Genetics Commons^™

The Competition Between Splicing And 3′ Processing Shapes The Human Transcriptome, Lindsey V. Soles, Shuangyu Li, Liang Liu, Kristianna S.K. Sarkan, Erik G. Alvstad, Lusong Tian, Yoseop Yoon, Marielle Valdez, Ivan Marazzi, Yongsheng Shi

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Eukaryotic pre-mRNA processing steps, including splicing and 3′ processing, are tightly coordinated, yet the underlying mechanisms remain incompletely understood. U1 snRNP has been proposed to inhibit 3′ processing at intronic polyadenylation (IPA) sites through a splicing-independent mechanism termed telescripting. In contrast, we discovered that disrupting splicing by using six different methods—targeting various key components such as U1 snRNP, U2 snRNP, U2AF, and SF3b—activates 3′ processing at thousands of IPA sites. Notably, splicing inhibition, especially of U1 snRNP, induced widespread premature transcription termination within gene bodies through both IPA-coupled and IPA-independent mechanisms. Inhibition of different splicing factors activated overlapping and distinct …

Quantifying Genetic Diversity In Nematode Feeding Rate, Jacob King

Honors Theses

Understanding how populations persist under changing environmental conditions is a central question in ecology and evolutionary biology. Variation in traits related to resource acquisition may play a key role in determining population survival when resources are limited or fluctuate over time. In this study, I investigated how variation in feeding-related traits influences population persistence using a combination of computational modeling and laboratory experiments. I developed a stochastic, individual-based consumer–resource model to simulate population dynamics across varying levels of trait variance and resource regimes. Across 60,000 simulated populations, increased trait variation consistently reduced extinction risk and extended persistence time, although the …

Navigating The Genetic Frontier: Clinical And Ethical Implications Of Free Genetic Testing In India, Preetha Vijayalakshmi

Journal Of Indian Physician Associates

The expansion of free genetic testing services in India, resulting from government policies like the Ayushman Bharat Digital Mission, corporate-sponsored initiatives, and international collaborations, makes it easier to access genomic services for early identification of inherited disorders such as thalassemia, sickle cell anemia, and certain genetic kidney diseases, particularly in tribal populations. However, this review reveals significant clinical and ethical challenges. Clinically, Western-based genotyping platforms, not tailored to India’s genetic diversity, risk inaccurate results, including false positives and negatives, complicating clinical decision-making. A shortage of genetic counsellors and inadequate post-test care leaves patients, especially in rural areas, struggling within fragmented …

Morphological And Dietary Consequences Of Hybridization Between Mexican Ducks And Western Gulf Coast Mottled Ducks In A Human-Altered Landscape, Vergie Miranda Musni

Open Access Theses & Dissertations

Hybrid zones provide unique opportunities to study morphological and ecological consequences of hybridization. While landscape genetic studies confirm a newly established contact zone between Mexican Ducks (Anas diazi) and Western Gulf Coast Mottled Ducks (Anas fulvigula maculatus), I provide the first quantitative morphological comparisons of the two taxa and their hybrids in Chapter 1. First, I report significant differences among parental species in lamellar density, body mass, tarsus length, and wing chord lengths, with hybrids exhibiting intermediate or backcross-aligned phenotypes. In contrast, measured bill dimensions did not differ significantly between parental taxa. Despite substantial overlap in bill morphology between Mexican …

Using The Flexon Approach To Rnai For Analysis Of Gene Function In Gonadal Development In C. Elegans, Andrew D. Spalding

Undergraduate Theses

C. elegans, a nematode worm, was used as a model organism to analyze the developmental effects of knocking down the expression of genes that are both essential to worm viability and highly enriched in reproductive tissues. In earlier research, approximately 70 C. elegans genes were identified that are both gonad-enriched and essential. To prioritize which genes should be the focus of future studies, a new strain of C. elegans was produced with three specific genetic variations that: 1) silence essential, somatic gonad-enriched gene expression, 2) limit the effects of this gene silencing to the gonad, and 3) yield a …

Investigating The Taxonomic Uncertainties Of Potentilla Rupincola, Natalie Elizabeth Hieber

Master's Theses

Landscape stewardship is an integral role for land managers that becomes more important when rare or endangered species occur within managed areas. Conservation across the landscape is a primary concern for land managers, but resources allocated for conservation can be limited due to many competing goals. Taxonomic uncertainty surrounding rare and endangered taxa, particularly plant taxa, that have historically been classified solely using morphological features further complicates conservation planning. One such taxon is Potentilla rupincola, a rare plant endemic to the eastern Rocky Mountains in Colorado. For over a century, botanists have debated whether P. rupincola is a distinct species …

