A Multi-Pronged Investigation To Identify Genes Affecting The Autoregulation Of Nodulation: Lasercapture Microdissection And The Barely Any Meristem Gene Family In Medicago Truncatula, Jacklyn Thomas

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The unique evolutionary adaptation of legumes for nitrogen-fixing symbiosis leading to nodulation is tightly regulated by the host plant. One pathway negatively regulates the number of nodules formed in response to the metabolic status of the shoot (carbon) and root (nitrogen); this long-distance systemic regulation is the autoregulation of nodulation (AON) pathway. AON is a root to shoot pathway that allows the plant to limit the number of nodules formed on roots. Central to the receptor complex in the shoots is a leucine-rich-repeat receptor-like kinase (LRR-RLK) called MtSUNN mutation of which results in plants with too many nodules. SUNN …

Large Genomes Assembly Using Mapreduce Framework, Yuehua Zhang

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Knowing the genome sequence of an organism is the essential step toward understanding its genomic and genetic characteristics. Currently, whole genome shotgun (WGS) sequencing is the most widely used genome sequencing technique to determine the entire DNA sequence of an organism. Recent advances in next-generation sequencing (NGS) techniques have enabled biologists to generate large DNA sequences in a high-throughput and low-cost way. However, the assembly of NGS reads faces significant challenges due to short reads and an enormously high volume of data. Despite recent progress in genome assembly, current NGS assemblers cannot generate high-quality results or efficiently handle large genomes …

Data-Driven Biomarker Panel Discovery In Ovarian Cancer Using Heterogenous Data Fusion On Exosomal And Non-Exosomal Microrna Expression Data, Paritra Mandal

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Ovarian cancer (OC) is an aggressive gynecological cancer and is currently the 5th leading cause of deaths due to cancer in women. High mortality rates are attributable to the vague pathogenesis and asymptomatic nature of the early stages. The development of a liquid biopsy for routine OC screening could help identify the disease at an earlier stage, making treatments more likely to be effective thereby increasing survival rates. Exosomes, small (~100nm) extracellular vesicles present in body fluids, have been shown to contain cancer-progression, onset, and related factors, making them good candidates for use in liquid biopsies. However, to date, only …

Clinical And Molecular Characterization Of Key Features Of Phelan-Mcdermid Syndrome And Potential Approaches To Clinical Trials, Bridgette Moffitt

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Phelan-McDermid Syndrome (PMS) is a rare neurodevelopmental disorder that involves chromosomal abnormalities on 22q13.3 and pathogenic variants with the SHANK3 gene. SHANK3 encodes for a critical scaffolding protein that is important in post-synaptic density, function, and maintenance of excitatory synapses. Haploinsufficiency of SHANK3 is considered the major cause of the neurological phenotype of PMS. These studies focused on further characterizing the neurologic phenotype of sleep disturbances in individuals with PMS.

Sleep disturbances are a common feature of PMS, however there is little research available on the subject matter. We reviewed the literature on sleep disturbances and used the Phelan-McDermid Syndrome …

Modeling Electrostatics In Molecular Biology And Its Relevance With Molecular Mechanisms Of Diseases, Mahesh Koirala

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Electrostatics plays an essential role in molecular biology. Modeling electrostatics in molecular biology is complicated due to the water phase, mobile ions, and irregularly shaped inhomogeneous biological macromolecules. This dissertation presents the popular DelPhi package that solves PBE and delivers the electrostatic potential distribution of biomolecules. We used the newly developed DelPhiForce steered Molecular Dynamics (DFMD) approach to model the binding of barstar to barnase and demonstrated that the first-principles method could also model the binding. This dissertation also reflects the use of existing computational approaches to model the effects of Single Amino Acid Variations (SAVs) to reveal molecular mechanisms …

Deciphering Medicago Truncatula Nodulation Using Time-Series Transcriptomic Data At Multiple Levels Of Resolution: Organ, Tissue, And Single-Cell, Yueyao Gao

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Use of chemical nitrogen fertilizers has environmental repercussions such as global warming, soil contamination, and aquatic eutrophication. Legumes form a symbiotic association with nitrogen-fixing bacteria (rhizobia sp.) to obtain atmospheric nitrogen through the formation of a specialized root structure called a nodule. Understanding the transcriptional reprogramming during nodulation is a powerful approach to decipher the genetic control of nodulation, with the goal of engineering nitrogen-fixing symbiosis into non-leguminous crops. This dissertation focuses on the analytics of bulk, tissue-specific, and single-cell RNA-seq technologies and how I utilized them to discover a collection of genes to aid in deciphering nodulation mechanisms in …

