Other Genetics and Genomics Commons^™

Deconstructing Systemic Sclerosis Heterogeneity: From Patient Subtypes To Pathogenic Fibroblasts, Rezvan Parvizi

Dartmouth College Ph.D Dissertations

This thesis advances heterogeneity as the central barrier both to interpreting therapeutic response and to identifying the molecular regulators that drive fibrosis in systemic sclerosis (SSc). In SSc, heterogeneity is manifest at every level at which the disease can be measured: clinically, in the variable extent of skin and organ involvement; molecularly, in the distinct gene-expression programs that distinguish otherwise comparable patients; and cellularly, in the diverse fibroblast populations from which the fibrotic signal ultimately arises.

Leveraging longitudinal skin transcriptomics from a large cohort treated with mycophenolate mofetil (MMF), the first study demonstrates that intrinsic molecular subtypes are dynamic rather …

Effects Of M6a Dna Methylation By Bacterial Methyltransferase In Colorectal Cancer, Fabian Alejandro Mendoza Galvan

Dissertations and Theses (Open Access)

Effects of m6A DNA methylation by bacterial methyltransferase in colorectal cancer Fabian Alejandro Mendoza Galvan Advisory Professor: Angela H. Ting, Ph.D. Fusobacterium nucleatum animalis (Fna) is found in the human oral cavity and gut. A distinct clade of Fna is primarily enriched in the tumor microenvironment (TME) and within colorectal cancer (CRC) cells. This clade DNA methylation pattern is primarily catalyzed by a cell-cycle regulated methyltransferase (CcrM) ortholog, M.FnI, that targets the GANTC sequence motif through methyl-6-Adenine (m6A) DNA methylation. We hypothesized that M.FnI enzyme can induce m6A methylation abnormalities in CRC cells to promote cancer progression. Evidence for endogenous …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Development Of Self-Assembled Polymeric Polyplexes For Microrna Delivery: Toward Treatment Of Alcohol-Associated Liver Disease, Marjina Akter Kalpana

Theses & Dissertations

Self-assembled polymeric polyplexes have the potential to serve as an RNA interference (RNAi) delivery platform for the combined inhibition of CXCR4 and miR-155 in the treatment of alcohol-associated liver disease (AALD). A central challenge in RNA delivery is balancing the extracellular stability of polyplexes, cellular uptake, and intracellular release of RNA cargo. We developed polymeric polyplexes using the CXCR4-antagonist polymer PAMD, designed to target CXCR4 on activated hepatic stellate cells (HSCs) and deliver therapeutic miRNA to activated Kupffer cells (KCs) in fibrotic liver. We improved the polyplexes by cholesterol modification of PAMD and by PEGylation of PAMD-Ch. The cholesterol modification …

A Persistent Homology Framework For Scrna-Seq: Assessing Clustering Robustness And Quantifying Preprocessing And Integration Effects On Topological Features., Jonah Daneshmand

Electronic Theses and Dissertations

As single-cell RNA sequencing (scRNA-seq) data expands, robust methods for integrating diverse datasets are critical. This dissertation applies Persistent Homology (PH), a technique from Topological Data Analysis (TDA), to a collection of scRNA-seq datasets spanning eight tissue types to quantify how data integration affects topological features and biological interpretability. We assessed global topological structure using Betti curves, Euler characteristics, and persistence landscapes across raw, normalized, and integrated data representations. Our analysis revealed a performance inversion: while conventional methods excelled on unintegrated data, high-granularity topological methods, particularly those sensitive to global data structure, became superior after integration. This suggests a synergy …

Improved Model For Neurodegeneration In C. Elegans, Jean-Pierre Arditi

Graduate Theses and Dissertations (2019 - present)

