Genetics and Genomics Commons^™

Neogene And Quaternary Events Shaped Diversification And Speciation In Bhutanese Rheophilic Fishes Of The Family Nemacheilidae (Cypriniformes) And Sisoridae (Siluriformes), Karma Wangchuk

Graduate Theses and Dissertations

Biogeography of the Himalayan region [to include the Qinghai-Tibetan Plateau (QTP)] evolved over a ~30M year span, catalyzed by the collision of the Indian and Eurasian plates. The resulting uplift produced major ecological and climatic effects, that in turn drove the diversification of biodiversity. As a result, the QTP is designated as a global biodiversity hotspot particularly vulnerable to cumulative climatic effects, including shrinking distributions, declining numbers, and local extinctions. Understanding how the biodiversity within the Himalaya/ QTP was established and maintained is a necessary first step in prioritizing conservation efforts.

Fishes in global montane regions, such as the Himalaya, …

Characterization Of Adiposity And Inflammation Genetic Pleiotropy Underlying Cardiovascular Risk Factors In Hispanics., Mohammad Yaser (Anwar)

Electronic Theses and Dissertations

The observed overlap between genetic variants associated with both adiposity and inflammatory markers suggests that changes in both adiposity and inflammation could be partially mediated by common pathways. The pervasive but sparsely characterized “pleiotropic” genetic variants associated with both adiposity and inflammation have been hypothesized to provide insight into the shared biology. This study explored and characterized the genetic pleiotropy underpinning adiposity and inflammation using genetic and phenotypic observations from the Cameron County Hispanic Cohort (CCHC). A total of 3,313 samples and >9 million single nucleotide polymorphisms (SNPs) were examined in this study. Mixed model genome-wide association studies (GWAS) were …

Epigenetic Regulation Of Prostate Cancer, Ruixin Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Prostate cancer is (PCa) the second leading cause of cancer death in males in the United State, with 174,650 new cases and 31,620 deaths estimated in 2019. It has been documented that epigenetic deregulation such as histone modification and DNA methylation contributes to PCa initiation and progression. EZH2 (enhancer of zeste homolog 2), the catalytic subunit of the Polycomb Repressive Complex (PRC2) responsible for H3K27me3 and gene repression, has been identified as a promising target in PCa. In addition, overexpression of other epigenetic regulators such as DNA methyltransferases (DNMT) is also observed in PCa. These epigenetic regulators undergo extensive post-translational …

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 …

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 …

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

Dissertations and 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 …

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

Dissertations and 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 …

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

Dissertations and 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 …

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 and 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 …

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

Dissertations and 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 …

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

Dissertations and 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, …

Polerovirus Genomic Variation And Mechanisms Of Silencing Suppression By P0 Protein, Natalie M. Holste

School of Biological Sciences: Dissertations, Theses, and Student Research

The family Luteoviridae consists of three genera: Luteovirus, Enamovirus, and Polerovirus. The genus Polerovirus contains 32 virus species. All are transmitted by aphids and can infect a wide variety of crops from cereals and wheat to cucurbits and peppers. However, little is known about how this wide range of hosts and vectors developed. In poleroviruses, aphid transmission and virion formation is mediated by the coat protein read-through domain (CPRT) while silencing suppression and phloem limitation is mediated by Protein 0 (P0)—a protein unique to poleroviruses. P0 gives poleroviruses a great advantage amongst plant viruses and diversifies polerovirus species, but the …

The Design And Validation Of A Qpcr-Based Approach To Cell Quantification Of Fungal-Algal Symbioses, Isabelle Katherine Garlotte

Honors Theses

Symbiotic relationships are extremely common in virtually all species. These relationships between organisms, particularly mutualistic symbioses, can have an incredibly large impact and can greatly affect the evolution of the species involved. Of particular interest is the suspected mutualistic relationship between green algae and fungi that may hold key evidence of how terrestrial plants evolved. In this experiment we established a method of quantifying the cells of each species involved in these symbioses through qPCR analysis to determine if the relationships are truly mutualistic. We developed a system for using DNA copies as a proxy for cell count in co-cultures …

Bayesian Variable Selection Methods For Genome-Wide Association Studies With Categorical Phenotypes, Benazir Rowe

UNLV Theses, Dissertations, Professional Papers, and Capstones

Genome-wide association studies (GWAS) attempt to find the associations between genetic markers and studied traits (phenotypes). The problem of GWAS is complex and various methods have been developed to approach it. One of such methods is Bayesian variable selection (BVS). We describe the BVS methods in detail and demonstrate the ability of BVS method Posterior Inference via Model Averaging and Subset Selection (piMASS) to improve the power of detecting phenotype-associated genetic loci, potentially leading to new discoveries from existing data without increasing the sample size.

