Genetics and Genomics Commons^™

Mucin And Splice Variant Profiles Of Pancreatic Adenocarcinoma Predict Patient Survival And Subtyping, Christopher M. Thompson

Theses & Dissertations

PDAC is a pancreatic epithelial malignancy and demonstrates aggressive progression and bleak patient prognosis. Despite decades of research, the evolution of novel diagnostics and intervention modalities for PDAC is stagnant. This dissertation explores the characteristic aberrant and elevated expression of mucins in PDAC. Beginning with the hypothesis that mucins are associated with disease aggressiveness, analysis of PDAC patient survival in TCGA revealed no associations between single mucin expression and patient survival. This led to the underlying issue of PDAC tumor cellularity since this disease demonstrates variability in the proportion of cancer cells within the tumor. Tumor purity assessed with the …

Codon Bias Can Determine Sorting Of A Potassium Channel Protein, Anja J. Engel, Marina Kithil, Markus Langhans, Oliver Rauh, Matea Cartolano, James L. Van Etten, Anna Moroni, Gerhard Thiel

Nebraska Center for Virology: Faculty Publications

Due to the redundancy of the genetic code most amino acids are encoded by multiple synonymous codons. It has been proposed that a biased frequency of synonymous codons can affect the function of proteins by modulating distinct steps in transcription, translation and folding. Here, we use two similar prototype K⁺ channels as model systems to examine whether codon choice has an impact on protein sorting. By monitoring transient expression of GFP-tagged channels in mammalian cells, we find that one of the two channels is sorted in a codon and cell cycle-dependent manner either to mitochondria or the secretory pathway. …

Big Five Personality Traits And Political Orientation: An Inquiry Into Political Beliefs, Ian E. Phillips

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Personality research centered on the Big Five personality traits has heavily impacted our understanding in regards to what forces orient a person on a political spectrum. Examining how personality differences interact with political orientation, this research seeks to provide information on what makes someone either more or less likely to be liberal or conservative based on their temperament. In this paper, previous personality research is synthesized into one discussion, centered on what the effects of each trait are and how they impact political orientation, the heritability of personality, and what implications there are for such research in the realm of …

Evolutionary Conservation Of The Heterochronic Pathway In C. Elegans And C. Briggsae, Maria Ivanova, Eric G. Moss

Rowan-Virtua Research Day

Heterochronic genes control the sequence and timing of developmental events during four larval stages of Caenorhabitis nematodes. Mutations in these genes may cause skipping or reiteration of developmental events.

C. briggsae is a close relative of C. elegans. These species have similar morphology and share the same ecological niche. C. briggsae undergoes the same developmental pathway consisting of four larval stages before reaching adulthood. It also has the same set of heterochronic genes.

Lin-28 is one of the heterochronic genes that also exists in other animals from flies to humans. It conservatively blocks the maturation of let-7 miRNA, the process …

Chloroplast Genomes In Populus (Salicaceae): Comparisons From An Intensively Sampled Genus Reveal Dynamic Patterns Of Evolution, Jiawei Zhou, Shuo Zhang, Jie Wang, Hongmei Shen, Bin Ai, Wei Gao, Cuijun Zhang, Qili Fei, Daojun Yuan, Zhiqiang Wu, Luke R. Tembrock, Sen Li, Cuiha Gu, Xuezhu Liao

Aspen Bibliography

The chloroplast is one of two organelles containing a separate genome that codes for essential and distinct cellular functions such as photosynthesis. Given the importance of chloroplasts in plant metabolism, the genomic architecture and gene content have been strongly conserved through long periods of time and as such are useful molecular tools for evolutionary inferences. At present, complete chloroplast genomes from over 4000 species have been deposited into publicly accessible databases. Despite the large number of complete chloroplast genomes, comprehensive analyses regarding genome architecture and gene content have not been conducted for many lineages with complete species sampling. In this …