During Alzheimer's disease (AD), insoluble amyloid beta (AP) peptides accumulate to form extracellular aggregates (plaques). The direct cause of neuronal dysfunction observed in AD has been broadly investigated. The amyloid hypothesis states that AP plaques are neurotoxic, but recent studies support the AP oligomer hypothesis, which states that intracellular AP (iAP) is neurotoxic. To test this hypothesis, I used CRISPR-Cas9 gene editing to generate two transgenic Caenorhabditis elegans (C. elegans) strains. I generated a strain (RSLl 11) using the rab-3 promoter to co-express GFP in neurons, which showed no gross behavioral changes but had a 50% reduced egglaying rate. RSLl …

Breeding Biofortified Protein Rich Organic Pulses For Better Human Health, Sonia Salaria

All Dissertations

Pulse crops are dry grains of legumes, the second most consumed plant crops in the world after cereals. These crops are one of the primary sources of plant-based protein and contain high concentrations of pre-biotic carbohydrates, minerals and vitamins. Recognizing the health benefits of pulses intake, their demands as sustainable food and changes in people’s diet preferences for plant-based protein have increased awareness for pulses consumption. With this scenario, improving the nutritional profile of pulse crops for rich nutrition has been an opportunity for breeders to explore and tailor the available germplasm to develop nutrient dense pulses. Furthermore, the genomic …

Exploring Muslim American Attitudes Toward Genetic Testing: Perceptions, Barriers, And Ethical Considerations, Hannah Mahmoud

University Honors Theses

This thesis explores perceptions and attitudes toward genetic testing within the Muslim American community, a group often underrepresented in genomic research and public health discourse. Using a community-distributed digital survey, data was collected from 50 self-identified Muslim Americans on their familiarity with genetic testing, reproductive and ethical considerations, and the influence of religious factors. While only 18% had undergone genetic testing themselves, many were familiar through family or friends, and most expressed cautious interest—especially when results could influence future family planning. Education level, age, and religious values shaped both comfort and understanding.

A key theme was the desire for culturally …

Investigating The Effects Of Sod1 Knockout On Oxidative Stress And Stress Coping Styles In Zebrafish Using Crispr Technology, Tai Prauner, Ryan Wong

Theses/Capstones/Creative Projects

Reactive oxygen species are byproducts of cellular metabolism that, when not efficiently neutralized, can damage DNA, proteins, and lipids. Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide radicals into less harmful molecules. While its molecular function is well documented, the role of SOD1 in shaping stress-related behavior remains underexplored. This project aimed to establish foundational tools for studying the behavioral impact of SOD1 knockout across proactive and reactive stress-coping styles in zebrafish.

To support future gene-editing experiments, microinjection and breeding protocols were refined across wildtype AB, proactive, and reactive zebrafish lines. No embryos were injected with CRISPR-Cas9 …

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …

The Influence Of Scientific, Genetic, And Health Literacy On Carrier Screening Decision-Making, Brenna D. Albracht

Dissertations and Theses (Open Access)

For those wishing to assess their reproductive risks and make informed decisions in their reproductive planning, carrier screening for autosomal recessive and X-linked conditions, as well as cell-free DNA (cfDNA) screening for aneuploidy, are recommended during pregnancy. Despite similarities in purpose, sample requirements, insurance coverage, and safety, a lower percentage of individuals elect carrier screening than cfDNA screening, suggesting there may be a disconnect in what patients perceive as valuable information for their pregnancy. Previous studies have attempted to explain the factors associated with carrier screening uptake or decline; however, no models have yet accounted for a patient’s literacy level …

The Role And Expression Of Pros-1 In The C. Elegans Gonad, Brandon W. Thomas, Mary B. Kroetz, Roberta Challener

Undergraduate Theses

The nematode, formally known as Caenorhabditis elegans, has served as an excellent model organism in understanding fundamental biological processes, including those governed by conserved genes like pros-1. pros-1 is partially responsible for the formation of tubular structures within the organism. Glial cells and excretory canals are both examples of tubular structures governed by pros-1. pros-1 orchestrates the embryonic development of these cell types by modulating cell proliferation and differentiation, thus ensuring proper morphogenesis and organogenesis. Its regulatory influence likely extends beyond embryogenesis, potentially affecting reproductive processes as well. Furthermore, the evolutionary conservation of pros-1 underscores its significance …

