Genomics Commons^™

A Cophylogenetic Analysis Of Fungus Gardening Ants And Their Symbiotic Fungi, Katherine Beigel

Biology Theses

Fungus-growing ants (Tribe Attini) and their fungal cultivars share a 50-million-year coevolutionary history. Large scale phylogenetic analyses depict a strong co-phyletic signal among ants and their farmed fungi yet fungus sharing among unrelated ant lineages is somewhat widespread. An overview of sharing has been hampered by a lack of genetic markers that exhibit intraspecific variation and surveys across geographic regions. For example, previous studies have shown similar sequences of the internal transcribed spacer (ITS) region of fungus in different species of Trachymyrmex, suggesting that these ant species are farming the same fungal clone. To examine whether this was a …

Effects Of Tempeh Fermentation On Soy Free And Bound Phenolics: Release, Transformation, And Stimulated Production, Amadeus Driando Ahnan

Doctoral Dissertations

The fermentation of tempeh, a traditional source of protein originated in Indonesia, has been reported to enhance the health-promoting potentials of various grains, legumes, and beans. Tempeh fermentation on soybeans can modulate the bioavailability of phenolic compounds, particularly isoflavones, bioactive compounds that have been found to be protective against lung, prostrate, and colon cancers. However, the mechanism of the protective benefits was unknown. Using whole-food and in vitro models, this study addressed this research gap by investigating the effects of tempeh fermentation using various cultures on the compositions of soy free, bound, and minor phenolics, as well as their antioxidative, …

Genetic And Clinical Determinants Of Racial/Ethnic Differences In Multiple Myeloma Susceptibility And Outcomes Focusing On Hispanics, Alem Belachew

Dissertations & Theses (Open Access)

Multiple Myeloma (MM) constitutes 10% of diagnosed hematologic malignancies in the US, with over 12,000 deaths recorded each year. Race/ethnicity is a well-known MM risk factor, where individuals of African descent have over 2- to 3-fold increased risk of incidence compared to those of European descent. Additionally, Hispanics are diagnosed approximately three years younger than white American counterparts, for unknown reasons. Differences in clinical phenotype are also present for MM patients by ancestry, including varying rates of common initiation mutations such as IgH translocations and TP53 mutation between patients of European and African descent. Studies have begun to interrogate the …

The Effect Of Nuclear Perturbations On The 3d Organization Of The Genome, Rosela Golloshi

Doctoral Dissertations

Cells in our body experience constant mechanical forces that influence biological functions such as growth and development. The nucleus has been implicated as a key mechanosensor and can directly influence chromatin organization and epigenetic alterations leading to gene expression changes. However, the mechanism by which such mechanical forces lead to genomic alterations and expression of mechanosensitive genes is not fully understood. The work presented in this dissertation investigates the effect of mechanical and epigenetic perturbations on the 3D genome organization. To investigate this 3D genome folding, we use Chromosome Conformation Capture followed by high throughput sequencing (Hi-C) (Chapter-1) which identifies …

3d Genome Architecture Under Stress: A Survey Of Ionizing Radiation, Progeria, And Osmotic Stress, Jacob Tyler Sanders

Doctoral Dissertations

The human nucleus contains 2 meters of DNA which is intricately folded into a three-dimensional (3D) structure. It has become increasingly clear that this 3D structure plays an important role in the expression of genes. Proper gene expression is necessary for cellular homeostasis, cell state, and response to environmental/physical perturbations. Faithful repair of damage DNA damage is necessary to prevent genomic aberrations, such as translocations, which may lead to misregulation of gene expression. Hi-C, a sequencing technique that labels proximal chromatin interactions, provides a clearer picture of how the genome is spatially organized within the nucleus. Here, we discuss the …

Population Structure Of A Federally Endangered Plant (Astragalus Jaegerianus Munz, Fabaceae) With Limited Range Using Microsatellites, Sueann Neal

