Genetics and Genomics Commons^™

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.

Edna Surveys For The Critically Endangered Caribbean Staghorn Coral, Acropora Cervicornis (Lamarck, 1816), Pari Elaine Cribbins

All HCAS Student Capstones, Theses, and Dissertations

Historically, Acropora cervicornis was a dominant coral on Caribbean reef systems, but an outbreak of white band disease in the late 1970s marked the beginning of devastating, multi-decadal population declines that led to the coral being listed as “critically endangered” on the IUCN Red List in 2022. Today, after a record-setting marine heat wave in 2023 triggered a mass bleaching event on Florida’s Coral Reef (FCR), A. cervicornis is considered functionally extinct on the FCR. While individuals of A. cervicornis do remain on the FCR, the small population size of the coral makes in situ surveys difficult. However, surveys using …

Generating Predictive Gene Expression Signatures For Alzheimer's Disease Using Postmortem Brain Tissue, Ashley Duche

Pharmaceutical Sciences (PhD) Dissertations

Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and tau protein aggregates. These pathological features develop in specific brain regions, but why some areas are more vulnerable to early AD-related changes remains unclear. To address this, predictive gene expression signatures were developed to explore the molecular mechanisms underlying regional susceptibility to AD pathology.

Methods: This was performed using postmortem brain (PMB) tissue from participants in the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) to generate gene expression signatures from six brain …

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 …

Citrullus Amarus Drought Tolerance: An Above And Below Ground Analysis, Ben A. Hyland

All Theses

Ever rising environmental temperatures threaten global food security by worsening severity and increasing the occurrence of drought. Commercially cultivated watermelon (Citrullus lanatus), have reduced drought tolerance due to a narrow genetic base caused by breeding for desirable traits such as sweetness, size, and flesh/rind color. Comparatively, the crop wild relative desert watermelon variety (Citrullus amarus), while more drought tolerant than their commercially cultivated relatives (C. lanatus), still require large amounts of water to grow and produce reliable fruit yields. Watermelon root morphology plays a key role in their ability to tolerate drought, with more …

The Genetic And Environmental Determinants Of Stress Resilience Across Model Systems, Carson Len Stacy

Graduate Theses and Dissertations

Survival in fluctuating environments demands that organisms effectively anticipate and respond to future challenges. This capacity is shaped by both genetic background and environmental context. In this dissertation, I apply a population aware lens to explore how genetic diversity and environmental conditions intersect to shape stress survival. Integrating functional genomics and transcriptomics in Saccharomyces cerevisiae (brewer’s yeast) and a vertebrate (common canary) system, I dissect gene-by-environment (GE) interactions that underpin resilience. First, I move beyond a single reference genome by using a pan-genomic CRISPR knockout screen to assess osmotic stress survival across diverse S. cerevisiae isolates. This analysis reveals a …

Structure And Function Studies On Trna Splicing Endonuclease, Justin G. Underwood

Dissertations and Theses (Open Access)

A subset of eukaryotic pre-tRNAs have introns that must be spliced out to become mature molecules capable of functioning in translation. This essential processing step is performed by tRNA splicing endonuclease (TSEN), a highly conserved heterotetramer with two catalytic and two structural subunits. In addition to this conserved function, archaeal TSEN also processes pre-rRNA and yeast TSEN cleaves some mRNAs that encode mitochondrial proteins to initiate mRNA degradation. Interestingly, single amino acid mutations in TSEN cause the human Mendelian disease pontocerebellar hypoplasia (PCH) by an unknown mechanism. Recently, several groups have determined the structure of human TSEN, revealing similarities and …