Heat Stress Response And Excystation In Entamoeba Histolytica, Irem Bastuzel

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Entamoeba histolytica is a water- and food-borne intestinal protozoan parasite that causes amoebiasis and liver abscess and is responsible for symptomatic disease in approximately 100 million people each year leading to ~ 100,000 deaths. The most common disease transmission follows the oral-fecal route, but it can also be transmitted by mechanical vectors such as animals carrying the amoeba from contaminated sources to water systems. In rare cases, disease transmission has been recorded in some patients in which men-to-men sexual practices were preferred.

The life cycle of E. histolytica starts through ingestion of infectious cysts, which are non-dividing, quadri-nucleated structures surrounded …

Genetics And Genomics Education Among Physician Assistants, Wesley Patterson

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This dissertation comprises five chapters to describe genetics and genomics education among physician assistant/associate (PA) students and practicing PAs. Chapter I introduces the gap in supply and demand of genetic services, the need for non-genetics healthcare providers to fill the gap, and the PA profession as a solution.

Chapter II is a rapid literature review that summarizes the available literature regarding genetics and genomics education for PAs. A paucity of literature exists to describe the current state of PA genetics-genomics education. The few studies retrieved describe content being taught in PA programs, the number of genetics-genomics contact hours PA students …

Characterization Of Mef2c-Related Disorders: Genotype, Phenotype, And Gene Pathway Dysregulation, Jessica Ann Cooley Coleman

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MEF2C­-related disorders are characterized by intellectual disability, developmental delay, lack of speech, seizures, stereotypic movements, hypotonia, and brain abnormalities and are caused by pathogenic alterations involving the MEF2C gene. Despite published cases, MEF2C­-related disorders are difficult to recognize clinically. These studies sought to further characterize MEF2C­-related disorders by investigating the genotypes, phenotypes, and gene functions (or dysfunctions) associated with the disorder.

Tremors have been reported in some patients with MEF2C­-related disorders, but the concept of tremors has been complicated by vague definitions and numerous categorization methods. We performed a concept analysis following the Walker and Avant …

Identification Of Genetic Factors Underlying Megaesophagus And Startle Disease In Dogs, Sarah M. Bell

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Dogs provide an excellent model for human hereditary disease research; thus, the development of canine genomic tools has been prioritized in recent years. Today, SNP arrays, multiple genome assemblies, and multi-breed reference panels containing whole genome resequencing (WGS) data from hundreds of canids are available to facilitate genome-wide genotyping in the dog. Herein, a variety of genome-wide techniques are employed to identify the genetic factors underlying congenital idiopathic megaesophagus (CIM) in two breeds, German shepherd dogs (GSDs) and Great Danes, and startle disease in Spanish greyhounds.

CIM is a complex canine esophageal motility disorder characterized by ineffective peristalsis and esophageal …

Effects Of Continuous In Situ Low-Dose Ionizing Radiation On Microorganisms, Molly E. Wintenberg

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Precise detection and monitoring of nuclear fuel cycle, enrichment, and weapon development activities are critical for supporting warfighter preparation in chemical, biological, radiological, nuclear, and explosives (CBRNE) operations, clandestine activities, and nuclear compliance. A biological sensing system could serve as an alternative to traditional detection methods by using organic material naturally present in the environment to discreetly detect residual trace nuclear material. Microorganisms provide an optimal platform for an alternative sensing system; however, their response to low levels of ionizing radiation is poorly characterized. Combining the power of next-generation sequencing and transcriptomic analysis, this dissertation takes an approach to obtain …

Identification Of Biomarker Systems Of Autism Spectrum Disorder And Uterine Cancer, Allison Hickman

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Complex diseases and disorders pose a challenge to scientists due to their variable and often inconsistent genetic and environmental underpinnings across affected individuals. Because of this variability, large condition-specific datasets and corresponding analytical tools and approaches are being curated as resources to investigate potential genetic trends in complex diseases and disorders. In this Dissertation, I used DNA- and RNA-based resources to discover polygenic biosignatures associated with Autism Spectrum Disorder (ASD) or uterine cancer. To explore the intersection of small-effect common DNA variants and regulation in ASD, I discovered and analyzed trends in allelic associations at eQTLs within ASD-affected individuals. Association …