Genomics, Exometabolomics, And Metabolic Probing Reveal Conserved Proteolytic Metabolism Of Thermoflexus Hugenholtzii And Three Candidate Species From China And Japan, Scott C. Thomas, Devon Payne, Kevin O. Tamadonfar, Cale O. Seymour, Jian Yu Jiao, Senthil K. Murugapiran, Dengxun Lai, Rebecca Lau, Benjamin P. Bowen, Leslie P. Silva, Katherine B. Louie, Marcel Huntemann, Alicia Clum, Alex Spunde, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, I. Min Chen, Dimitrios Stamatis, T. B.K. Reddy, Ronan O’Malley, Chris Daum, Nicole Shapiro, Natalia Ivanova, Nikos C. Kyrpides, Tanja Woyke, Emiley Eloe-Fadrosh, Trinity L. Hamilton, Paul Dijkstra, Brian P. Hedlund

Life Sciences Faculty Research

Thermoflexus hugenholtzii JAD2 , the only cultured representative of the Chloroflexota order Thermoflexales, is abundant in Great Boiling Spring (GBS), NV, United States, and close relatives inhabit geothermal systems globally. However, no defined medium exists for T. hugenholtzii JAD2 and no single carbon source is known to support its growth, leaving key knowledge gaps in its metabolism and nutritional needs. Here, we report comparative genomic analysis of the draft genome of T. hugenholtzii JAD2 and eight closely related metagenome-assembled genomes (MAGs) from geothermal sites in China, Japan, and the United States, representing “Candidatus Thermoflexus japonica,” “Candidatus Thermoflexus tengchongensis,” and “Candidatus …

Has Maize Overtaken Our Reality? A Personal Briefing, Biochemical Comparison, Agrigenomics, And History Of Maize, Nader Pahlevan

Honors Theses

Maize (Zea mays ssp. Mays) is a revolutionary cereal grain that has raced to the world’s most popular staple crop, transforming societies and impacting history. This paper aims to build and portray the story maize has created through its journey to world domination. The important details that encompass this literature are maize’s cultural significance in my life’s story, the comparison of various starches broken down into amylose and amylopectin ratios, a summative historical account on maize’s spread throughout numerous parts of the old world, and the genetical analysis of maize that explains the key features that have led …

Using Crispr-Cas9 To Characterize The Role Of Gli-Similar 3 (Glis3) In Insulin Regulation, Pancreatic Development, And Type 2 Diabetes, Lilyanne Grieve

Honors College Theses

The prevalence of type 2 diabetes continues to rise nationally and internationally, impacting millions of people worldwide. Type 2 diabetes results from insulin resistance leading to chronic hyperinsulinemia and dysfunction of the insulin producing β cells of the pancreas. While environmental factors can influence the development of type 2 diabetes, research has shown genetics are also involved. Gli-similar 3 (Glis3), a Krüppel-like zinc finger transcription factor, has been identified as a novel regulator of insulin transcription. Evidence has shown that loss-of-function Glis3 mutations decrease insulin expression, implicating Glis3 in the development of type 2 diabetes. However, the distinct role Glis3 …

Covid-19 And The Differential Dilemma, Sharlee Climer

Computer Science Faculty Works

The conundrums of choosing candidate genes, via differential expression between treated and mock specimens, are tackled by Ghandikota et al. in this issue of Patterns in their efforts to tease out genetic patterns that are characteristic of coronavirus disease 2019 (COVID-19) outcomes.

Mapping And Characterization Of Mutagen Sensitivity Genes In Drosophila Malanogaster, Alexis Nystrom

Graduate Theses

The information contained within DNA is vital to directing all biological processes. All organisms have repair mechanisms in place to repair DNA damage quickly and efficiently. Without these repair pathways, DNA can acquire harmful mutations that can compromise the survival of an organism. Studies of DNA repair in Drosophila melanogaster have focused on mutagen sensitive (mus) mutants, each of which contain a mutation that renders them incapable of performing DNA repair. Since a majority of these mus genes are unmapped, the goal of this project was to determine what genes in the Drosophila melanogaster genome are mus106 and mus108. Presence …

Involvement Of The Ino80 Chromatin Remodeling Complex In Cell Division And Genomic Stability, Ethan Chen

Biomedical Engineering Undergraduate Honors Theses

Cell division is a vital biological process for growth and development in both single and multi-cellular organisms—whereby the cell must duplicate its organelles and genome in entirety and appropriately distribute the copied contents to the daughter cells. Cells undergo a cycle of two distinct phases: interphase and mitosis. During interphase, the cell replicates its genomic DNA (in the form of chromosomes) located within the nucleus. DNA replication is carried out in a euchromatin state, where the chromosome structure is loose and easily accessible by DNA polymerase and other replication enzymes. Upon the completion of replication, chromatin is condensed into highly …