Sorghum Grain Secondary Metabolites And Underlying Genetics To Reduce Foodborne Pathogens In Poultry, Maria A. Conti

All Dissertations

The rise in antibiotic-resistant pathogens poses a threat to the poultry industry's ability to maintain animal health, prompting growing interest in alternatives to synthetic antibiotics. The use of non-tannin sorghum [Sorghum bicolor (L.) Moench] in poultry rations offers a valuable alternative, as this cereal grain has a high bioactive profile that can provide health benefits, including antimicrobial (AM) activity. The scope of this study was to examine the AM potential of non-tannin sorghum grain against Clostridium perfringens, a major foodborne pathogen that negatively impacts poultry health and production. To that end, the inhibitory effects of a non-tannin sorghum …

The Genetic Basis Of High Transformation Efficiency In The Model Yeast Saccharomyces Cerevisiae, Mary Kathryn E. Cheek

Biological Sciences Undergraduate Honors Theses

Transformation, a type of horizontal gene transfer, describes the uptake, maintenance, and integration of environmental DNA by cells. Despite the known effects of transformation on evolutionary processes, little is known about the genetic basis of this phenomenon. Saccharomyces cerevisiae is a eukaryote able to transform at quantifiable rates when made chemically competent and treated with a heat shock. S. cerevisiae also has variation in transformation efficiencies between various strains, and high recombination rates allow for sufficient allele “shuffling” in intercross populations. This project utilizes a bulk segregant analysis approach to compare sequencing data between transformant pools and non-transformant pools of …

Precursor Rna Properties Driving Cryptic 3’ Splice Site Selection In Sf3b1 Mutant Malignancies, Austin A. Herbert

All Dissertations

SF3B1 is a core component of the spliceosome involved in branch point recognition and 3’ splice site selection. SF3B1 is commonly mutated in myelodysplastic syndromes and other blood cancers with the K700E mutation being the most frequent. This mutation of SF3B1 induces cryptic 3’ splice site activation in hundreds of genes. Introduction of such cryptic 3’ splice sites can shift the reading frame of protein coding transcripts, causing the transcript to be tagged for nonsense-mediated decay or resulting in the production of a truncated protein. Both these scenarios can lead to down-regulated protein expression. Sequence and structural properties of precursor …

Genetic Screen For Regulators Of Pol4, A Dna Repair Polymerase In Saccharomyces Cerevisiae, Pasang Dolma Sherpa

Theses and Dissertations

In Saccharomyces cerevisiae, DNA polymerase 4 (POL4) is the beta repair polymerase, the product of the POL4 gene, and is involved in base excision repair (BER) and microhomology-mediated end joining (MMEJ). Despite its involvement in these repair pathways and its conservation across eukaryotes, deletion of POL4 shows no detectable phenotype under standard laboratory conditions. I hypothesized that unknown genes act as backup systems, providing redundant activities that allow pol4Δ cells to survive. To test this, a genetic screen for mutants showing synthetic lethality with pol4Δ was implemented. I constructed a strain lacking the POL4 gene and carrying …

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

All Dissertations

Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Dissecting The Complex Genomic Landscape Underlying Oxidative Stress Resistance Using Natural Variation In Yeast, Sonali Lakshika Anne Lenaduwe

Graduate Theses and Dissertations

Stress is experienced across the tree of life. Survival in fluctuating environments depends on a robust genetic architecture. This dissertation examines the genetic and metabolic determinants underlying one such adaptive response: cross-protection. Leveraging natural variation in the stress responses of budding yeast, Saccharomyces cerevisiae, I examine the genetic variation contributing to ethanol-induced cross-protection against oxidative stress. Acquired stress resistance, in which mild pre-exposure improves survival to subsequent stresses, is prevalent across diverse organisms and can involve both same-stress and cross-protection. Using high-throughput bulk segregant analysis (BSA-seq) and advanced intercross mapping populations derived from natural yeast isolates, I identify quantitative trait …

Using The Flexon Approach To Rnai To Identify Essential Genes That Affect Gonadal Development In C. Elegans, Joyce S. Lefevers

Undergraduate Theses

To elucidate the molecular role of essential genes in the gonadal development of Caenorhabditis elegans (C. elegans) it is necessary to utilize specialized molecular techniques such that the phenotypic effects of gene knockdown can be studied while the viability of the organism is preserved. Shaffer and Greenwald (2022) developed the floxed exon (flexon), a tool that improves upon previous approaches to spatiotemporal control of gene expression. The flexon subunit is made up of an artificial exon with a stop cassette flanked by artificial introns which, when inserted into a gene of interest, prevents the expression of that gene. …