The Impact Of Paternal Obesity On Placental Development And Function During Pregnancy, Delaney G. Wolfe, Delaney G. Wiolfe

Department of Nutrition Student Projects

Paternal obesity is a rising concern in conception and reproductive health, with increasing evidence suggesting its impact on pregnancy outcomes. While maternal obesity's effects on fetal development and placental function are well-documented, the role of paternal obesity remains less understood. The placenta, crucial for nutrient exchange and fetal development, can be disrupted by inflammation, oxidative stress, and epigenetic modifications, potentially leading to long-term health implications for both maternal and fetal health. Understanding the paternal influence on placental development is essential for improving pregnancy outcomes and offspring
health. This study aims to investigate the relationship between paternal obesity on placental function …

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …

Investigating The Dna-Binding Role Of Tbp1 In Toxoplasma Gondii: Expression And Characterization Of A Recombinant Protein, Madison T. Jeckell

Honors Theses and Capstones

Toxoplasma gondii is an obligate intracellular parasite with a complex life cycle and an unusual transcriptional machinery compared to other eukaryotes. Unlike most organisms, Toxoplasma lacks multiple well-conserved promoter motifs and has multiple TATA-binding proteins (TBPs), including TBP1, whose function in DNA binding and transcription regulation is poorly understood. This study aimed to generate and express a recombinant TBP1 protein from Toxoplasma to enable future DNA-binding assays and motif identification. Using RT-PCR, the TgTBP1 gene was amplified and cloned into a pGEX vector to produce a GST-tagged protein. The recombinant plasmid was transformed into E. coli BL21 cells, and protein …

The Role Of Horizontal Gene Transfer In Antibiotic Resistance Amidst Prevalent Community And Healthcare-Associated Mrsa Rates, Gabrielle Nascimento

Honors College Theses

In recent decades, cases of community-acquired MRSA (CA-MRSA) and healthcare-associated MRSA (HA-MRSA) have been on the rise. The ability of antibiotic resistance to transfer between microorganisms greatly expands its threat to the effective treatment and containment of bacterial infections. The mecA gene is found on a mobile cassette within the Staphylococcal cell and encodes for PBP2a, an alternate version of penicillin-binding protein (PBP) with less binding affinity for β-lactam antibiotics, increasing resistance to the effects of antibiotics. The goal of this research is to investigate the horizontal transfer of the mecA gene between various Staphylococcus species as well as to …

Karyotyping As A Method To Verify Phylogenetic Relationships Among The Enneacanthus Species, Ophelia A. Anderson

Theses and Dissertations

The Enneacanthus genus consists of three species of freshwater fish endemic to eastern North America: E. obesus (Banded Sunfish), E. gloriosus (Blue Spotted Sunfish), and E. chaetodon (Black Banded Sunfish). Previous studies using molecular data suggest that E. obesus and E. gloriosus are more closely related, with E. chaetodon as the most distantly related species in the genus. This study investigates the phylogenetic relationship among the Enneacanthus species, using karyotype characteristics - chromosome number, morphology and fundamental number - as comparative metrics. Chromosome spreads were obtained from scale and gill epithelium samples collected between 1993 and 1994. Prepared slides …

Dna Methylation Variation In Eastern Diamondback Rattlesnakes (Crotalus Adamanteus) On A Georgia Barrier Island, Megan Hoog