We present several ways to improve and extend the applicability of piMASS for GWAS. The …

Novel Polymorphisms Of Zrsr2 And Gpm6b Gene Homologs And Their Use In Sex Identification Of Bovine And Porcine Species, Evan K. Peterson

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Accurate and cost-effective PCR based sex identification is important in animal production because it gives producers the ability to determine the sex of embryos prior to transfer, saving time and money. The most efficient PCR sex identification assays work by using a single primer pair to amplify a specific target region located on the Y-chromosome and a second, separate target region on the X-chromosome.

This thesis reports the design of two novel assays. The first assay was designed to target the Zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2 (ZRSR2) gene found on the X-chromosome and its Y-chromosome …

Assessment Of Genetic Diversity In Largetooth Sawfish, Pristis Pristis, Populations Over The 20th Century, Ann Fearing

Master's Theses

The Critically Endangered Largetooth Sawfish, Pristis pristis, experienced global declines in range and abundance over the past century and Australia is now their last stronghold. This research aimed to understand whether these declines have been accompanied by a reduction in levels of genetic diversity. Using P. pristis tissue samples sourced from natural history specimens, three fragments (616-bp, 386-bp, 141-bp) in the mitochondrial DNA (mtDNA) control region were PCR-amplified. At each fragment, significant genetic structure was found in P. pristis overall (Φ_ST=0.946, N=9; 0.813, N=54; 0.771, N=99). The Indo-West Pacific and Atlantic/Eastern Pacific each harbor genetically distinct lineages of …

Development And Use Of An Environmental Dna Tool To Monitor Recovery Of The Critically Endangered Smalltooth Sawfish, Pristis Pectinata, In The Northwest Atlantic, Ryan N. Lehman

Master's Theses

The Critically Endangered Smalltooth Sawfish, Pristis pectinata, was once common in the tropical and subtropical waters of the Atlantic Ocean; however, following global declines in range and abundance over the past century, individuals were restricted to the waters of south and southwest Florida (SWFL) by about the 1980’s. Recently, public encounter reports have emerged in historically occupied habitats in United States waters, suggesting individuals are present in, or re-occupying, these areas, although the status of P. pectinata outside of SWFL is not currently well understood. Targeted environmental DNA (eDNA) surveys were chosen to assess the occurrence of P …

Estimation Of Additive And Dominance Effects Of A Mutant Glutathione S-Transferase Gene On Anthocyanin And Proanthocyanidin Content In Muscadine Grape (Vitis Rotundifolia), Autumn Brown

Horticulture Undergraduate Honors Theses

The skin color of muscadine grapes (Vitis rotundifolia) is typically classified as black or bronze. A glutathione S-transferase, VrunGST4, has been identified as a candidate gene for berry skin color in muscadine grapes. A molecular marker was developed within VrunGST4 to distinguish between muscadine genotypes (cultivars and selections) with bronze (T:T), heterozygote black (C:T), and homozygote black (C:C) berries. The objectives of this study were to determine whether there was a correlation between berry skin color and total anthocyanin content and to calculate additive and dominance effects of VrunGST4 in determining total anthocyanins in the berries and …

Whole Genome Sequencing Identified A 16 Kilobase Deletion On Eca13 Associated With Distichiasis In Friesian Horses, E. A. Hisey, H. Hermans, Z. T. Lounsberry, F. Avila, R. A. Grahn, K. E. Knickelbein, S. A. Duward-Akhurst, M. E. Mccue, Theodore S. Kalbfleisch, M. E. Lassaline, W. Back, R. R. Bellone

Veterinary Science Faculty Publications

BACKGROUND: Distichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait.

RESULTS: A genome wide association study (GWAS) …

A Primary Human T-Cell Spectral Library To Facilitate Large Scale Quantitative T-Cell Proteomics., Harshi Weerakoon, Jeremy Potriquet, Alok K Shah, Sarah Reed, Buddhika Jayakody, Charu Kapil, Mukul K Midha, Robert L Moritz, Ailin Lepletier, Jason Mulvenna, John J Miles, Michelle M Hill

Articles, Abstracts, and Reports

Data independent analysis (DIA) exemplified by sequential window acquisition of all theoretical mass spectra (SWATH-MS) provides robust quantitative proteomics data, but the lack of a public primary human T-cell spectral library is a current resource gap. Here, we report the generation of a high-quality spectral library containing data for 4,833 distinct proteins from human T-cells across genetically unrelated donors, covering ~24% proteins of the UniProt/SwissProt reviewed human proteome. SWATH-MS analysis of 18 primary T-cell samples using the new human T-cell spectral library reliably identified and quantified 2,850 proteins at 1% false discovery rate (FDR). In comparison, the larger Pan-human spectral …

The Proteasome Activators Blm10/Pa200 Enhance The Proteasomal Degradation Of N-Terminal Huntingtin., Azzam Aladdin, Yanhua Yao, Ciyu Yang, Günther Kahlert, Marvi Ghani, Nikolett Király, Anita Boratkó, Karen Uray, Gunnar Dittmar, Krisztina Tar