An Open Letter To Leslie, Anne G. Kinne Phd

Journal of Conscious Evolution

This article celebrates the life and work of dear friend and mentor, Allan Leslie Combs, acknowledging his continued presence in my life. Interweaving stories of our relationship with his insights on integral consciousness, Bateson’s concept of aphanipoiesis, Varela et al.’s notion of autopoiesis, and using narrative, storytelling, and autoethnographic methodologies, I tell a tale of becoming that troubles and haunts my past. The sticky tendrils of Ancestral trauma and its transhistorical epigenetic inheritance, once acutely troublesome, are shifting due in large part to the contents of this letter. Woven together, these conscious, intersecting, and interactive lenses show how Leslie has …

Characterization Of Mitochondrial Dna Repair Components And Repair Choices At Targeted Double-Strand Breaks In Arabidopsis Thaliana, Moira Rodriguez

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Plant mitochondrial genomes are complex when compared to most other eukaryotic mitochondrial genomes. They are large and variable in size, expand and rearrange frequently, abundant in non-tandem repeats, but maintain a very low synonymous substitution rate in the remaining coding regions. Many of these complexities can be explained by the increased use of double-strand break repair for DNA damage. To advance the understanding of mitochondrial genome dynamics as it relates to double-strand break repair, we performed a forward genetics screen to identify proteins involved in DNA repair in plant mitochondrial genomes. Through this screen, we identified an RNA/DNA helicase, Suv3, …

From Morphology To Machine Learning And Genomics: Understanding Phenotypic Variation In Wild Ducks, Sara Gonzalez

Open Access Theses & Dissertations

Understanding the genetic underpinning and distribution of phenotypic variation within and between divergent groups is core towards shedding light into how populations diverge and adapt, as well as how hybridization breaks or builds on these scenarios; and thus, central to evolutionary biology. In wild organisms, however, quantifying and linking phenotypic traits to underlying genetic processes, like mutation, gene expression, epigenetics and allele interactions, remains challenging. This difficulty arises from the complex interplay between morphology, environment, and gene regulation, as well as the logistical barriers of collecting and standardizing large-scale data across individuals and populations. As a result, researchers are increasingly …

Context Dependent Regulation Of Dicer Function During Oocyte-To-Embryo Transition, Nick A. Newkirk

Dissertations and Theses (Open Access)

Over two decades ago, Dicer was discovered as the primary enzyme responsible for the generation of small RNAs known as the microRNAs (miRNAs) and short interfering RNAs (siRNAs). Spatiotemporal regulation of Dicer-dependent small-RNA biogenesis affects many aspects of biology, including aging, disease progression, fertility, and cancer. Interestingly, a distinct population of Dicer-dependent small RNAs, known as the endogenous siRNAs (endo-siRNAs), are uniquely abundant in the germ cells and gametes, and are critical for normal fertility. Despite their function regulating new life, the mechanisms controlling their biogenesis and subsequent germ cell functions remain poorly defined. Work to parse these mechanisms in …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Neural Rrp6 Depletion Drives Circrna Accumulation And Motor Impairment In Drosophila Melanogaster Neurons, Joseph Serio

Honors Theses

Circular RNAs (circRNAs) are a class of ubiquitous eukaryotic RNAs created by back splicing. These noncoding RNAs can modulate gene expression and are implicated in aging and neurodegenerative diseases. To limit the contribution of circRNAs to aging and pathobiology, it is essential to understand how turnover of these molecules is regulated, as it is not clear which enzymes are chiefly responsible for degrading circRNAs in neurons. This study evaluates the roles of ribonucleases potentially involved in neural circRNA turnover using the model fly Drosophila melanogaster. A mifepristone-activated GAL4/UAS GeneSwitch expressed RNAi transgenes and inactivated the ribonucleases. Flies were evaluated on …

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 …

Effects Of Urbanization On The Population Genetics And Morphology Of The White-Footed Mouse (Peromyscus Leucopus) Across An Urban–Rural Gradient, Sydney A. Morton

