Genetics and Genomics Commons^™

Ndrg1 And Myelin-Related Disease: Alcoholism And Chemotherapy-Induced Neuropathy, Guy Harris

Theses and Dissertations

Alcohol use disorder (AUD) is a prevalent neuropsychiatric disease with profound health, social, and economic consequences. With an estimated 50% heritability, identifying genes that engender risk and contribute to the underlying neurobiological mechanisms represents an important first step in developing effective treatments. Gene expression studies are an important source of candidate genes for studying AUD, providing windows into the molecular machinery engaged by the brain in response to ethanol. Our laboratory has implicated N-myc down-regulated gene 1 (Ndrg1) as a potential candidate gene that modulates ethanol-induced changes in myelin-related gene expression and acute sensitivity to ethanol. Analysis of …

Transcriptomic Profiling Of Postmortem Prefrontal Cortex And Nucleus Accumbens From Chronic Alcohol Abusers., Eric S. Vornholt

Theses and Dissertations

Alcohol use disorder (AUD) is a debilitating psychiatric illness that develops from a combination of genetic and environmental factors. While it is well documented that AUD is heritable, the shift from recreational alcohol use to abuse/dependence is poorly understood. In this dissertation, using postmortem brain tissue from individuals with alcohol dependence (AD), we profiled the genome-wide expression of circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) to better understand the impact of gene expression on the development of AUD. To achieve this, we performed two independent studies that explore transcriptome differences between AD cases and controls. The first of …

The Origin And Evolution Of Flower Characters In Angiosperms With A Case Study On The Genetic Basis Of Zygomorphic Corolla Development In Bee And Hummingbird Pollinated Species Of Schizanthus (Solanaceae), Ghadeer Bukhari

Theses and Dissertations

This Ph.D. dissertation investigates two main projects separated into two chapters, one for each. The first chapter explores the evolution of flowering plants (angiosperms), a macro-scale study. The second project is on a micro-scale that focus on exploring the genes that regulate the similarities and the differences of flower morphology reflecting their different pollination syndromes in two species of Schizanthus (Solanaceae), i.e., S. pinnatus, a bee-pollinated flower, and S. grahamii, a hummingbird- pollinated flower.

In the first chapter, I used floral diagrams to study the origin and the evolution of floral traits in angiosperms, a new set of morphological data …

Novel Strategies To Overcome Carboplatin Resistance In Triple Negative Breast Cancer Using Patient Derived Xenografts, Mohammad A. Al Zubi

Theses and Dissertations

Triple-negative breast cancer (TNBC) patients have a poor prognosis and rely on chemotherapeutic treatment as standard of care. Often, they develop chemotherapy resistance, which leaves them without more therapeutic options, like targeted therapy. New models have been developed to test targeted inhibitors in human tumors, and they are known as patient-derived xenografts (PDX). These tumors are obtained from patients, then established and maintained in mice where they areused for tumor studies. In this work, we characterized 14 PDXs for their primary tumor growth rate and investigated metastatic propensity using spontaneous and experiment metastasis models. We utilized RNA-sequencing to characterize contributions …

The Gamma-Globin Repressors Klf1, Bcl11a, And Mbd2: Knowledge Gaps In The Literature, Lauren Nufer

Theses and Dissertations

β-hemoglobinopathies affect millions of people around the world. Research into treatments for these conditions has focused on methods to increase γ-globin expression, because increased levels of γ-globin ameliorate or reduce the severity of symptoms. As more and more studies have been done, a few proteins have emerged as having crucial roles in γ-globin repression and have been established as key genes to study. These are Krüppel-like factor 1 (KLF1), B cell CLL/lymphoma 11A (BCL11A), and methyl binding domain 2 (MBD2). The roles of these proteins in the switch from fetal to adult hemoglobin and in repressing γ-globin expression have been …

Analysis Of Genetic Structure And Pathogen Dynamics Of Ixodes Scapularis In Southwestern Virginia, Leemu Jackson