Genetic And Mirna Transcriptomic Analysis Of Autoregulation Of Nodulation Signaling In Medicago Truncatula, Diptee Chauligain

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Legumes can source nitrogen from the air through biological nitrogen fixation inside root nodules formed in a symbiosis with rhizobia. A complex root-to-shoot-to-root signaling pathway called Autoregulation of Nodulation (AON) controls the number of nodules formed depending on the plant’s nitrogen requirements. In Medicago truncatula, the MtSUNN receptor complex in the shoot binds to the root-generated AON signals, peptides called MtCLEs, resulting in downregulation of miR2111 expression in the shoot, with the effect of decreased transport of miR2111 to the roots. Decreased miR2111 levels in the roots then cause an increase in transcript levels of the miR2111 targets MtTML1 …

Development Of New Bioinformatic Approaches For Human Genetic Studies, Jose Andres Guevara Coto

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The development of bioinformatics methods for human genetic studies utilizes the vast amount of data to generate new valuable information. Machine learning and statistical coupling analysis can be used in the study of human diseases. These diseases include intellectual disabilities (ID), prevalent in 1-3% of the population and caused primarily by genetics. Although many cases of ID are caused by mutations in protein-coding genes, the possible involvement of long non-coding RNAs (lncRNAs) in ID due to their role in gene expression regulation, has been explored. In this study, we used machine learning to develop a new expression-based model trained using …

Exploring The Interface Of Genetics, Genomics, And Older Adults, Scott Emory Moore

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This dissertation addresses the interface of genetics, genomics, and older adults through a collection of three manuscripts that examine genetic and genomic testing and decision-making across age groups. The dissertation offers evaluations of a new lens for decision-making in genetics and genomics, a contextualization of the differences and similarities of perceptions and beliefs that exist among age groups engaging in direct-to-consumer personal genetic testing (DTC PGT), an identification of two factors that influence the decision to engage in DTC PGT, and an expansion of the current applications of Protection Motivation Theory to include disclosure, finance, and advance directive-management behaviors related …

The Role The N-Terminal Domain Plays In Spidroin Assembly, Krystal Audrey Cadle

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One of the most interesting biomaterials known to man is spider silk. These fibers, composed primarily of protein, show beneficial mechanical and biological properties that have many uses in medical and industrial fields. Spider silk proteins (spidroins) are composed of three core components that consists of a C-terminal domain (CTD), repeat domain (R), and N-terminal domain (NTD). The NTD and CTD are highly conserved and are believed to form “multimeric strands” that make up spider silk. Although it is known that the NTD undergoes a conformational change that results in stable homodimer formation at acidic pH , the way in …

Tackling Adverse Environment—Molecular Mechanism Of Plant Stress Response And Biotechnology Tool Development, Ning Yuan

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Abiotic and biotic stresses such as drought, salt, nutrition starvation, and pathogen infection are major factors threatening our agricultural production. With the rapidly increasing population and limited arable land area, genetic engineering of crops for new products with more stable and higher yield than conventional cultivars under adverse environment provides a powerful new tool for use in developing novel GMOs (Genetically Modified Organisms) to feed the large population in the immediate future. To develop novel GMOs with enhanced performance under adverse conditions, we need first to understand molecular mechanisms underlying plant stress response. To better understand how signaling transduction pathway …

Microrna-Mediated Plant Development And Response To Environmental Stress In Perennial Grasses, Shuangrong Yuan

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World population will pass nine billion by 2050, while the agricultural land area will not increase dramatically in the coming decades. To meet the ever-increasing food demand, genetically engineered crops have been rapidly adopted for crop productivity. MicroRNAs have become increasingly attractive as targets in crop genetic modification due to their regulatory role in fine-tuning many essential biological processes. My research explores the potentials of microRNA528 (miR528) and miR396 for use in genetic modifications of the important agronomic traits of plant development, abiotic stress response, and/or flowering time control in an economically and environmentally important perennial monocot species, creeping bentgrass …