Master's Theses

Urbanization alters landscapes in ways that can reshape wildlife populations by changing habitat connectivity, resource availability, and selective pressures. To investigate how urbanization influences both genetic differentiation and morphology in small mammals, I examined Peromyscus leucopus (PELE) across an urban–rural gradient in northern Georgia. Using RADseq SNP data from PELE individuals across 13 sites, I quantified pairwise genetic differentiation (F_ST) and tested how various environmental variables, including impervious surface cover, human population density, and tree canopy cover, predict genetic differentiation after accounting for geographic distance. Genetic differentiation increased with geographic distance and, after controlling for isolation by …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

School of Medicine Faculty Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

Immunological Surveillance Against Cancer Across Mammals, Orsolya Vincze, Piotr Minias, Alexandre Corthay, Fernando Colchero, Jean-François Lemaître, Louise Maille, Tamás Malkócs, Justus Hagemann, Dalia A. Conde, Samuel Pavard, Antoine M. Dujon, Beata Ujvari, Frédéric Thomas, Amy M. Boddy, Carlo C. Maley, Damien Chevallier, Tuul Sepp, Thomas Pradeu, Mathieu Giraudeau

Presidential Fellows Articles and Research

Contrary to expectations based on their higher cell numbers, larger and longer-lived species do not face dramatically increased risk of cancer. This strongly suggests that evolution has fashioned natural cancer resistance mechanisms, yet our knowledge remains limited on what these mechanisms might be. The cancer immunological surveillance hypothesis, proposed by Burnet and Thomas in the 1950s, highlights immunity as a key factor determining species-specific cancer resistance. Here we address the original, evolutionary interpretation of this hypothesis by investigating the relationship between cancer mortality risk and markers of efficient antigen presentation. Our results show that the expansion of the MHC class …

Population Structure Analysis Of Four Basal Higher-Attines Using Bioinformatic Approaches, Gabriel Mcdanield

Biology Theses

Metapopulations within the family Formicidae are unique among other animals due to the large colonies they build, and the mating strategies required to fertilize a specialized reproductive caste that will often produce young for the life of the colony. One group of ants, the fungus-gardeners (tribe Attini). The population structure of North American non-leafcutting, fungus-gardening ants has been understudied, especially in the southwest of the United States. Additionally, not much is known about their dispersal biology, so the dynamics of dispersal of these species and how they affect population structure is likewise not well known. To shed light on the …

Chronosort: Revealing Hidden Dynamics In Alphafold3 Structure Predictions, Matthew J. Argyle, William P. Heaps, Corbyn Kubalek, Spencer Gardiner, Bradley C. Bundy, Dennis Della Corte

Faculty Publications

Protein function emerges from dynamic conformational changes, yet structure prediction methods provide only static snapshots. While AlphaFold3 (AF3) predicts protein structures, the potential for extracting dynamic information from its ensemble predictions has remained underexplored. Here, we demonstrate that AF3 structural ensembles contain substantial dynamic information that correlates remarkably well with molecular dynamics simulations (MD). We developed ChronoSort, a novel algorithm that organizes static structure predictions into temporally coherent trajectories by minimizing structural differences between neighboring frames. Through systematic analysis of four diverse protein targets, we show that root-mean-square fluctuations derived from AF3 ensembles can correlate strongly with those from MD …

Epigenetic Landscape In Lysosomal Storage Disorders: Mechanisms And Modulation, Andrés Felipe Leal, Harry Pachajoa, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Lysosomal storage disorders (LSDs) are rare substrate-accumulating diseases primarily characterized by mutations in genes encoding proteins involved in lysosomal function, most of which have enzymatic activity. Resulting lysosomal dysfunction leads to the overaccumulation of non- or partially degraded substrates. While it is true that enzyme deficiency is the primary cause of LSDs, the epigenetic alterations in DNA methylation, miRNA expression, and histone modifications appear to be critical mechanisms involved in the pathogenesis of LSDs. As epigenetic marks are, in most cases, reversible, their study becomes vital to developing strategies aimed at reversing epigenome alterations. Although classical therapeutic alternatives aim to …