Pando's Lessons: Restoration Of A Giant Aspen Clone, Paul C. Rogers, Jody Gale, Darren Mcavoy

Aspen Bibliography

A 106 acre (43 ha) aspen clone lives in the Fishlake National Forest in south-central Utah. Clones are comprised of multiple aspen stems, called ramets, which are genetically identical. This particular colony of ramets was named “Pando” (Latin for “I spread”) by researchers believing it to be the largest living organism by mass on earth. Recently, forest managers have noted a rapid dying of mature stems without recruitment of younger trees. This unsustainable situation has galvanized restoration efforts at Pando. Human interventions caused this imbalance; restoration will rely on protection, monitoring, and innovation. As a laboratory, this forest icon may …

Insecticidal Rna Interference, Thinking Beyond Long Dsrna, Alex S. Flynt

Faculty Publications

Over 20 years ago double-stranded RNA (dsRNA) was described as the trigger of RNAi interference (RNAi)-based gene silencing. This paradigm has held since, especially for insect biopesticide technologies where dsRNAs, similar to those described in 1998, are used to inhibit gene expression. In the intervening years, investigation of RNAi pathways has revealed the small RNA effectors of RNAi are diverse and rapidly evolving. The rich biology of insect small RNAs suggests potential to use multiple RNAi modes for manipulating gene expression. By exploiting different RNAi pathways, the menu of options for pest control can be expanded and could lead to …

Characterization Of A Putative Helicase In Rifampicin Resistance Of Mycobacterium Abscessus:, Aavrati Saxena

Legacy Theses & Dissertations (2009 - 2024)

Mycobacterium abscessus (Mab), a non-tuberculous environmental mycobacterium is one of the emerging pathogens. The number of Mab infections has doubled in the past decade. It is also an opportunistic pathogen usually infecting immunocompromised individuals and causing numerous skin and soft tissue infections. It commonly causes lung infections in people who are already infected with one or other lung infections such as tuberculosis. The treatment of Mab infections is difficult because of its intrinsic resistance to most of the antibiotics available. This project studies Rifampicin (RIF) resistance in Mab, as RIF is a well-established treatment for other mycobacterial infections including tuberculosis, …

Implementing Crispr-Cas9 Gene Editing System In Microbotryum., Stevana Reese Schauer

College of Arts & Sciences Senior Theses

Microbotryum dianthorum is a species of smut fungus which causes infection in plants in the Dianthus genus. The infection process is aided by small-secreted proteins known as effectors. Effectors may aid in the infection process because they are secreted by the fungus and can enter plant tissue, possibly to facilitate infection and/or manipulate the host. Thus, it is of interest to investigate the genes for these effectors to determine their role in the infection process. One method to study genes is through gene disruption, via the CRISPR/Cas9 gene editing system, but this has not yet been implemented in Microbotryum dianthorum …

Mapping The Domain Of Rna Helicase Ddx1 That Interacts With The Ns1 Of Influenza A Viruses, Elise Wyatt

Biomedical Engineering Undergraduate Honors Theses

Of the known influenza virus strains, influenza A viruses (IAVs) are the most catastrophic due to their highly contagious nature and possibly life-threatening symptoms. IAVs invade a host cell and enter the nucleus where they use the cell’s nuclear machinery for replication of their viral RNA genome which is then exported to neighboring cells to establish a productive infection. Host pathogen recognition receptors (PRRs) respond to viral infection by signaling the cell to produce type I interferons (IFNs) to fight the foreign invader. Non-structural protein 1 (NS1) of IAVs, a major component in the regulation of viral replication, opposes host …

Identification Of Proteins That Contribute To Yeast Heat Stress By Lysine Acetylation, Weijia Shi

Biological Sciences Undergraduate Honors Theses

Evidence is emerging that protein lysine acetylation may be a novel type of post-translational modification (PTM) contributing to the mechanisms of yeast heat stress responses. Proteomics studies including ours have identified over 1,000 acetylated proteins in the yeast proteomes that are composed of about 6,000 proteins. Our lab recently identified 596 proteins that underwent acetylation changes during heat shock by mass spectrometry. However, the role of lysine acetylation on specific residues of specific proteins in yeast thermotolerance remains largely unknown. This study selected 43 proteins from our lab’s previous work and examined their possible contributions to yeast heat stress responses. …