Phosphotransacetylase And Xylulose 5-Phosphate/Fructose 6-Phosphate Phosphoketolase: Two Eukaryotic Partners Of Acetate Kinase, Tonya Taylor

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Although acetate is a predominant metabolite produced by many eukaryotic microbes, far less attention has been given to acetate metabolism in eukaryotes than in bacteria and archaea. Acetate kinase (Ack), which catalyzes the reversible phosphorylation of acetate from ATP, is a key enzyme in bacterial acetate metabolism. Ack primarily partners with phosphotransacetylase (Pta), which catalyzes the generation of acetyl phosphate from acetyl-CoA, but can also partner with xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (Xfp), which produces acetyl phosphate from either xylulose 5-phosphate or fructose 6-phosphate. The Ack-Pta pathway, found primarily in bacteria, is also present in lower eukaryotes such as the green …

Genetic Dissection Of Neuromuscular Diseases Affecting Domestic Dogs, Caitlin Rinz

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The domestic dog, Canis familiaris, has a unique population structure that lends itself to the study of hereditary diseases. Purebred dogs populations are genetically isolated and as a result are affected by more than 400 naturally occurring diseases, many of which have human counterparts. In the last 15 years, dogs have emerged as a model for the study of human hereditary diseases, fueling the development of resources including a 7.6X coverage reference genome and single nucleotide polymorphism (SNP) genotyping arrays.

Congenital myasthenic syndrome (CMS) is a neuromuscular disorder of both humans and dogs in which transmission across the neuromuscular …

Conserved Noncoding Sequences Regulate Steady-State Mrna Levels In Arabidopsis Thaliana, Jacob Spangler

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Arabidopsis thaliana has undergone three whole genome duplications within its ancestry, and these events have dramatically affected its gene complement. Of the most recent whole genome duplication events (&alpha event), there remain 11,452 conserved noncoding sequences (CNSs) that have been retained proximal to &alpha duplicate gene pairs. As functional DNA elements are expected to diverge in sequence at a slower rate than nonfunctional DNA elements, the retained CNSs likely encode gene regulatory function. Within this dissertation I provide evidence for the regulatory role of CNSs within Arabidopsis thaliana. Using a collection of over 5,000 microarray RNA expression profiling datasets, I …

Characterization Of Two Type Iv Collagens Involved In Autosomal Recessive Hereditary Nephropathy, Keri Tabb

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The glomerular basement membrane (GBM) of the kidney is highly specialized and required for filtration of waste products from the bloodstream. One of the major structural and functional units of the GBM is a network composed of type IV collagen heterotrimers, or protomers. Early in development of the human and dog, an isoform switch occurs, and the α1α1α2 (IV) network found in the nascent GBM is replaced with α3α4α5 (IV) protomers. Mutations in any of the genes encoding proteins found in the mature GBM network may prevent protomer formation and cause a progressive disorder leading to end stage renal failure …

Analysis Of Genotype, Phenotype, And Age Progression In Phelan-Mcdermid Syndrome, Sara Sarasua

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Phelan-McDermid syndrome is a developmental disability syndrome associated with deletions of the terminal end of one copy of chromosome 22q13. The observed chromosomal aberrations include simple terminal deletions, interstitial deletions, deletions and duplications, and duplications without deletions. All patients have some degree of developmental disability and many also have hypotonia, autism, minor dysmorphic features, and seizures. I performed an epidemiological and cytogenetic investigation to better understand the etiology of Phelan-McDermid syndrome and to provide information to patients and their families, clinicians, and researchers investigating developmental disabilities. Deletions vary widely in size, from 60 kb to more than 9 Mb, but …

Molecular Genetics Of Nodule Number Regulation: Cloning, Characterization And Functional Studies Of The Root Determined Nodulator1 (Rdn1) Gene In Medicago Truncatula, Tessema Kassaw

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Nitrogen is critical to life. However, the majority of nitrogen on earth (in the atmosphere) is inert and unavailable to nearly all organisms. Metabolically diverse prokaryotes are the only organisms capable of fixing atmospheric nitrogen; rhizobia set up a symbiosis with legume plants allowing the plants to benefit from this ability. Since nodulation and the subsequent nitrogen fixation processes are energy intensive, the host plant must balance hosting of the rhizobia by limiting the number of nodules it forms through a mechanism called Autoregulation of Nodulation (AON). My study of mutants in the model legume Medicago truncatula defective in AON …