Electronic Theses, Projects, and Dissertations

Studies on population genetics examine the relationship and effects of population structure, migration, gene flow and demographic history, and are therefore important in the conservation of endangered species. Astragalus jaegerianus, a critically federally endangered species found in a geographically restricted range is investigated to determine population structure and genetic variation. Previous research on A. jaegerianus focused on DNA sequence data for cpDNA and nrDNA showed no variation. Further research on A. jaegerianus utilizing AFLP’s on the whole genome indicated substantial gene diversity and population structure consistent with geographically widespread species. AFLP research is a cost-effective process to identify levels …

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations & Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

The Genome-Wide Roles Of The Lung Lineage Transcription Factor Nkx2-1 In The Regulation Of Opposing Cell Fates In Vivo, Danielle Renae Little

Dissertations & Theses (Open Access)

Lineage transcription factors mark, promote, and maintain multiple distinct cell types originating from a common progenitor. Despite their essential role, how such factors function and bind genome wide to orchestrate the epigenetic changes necessary to form and maintain these identities in vivo is unclear. One lineage transcription factor NK Homeobox 2-1 (NKX2-1) is expressed throughout the lung epithelium during development and was thought to be lost in the extraordinarily thin cell type required for gas exchange– the alveolar type 1 (AT1) cell. Complementing precise genetic knockouts with cell type-specific ChIP-seq, ATAC-seq, and scRNA-seq, our study shows that AT1 and AT2 …

A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a very poor patient prognosis (5-year survival of ≤ 7%). While transcriptional profiling has aided in the classification of this disease into at least two broader subtypes, this alone has so far been insufficient to inform on more nuanced patterns of oncogenic dependency. We hypothesized that a more comprehensive and granular characterization of PDAC disease diversity is required to establish relevant context for targeted therapy. To this end, we sought to establish an integrated platform to: i) more comprehensively characterize differential oncogenic signaling across our tumor models, and ii) establish …

Decoding The Evolutionary Response To Prostate Cancer Therapy Using Plasma Genome Sequencing, Naveen Ramesh

Dissertations & Theses (Open Access)

Investigating genome evolution in response to therapy is difficult in human tissue samples due to the difficulty in accessing metastatic tumor sites and logistical challenges of collecting longitudinal samples. To overcome these issues, we developed an unbiased whole-genome plasma DNA sequencing approach called PEGASUS that concurrently measures genomic copy number and exome mutations from archival cryostored plasma samples. This approach was applied to study longitudinal blood plasma samples from prostate cancer patients. A molecular characterization of archival plasma DNA from 233 patients and genomic profiling of 101 patients identified clinical correlations of aneuploid plasma DNA profiles with poor survival, increased …

Carbon Metabolism In Cave Subaerial Biofilms, Victoria E. Frazier

Masters Theses

Subaerial biofilms (SABs) grow at the interface between the atmosphere and rock surfaces in terrestrial and subterranean environments around the world. Multi-colored SABs colonizing relatively dry and nutrient-limited cave surfaces are known to contain microbes putatively involved in chemolithoautotrophic processes using inorganic carbon like carbon dioxide (CO₂) or methane (CH₄). However, the importance of CO₂ and CH₄ to SAB biomass production has not been quantified, the environmental conditions influencing biomass production and diversity have not been thoroughly evaluated, and stable carbon and nitrogen isotope compositions have yet to be determined from epigenic cave SABs. …

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Quantifying Structure And Variation In Complex Phylogenetic Data, Genevieve Geraldine Mount

LSU Doctoral Dissertations

Identifying the source and structure of variation in nature is crucial to understanding fundamental aspects of evolution. Despite a recent plethora of genetic and morphological data, many interesting questions about the relationships between different groups remain unresolved. My dissertation evaluates three approaches for identifying and quantifying the variation within phylogenetic datasets. Characterizing variation within datasets and across analytical methods gives insight into biologically interesting characters, unusual evolutionary processes, and areas for model improvement.