Articles, Abstracts, and Reports

The Blm10/PA200 family of proteasome activators modulates the peptidase activity of the core particle (20S CP). They participate in opening the 20S CP gate, thus facilitating the degradation of unstructured proteins such as tau and Dnm1 in a ubiquitin- and ATP-independent manner. Furthermore, PA200 also participates in the degradation of acetylated histones. In our study, we use a combination of yeast and human cell systems to investigate the role of Blm10/PA200 in the degradation of N-terminal Huntingtin fragments (N-Htt). We demonstrate that the human PA200 binds to N-Htt. The loss of Blm10 in yeast or PA200 in human cells results …

Evaluation Of The Xpert Carba-R Nxg Assay For Detection Of Carbapenemase Genes In A Global Challenge Set Of Pseudomonas Aeruginosa Isolates, Fred C. Tenover, Christian M. Gill, Tomefa E. Asempa, Isabella A. Tickler, Caitlin M. Dela Cruz, David P. Nicolau

Biology Faculty Publications

The growing prevalence and diversity of carbapenemase producers among carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates warrants an expansion of detection capabilities. The purpose of this study was to evaluate the performance of the commercially available Xpert Carba-R (Carba-R) and the research-use-only Xpert Carba-R NxG (Carba-R NxG) in a global collection of P. aeruginosa. The challenge set included 123 P. aeruginosa clinical isolates from 12 countries. Isolates were previously categorized via PCR or whole-genome sequencing. Carbapenemase classes tested include VIM, IMP, NDM, SPM, KPC, and GES. Non-carbapenemase (non-CP)-harboring isolates were also tested (negative control). Isolates were tested using the Carba-R NxG and …

Pathway-Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Jem Bagchee-Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

No abstract provided.

A Pilot Study Comparing The Efficacy Of Lactate Dehydrogenase Levels Versus Circulating Cell-Free Micrornas In Monitoring Responses To Checkpoint Inhibitor Immunotherapy In Metastatic Melanoma Patients., Matias A Bustos, Rebecca Gross, Negin Rahimzadeh, Hunter Cole, Linh T Tran, Kevin Tran, Ling Takeshima, Stacey L Stern, Steven O'Day, Dave Hoon

Articles, Abstracts, and Reports

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients' disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients' responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 …

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 …

The Effect Of Fcgammariia Polymorphisms On Dengue Outbreak Severity, Leah Darwin, Richard V. Clarke

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Genetic Polymorphism Of Bitter Taste Perception In Tempe, Arizona And Its Association With Nutritional Status, Daniel Woodley, Benjamin Cabrera

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Spatio-Temporal Dynamics Of Fungal Communities And Their Effects On Plants, Kel Cook

Biology ETDs

Fungi perform several critical functions in the environment. Spatiotemporal distributions of fungal communities will mediate when and where these functions happen and how they vary across the landscape. I first explored tropical tree canopy fungal community variation at small spatial scales and documented near total turnover of fungi across sub-meter distances and among adjacent substrates. The second chapter analyzed fungal turnover over the course of three years, where community stability was driven primarily by abundant fungi. In the third chapter, I tested effects of the environment, including host plant and habitat, on canopy fungal communities and found only small effects, …

A Comprehensive Spectral Assay Library To Quantify The Escherichia Coli Proteome By Dia/Swath-Ms., Mukul K Midha, Ulrike Kusebauch, David Shteynberg, Charu Kapil, Samuel L Bader, Panga Jaipal Reddy, David S Campbell, Nitin Baliga, Robert L Moritz

Articles, Abstracts, and Reports

Data-Independent Acquisition (DIA) is a method to improve consistent identification and precise quantitation of peptides and proteins by mass spectrometry (MS). The targeted data analysis strategy in DIA relies on spectral assay libraries that are generally derived from a priori measurements of peptides for each species. Although Escherichia coli (E. coli) is among the best studied model organisms, so far there is no spectral assay library for the bacterium publicly available. Here, we generated a spectral assay library for 4,014 of the 4,389 annotated E. coli proteins using one- and two-dimensional fractionated samples, and ion mobility separation enabling deep proteome …

Identification Of Novel Host Genes Required For Antiviral Immunity And Viral Genome Replication In C. Elegans, Fei Meng

LSU Doctoral Dissertations

RNA interference (RNAi) is a wide-spread gene silencing mechanism that control diverse biological functions and triggered by small interfering RNAs (siRNAs) processed from the viral genome or its replication intermediates. Mechanistic studies of antiviral RNAi in Caenorhabditis elegans has led to the identification of several critical factors involved in the process. As a result, whether antiviral RNAi requires additional novel genes remains to be an open question.

Viruses are intracellular parasites that rely on host products for reproduction. Disrupting their interaction with host factors can significantly compromise their replication and keep them under control. Thus, identification of host genes …