College of Graduate Studies: Theses & Dissertations

The Eastern Diamondback Rattlesnake (Crotalus adamanteus, EDB) is the largest rattlesnake in the world and is thought to be declining in many portions of its range. Genetic venom studies in the Southeast United States have shown evidence of fine-scale differences within two main geographic groups on Jekyll Island. My objective is to expand on this finding to determine if epigenetic mechanisms, specifically DNA methylation, varies among different populations of EDB in similar environments, age classes, and sexes. I collected EDB blood samples through a partnership with the Jekyll Island Authority and screened 44 individuals for epigenetic variation from …

“Regression To The Mean”: The Confluence Of Eugenics And Statistics In The 19th And 20th Centuries, Emrys G. King

Pomona Senior Theses

The work of this thesis is twofold — first, qualitatively characterizing the confluence between the British eugenics and statistics movements in the late 19th and early 20th centuries, and second, quantitatively analyzing the effect of this foundation on pedagogical materials in the growing field of statistics between 1880 and 1970. Towards the first goal, the history of the method of least squares, state statistics, and positive and negative eugenics are outlined, followed by a close reading of the foundational texts authored by Francis Galton and Karl Pearson that introduced linear regression. Towards the latter goal, English-language statistics textbooks published between …

Rna Secondary Structures: Structure-Function Studies In Viral And Neurodegenerative Diseases, Caylee Cunningham

Electronic Theses and Dissertations

The studies within this dissertation highlight the importance of RNA structure and function, highlighting potential mechanisms in the pathogenesis of the SARS-CoV-2 virus and hallmarks of ALS. Specifically, the s2m, a 41-nt structure found within the hyper variable region of the 3’ UTR of the SARS-CoV-2 virus, was investigated as this element has no definitive role in viruses but its high conservation in several viral families warrants investigation. We used various biophysical techniques to determine if a palindromic sequence in the terminal loop could participate in dimerization activities, which may have implications in recombination and the longevity of the virus. …

Exploring The Role Of The Arginine-Methylation Writer-Reader Pair Prmt5/Snd1 In Jak2-Mutant Myeloproliferative Neoplasms, Rocio Rubiano

Dissertations and Theses (Open Access)

Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible …

Investigating The Role Of Ebf3a In Craniofacial Development, Shujan A. Sharafeldeen

Undergraduate Theses, Capstones, and Recitals

Proper craniofacial development requires many genes. Single-cell RNA sequencing (scRNA-seq) allows us to identify genes expressed in precursor cells for craniofacial structures, but the function of many of these genes in craniofacial development has yet to be characterized. In our scRNA-seq of cranial neural crest cells (NCCs), which are precursor cells for the craniofacial skeleton, we found a gene called early B-cell factor 3 (ebf3a) that may be involved in craniofacial development. In our scRNA-seq data, ebf3a expression is restricted to cranial NCCs of the dorsal and ventral domains of pharyngeal arches 1 and 2. In humans, damaging variants in …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Patient Preferences For Ultrasound Soft Sign Disclosure With Prior Negative Cfdna Screening, Disha Patel

Dissertations and Theses (Open Access)

Soft signs are nonstructural fetal anomalies that can be identified by the second-trimester comprehensive ultrasound examination. In isolation, soft signs are insufficient to diagnose chromosome conditions but can adjust an individual's risk for aneuploidy, primarily Down syndrome. In the age of noninvasive cell-free DNA (cfDNA) prenatal screening, which exhibits superior sensitivity and specificity for aneuploidy compared to what can be provided by soft sign risk adjustment, the utility of these soft signs is arguably waning. Thus, this study aimed to establish patient preferences for whether and how soft signs are disclosed in pregnancy to inform recommendations for disclosure. A survey …

Documenting The Southern Range Terminus Of The Wood Frog (Lithobates Sylvaticus) In North America, Christian Braswell

Theses

The Wood Frog (Lithobates sylvaticus) holds a remarkable position in North American amphibian biology, with its range extending from the Arctic Circle down to the near sub-tropical southeastern United States. This thesis presents a novel quantitative polymerase chain reaction analysis (qPCR) primer specific to L. sylvaticus and a survey effort regarding the southernmost distribution and detection of this species in Alabama through the application of environmental DNA (eDNA) sampling techniques. By investigating historical data and employing advanced genetic methodologies, this research provides insights into the contemporary status and distribution of the Wood Frog. This research is important to …