From Bench To Bedside: Unraveling The Role Of Sarm1 In Chronic Human Neurodegenerative Disease, Caitlin Dingwall

Arts & Sciences Graduate Student Theses and Dissertations

Axon degeneration (AxD) is an early and often causative event in many neurodegenerative diseases, yet no treatments exist to halt the breakdown of axons. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. NMNAT2 is a highly labile protein produced in the soma and trafficked into the axon. Nerve injury blocks axonal transport and leads to rapid depletion of axonal NMNAT2, causing NMN buildup and NAD+ loss. Recent breakthroughs led to the discovery that SARM1 is activated by an increase in the NMN to NAD+ ratio. While the SARM1 axon degeneration pathway …

Biomechanical Effects Of Bilateral Torsion And Skeletal Fusion: A Case Study, Linnéa Forbes

Honors Projects

As part of both a personal endeavor and an academic project, I have investigated the aetiology and treatment of seemingly idiopathic and debilitating leg pain in a patient over the past 10 years. Via collaboration with medical professionals at Cincinnati Children’s Hospital, Cincinnati Premier Physical Therapy, and Cincinnati Women’s TriHealth, I have identified sources of pain at the anatomical level. The combination of internal femoral torsion, external tibial torsion, pes planus, and bony fusions appear to be major perpetuators of the pain. An effective treatment continues to be evasive. To date, I have attempted to find answers through genetic approaches, …

Amyloid Beta-42 Neurotoxicity In Drosophila Retinal Development, Shay O. Sims, Pierce Duncan, Malachi Abon, Jacob G. Smith

Create@State

Alzheimer's disease (AD) represents one of the most prevalent neurodegenerative disorders globally. Thus far, the underlying mechanisms associated with the pathogenesis of AD are innately elusive. Two hallmarks associated with the progression of AD exist, including Amyloid-Beta 42 (Aβ42) protein plaque formation and hyperphosphorylation of tau proteins in neurons. Amyloid-beta is known to concentrate with other neuronal proteins as complexes form, including the cytoskeletal protein actin. However, whether actin contributes to neuronal decline in AD is unknown. To further understand the cellular cascades associated with AD, we investigated the role of cytoskeleton dynamics in modulating oxidative stress and neuroinflammation within …

Variation In Infection Prevalence Of Splendidofilaria Pectoralis Across Alaskan Grouse Populations, Anahi Garcia Valdez, Diego Martinez

Create@State

In recent years, rapid climate change has altered species distributions worldwide and influenced parasite transmission dynamics in wildlife systems. Parasite infections play an important role in shaping patterns of disease distribution across species and populations. Understanding variation in infection prevalence across geographic regions and host demographic groups is essential for interpreting these patterns. Splendidofilaria pectoralis is a filarial nematode that infects the connective tissues of grouse (Aves: Tetraonini) in Alaska and has been moving northward as the climate warms. However, relatively little is known about the variation in prevalence of the nematode across geography and demography. This project examines variation …

Impact Of One Nucleotide On Organ Enumeration And Phyllotaxy In Arabidopsis Thaliana, Hazel R. Frans, Tara Phelps-Durr

SACAD: Scholarly Activities

Arabidopsis thaliana is a model organism used by scientists to study plant genetics, development, and physiology. CRISPR-Cas9 is a biotechnology tool adapted from a bacterial defense mechanism to precisely edit DNA using a guide mRNA and a Cas9 protein. This project aims to create CRISPR-CAS9 mutations in the APETALA3 (AP3) gene of the model plant Arabidopsis thaliana. AP3 is a class B gene critical to the petal and stamen development of Arabidopsis flowers. The AP3 protein contains a MADS domain, which binds directly to DNA and may be responsible for the expression of the CaRG-box genes. AP3 works in conjunction …

Ultrasonography Accompanied By Genetic Testing In Feline Polycystic Kidney Disease, Thao Phuong Vu, Thong Quang Le, Ha Nguyen Nhat Tran, Khoa Hoang Dang Le, Anh Phu Nam Bui

The Thai Journal of Veterinary Medicine

Autosomal dominant polycystic kidney disease (ADPKD), caused by the PKD1 c.10063C>A mutation, is a prevalent inherited feline disorder, but its allele frequency in Vietnam remains unidentified. This study aimed to determine the carrier frequency of this variant in British Shorthair, Maine Coon, and Ragdoll cats in Ho Chi Minh City and to correlate genotype with ultrasonographic phenotype. Ninety-seven client-owned cats were genotyped for the pkd1 mutation using PCR-RFLP. A subset of 47 cats also underwent abdominal ultrasonography to detect renal cysts. Genotypic results were correlated with sonographic findings, and risk factors were analyzed using chi-square tests and odds ratios …

