Genetics and Genomics Commons^™

The Rna-Binding Protein Hur Modulates The Expression Of The Disease-Linked Ccl2 Rs1024611g-Rs13900t Haplotype, Feroz Akhtar, Joselin Hernandez-Ruiz, Ya-Guang Liu, Roy G. Resendez, Denis Feliers, Liza D. Morales, Alvaro Diaz-Badillo, Donna M. Lehman, Rector Arya, Juan Carlos Lopez-Alvarenga, John Blangero, Ravi Duggirala, Srinivas Mummidi

School of Medicine Publications

CC-chemokine ligand 2 (CCL2) is involved in the pathogenesis of several diseases associated with monocyte/macrophage recruitment, such as HIV-associated neurocognitive disorder (HAND), tuberculosis, and atherosclerosis. The rs1024611 (alleles: A>G; G is the risk allele) polymorphism in the CCL2 cis-regulatory region is associated with increased CCL2 expression in vitro and ex vivo, leukocyte mobilization in vivo, and deleterious disease outcomes. However, the molecular basis for the rs1024611-associated differential CCL2 expression remains poorly characterized. It is conceivable that genetic variant(s) in linkage disequilibrium (LD) with rs1024611 could mediate such effects. Previously, we used rs13900 (alleles: C>T) in the CCL2 …

Explainable Convolutional Neural Network Model Provides An Alternative Genome-Wide Association Perspective On Mutations In Sars-Cov-2, Parisa C. Hatami, Richard Annan, Luis Miranda, Jane L. Gorman, Mengjun Xie, Letu Qingge, Hong Qin

Computer Science Faculty Publications

Identifying informative genomic features in SARS-CoV-2 can help clarify patterns of viral evolution. In this study, we developed an explainable convolutional neural network (CNN) model to classify SARS-CoV-2 genomic sequences into the WHO-designated Variants of Concern (VOCs), Alpha, Beta, Gamma, Delta, and Omicron. Using a balanced dataset of genomes, the classification CNN achieved 99.96% accuracy on the held-out test set. To interpret the model’s predictions, we applied SHapley Additive exPlanations (SHAP) to estimate the contribution of each nucleotide position to VOC-label prediction and compared aggregated attributions with a chi-square GWAS baseline applied to the same categorical labels. SHAP prioritized several …

Bio-Orthogonal Chemistry-Based Strategy To Turn-On And Turn-Off Crispr-Cas9 Gene Editing In Solution And In Live Cells, Bhoomika Pandit

Electronic Theses & Dissertations (2024 - present)

The CRISPR–Cas9 system is a widely popular tool for genome engineering. There is a strong interest in developing tools for temporal control of CRISPR-Cas9 activity to address some of the challenges and to broaden the scope of potential applications. In this thesis I describe two biorthogonal based approaches to either Turn-ON and Turn-OFF CRISPR-Cas9 gene editing.

In first project work I describe a bio-orthogonal chemistry-based approach to Turn-ON Cas9 nuclease activity with temporal precision. We report a TCO-acylimidazole reagent that acylates 2′-OH groups of RNA. Poly-acylation (“cloaking”) of RNA was optimized in vitro using a model 18-nt oligonucleotide, as well …

Mechanisms Of Glyphosate Toxicity: Uptake, Mitochondrial Function, And Metabolism, Dionysios Patriarcheas

Graduate Theses, Dissertations, and Problem Reports (ETD)

Glyphosate, the most widely used herbicide in the world, is an inhibitor of chorismate biosynthesis, the precursor of aromatic amino acids. The target of glyphosate is absent in animals, but findings reporting toxicity in model organisms without a known mechanism or target are increasing. Saccharomyces cerevisiae is a useful and versatile model for understanding molecular mechanisms of toxicity. In yeast, previous work has shown that the aspartate/glutamate permease Dip5 is the proposed transporter for glyphosate and that mitochondrial metabolism has been implicated in response to glyphosate toxicity. This dissertation aimed to identify the effects of glyphosate on mitochondrial function through …

