Genetics and Genomics Commons^™

A Review Of How Bioinformatics And Genome Sequencing Are Affecting Precision Medicine, Taylor S. Hickey

Honors Program: Senior Projects (Public)

Advancement in genomic sequencing and bioinformatics methods have been affecting biomedical research through precision medicine, especially in the area of cancer. Vaccine therapies can be developed using neoantigens that target specific mutations in tumors. The goals of this research are to identify mutations that lead to cancer and then define subpopulations in which patients can easily be identified. The future goal is to have targeted vaccines that are specific to each subpopulation ready to be used in treatment of their cancer. Limitations to reaching these goals have been due to tumor heterogeneity, cancer location, and difficulty in creating neoantigens for …

Comparing Efficiency, Empowerment, And Satisfaction Between Individual And Group Genetic Counseling For Prostate Cancer, Sarah Marie Dickman

Theses and Dissertations

A hereditary cause for prostate cancer can be identified in 5-17% of cases, which can impact treatment and cancer screening recommendations for patients and their families. Increased demand for genetic testing has necessitated consideration of alternative genetic counseling service delivery models to meet needs. Studies have shown that group genetic counseling increases efficiency while maintaining the same patient benefits as individual genetic counseling, but research has mainly focused on patients who were assigned female at birth (AFAB). The purpose of this study was to evaluate the utility of group genetic counseling for prostate cancer by assessing participants’ satisfaction and feelings …

Evaluating Health Awareness In Cancer Genetics Amongst The Black And African American Community In South Carolina, Annika Jaliya Gadson

Theses and Dissertations

Historically minoritized individuals are underrepresented in genomic research which limits the ability to fully understand genetic variation within the population (Sirugo et al., 2019). This creates bias that questions the effectiveness of guidelines for genetic testing, predictive risk values, and medical management. Disparities in cancer genetics may be attributed to historical events that have cultivated mistrust in research and medicine, institutional bias, provider skepticism in patient reporting of medical symptoms, and limited access to genetic testing (Saulsberry et al., 2013). More exploration is needed to better understand how to increase access and awareness of cancer genetic services to Black and …

Piloting A Spanish-Language Web-Based Tool For Hereditary Cancer Genetic Testing, Gretter Manso

USF Tampa Graduate Theses and Dissertations

Cancer genetic services (including genetic counseling and testing) help identify patients and families at increased risk of developing cancer so that steps can be taken to reduce risks or find cancers early. Receipt of genetic services in the Hispanic/Latinx population is low due, in part, to a shortage of Spanish-speaking genetic counselors. To address this concern, a 12-minute online tool designed to inform individuals about cancer genetic services was translated into Spanish. The objectives of this pilot study were to determine if the educational tool improves knowledge and informed decision making and to assess usability and appropriateness of the tool …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Genetic And Pharmacogenetics Associations Of Cancer Disparities In Appalachia, Nan Lin

Theses and Dissertations--Pharmacy

Individuals residing in Appalachian regions have significant health disparities, including higher cancer incidence and mortality rates. Previous studies have addressed the impact of socioeconomic status and environmental risk factors on Appalachia cancer disparities, while few studies have evaluated genetic risk factors.

Germline whole exome sequencing samples from 7,078 individuals with cancer (759 Appalachians) were evaluated. Demographics and relatedness were assessed using KING. Ethnicity was verified by principal component analysis using TRACE, which included 6,034 individuals (85%) of European genetic ancestry. After QC filtering, 5,980 individuals were analyzed. To assess the overall predisposition of hereditary disease, gene level frequency of likely …

The Genetics Of Skin Cancer: What Genes Drive The Development Of Basal Cell Carcinoma, Squamous Cell Carcinoma, And Melanoma?, Cassandra Poole, Abagail Pack, Elizabeth Whitehead, Virginia Marshall

Fall Showcase for Research and Creative Inquiry

Skin cancer is one of the most common forms of cancer worldwide. The American Academy of Dermatology estimates that 9500 people in the United States are diagnosed with skin cancer every day, and that 1 in 5 Americans will be diagnosed with skin cancer by age 70. With such a high prevalence of disease, understanding how skin cancer develops and how it can be treated is extremely important. This project aims to analyze the genes involved in the development of the three most common forms of skin cancer: basal cell carcinoma, squamous cell carcinoma, and melanoma.