Family Cancer History And Pedigrees As A Public Health Intervention For Promoting Health And Preventing Prostate Cancer In African American Men, Holisa Wharton

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ABSTRACT
Prostate cancer is the most common cancer diagnosed in men and the second leading cause of cancer death among men in the United States. African-American men have substantially higher prostate cancer incidence and mortality than European-American men. It is unclear whether this incidence is due to acquired DNA changes (sporadic cancer) or if germline Mendelian genetics/genomics (inherited cancer) is the source of this health disparity. To explore this cause, the focus of this dissertation paper is family health history and hereditary prostate cancer. A family history tool is the most commonly used predictive instrument for hereditary prostate cancer. The …

Mapping Quantitative Trait Loci Associated With Resistance To Bacterial Spot (Xanthomonas Arboricola Pv. Pruni) In Peach, Nannan Yang

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Bacterial spot, caused by Xanthomonas arboricola pv. pruni (Xap), is a serious disease that can affect peach fruit quality and production worldwide. This disease causes severe defoliation and blemishing of fruit, particularly in areas with high rainfall, strong winds, high humidity and sandy soil. The molecular basis of its tolerance and susceptibility in peach is yet to be understood. To study the genetics of the peach response to Xap, an F2 segregating population between two peach cultivars, `Clayton', a resistant phenotype, and `O'Henry', which is very susceptible to Xap, was created. Phenotypic data for leaf and fruit response to Xap …

Genetic Engineering Of Turfgrass For Enhanced Performance Under Environmental Stress, Man Zhou

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Turfgrass species are agriculturally and economically important perennial crops that are susceptible to biotic stress (e.g. fungal pathogens) and abiotic stress (e.g. salinity and drought). Every year, environmental stress significantly influences turfgrass quality and production causing economic loss globally. My research explores the feasibility of using two novel transgenes - Penaeidin4-1 (Pen4-1) from the shrimp, Litopenaeus setiferus, and microRNA319a (miR319a) from the rice, Oryza sativa, to genetically engineer turfgrass for enhanced tolerance to environmental stress.
The antimicrobial peptide - Pen4-1 has been reported to possess in vitro antifungal and antibacterial activities against various economically important pathogens. In this study, two …

Population Genetics And Species Interactions: From Theory To Agro-Ecosystems, Cynthia Climer

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Population genetics is the study of allele frequency distributions and changes due to evolutionary processes such as selection, adaptation, genetic drift and gene flow to understand how these processes impact populations over space and time. Population genetics theory can be utilized to understand not only population level interactions, but also interactions among closely related species. In this dissertation I have utilized population genetics in three conceptually related projects. Utilizing genome-wide gene coding markers, I have tested the impact of population size changes on the genetic diversity of coding genes in a model system (Arabidopsis lyrata subsp. petraea). This study tests …

The Genetics Of Metal Uptake In Caulobacter Crescentus: Characterization Of Regulators And Identification Of Receptors, Leah Howell

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Caulobacter crescentus is an oligotrophic, Gram negative bacterium with a dimorphic lifecycle. It is a model system for cell cycle regulation and cellular development. Since C. crescentus resides primarily in freshwater, this microorganism can also serve as a model system for nutrient uptake by oligotrophic freshwater species. This study focused on TonB-dependent receptors and metal-dependent regulators in C. crescentus.
To maintain appropriate levels of iron within the cell, bacteria have evolved mechanisms to control iron uptake, storage, and use. In microbes, there are two protein families possessing members that accomplish this: Fur and Rrf2. In the C. crescentus genome, there …

Candidate Gene Studies In Patients With Autism Spectrum Disorder, Pamela Jackson

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Autism Spectrum Disorder is a grouping of disorders that range from the diagnosis of Asperger Syndrome to Autistic Disorder (formally known as autism). Attention Deficit Disorders and Pervasive Developmental Disorder-Not Otherwise Specified are also a part of this spectrum of disorders. Autism Spectrum Disorder affects one out of every 110 children and has a male to female ratio of 4:1. This has led to the need to identify genes that may be causative for this disorder.
Several genome-wide scans have been conducted and have identified locations in the human genome that may contain causative genes for Autism Spectrum Disorder. One …