Genetics Of Mycangial Development And Host Colonization Within The Ambrosia Symbiosis, Mckeon James Laws

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ambrosia beetles, a polyphyletic group of weevils, utilize pouch-like structures at various locations on the body to transport for their sole food source, their fungal partner. Ambrosia fungi are known to originate from multiple unrelated fungal lineages with no consensus of traits required to become a fungal cultivar. While the biology and ecology of both partners is in many cases well understood, the genetic underpinnings of this fascinating mutualism remain a mystery. The aim of this dissertation is to add to the understanding of the ambrosia symbiosis by providing insights into its molecular and genetic underpinnings through RNA sequencing data, …

Phylogeography, Fungal Host Specificity, And Fitness In The Corallorhiza Maculata Species Complex, Hana Thixton-Nolan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mycoheterotrophic plants exploit fungi for most or all nutritional needs, providing a compelling system to address the evolutionary consequences of genome reduction, population-level variation, and germination requirements. I am using the widespread Corallorhiza maculata species complex to address questions of genomic variation, fungal host specificity, morphological variation, and germination requirements across the broad geographic range from Mexico to northern North America. This complex contains C. bulbosa, C. macrantha, and C. mertensiana, the latter with three varieties (maculata, occidentalis, and mexicana). These taxa vary in flowering time, floral morphology, and fungal associations. However, the degree …

A Fine-Scale Genomic Study Of Cheat Mountain Salamanders (Plethodon Nettingi) On Managed Public Land, Amylynn Nicole Ephraim

Graduate Theses, Dissertations, and Problem Reports (ETD)

Habitat fragmentation has the potential to isolate localized populations, particularly those which are understood to have limited dispersal capabilities. This isolation can reduce genetic diversity through the effects of inbreeding depression, and small populations are more susceptible to the impacts of genetic drift. In this study, I aim to understand the level of genetic connectivity between known occupied patches of Cheat Mountain salamanders (Plethodon nettingi; CMS) on managed public land. CMS are a federally threatened, high-elevation, West Virginia endemic species associated with red spruce (Picea rubens) forests. I used double-digest restriction site associated DNA (ddRAD) sequencing …

Integrating Genetic Modifier Genotype With Serum Proteomics In Duchenne Muscular Dystrophy Clinical Trials Links Ltbp4 Genetic Modifier To Il-23/Cd93 Pathways In Muscle, Utkarsh J. Dang, Yuan Fang, Daniele Sabbatini, Elena Pegoraro, Luca Bello, Paula R. Clemens, Michela Guglieri, John Van Den Anker, Jesse Damsker, Laura Hagerty, Yetrib Hathout, Michael Ziemba, Lauren Morgenroth, Surajit Bhattacharya, Kanneboyina Nagaraju, Jyoti K. Jaiswal, Eric P. Hoffman

Mathematics & Statistics Faculty Publications

Genetic modifiers of Duchenne muscular dystrophy (DMD) that alter disease severity or response to therapy have been reported using natural history or registry data sets of older corticosteroid-treated patients. We tested associations of genetic modifiers on motor function outcomes in young (4 to <  7 years) steroid naïve clinical trial participants. Participants in clinical trials (VBP15-002/003 [n = 48]; VBP15-004 [n = 121]; DNA available for n = 110) were genotyped for eight published genetic modifier loci, and associations of genotypes with baseline motor function defined via an age-adjusted linear model. Corticosteroid drug response was modeled by genotype-stratified placebo vs. steroid treatment at 12- and 24-weeks posttreatment (mixed model for repeated measures). …

Data From: Complete Mitochondrial Genomes Of The Spring Pygmy Sunfish (Elassoma Alabamae), Kayla M. Fast, David Lee Pounders, Mayah P. Peterson, Michael W. Sandel