Network-based community detection approaches offer a powerful tool to describe variation in phylogenetic signal across the genome (i.e., gene tree variation). In Chapter 2, I investigate the …

From Phocine Distemper To Avian Influenza: A Study Of Immunogenetic Diversity In Two Sympatric Pinniped Species, Alayna K. Gigliotti

Electronic Theses and Dissertations

Gray (Halichoerus grypus) and harbor (Phoca vitulina) seals are sympatric species that inhabit the North Atlantic and have been subject to mortality events from disease outbreaks, particularly phocine distemper and avian influenza virus. Across mortality events, gray seals tend to exhibit a higher survival rate, which could be explained by various ecological factors impacting rates or direction of selection in parts of the genome related to the immune system. These factors could include haul-out site density, habitat, and degree of inter/intraspecies interaction. This research aims to compare genetic diversity within the Major Histocompatibility Complex (MHC) class …

Structure And Evolution Of Lizard Immunity Genes, Trent Santonastaso

University of New Orleans Theses and Dissertations

One of the most important gene families to play a role in adaptive immunity is the major histocompatibility complex (MHC). MHC class II loci are considered to be the most variable loci in the vertebrate genome, and studies have shown that this variability can be maintained through complex co-evolutionary dynamics between host and parasite. Despite the rich body of research into the MHC, there is comparatively little understanding of its genomic architecture in reptiles. Similarly, loci associated with innate immunity have received little attention in reptiles compared to other vertebrates. In the first chapter, we investigated the structure and organization …

Linking Crude Oil And Dispersant Effects To Gene Expression Of Marine Sponge Cinachyrella, Yvain Desplat

All HCAS Student Capstones, Theses, and Dissertations

Because of their filter-feeding lifestyle, sponges (Phylum Porifera) have shown to be bio-accumulators of heavy metals, and bio-monitors for polychlorobiphenyl (PCB) contaminants. Furthermore, marine sponges have been shown to be regulators of reef ecosystems by fulfilling many ecological functions. However, very little is known about their behavior in the face of environmental changes. Consequently, our lab has developed the reef sponge Cinachyrella spp. as novel experimental model. We have designed an experiment to study the effects of WAF (Water Accommodated Fraction), Corexit 9500 dispersant, and CE-WAF (Chemically Enhanced Water Accommodated Fraction)mixtures, in an effort to mimic the conditions of the …

Identification Of Trim24 Domain Essentiality In Primary Trim24coe Carcinosarcoma Cell Lines, Cem Dede

Dissertations & Theses (Open Access)

Regulation of transcriptional control is a critical feature for organismal development and survival. Because of its effects on chromatin-controlled expression, disruptions of this delicately tuned mechanism are an important factor in development of tumorigenesis. Therefore, there is a growing interest in targeting these control mechanisms for their potential therapeutic values.

Our lab previously discovered the epigenetic regulator function of Tripartite motif protein 24 (TRIM24) through its H3K4me0 and H3K23ac dual histone signature reader function, its negative regulatory effect on the p53 tumor suppressor, in addition to its shown oncogenic driving capacity on immortalized mammary epithelial cells when overexpressed. Although TRIM24 …

Statistical Methods For Resolving Intratumor Heterogeneity With Single-Cell Dna Sequencing, Alexander Davis

Dissertations & Theses (Open Access)

Tumor cells have heterogeneous genotypes, which drives progression and treatment resistance. Such genetic intratumor heterogeneity plays a role in the process of clonal evolution that underlies tumor progression and treatment resistance. Single-cell DNA sequencing is a promising experimental method for studying intratumor heterogeneity, but brings unique statistical challenges in interpreting the resulting data. Researchers lack methods to determine whether sufficiently many cells have been sampled from a tumor. In addition, there are no proven computational methods for determining the ploidy of a cell, a necessary step in the determination of copy number. In this work, software for calculating probabilities from …