Undergraduate Honors Theses

Ixodes scapularis, or the blacklegged tick, is the primary vector of Borrelia burgdorferi. This pathogen is the causative agent of Lyme disease, the most common vector-transmitted disease in the United States. Although I. scapularis is distributed throughout the eastern U.S., Lyme disease is only considered endemic in the northeastern region of the country. Prior to 2007, Lyme disease was uncommon in Virginia, but since then cases of Lyme disease have increased dramatically with a hotspot forming in the Roanoke-Blacksburg area. The purpose of the current study was to determine whether B. burgdorferi prevalence and the genetic structure of I. …

Analysis Of Two Maize Mutations That Arose After Exposure To Radiation From A Plutonium-Beryllium Source And Developing Molecular Markers For Antimorph Aei1-5180, An Alternative To Aei To Increase Amylose Content In Maize Endosperm, Prameela Awale

Electronic Theses and Dissertations

This thesis consists of two independent projects dealing with two different aspects of maize. The first project is about the maize reproduction, where we try to uncover the candidate genes of two mutations that affect pollen viability and successful fertilization. The second project is about maize endosperm starch, where we developed molecular markers to characterize a mutant allele that knocks a major starch branching enzyme in maize.

Analysis of two maize mutations that arose after exposure to radiation from a plutonium-beryllium source
Maize is a monoecious and diclinous plant. Sexual reproduction takes place by the fusion of haploid male and …

Crispr/Cas9 Whole Genome Screens Reveal Novel Regulators Of Endocytic Processes In Macrophages, Jared Wollman

Electronic Theses and Dissertations

Macrophages maintain tissue homeostasis by identifying and eliminating threats within their tissue microenvironment. Pattern recognition receptors allow macrophages to recognize and internalize specific ligands while macropinocytosis allows the internalization of all extracellular solutes from their environment. Without pattern recognition receptors, pathogens may grow unchecked if they cannot be detected, and without macropinocytosis, macrophages struggle to detect and move around their environment. This thesis presents the results of CRISPR/Cas9 whole-genome screens used to identify the regulators of both endocytosis (Chapter 2) and macropinocytosis (Chapter 3). In Chapter 2, we report genes regulating dextran uptake in primary murine macrophages and reveal Mrc1-mediated …

A Basic Ddradseq Two‐Enzyme Protocol Performs Well With Herbarium And Silica‐Dried Tissues Across Four Genera, Ingrid E. Jordon‐Thaden, James B. Beck, Catherine A. Rushworth, Michael D. Windham, Nick Diaz, Jason T. Cantley, Christopher T. Martine, Carl J. Rothfels

Biology Faculty Publications and Presentations

PREMISE: The ability to sequence genome-scale data from herbarium specimens would allow for the economical development of data sets with broad taxonomic and geographic sampling that would otherwise not be possible. Here, we evaluate the utility of a basic double-digest restriction site–associated DNA sequencing (ddRADseq) protocol using DNAs from four genera extracted from both silica-dried and herbarium tissue.

METHODS: DNAs from Draba, Boechera, Solidago, and Ilex were processed with a ddRADseq protocol. The effects of DNA degradation, taxon, and specimen age were assessed. RESULTS: Although taxon, preservation method, and specimen age affected data recovery, large phylogenetically informative data sets were …

Patterns Of Epiphytic Lichen Abundance On Aspen Stands In Proximity To Roads Of Varying Vehicular Traffic, D. Aragon, C. Castillo, J. Moffroid, G. Thomas

Aspen Bibliography

Although present in nearly any wild space with available moisture and on a wide variety of substrates, lichen, and its importance as a bioindicator for an ecosystem, is often overlooked. As air pollution becomes a greater concern for flora, fauna, and even humans, the story told by lichen growth becomes more useful as we try to make sense of the downstream effects of anthropogenic contributions to poor air quality. One such human-driven pollutant is the level of emissions that result from vehicular travel. The Jackson Hole area has experienced a large increase in vehicular traffic in the past five to …

Pando Clone Recovery: Repeat Photos 2014-2019, Mary O'Brien, Marc Coles-Ritchie

Aspen Bibliography

The world's largest known clone of aspen (Populus tremuloides), called the "Pando Clone" is located in the Fishlake National Forest in central Utah. For many decades, significant pressure from ungulate (deer and cattle) browsing has prevented growth of young aspen stems in to trees that would replace the mature trees as they die of natural causes. There has been concern that this impressive 104-acre Pando Clone could be lost altogether due to the excessive browsing of young aspen stems. In 2013, 16 acres of this clone were fenced to exclude all ungulates (deer and cattle) so that recovery …

Aging Induces B Cell Defects And Decreased Antibody Responses To Influenza Infection And Vaccination, Daniela Frasca, Bonnie B. Blomberg

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function.