G-Quadruplex Dna-Driven Genomic Instability Under Ber Loss, Addison Belick, Claryssa Gutierrez, Joslynn Rosas, Andrea Vargas

Posters - 2026

Base Excision Repair (BER) is a cellular tool that can repair damaged DNA (Hindi et al., 2022, Cellular and Molecular Life Sciences). G-quadruplexes (G4s) are unique 4-stranded structures in DNA or RNA that are rich in guanine (Gray et al., 2023, Nat. Chem. Biol). The purpose of this study is to understand whether BER contributes to the removal of G4s in DNA. This will determine if the BER-deficient yeast is more sensitive to treatment with G4-binding drugs than the BER-proficient yeast. We will replace the APN1 gene in the yeast genome with the URA3 gene, because the wild type yeast …

Fisheries Management Paper No.312: Discussion Paper On Management And Licensing Options For The Charter Industry - Statewide Strategic Review Of Western Australia’S Charter Fishing Sector, Department Of Primary Industries And Regional Development, Western Australia

Fisheries Management Papers

This consultation paper has been prepared to support the statewide strategic review of Western Australia’s (WA) charter fishing sector, which was initiated as a government commitment.

The paper details issues and proposals relating to the management and licensing framework, development opportunities and representation model for the charter fishing industry. The proposals have been developed in consultation with the Charter Review Working Group. The Department of Primary Industries and Regional Development (DPIRD) now seeks comment from relevant stakeholders on the issues and proposals outlined within this paper.

Comments provided will assist in providing advice and recommendations to the Minister for Fisheries …

Untangling G-Quadruplexes In Dna: The Effects Of Nucleotide Excision Repair, Jaidelin Alvardo, Abiageal Riley, Erick Morales Orrante, Raynne Malik

Posters - 2026

Nucleotide Excision Repair (NER) remo ves bulky DNA lesions that are attributed to UV irradiation, environmental mutagens, and chemo-therapeutic agents (Schärer, CSH Perspectives Biology, 2013). G4- quadruplexes are formed by four guanines hydrogen bonded together to form a planar ring, and stacking of the hydrophobic G quartets stabilizes the quadruplex structure Capra et al.,PLoS Computational Biology, 2010). A surplus of this structure is linked to genomic Instability and cancer development.

Prior studies indicate that because NER eliminates large lesions of DNA, there may be a link to the removal of G4-quadruplexes through Nucleotide Excision Repair (De Magis et al, Nature,2020). …

Comparing Stress Levels And Experiences Between Mothers And Fathers Of Children With Angelman Syndrome, Katherine Helen Fix

Theses and Dissertations

Angelman syndrome (AS) is a neurogenetic disorder characterized by significant developmental and cognitive impairments, disruptive behaviors, and a hallmark happy demeanor. Past studies have shown that certain features of AS contribute to increased parental stress. Other studies report that in general the stress of parents of children with disabilities is influenced by stereotypical gender roles surrounding factors including daily care taking tasks, financial responsibility, and medical care involvement. This study aimed to compare perspectives among mothers and fathers of individuals with AS to identify discrepancies and themes relating to stress, specific hardships, and caregiving roles. Parents of children with AS …

Understanding P53 Regulation On Transposable Elements In Cancer, Xuan Qu

Arts & Sciences Graduate Student Theses and Dissertations

Transposable elements (TEs), traditionally known as “jumping genes”, are known to have the ability to move in the genome and alter the activation of transcriptions from nearby genes. Taking up nearly half of the human genome, TEs have evolved, and some have been selected to play important roles in biological processes. We found that in human diseases such as cancer, global hypomethylation resurrects many ordinarily silenced TEs. These TEs can often serve as alternative promoters for oncogenes and play functionally meaningful roles in driving disease processes. One of the top genetic mutation status that correlates with differential numbers of TE …

Dissecting The Etiology Of Alcohol Use Disorder By An Integrative Heritable Component Approach, Ivy Garrenton

Computer Science Theses & Dissertations

Alcohol Use Disorder (AUD) is a pervasive condition characterized by complex interplay among genetic, phenotypic, and environmental factors. Although previous studies have identi fied genetic loci associated with alcohol consumption, these efforts have not captured the genetic heterogeneity and gene-environment interactions underlying AUD pathogenesis. To address this critical gap, we developed a novel statistical methodology that integrates phenotypic, genotypic, and environmental data through an environmentally modified Genetic Relationship Matrix (GRM) to derive AUD-related traits with enhanced heritability.

