IVD structural or functional genes, and the provocation of IVDD. Though the sample size was limited in scale and age, these findings suggest that further IVDD research into the association of variants in collagen, aggrecan and the insulin-like growth factor receptor genes of young patients with an early presentation of disc degeneration and minimal exposure to suspected risk factors is merited.
ContributorsFulton, Travis (Author) / Liebig, Juergen (Thesis advisor) / Neisewander, Janet (Committee member) / Theodore, Nicholas (Committee member) / Arizona State University (Publisher)
Created2016
Description
Sepsis is a deadly and debilitating condition resulting from a hyperinflammatory response to infection. Most organ systems are severely impacted, including the neurological complications for survivors of sepsis. Sepsis associated encephalopathy (SAE) is characterized by dysregulated molecular pathways of the immune response impinging upon normal central nervous system (CNS) function and ultimately resulting in lasting cognitive and behavioral impairments. Sepsis predominantly occurs in a few neonates but mostly elderly individuals where they are at high risk of sepsis-induced delirium and other neurological implications that may have overlap with neurodegenerative diseases. This study seeks to identify gene candidates that exhibit altered transcriptional expression in tissues between pigs injected with saline control vs lipopolysaccharide (LPS) to model the early inflammatory aspects of the septic response. Specifically, brain frontal cortex was examined to see which genes and pathways are altered at these early stages and could be targeted for further investigation to alter the cognitive/behavioral decline seen in sepsis survivors. This experiment uses a bulk RNA-seq approach on Yorkshire pigs to identify the variance in gene expression profile. Data analysis showed several gene candidates that were downregulated in the brain in response to LPS that point to early endothelial cell disruption, including OCLN (occludin), SLC19A3 (thiamine transporter), and SLC52A3 (riboflavin transporter). Genes that were upregulated in LPS brain samples implicate endothelial cell dysfunction as well as immune/inflammatory alterations, possibly due to alterations in microglia, the primary immune cell of the brain. Several studies are now underway to understand the cellular origin of these transcriptional changes, as well as analyzing the molecular signatures altered in response to sepsis in whole blood and kidney using bulk RNAseq. In conclusion, specific gene candidates were identified as early changes in the septic brain that could be targets to prevent long-term cognitive and behavioral changes in future studies, establishing a baseline panel to interrogate in animal models with the goal of advancing treatments for human patients who experience sepsis.
ContributorsNeill, Ryan (Author) / Fryer, John D (Thesis advisor) / Hogue, Ian (Thesis advisor) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2021
Description
Background: Dyslexia is a neurodevelopmental impacting reading and writing ability present in around 5 to 9 percent of the population. The etiology of the condition is not currently well understood.
Purpose: To identify new genes of interest regarding the etiology of dyslexia, describe the interaction of those genes within known gene networks, and discuss potential relationships between their expression in the early developing brain and phenotypic outcomes.
Method: With informed consent, participants’ phenotypic and exome data were collected. Phenotypic data were collected using assessments measuring reading and spelling ability. Exome data were collected via saliva samples and processed at the UW-CRDR. Exome data were then filtering using Seqr and compared across participant families. Certain genes with identical variations were visually validated using the Integrated Genome Viewer, and then investigated using STRING Network Analysis and the Human Brain Transcriptome.
Results: Three genes were identified: BCL6, DNAH1, and DNAH12. Protein-protein interactions were confirmed between DNAH1 and DNAH12 via STRING Network Analysis. BLC6 and DNAH1 experience higher postnatal expression in the cerebellar cortex. DNAH12 experiences higher prenatal expression in the hippocampus.
Discussion: The findings appear to be consistent with a heterogenous and polygenic model of dyslexia. The correlation between the participants’ genotypes and phenotypes is not strong enough to draw significant conclusions regarding genotype/phenotype connections. A larger participant sample size and analysis of a large pool of shared genes may reveal a clearer relationship.
ContributorsBanta, Claire (Author) / Peter, Beate (Thesis director) / Liu, Li (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / College of Integrative Sciences and Arts (Contributor)
Created2024-05