The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown

Dartmouth College Ph.D Dissertations

The Epithelial-to-Mesenchymal transition, a critical cellular process in development, is frequently co-opted by solid tumors to promote invasion and metastasis. In particular, the hybrid or intermediate EMT state, possessing both epithelial and mesenchymal characteristics, is associated with increased cancer stemness and plasticity. Similarly, intra-tumoral heterogeneity in solid tumors, in particular breast cancer, is associated with poor prognosis, tumor growth, proliferation, drug resistance, and metastasis. We sought to understand the link between the generation of intra-tumoral heterogeneity and the intermediate EMT state and their impact on tumor progression and patient prognosis. As part of my thesis work, I developed a model …

Host-Pathogen Coevolution Between Tasmanian Devils (Sarcophilus Harrisii) And Devil Facial Tumor Disease, Dylan Garret Gallinson

USF Tampa Graduate Theses and Dissertations

Coevolution is a driving force of rapid evolution, yet the complexity of coevolutionary interactions has made it difficult to characterize the genomic basis of traits mediating such relationships. Coevolutionary dynamics are especially important in host-pathogen systems where the host and pathogen must constantly adapt to one another. The Tasmanian devil and its species-specific transmissible cancer, devil facial tumor disease (DFTD), provide the rare opportunity to study host-pathogen coevolution in a complex natural system. Extensive spatiotemporal devil sampling, high linkage disequilibrium in devils, and a large selective pressure imposed by DFTD facilitate a system tractable for study. Here, we characterized devil …

Origin And Epigenetic Regulation Of Cutaneous T Cell Lymphoma, Carly M. Harro

USF Tampa Graduate Theses and Dissertations

The pathogenesis of Cutaneous T cell lymphoma (CTCL) remains unclear. Using conditional knockout mice, we found that ablation of the genomic organizer Special AT-rich sequence-binding protein-1 (Satb1) caused malignant transformation of mature, skin-homing, Notch-activated CD4+ and CD8+ T cells into progressively fatal lymphoma. Mechanistically, Satb1 restrained Stat5 phosphorylation and the expression of skin-homing chemokine receptors in mature T cells. H3K27 and H3K9 trimethylation occluded the SATB1 promoter in Sézary cells, while inhibition of SUV39H1/2 methyltransferases (unlike EZH2 inhibition), restored protective SATB1 expression and selectively abrogated the growth of primary Sézary cells more effectively than romidepsin. Additionally, using single-cell RNA/TCR sequencing …

Functional Characterization Of Cancer-Associated Dna Polymerase Ε Variants, Stephanie R. Barbari

Theses & Dissertations

Replicative DNA polymerases ε (Polε) and δ (Polδ) achieve high fidelity DNA synthesis through a precise balance of polymerization and exonucleolytic proofreading. Errors that escape proofreading are corrected by DNA mismatch repair (MMR). Ultramutated human cancers with proficient MMR carry alterations in the exonuclease domain of Polε, which were initially predicted to abolish proofreading. However, functional studies in yeast of the most recurrent Polε-P286R variant suggested defects beyond a loss of exonuclease activity. Indeed, biochemical analysis of the yeast Polε-P286R analog revealed increased polymerization capacity in addition to decreased proofreading, which enables efficient mismatch extension and bypass of replication-blocking non-B …

Targeting Plasma Membrane Phosphatidylserine Content To Inhibit Oncogenic Kras Function, Walaa E. Kattan

Dissertations and Theses (Open Access)

The small GTPase KRAS, which is frequently mutated in human cancers, must be localized to the plasma membrane (PM) for biological activity. We recently showed that the KRAS C-terminal membrane anchor exhibits exquisite lipid-binding specificity for select species of phosphatidylserine (PtdSer). We therefore investigated whether reducing PM PtdSer content is sufficient to abrogate KRAS oncogenesis. Oxysterol-related binding proteins ORP5 and ORP8 exchange PtdSer synthesized in the ER for phosphatidylinositol-4-phosphate (PI4P) synthesized in the PM. We show that depletion of ORP5 or ORP8 reduced PM PtdSer levels, resulting in extensive mislocalization of KRAS from the PM. Concordantly, ORP5 or ORP8 depletion …

Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula

Dissertations and Theses (Open Access)

G-quadruplexes are non-B DNA structures formed by four or more runs of repeated guanines that confer unique features to living organism’s genomes. These sequences are enriched in regulatory regions, such as promoters and 5’ UTRs, and have distinct regulatory roles in both health and disease states. Even though previous studies showed the impact of G4 in gene expression, none of them summarized the location-specific effect of G4. Also, there is no broad understanding about the most common G4 repeat in the human genome, named here as G4-22, and how it links to the evolution of mammals and their biology. In …

Understanding The Pathogenesis Of Renal Medullary Carcinoma, Melinda Soeung

Dissertations and Theses (Open Access)

Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the …

An Investigation On The Irish Population’S Attitudes And Knowledge Towards Genetic Screening For Cancer, Emer Mccarthy, Ada Fleming, Dawn Hannah Cronin