Results: Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure …

The Effects Of Parental Factors And Personal Attributes On Birth Control Use Under The Genetic Influences Of 5-Httlpr Among Adolescents, Hyun-Jin Cho

Legacy Theses & Dissertations (2009 - 2024)

The purpose of this study was (a) to examine relationships between parental influences and personal attributes on birth control use and (b) to identify genetic influences on such relationships by comparing the frequencies of common genetic variants—short allele vs. long allele—in 5-HTTLPR among adolescents (N = 5,852). Data from the Wave 1 and Wave 4 of the National Longitudinal Study of Adolescent Health were used to examine the birth control use of adolescents who were in 7th through 12th grade in 1994–1995. Multi-group Structural Equation Modeling analyses were used to identify the relationship among factors. Results did not find significant …

Role Of Microrna-483 In Pancreatic Β-Cells, Jackson Waugh

Dissertations, Master's Theses and Master's Reports

Insulin is an essential hormone produced by β-cells in the pancreas. The release of insulin is tightly regulated in healthy people in order to control blood sugar level in our body. However, people with Type 2 Diabetes have insufficient insulin secretion from pancreatic β-cells, leaving to high blood sugar (hyperglycemia) and β-cell failure. microRNAs (miRNAs or miR) are newly discovered small regulatory molecules and have emerged as important regulator of cell growth, differentiation, and organ function. Altered miRNA function has been implicated in the pathogenesis of a variety of human disease, including diabetes. In this report, we focus on dissecting …

Genome-Wide Sequence Analyses Of Ethnic Populations Across Russia, Daria V. Zhernakova, Vladimir Brukhin, Sergey Malov, Taras K. Oleksyk, Klaus Peter Koepfli, Anna Zhuk, Pavel Dobrynin, Sergei Kliver, Nikolay Cherkasov, Gaik Tamazian, Mikhail Rotkevich, Ksenia Krasheninnikova, Igor Evsyukov, Sviatoslav Sidorov, Anna Gorbunova, Ekaterina Chernyaeva, Andrey Shevchenko, Sofia Kolchanova, Alexei Komissarov, Serguei Simonov, Alexey Antonik, Anton Logachev, Dmitrii E. Polev, Olga A. Pavlova, Andrey S. Glotov, Vladimir Ulantsev, Ekaterina Noskova, Tatyana K. Davydova, Tatyana M. Sivtseva

Biology Faculty Articles

The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation. Here we report the characterization of genome-wide variation of 264 healthy adults, including 60 newly sequenced samples. People of Russia carry known and novel genetic variants of adaptive, clinical and functional consequence that in many cases show …

Host Transcriptional Response To Persistent Infection With A Live-Attenuated Porcine Reproductive And Respiratory Syndrome Virus Strain, Jayeshbhai Chaudhari, Chia-Sin Liew, Aspen M. Workman, Jean-Jack Riethoven, David J. Steffen, Sarah Vitosh-Sillman, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. To investigate the mechanisms of PRRSV persistence, we performed a transcriptional analysis of inguinal lymphoid tissue collected from pigs experimentally infected with an attenuated PRRSV strain at 46 days post infection. A total of 6404 differentially expressed genes (DEGs) were detected of which 3960 DEGs were upregulated and 2444 DEGs were downregulated. Specifically, genes involved in innate immune responses and chemokines and receptors associated with T-cell homing to lymphoid tissues were down regulated. As a result, homing of virus-specific …

Geographic Distribution Of Bacillus Thuringiensis Cry1f Toxin Resistance In Western Bean Cutworm (Lepidoptera: Noctuidae) Populations In The United States, Brad S. Coates, Craig A. Abel, Katharine A. Swoboda-Bhattarai, Debra E. Palmquist, Débora Goulart Montezano, Sarah N. Zukoff, Yangzhou Wang, Jeffery D. Bradshaw, Christina D. Difonzo, Elson Shields, Kelley J. Tilmon, Thomas Hunt, Julie A. Peterson