Research Data

The Spring Pygmy Sunfish, Elassoma alabamae (Mayden, 1993), is a small species of sunfish (Centrarchiformes) endemic to tributaries to the middle Tennessee River in north Alabama. Elassoma alabamae is the most geographically restricted member of Elassoma and the only species found above the fall line. This species was twice considered extinct and was listed under the Endangered Species Act (ESA) as threatened in 2013. To date, surveys for this species have been limited to traditional invasive methods using dipnets and seines. In order to reduce impacts on sensitive populations, we sequenced the mitochondrial genome with the intent of developing a …

Mitochondrial Disorders Should Be Considered As A Differential Diagnosis Of Thiamine Deficiency, Josef Finsterer

HCA Healthcare Journal of Medicine

This letter to the editor addresses limitations to diagnosing thiamine deficiency for multisystem disorders and discusses the potential differential diagnoses that must be considered.

Esat-6 And Cfp-10 Reactive Igg In Patients With Tuberculosis Inhibits Intracellular Bacteria, Joshua R. Miles, Pei Lu, Shuangyi Bai, Genesis P. Aguillón-Durán, Javier E. Rodríguez-Herrera, Bronwyn M. Gunn, Blanca I. Restrepo, Lenette L. Lu

School of Medicine Publications

Perspectives beyond the CD4 T cell interferon (IFN)-γ paradigm are needed to understand immunity in tuberculosis (TB). Growing data in patients across a spectrum of TB highlight that changes in antibody Fc domain glycosylation and Fc effector functions correlate with disease and impact Mycobacterium tuberculosis (Mtb) infection. How antigen-specific antibodies within polyclonal responses affect bacteria is less clear. This study examines antibodies targeting ESAT-6 and CFP-10, Mtb virulence proteins essential for pathogenesis. Data from patients with TB show that polyclonal immunoglobulin (Ig)G reactive to ESAT-6 and CFP-10 diverges from other Mtb and non-Mtb antigens with enhanced sialylation, …

A Tissue Renewal-Based Mechanism Drives Colon Tumorigenesis, Ryan M. Boman, Gilberto Schleiniger, Christopher Raymond, Juan P. Palazzo, Anne Shehab, Bruce M. Boman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Our Goal is to identify how colorectal cancer (CRC) arises in the single-layered cell epithelium (simple columnar epithelium) that lines the luminal surface of the large intestine. Background: We recently reported that the dynamic organization of cells in colonic epithelium is encoded by five biological rules and conjectured that colon tumorigenesis involves an autocatalytic tissue renewal reaction. Introduction Our objective was to define how altered crypt turnover explains tissue disorganization that leads to adenoma morphogenesis and CRC. Hypothesis: Changes in rate of tissue renewal-based cell polymerization leads to epithelial expansion and tissue disorganization during adenoma histogenesis. Methods: Accordingly, we created …

Developing A Tool To Measure Resistance To Sustainable Food Choices: A Pilot Study In Ireland And The Netherlands, Kate Flanagan, Bart Sinteur, Patricia J. Bulsing, John M. Kearney

SURE Journal: Science Undergraduate Research Experience Journal

Consumer uptake of a sustainable diet is critical for addressing environmental challenges and promoting public health. Understanding why consumers resist adopting sustainable eating habits can inform targeted interventions and policies. This pilot study examines whether a newly developed scale can effectively detect consumer resistance to a sustainable diet. Currently, there is a lack of research on a tool to measure consumer resistance to a sustainable diet, highlighting the need for a reliable instrument.

The aim of this study is to develop a scale, based on existing literature, to measure consumer resistance to a sustainable diet. Additionally, the study aims to …

Editorial-Sure Journal Volume 7, Issue 2, Geraldine M. Dowling, Eva Campion, Sinead Loughran, Ariane Perez-Gavilan, Josephine Treacy

SURE Journal: Science Undergraduate Research Experience Journal

No abstract provided.