International Undergraduate Journal of Health Sciences

Genetic mutations are alterations in DNA that may result in the development of a disease later in life. A BRCA gene is a tumour suppressor gene that helps to prevent the development of some cancers, particularly breast cancer. If a mutation occurs, this gene no longer functions at preventing these cancers. Genetic screening is when a population is tested for a mutation in an attempt to identify a group of people that are positive for the mutation. This can help identify cancer in different populations as well as track their inheritance. This study was conducted online, questioning the Irish populations …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, Iujhs Full Issue

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

A Forward Genetic Screen To Identify Human Genes Of Interest And Their Roles In Ovarian Cancer, Susan A. Ihejirika

Honors College Theses

Drosophila melanogaster, fruit flies, are very important for modeling and studying human diseases. This study identifies human genes of interest and their contributions to epithelial ovarian carcinogenesis and progression as well as the roles orthologs of these genes play in Drosophila melanogaster. This is important because ovarian cancer is the most common cause of death among the gynecological cancers. This identification of genes was carried out using a forward genetic screen employing the widely used GMR-Gal4 driver/UAS-transgene system. The GMR-Gal4 driver is commonly utilized to express transgenes in the developing eye of the fruit fly. Transgenes that are expressed using …

Assessing Genetic Counselors' Clinical Approach And Practices Regarding Pathogenic/Likely Pathogenic Variant Downgrades, Grant Bonesteele

Dissertations and Theses (Open Access)

Although rare, variant downgrades from a pathogenic/likely pathogenic (P/LP) variant to a variant of uncertain significance can have a significant impact on patients and their families in the clinical cancer setting. However, there is a lack of literature about how to approach these potentially challenging cases as a genetic counselor. Therefore, we aimed to characterize genetic counselors’ experiences, approach, and practices to variant downgrade cases using an online survey. The survey asked participants how they would approach variant downgrade scenarios involving the CDH1 or ATM genes with variable family histories. Genetic counselors appear to be united in whether they would …

Mixture Model Approaches To Integrative Analysis Of Multi-Omics Data And Spatially Correlated Genomic Data, Ziqiao Wang

Dissertations and Theses (Open Access)

Integrative genomic data analysis is a powerful tool to study the complex biological processes behind a disease. Statistical methods can model the interrelationships of the involved gene activities through jointly analyzing multiple types of genomic data from different platforms (vertical integration), or improve the power of a study through aggregating the same type of genomic data across studies (horizontal integration). In this dissertation, we propose statistical methods and strategies for integrative multi-omics data in association analysis of disease phenotypes, with an emphasis on cancer applications.

We develop a new strategy based on horizontal integration by leveraging publicly available datasets into …

Detection And Quantification Of Γ-H2ax Using A Dissociation Enhanced Lanthanide Fluorescence Immunoassay, Felicite K. Noubissi, Amber A. Mcbride, Hannah G. Leppert, Larry J. Millet, Xiaofei Wang, Sandra M. Davern

Biology Faculty Research

Phosphorylation of the histone protein H2AX to form γ-H2AX foci directly represents DNA double-strand break formation. Traditional γ-H2AX detection involves counting individual foci within individual nuclei. The novelty of this work is the application of a time-resolved fluorescence assay using dissociation-enhanced lanthanide fluorescence immunoassay for quantitative measurements of γ-H2AX. For comparison, standard fluorescence detection was employed and analyzed either by bulk fluorescent measurements or by direct foci counting using BioTek Spot Count algorithm and Gen 5 software. Etoposide induced DNA damage in A549 carcinoma cells was compared across all test platforms. Time resolved fluorescence detection of europium as a chelated …

Assessing The Anticipated Needs Of Transgender Patients In Cancer Genetic Counseling, Jacqueline Baquet

Theses and Dissertations

Most cancers are sporadic, but 5-10% of all cancer is hereditary, or caused by a heritable genetic mutation. A patient’s medical history, family history, genetic test results, intact organs (e.g., ovaries) at an increased risk for developing cancer, and the availability and accessibility of interventions are used to make recommendations for cancer-risk management. In addition to basic medical care, transgender patients have healthcare needs that differ from those of cisgender patients such as expert care related to using hormones or having gender-affirming surgery, as well as unique mental health concerns. Transgender individuals may also experience a greater number of barriers …

Exploration Of Patient Communication Preference Regarding Reclassified Genetic Test Results, Cooper Nicole Hall

Theses and Dissertations

Genetic testing is becoming increasingly used to detect individuals who are predisposed to developing cancer. If genetic testing identifies a variant in an individual’s DNA, the testing laboratory uses available data to classify the variant as either disease-causing or benign. When limited data is available regarding a variant’s pathogenicity and the risk of cancer for an individual is not clear, the variant is classified as a “variant of uncertain significance” (VUS). If new data is discovered, the VUS may be reclassified. There is a gap in current literature regarding desired communication for a reclassified genetic test result. There are no …