West Central Research and Extension Center, North Platte

The western bean cutworm (WBC), Striacosta albicosta (Lepidoptera: Noctuidae), can be a severe pest of transgenic corn in the western Plains and Great Lakes regions of North America, including on hybrids expressing the Bacillus thuringiensis (Bt) Cry1F toxin. The level and geographic distribution of Cry1F resistance are not completely known. Neonate S. albicosta from 10 locations between Nebraska and New York state were subjected to dose–response trypsin-activated native Cry1F toxin overlay bioassays. In 2017, the mean estimated lethal concentration causing 50% larval mortality (LC50) ranged from 15.1 to 18.4 μg Cry1F cm−2, and were not significantly different among locations. In …

Assessing Pepper Pungency By Using Rt-Qpcr To Measure Pun1 Expression, Sam Blechman

Williams Honors College, Honors Research Projects

Capsicum spp. evolved capsaicin as a chemical defense to deter consumption of its fruits by mammals, allowing birds to disperse the seeds throughout a greater range. The Pun1 locus codes for a capsaicin synthase (CS), the expression of which is a direct determinant of capsaicin accumulation. RT-qPCR was used to measure low-abundance mRNA transcripts. The aim of this study was to use RT-qPCR to measure Pun1 expression in cDNA synthesized from total RNA extracted from placental tissue of Capsicum annuum and chinense cultivars. A secondary aim was to troubleshoot the protocol designed for this experiment to verify the efficacy of …

Structural Biology Of The Enterovirus Replication-Linked 5'-Cloverleaf Rna And Associated Virus Proteins, Steven M. Pascal, Ravindranath Garimella, Meghan S. Warden, Komala Ponniah

Chemistry & Biochemistry Faculty Publications

Although enteroviruses are associated with a wide variety of diseases and conditions, their mode of replication is well conserved. Their genome is carried as a single, positive-sense RNA strand. At the 5′ end of the strand is an approximately 90-nucleotide self-complementary region called the 5′ cloverleaf, or the oriL. This noncoding region serves as a platform upon which host and virus proteins, including the 3B, 3C, and 3D virus proteins, assemble in order to initiate replication of a negative-sense RNA strand. The negative strand in turn serves as a template for synthesis of multiple positive-sense RNA strands. Building on structural …

Temperate Eurasian Origins Of Hawaiian Chenopodium (Amaranthaceae) Plus Description Of A New Species Endemic To Moloka‘I, Jason T. Cantley, Angela J. Mcdonnell, J Branson, S R. Long, W Garnett, Christopher T. Martine

Faculty Journal Articles

Chenopodium taxa of Hawai‘i are tetraploids distinguished from other members of the circumglobally distributed genus by minute morphological characters. Because of these reasons, the geographic origin of Hawaiian Chenopodium has remained unclear. Across the Hawaiian Archipelago, Chenopodium taxa are morphologically variable and grow in highly disparate xeric habitats, especially in terms of precipitation, temperature, wind, salt spray, and solar irradiation. Habitats include dry subalpine shrublands, sandy beach strand of atolls in the Northwest Hawaiian Islands, dry forests, and precipitously tall sea cliffs of northwestern Moloka‘i. From the Moloka‘i sea cliffs, which are battered by high energy winds, salt spray, and …

Investigating The Effect Of Ethanol On Wnt7a And Its Potential Implications In Fetal Alcohol Spectrum Disorder, Erika Lytle

Honors Undergraduate Theses

Fetal Alcohol Spectrum Disorders (FASDs), are caused by maternal alcohol consumption during pregnancy [3]. FASD encompasses a wide variety of cardiac and neural anomalies, while also associated with improper limb development, abnormal craniofacial features, problems within the central nervous system (CNS), and disabilities in learning and communication. Gene-regulating FASDs have not been well studied during the crucial phases of early embryonic development. Genes within the Wnt/Beta-catenin pathway control a vast amount of embryonic developmental processes. Among them is the Wnt7a gene, a significant downstream gene regulator which positively controls neural stem cell proliferation and cardiomyocyte differentiation on a large scale …

Regulation Of The Egfr Epigenetic Landscape In Glioblastoma Multiforme, Anishaa Sivakumar