Artificial Intron Technology To Generate Conditional Knock-Out Mice, Amber N. Thomas-Gordon

Dissertations & Theses (Open Access)

Genetic engineering has been re-shaped by the invention of new tools in modern biotechnology in a way that offers precision and efficiency in modifying the genome at a single nucleotide level and/or allowing precise control of gene expression. Such gene manipulation brings about significant findings and revelations in comprehending more about embryonic development, cellular and physiological functions, and disease pathology. Current methods used to produce conditional knockouts have limitations on conditional allele placement and modification varies among genes in different organisms. Thus, a system for generating conditional alleles with fidelity remains a challenge. My goal was to examine an approach …

Comparative Secretomics And Functional Analysis Of Effectors Utilized By The Microbotryum Genus Of Anther-Smut Fungal Pathogens, And Their Role In Host-Specificity., William Christopher Beckerson

Electronic Theses and Dissertations

Understanding how pathogens evolve in response to changes in their host is paramount to combating the spread of emergent strains of disease. This is particularly true for plant pathogens that cause billions of dollars of damages to crops globally, every year. Understanding the molecular interactions between pathogens and their hosts therefore sheds light on the coevolutionary arms race that can result in host-specificity and host-shifts in plant pathogens. This research approaches the question of how fungal pathogens interact with their plant hosts utilizing both unique and shared arsenals of secreted proteins (SPs) during infection, and addresses the question of whether …

Accessory Genes Contribute To Rewiring The Transcriptional Network In Fusarium Oxysporum, He Yang

Doctoral Dissertations

The presence of accessory chromosomes is one of the most fascinating features in the genomes of Fusarium oxysporum (Fo) species complex that includes both plant and animal pathogens. In plant-pathogenic Fo strains, these accessory chromosomes govern host-specific pathogenicity through unique sets of virulence factors, including secreted effectors and plant cell wall degrading enzymes, while the identity of such factors are largely unknown in human infecting strains. This dissertation is composed of three projects that focused on studying the gene composition and transcriptional regulation of human-pathogenic Fo strains. The first project deciphered the genome of the clinical Fo strain, …

Epigenetics A Decolonizing Science, Wade Paul

Electronic Thesis and Dissertation Repository

Epigenetics is the study of gene expression that does not entail alterations to the actual DNA. Decolonization is a theoretical and political movement that seeks to deconstruct colonial institutions and ideologies and reconstruct new and balanced approaches that accept and respect Indigenous worldviews. This project studies the decolonizing potential of epigenetics. Using genealogy as the method, the study establishes a long history of reductionist and deterministic thought that shaped the study of genetic science. Particular instances like thrift gene theory are explored to highlight how genetic explanations have been detrimental to the health and wellbeing of Indigenous people and illustrate …

Machine Learning With Digital Signal Processing For Rapid And Accurate Alignment-Free Genome Analysis: From Methodological Design To A Covid-19 Case Study, Gurjit Singh Randhawa

Electronic Thesis and Dissertation Repository

In the field of bioinformatics, taxonomic classification is the scientific practice of identifying, naming, and grouping of organisms based on their similarities and differences. The problem of taxonomic classification is of immense importance considering that nearly 86% of existing species on Earth and 91% of marine species remain unclassified. Due to the magnitude of the datasets, the need exists for an approach and software tool that is scalable enough to handle large datasets and can be used for rapid sequence comparison and analysis. We propose ML-DSP, a stand-alone alignment-free software tool that uses Machine Learning and Digital Signal Processing to …

Gene Regulation And Cell Fate Choice In The Developing Vertebrate Retina, Sruti Patoori

Dissertations, Theses, and Capstone Projects

The diverse neuronal cell types in the vertebrate retina all originate from multipotent retinal progenitor cells (RPCs). These undergo a series of molecular changes driven by developmental gene regulatory networks (GRNs) as they divide to generate RPCs which are more restricted in their potential fates. It is crucial to understand these GRNs and changes to gene expression in order to understand how cell identity is established during retinal development. In particular, the GRN that promotes the development of cone photoreceptors and horizontal cells is not well-defined. This work focuses on two approaches to further elucidate the components of this regulatory …

Cancer Genetic Counselors’ Perceptions Of Nutritional Recommendations, Breann Reinsch

KGI Theses and Dissertations

Objective: The purpose of this research study is to understand the perspectives of genetic counselors who work with patients in the cancer setting and explore if nutrition is a consideration when counseling patients.