Dna Polymerase Ε: Replication Error Prevention And Consequences Of A Cancer-Associated Mutation, Chelsea R. Bulock

Theses & Dissertations

Genome integrity is necessary to prevent mutations and disease. During eukaryotic DNA replication, DNA polymerases ε (Polε) and δ (Polδ) synthesize the leading and lagging strand, respectively. Polε and Polδ also have exonuclease activity that acts in series with post-replicative mismatch repair (MMR) to remove replication errors. Defects in proofreading and MMR lead to an increase in mutations and cause cancer in humans. This dissertation focuses on several unresolved issues involving the relationship between Polε and Polδ in replication error avoidance. First, despite an abundance of data supporting the one-strand-one-polymerase replication fork model, defects in the fidelity of Polε have …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations and Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

Genomic And Transcriptomic Alterations In Metabolic Regulators And Implications For Anti-Tumoral Immune Response, Ryan J. King

Theses & Dissertations

Metabolic and immune alterations are ubiquitous hallmarks of cancer that are established during the foundational mutations and are further selected upon to generate highly aggressive tumors. Recent evidence suggests that cancer cells employ an altered metabolism to induce immune evasion. To further discover the relationship between metabolism and immunity in cancer, this thesis aimed to discover potential candidates of interest by first examining the mucin family for differences, as they exert a wide range of activities in cancer, including altered metabolism and immune alterations. Unique differences lead to further profiling in pancreatic and esophageal cancer. In pancreatic cancer, CD73 was …

Statistical Methods For Resolving Intratumor Heterogeneity With Single-Cell Dna Sequencing, Alexander Davis

Dissertations and Theses (Open Access)

Tumor cells have heterogeneous genotypes, which drives progression and treatment resistance. Such genetic intratumor heterogeneity plays a role in the process of clonal evolution that underlies tumor progression and treatment resistance. Single-cell DNA sequencing is a promising experimental method for studying intratumor heterogeneity, but brings unique statistical challenges in interpreting the resulting data. Researchers lack methods to determine whether sufficiently many cells have been sampled from a tumor. In addition, there are no proven computational methods for determining the ploidy of a cell, a necessary step in the determination of copy number. In this work, software for calculating probabilities from …

Effects Of Aurora Kinase C Expression On Retina Pigmented Epithelial Cell Migration, Proliferation, And Anchorage Independent Growth, Justin Bejar

Seton Hall University Dissertations and Theses (ETDs)

Cancer is a common and deadly disease in the United States with 1,806,590 new cancer cases in 2019 and 606,520 cancer deaths projected in 2020. These deaths are primarily due to the uncontrolled cell proliferation and migratory nature of the disease. Many cancer cells express genes normally restricted to meiotic cells. For example, Aurora Kinase C (AURKC) is known to regulate chromosome segregation in meiotic cells yet it is expressed in many different types of cancer, such as breast, prostate, colorectal, liver, cervical, thyroid, and testicular cancers. As a means to study the function of AURKC, an …

Assay Development For Isolation And Characterization Of Anticancer Properties Of Marine Fungi, Kyra Ricci

Honors Theses

Metabolites from fungi have potential use in the drug discovery process and have been used in the past to develop therapeutic agents for human use. Initial characterization of potential therapeutic properties of fungi is thus an important first step in identifying novel therapeutic compounds. In the present study, marine fungi were isolated from Myrtle Beach and assayed for anticancer properties using the soft agar colony formation assay in a 3D in vitro cellular environment. Many species were isolated from environmental samples, displaying unique morphologies and growth patterns. To optimize the soft agar assay in a six-well cell culture plate for …

10th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The Annual Postdoctoral Science Symposium (APSS) was initiated on August 4, 2011, by the MD Anderson Postdoctoral Association to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience.

APSS is a scientific symposium organized by postdoctoral fellows from The University of Texas MD Anderson Cancer Center that welcomes submissions and presentations from postdoctoral fellows from all Texas Medical Center affiliated institutions and other Houston area institutions. The APSS provides a professional venue for postdoctoral scientists to develop, clarify and refine their research as result of formal reviews and critiques …

A Look At Gene Control: Tracking The Ccnd1 Gene, Bryan Anders

Mahurin Honors College Capstone Experience/Thesis Projects

Cancer occurs when the cell does not properly control its own cell cycle. It then replicates in an out of control fashion leading to the death of various organs and then the demise of the organism as a whole. As it seems to have always been a problem for cell-based life, certain safeguards against cancer have been evolved over time. One such method comes in the form of prevention via cyclin proteins, which are encoded from cyclin genes. The gene that is the focus of this research is the CCND1, or cyclin D1, gene that controls the progression through various …