This approach demonstrated superior performance in both simulated and real-world datasets. Traits derived using the environmentally modified GRM exhibited significantly higher estimated heritability …

A Randomized Study Of Digital Versus Genetic Counselor Return Of Actionable Genetic Research Results To Biobank Participants (Respect3 Study), Anuja Rajendra Godbole, Elisabeth Wood, Brian Egleston, Lily Hoffman-Andrews, Sarah Brown, Sarah Howe, Sanjana Shastri, Rajia Mim, Justin Feng, Anjali Owens, Susan Domchek, Reed Pyeritz, Bryson Katona, Staci Kallish, Giorgio Sirugo, Joellen Weaver, Linda Fleisher, Kuang-Yi Wen, Elena Elkin, Katherine Nathanson, Daniel Rader, Angela Bradbury

Department of Medical Oncology Faculty Papers

BACKGROUND: There is consensus that research participants should be informed about plans for return of genetic research results. However, best practices for return of results in large biobank and cohort studies do not exist currently, and how best to communicate actionable genetic research results remains unclear. While having genetic counselors disclose these results may be ideal to ensure understanding, minimize distress, and optimize medical follow-up, genetic counselor (GC) workforce shortages and costs are barriers. The RESPECT3 study evaluates whether digital delivery alternatives for pre-disclosure education and return of actionable genetic research results is non-inferior to remote telehealth disclosure by a …

Multiplex Functional Assessment Of Variant Effect In The Retinal Transcription Factor Crx, James Lewis Shepherdson

Arts & Sciences Graduate Student Theses and Dissertations

The transcription factor Cone-Rod Homeobox (CRX) is a master regulator of photoreceptor cell fate. Sequence variants in CRX can cause Retinitis Pigmentosa, Cone-Rod Dystrophy, and Leber Congenital Amaurosis, all inherited causes of vision loss and blindness. CRX is the only gene implicated in the pathogenesis of all three of these diseases, which present with both rod- and cone-centric phenotypes of varying age of onset and severity. Several CRX variants have been reported to cause severe dominant disease through antimorphic genetic interactions with wild-type CRX, and yet these mutations are adjacent to variants which are benign or only cause mild, recessive …

Genetic Testing Motivations Among Men With A History Of Prostate Cancer: A Judgment-Based Analysis, Maximilian Junge

USF Tampa Graduate Theses and Dissertations

Identifying individuals at increased hereditary cancer risk through genetic testing can improve early detection, inform treatment decisions, and enhance outcomes for patients and their families. While prior research has largely focused on women, less is known about factors that motivate men with prostate cancer to pursue genetic testing. This study examined components of visual messaging that may influence motivation to undergo genetic testing among men with a self-reported history of prostate cancer. Participants completed a survey in which they viewed eight visual messages that systematically varied across three components: image type (family-focused vs. individualized treatment-focused), written content (familial risk-focused vs. …

Assessing Capability, Opportunity, And Motivation In Relation To Guideline Adherence For Inherited Cancer Risk, Cecilia L. Delisanti

USF Tampa Graduate Theses and Dissertations

Introduction: Although National Comprehensive Cancer Network (NCCN) guidelines provide cancer screening or risk reduction recommendations for individuals with germline pathogenic and likely pathogenic variants (GPVs) in actionable hereditary cancer genes, guideline adherence remains inconsistent, and the behavioral contributors to this gap remain understudied. To identify behavioral factors related to adherence across inherited cancer risk genes, this study used the COM-B model, which posits that capability, opportunity, and motivation shape health behaviors.

Methods: IMPACT study participants, all with GPVs in a variety of actionable genes, completed surveys (N=575). Minimal adherence was based on gene-specific NCCN guidelines. COM-B constructs (capability, opportunity, motivation) …

The Role Of The Virb Ligand Ctp In The Molecular Mechanism Of Transcriptional Anti-Silencing In Shigella Flexneri, Taylor M. Gerson, Monika M A Karney, Helen Wing

Life Sciences Faculty Research

In bacteria, nucleoid-structuring proteins bind and constrain DNA, often leading to transcriptional silencing. In Shigella spp., the histone-like nucleoid-structuring protein H-NS silences many genes on the large virulence plasmid. Upon a shift to human body temperature, VirB, a DNA-binding protein and key transcriptional regulator of the Shigella virulence cascade, is produced. VirB counteracts H-NS-mediated transcriptional silencing and belongs to a fast-evolving clade of the ParB superfamily. Like other ParB proteins, VirB binds the ligand CTP. While CTP is essential for the anti-silencing activity of VirB, the role of CTP in the mechanism of VirB-dependent anti-silencing has yet to be …