Production, Evaluation, And Selection Of Elite Quality Protein Popcorn (Qpp) Hybrids, Leandra Marshall Parsons

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

In 2017, twelve Quality Protein Popcorn (QPP) inbred lines were developed and selected as premier dent by popcorn crosses fit for hybridization and testing. These QPP inbred lines were derived from specific Quality Protein dent Maize (QPM) by ConAgra Brands® popcorn line crosses to produce high lysine, vitreous popcorn lines capable of near-equal popping characteristics compared to the original popcorn parents. The QPP hybridization project commenced in the summer of 2018 utilizing these 12 inbred QPP lines and crossing them in a full diallel. Since then, the production of QPP hybrids has employed a diverse set of selection factors evaluating …

Genomic Analysis Of Paenibacillus Larvae Bacteriophages, Casey Stamereilers

UNLV Theses, Dissertations, Professional Papers, and Capstones

American Foulbrood is the most destructive bacterial infection of the honeybee (Apis mellifera) and is caused by the Gram-positive, spore forming bacterium Paenibacillus larvae. Current treatment methods rely on antibiotics, but antibiotics treatments are experiencing a reduction in efficacy due to the recent rise in antibiotic resistant strains of P. larvae. This has been a major catalyst for exploration of alternative treatment methods. Phage therapy is an alternative treatment method that uses viruses that exclusively infect bacteria, known as bacteriophages (phages), to combat bacterial infections. Several experimental studies have shown that phages P. larvae phages are effective at lysing P. …

Investigating Pirna Expression And Function In Regenerating Tissue Of Segmented Annelid Capitella Teleta, Beatriz Schueng Zancanela

Honors Theses

Regeneration can be observed virtually in all animals and previous studies have identified numerous genes involved in this process. In some invertebrates, the P-element induced wimpy testis (PIWI) genes appear to have an essential role. One such organism is Capitella teleta, a widely accepted model for annelid development. PIWI proteins are associated with small non-coding RNA called PIWI-interacting RNAs or piRNAs, which are involved in transposon silencing in the germline cells of many animals. It was previously believed that these proteins were only expressed in germline cells, however, recent studies have shown expression in somatic tissues as well. The function …

The Diversity And Evolution Of Phenazine Biosynthesis Pathways In Enterobacterales, Christian Leise

Honors Theses

Enterobacterales is an order of Gram-negative bacteria that encompasses plant and animal pathogens and organisms of industrial importance. Some of these bacteria produce secondary metabolites classified as phenazines (Phz). Studies in other groups of microorganisms revealed that phenazines are redox-active and exhibit broad antibacterial, antifungal, and antiparasitic activity. Enterobacterales are known to produce phenazines, but details about the diversity, biochemistry, and function of phenazine metabolites in these organisms are missing. In this work, we screened the National Center for Biotechnology Information (NCBI) GenBank for genome sequences of phenazine-producing (Phz+) Enterobacterales. Additionally, genomes of Phz+ strains Pectobacterium carotovorum cc303 and …

Biases And Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens, Merve Dede

Dissertations and Theses (Open Access)

Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. Core essential genes are absolutely required for growth and proliferation in every cell type. On the other hand, context-dependent essential genes become essential in an environmental or genetic context. The concept of context-dependent gene essentiality is particularly important in cancer, since killing cancer cells selectively without harming surrounding healthy tissue remains a major challenge. The toxicity of …

Discovery Of Novel Ubiquitin- And Methylation-Dependent Interactions Using Protein Domain Microarrays, Jianji Chen

Dissertations and Theses (Open Access)

Post-translational modifications (PTMs) drive signal transduction by interacting with "reader" proteins. Protein domain microarray is a high throughput platform to identify novel readers for PTMs. In this dissertation, I applied two protein domain microarrays identifying novel readers for histone H2Aub1 and H2Bub1, and H3TM K4me3. Ubiquitinations of histone H2A at K119 (H2Aub1) and histone H2B at K120 (H2Bub1) function in distinct transcription regulation and DNA damage repair pathways, likely mediated by specific "reader" proteins. There are only two H2Aub1-specific readers identified and no known H2Bub1-specific readers. Using a ubiquitin-binding domain microarray, I discovered the phospholipase A2-activating protein (PLAA) PFU domain …