Genome Editing Using Crispr-Cas9 In Annual Killifish Species, Keria Moritsugu-Vandehey

University Honors Theses

CRISPR-Cas9 genome editing has been used successfully to knock out genes in model organisms such as zebrafish, turquoise killifish, and cichlid fish. CRISPR-Cas9 genome editing has not been verified in the annual killifish, Austrofundulus limnaeus. We hypothesize that targeted editing of the tyrosinase gene in embryos of A. limnaeus will lead to fish without the ability to produce black pigment. Embryos at the 1-cell stage were injected with a Cas9 cocktail containing a mix of guide RNA molecules that target the genomic sequence of the tyrosinase gene and either an mRNA coding for the Cas9 protein or Cas9 protein. …

Investigation Of Brain Function And Structural Development As Risk Factors Of Suicidal Thoughts And Behaviors, Yi Zhou

Theses and Dissertations

Background: Identifying risk factors for suicidal thoughts and behaviors, especially causal ones, will be imperative to improving screening and treatment interventions. To identify replicable brain-based risk factors, there is increasing evidence indicating the need for large sample sizes, in the hundreds to thousands, in order to achieve a sufficient level of statistical power to detect them. Furthermore, longitudinal studies of brain and behavioral factors will be essential to understanding how suicide develops, especially the transition from suicide ideation to attempt. While experimental studies may not be feasible or ethical, genetically informed methods for testing evidence for causation are an alternative …

Can Edna Be Used To Locate Shawnee Hills Cavefish Forbesichthys Papilliferus?, Megan Brandt, Timothy Spier Phd, Gary Zeruth Phd

Murray State Theses and Dissertations

Traditional stream fish sampling methods, such as seining and electrofishing, are time consuming, expensive, and limited to short stretches of stream. However, the analysis of environmental DNA (eDNA) from water samples promises to be a quick, inexpensive method for detecting fish. The streams of the Land Between the Lakes Recreational Area (LBL) are unique, undisturbed streams which contain many interesting fish species for which little information exists. One such rare species is the Shawnee Hills Cavefish Forbesichthys papilliferus, which is known to exist in a few LBL streams. However, the complete distribution of the Shawnee Hills Cavefish in LBL …

Practical Challenges In Delivering Dsrna For Woody Plant Protection, Zachary Bragg

Theses and Dissertations--Entomology

Unprecedented weather events associated with climate change, coupled with extensive anthropogenic stresses, have reduced the effectiveness of traditional forest pest management approaches, which can no longer keep pace with invasive species overwhelming naïve landscapes and native pests experiencing eruptive and expansive outbreaks. Double-stranded RNA-(dsRNA) mediated gene silencing, a type of RNA interference (RNAi), has been coopted for use as a biopesticide against a multitude of agricultural and horticultural pests and could serve as a powerful tool for woody plant protection. While effective initiation of gene silencing and subsequent mortality have been demonstrated in multiple tree pests, effective and efficient methods …

Determining Population Structure In Kentucky Parascaris Univalens Specimens, Constance Finnerty

Theses and Dissertations--Veterinary Science

Parascaris univalens is a highly pathogenic nematode that affects the gastrointestinal system of young horses. When unaddressed, this parasite causes severe intestinal impactions and even death. Parascaris univalens is also found to have an emergence of anthelmintic resistances, causing a concern for horse owners. Despite its clinical significance, very little work has been done on Parascaris univalens to identify its population structure. This study aimed to determine the population structure of Parascaris univalens through Illumina next generation sequencing (NGS) on three hierarchical categorizations: within a horse, within an isolated herd, and within horses in the state of Kentucky. A total …