A Genetic Interaction Between Ded1 And Hat1 In Saccharomyces Cerevisiae Reveals A Role For Hat1p In Cytoplasmic Rna Granule Accumulation, Audrey J. Panko, Aidan Winters, Nicholas R. Rothbard, Angela K. Hilliker

Biology Faculty Publications

Ded1p is an essential translation initiation factor that interacts with and is modulated by eIF4F. Ded1p also promotes the assembly and disassembly of stress granules, which contain nontranslating mRNAs and translation initiation factors. As Ded1p affects both mRNA storage and translation initiation, regulation of Ded1p's function may affect whether mRNAs are translated or localized to cytoplasmic RNA granules. To identify regulators of Ded1p in Saccharomyces cerevisiae, we screened for overexpression suppressors of the severe growth defect conferred by high levels of Ded1p. We found that overexpression of HAT1, a lysine acetyltransferase, can suppress the growth defect conferred by …

Regulation Of Chromatin Remodeling By The Post-Hsa Domain Of Brg1, A Subunit The Baf Atp-Dependent Chromatin Remodeling Complex, Min Sze Ewe

Theses & Dissertations

The ATP-dependent chromatin remodeler BAF complex regulates nucleosome positioning, chromatin accessibility, and tissue specific gene expression. Its catalytic subunit, BRG1, contains several regulatory domains including the post-HSA region, proposed to modulate ATPase activity. Multiple cancer-associated mutations map to these regulatory regions underscoring their importance, yet the precise role of the post-HSA region in chromatin remodeling remains poorly understood.

To investigate the function of the post-HSA domain, we ectopically expressed FLAG-tagged BRG1 with post-HSA deletion (Δpost-HSA BRG1) in mouse embryonic stem cells. Western blot analysis confirmed expression of the mutant protein. To determine the effects of mutant protein expression on chromatin …

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 …

Mechanistic Insight Of Neuropilin-2 Expression During The Progression Of Prostate Cancer, Sanika Bodas

Theses & Dissertations

Advanced prostate cancer represents a particularly aggressive and challenging form of prostate cancer (PCa) that shows resistance to both traditional therapies, such as androgen deprivation therapy, and newer treatment modalities like hormone therapies and immunotherapies. For patients diagnosed with advanced stages of PCa, treatment options are limited, and chemotherapy is often the last line of defense. Unfortunately, chemotherapy can severely diminish the quality of life, particularly in older patients, due to its harsh side effects, including fatigue, immune suppression, and overall physical decline. Despite these challenges, researchers and clinicians remain focused on developing more effective and targeted treatments for patients …

Function Of Drosophila Melanogaster Domesticated Transposable Element Protein Dplg3 In Oogenesis And Total Fitness, Aron Herrera

2025 Fall Honors Capstones Projects - Archive

Transposable elements (TEs) are selfish DNA segments capable of self-replication and reinsertion within genomes, often harming hosts. Rarely, host genomes can adopt TEs and use their proteins for new cellular functions through molecular domestication. One example primarily expressed in Drosophila melanogaster ovaries is DPLG3. Previous Betrán Lab students generated DPLG3 loss-of-function flies and found that their ovaries misregulated one primordial and 14 testis-specific genes, leading to variable ovarian malformations. However, it is unclear when during oogenesis these misexpressions occur. We will extract RNA from non-rudimentary ovaries at early and late stages to generate cDNA for qRT-PCR analysis of three …

Capillary Electrophoresis Vs Massively Parallel Sequencing: A Cost-Benefit Analysis, Samia Williams

Honors Projects

Massively Parallel Sequencing (MPS) is a new Forensic Science field allowing multiple samples to be sequenced simultaneously. In contrast to CE, multiple types of genetic markers including those from different nucleic acids can be used in the same assay. Additionally, MPS has opened the doors to certain fields of Forensic DNA Analysis like Forensic Investigative Genetic Genealogy and Forensic Phenotyping assays containing upwards of 100 SNPs. While quite expensive and requiring a high cost for initiating, MPS has the potential to save time and greatly increase the throughput of Forensic DNA Analysis in crime labs.