Background: Evidence on the influence of nutrition on cancer risk is increasing with retrospective cohort studies. The American Cancer Society states that smoking, body mass index (BMI), poor nutrition, and excess alcohol consumption are directly linked to cancer occurrences, therefore some cancers may be preventable through lifestyle changes (American Cancer Society, 2016). In cancer genetic counseling sessions, patients are often inquiring about nutritional recommendations. A majority of …

Use Of Embark Database And An Active Learning Protocol In A High School Classroom, Landon Goodreau

Honors Theses

With advances in technology, personal genome sequencing has become more affordable than ever before. With this wealth of genetic information come new individualized approaches to medicine and pharmacology, along with moral, legal, and ethical issues to carefully consider. Yet studies suggest that most members of the general public do not have the genetic literacy required to understand the implications of genomic data. It is important that today’s students are able to grasp concepts relating to their own genome to make informed medical decisions in the future. Here I describe an active learning-based activity designed to enhance high school students’ understanding …

A Genomic Analysis Of Bobcat Populations In North America With A Comparison To The Canada Lynx: An Assessment Of Local Adaptation To Unique Ecoregions And Phylogeography, Jennifer C. Broderick

Electronic Theses and Dissertations

Bobcats (Lynx rufus) are an ecologically and genetically diverse species with a large contiguous range throughout North America. The species not only has a wide array of phenotypic variation compared to other mammals, but shows marked adaptability across ecozones with differing ecological influences. It is these various selective pressures in distinctive parts of the continent that have likely led to localized adaptations within the bobcat metapopulations. The species is also marked by its ability to maintain connectivity and populations in anthropogenically developed areas, an advantage it has over other felids, including its close relative the Canada lynx ( …

Multiplexed Crispr Libraries For Cancer Functional Genomics, Jintan Liu

Dissertations & Theses (Open Access)

High-throughput forward genetic screenings are invaluable tools to systematically explore genetic interactions and to link gene disruption with disease contexts. The adaptation of CRISPR/Cas9 has improved the sensitivity and specificity of functional screenings. Despite this advance, there remains a long-standing need to improve functional screenings with smaller and more versatile pooled libraries. Capitalizing on the inherent multiplexing capability of a class 2 CRISPR enzyme AsCpf1, we developed a multiplexed, high throughput screening strategy that has avoided the usual trade-off between library size and library penetration, allowing library minimization without sacrificing gene targeting efficiency. We optimized the AsCpf1 protein for functional …

Loss Of Caspase-8 Function In Combination With Smac Mimetic Treatment Sensitizes Head And Neck Squamous Carcinoma To Radiation Through Induction Of Necroptosis., Burak Uzunparmak

Dissertations & Theses (Open Access)

Caspase-8 (CASP8) is one of the most frequently mutated genes in Head and Neck Squamous Carcinomas (HNSCC), and mutations of CASP8 are associated with poor overall survival. The distribution of these mutations in HNSCC suggests that they are likely to be inactivating. Inhibition of CASP8 has been reported to sensitize cancer cells to necroptosis, a unique cell death mechanism. Here, we evaluated how CASP8 regulates necroptosis in HSNCC using cell line models and syngeneic mouse xenografts. In vitro, knockdown of CASP8 rendered HNSCCs susceptible to necroptosis induced by a second mitochondria-derived activator of caspase (SMAC) mimetic, Birinapant, when combined …