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

Dissertations and Theses (Open Access)

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

Determination Of Human Shedding Propensity Based On Str Results, Genevieve Trapani

Student Theses

Trace DNA evidence may be discovered at a crime scene after having been deposited by a person of interest via active or passive transfer. Based on previous studies, passive transfer of one’s DNA is influenced by their shedding propensity, or probability of depositing a detectable amount of DNA through touch. Determining the shedding propensity of a person of interest can aid in trace DNA interpretation in forensic casework. This study explored STR profile quality and the presence of a DNA mixture for different skin surface locations, including fingertips before and after handwashing. As expected, unwashed fingers showed a higher prevalence …

Genetic Pathway Analysis Of Abnormal Facial Development In Nonsyndromic Cleft Lip And Palate, Lorena Maili

Dissertations and Theses (Open Access)

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect resulting from incomplete fusion of the facial prominences during development, which leaves a gap in the lip, primary palate and/or the secondary palate. NSCLP affects 135,000 NSCLP newborns worldwide each year based on a birth prevalence of 1 per 700 live births. While surgical treatments have dramatically improved, many long-term health issues persist, imposing significant medical, psychosocial and economic burdens. Familial aggregation and segregation analyses suggest genetic contributions underlie NSCLP, but despite decades of study, only a small portion of the NSCLP genetic liability …

Effects Of Respiratory Perturbations On Aging And Healthspan In Daphnia Magna, Millicent Nkiruka Ekwudo

Electronic Theses and Dissertations

Aging is a degenerative process characterized by a decline in physiological functions and cellular activities. Environmental and pharmacological interventions affecting longevity pathways have been extensively studied in model organisms. This study investigated the effect of chronic mild intermittent hypoxia (4 mg O2/L) or mild mitochondrial uncoupling with three doses of 0 (control), 0.1, 1, and 5 μM of 2,4-Dinitrophenol (DNP), on life history and gene expression in four clones of Daphnia magna. Interestingly, clones from intermittent ponds displayed better tolerance to hypoxia and DNP. Although neither treatments extended longevity, hypoxia increased fecundity and body size, and decreased food consumption and …

Computational Approaches To Delineate Transcriptional And Functional Heterogeneity In Pancreatic Cancer, Sanjana Srinivasan

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is an incurable disease characterized by poor survival, dense desmoplastic stroma and activating mutations in KRAS (>90%). These tumors are highly complex ecosystems composed of molecularly distinct sub-populations that exhibit a spectrum of genetic features and associated phenotypes. Despite recent advances in the transcriptomic characterization of PDAC into at least two tumor subtypes, this alone has been insufficient to define more specific patterns of oncogenic dependency. To fully leverage advancements in next generation sequencing and functional genomics, we have sought to establish computational methodologies to aid in refined target discovery, and to develop a novel …

Evaluating Insurance Approval Rates Of Exome Sequencing And Its Effect On Minority Patients' Access To Genetic Care, Katlyn Frane

Dissertations and Theses (Open Access)

Exome sequencing (ES) is often a standard step in the genetic testing process for patients with rare or complex disease. Despite clinical implementation of ES, insurance companies (payers) continue to deny this test. We investigated if the payer barrier is influenced by payer type, and if other demographic or clinical information correlated to ES approval and obtainment. To do this, a retrospective chart and clinical database review was completed on patients seen at a tertiary care center and community-based clinic. Patient demographics, clinical indications, and testing recommendations and outcomes were used to assess ES approval and obtainment. We found that …

Functions Of Dcp2 And Ski7 In Mrna Degradation, Minseon Kim, Ambro Van Hoof

Dissertations and Theses (Open Access)

Posttranscriptional gene regulation is essential to maintain gene expression fidelity. This is partially achieved by mRNA decay. When no longer required, mRNA is degraded by two alternative pathways. The decapping enzyme Dcp2 removes the 5` <sup>m7</sup>G cap of mRNAs, allowing Xrn1 to degrade the mRNA from the 5` end. Alternatively, mRNA is degraded from the 3` end by the RNA exosome.

While decapping by Dcp2 is a critical step in mRNA decay, its physiological function has been unclear. Null mutations of Saccharomyces cerevisiae DCP2 have been reported to be lethal in some studies but slow-growing in others. In this …