Honors Undergraduate Theses

Glioblastoma Multiforme (GBM) is the most lethal subtype of glioma (brain tumor), with a 5-year survival rate of merely 5.6% post diagnosis¹. The traditional study of glioblastoma has investigated the role of multiple genes in advancing its progression, including the upregulation of Epidermal Growth Factor Receptor (EGFR). However, there is at yet little research into the epigenetic factors that control EGFR, both in the precursor astrocytes and in glioblastomas themselves². EGFR and its regulation may play a significant role in the progression and development of GBM from astrocytes. Through modification of genomic pathways as observed in …

Association Between Maoa U Vntr Genetic Polymorphism And Aggression, Gender, And Race In Adolescents, Almaz Adair Johnson

Walden Dissertations and Doctoral Studies

A genetic polymorphism found in the upstream region of the monoamine oxidase A (MAOA) gene upstream variable number tandem repeat (u VNTR) has been shown to have an influence on aggression with mixed results. The purpose of this quantitative study was to examine the association between the u VNTR genetic polymorphism of the MAOA gene and aggression in an adolescent population 13–18 years of age. The conceptual framework was based on the biosocial model of antisocial behavior that indicates genes can influence aggressive behaviors with or without environmental influences. Data (N = 2506) from the National Longitudinal Adolescents and Adult …

Predicting Patterns Of Gene Family Evolution In Taxa With Similar Ecological Niches, Kim Vertacnik

Theses and Dissertations--Biology

To fully understand the genetic basis of adaptation, we need to know its predictability—the extent to which specific selective pressures and contexts can yield corresponding genetic changes. In particular, the repeated colonization of similar, specialized environments by different taxa is ideal for assessing the frequency of reoccurring changes in the same genes or functions. But compared to a growing body of literature on the convergent evolution of individual genes, far less is known about the repeatability of gene family evolution, where families (defined here as groups of genes that share sequence and functional similarity from common ancestry) can expand (gain …

Investigation Into The Roles Of Her9 And Capn5 During Retinal Development And Regeneration, Cagney Coomer

Theses and Dissertations--Biology

The formation of a healthy and functioning eye requires coordinated interactions between numerous signaling pathways and gene regulatory networks within the developing neural retina. Tight regulation of gene expression is required for cell specification and differentiation in this multilayered, light sensitive tissue. The photoreceptors are the light detecting cells of the retina, capable of functioning in both intense sunlight and dim light at night. When pigment cells of the photoreceptor outer segment are activated by light, a complex chain of events called phototransduction leads to the electrical signal cascade that is transmitted through the retina and ultimately to the brain …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Effects Of Thinning Regimes On Genetic Variation Of White Oak (Quercus Alba L.) In Upland Oak Forests Of Eastern Kentucky, Rachel Gayle Thunder

Theses and Dissertations--Forestry and Natural Resources

This research assesses the effects of silvicultural thinnings, varying in residual basal area and number of thinnings, on genetic diversity and relatedness of white oak (Quercus alba L.). The objectives were to (1) develop microsatellite DNA markers (simple sequence repeats, SSRs) for assessing the genetic diversity of white oak and (2) determine if thinnings significantly change the degree of diversity and relatedness in white oak stands. For objective 1, 84 primer pairs from previously predicted genomic SSRs of white oak were evaluated for consistent PCR amplification and polymorphism. Twenty of the 84 primer pairs amplified consistently and were confirmed …

Identification And Characterization Of Epigenetic Regulators In The Yellow Fever Mosquito, Aedes Aegypti, Shankar C. R. R. Chereddy

Theses and Dissertations--Entomology

Due to the increased interactions between the sylvatic and urban cycles of Aedes aegypti life cycle, there has been an increase in the incidence of vector-borne diseases. The risk involved through the transmission of viruses like Dengue, Zika, Yellow-fever and Chikungunya calls for an effective control method for the deadly vector. The possibility of pesticide resistance and the costs involved in producing new pesticides have pushed Sterile Insect Technique (SIT) into prominence. However, current methods used to sterize insects for SIT are not highly efficient. This study tackles current issues in mosquito control by identifying and characterizing epigenetic regulators that …

Current Dog Breeding Practices Impacts On Health And Preservation Of Purebred Dogs, Bridget E. Baker

Honors Theses and Capstones

No abstract provided.