Genetics and Genomics Commons^™

Genetics And Genomics Education Among Physician Assistants, Wesley Patterson

All Dissertations

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 A Potential Glucose Transporter In Trypanosoma Brucei, Matthew Morgan

All Theses

Trypanosoma brucei, the African trypanosome, is an organism heavily dependent on glucose for ATP production during the infectious stage of its life cycle. Here, we have explored the role of an uncharacterized protein designated “novel glucose transporter” (NGT) as a potential glucose transporter. Sequence analyses suggests that NGT shares similarities (either at the primary sequence level or structurally) with Trypanosome Hexose Transporters 1 (TbTHT1), and human GLUT3, both of which are membrane sugar transporters. NGT was localized by fluorescence microscopy to subcellular structures consistent with lysosomes. Silencing NGT expression with RNA interference in parasites resulted in a growth defect …

Identification Of Genetic Variants Underlying Maxillary Canine-Tooth Mesioversion And Small Body Size In Shetland Sheepdogs, Sydney R. Abrams

All Theses

The domesticated dog (Canis lupus familiaris) exhibits a unique population structure, with high levels of genetic homogeneity within breeds due to selective breeding. These closed breeding populations can result in breed-specific inherited disorders. Maxillary canine-tooth mesioversion (MCM) is a genetically complex dental anomaly observed nearly exclusively in the small Shetland Sheepdog breed. Here, we utilized a genome-wide approach to discover a locus of major effect on chromosome 9. Using whole-genome resequencing data from a bilaterally affected dog, we identified variants in two genes: FTSJ3, encoding an RNA methyltransferase, and GH1, encoding growth hormone. Independent genome-wide association …

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

All Dissertations

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

All Dissertations

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 …

Unraveling The Genetic Architecture Of Somatic Embryogenesis In Upland Cotton, Adam M. Canal

All Theses

Somatic embryogenesis is the de novo development of asexual embryos because of the plasticity of the plant cell. In tissue culture, the biochemical and genetic mechanisms of dedifferentiated callus tissues can be reprogrammed to transdifferentiate into developed, polarized embryos, which can ultimately regenerate into whole plants. Although this rarely occurs in nature, scientists have exploited this process for decades to regenerate whole plants following gene transformation or for micropropagation. While some species are amenable to in vitro regeneration, upland cotton is particularly recalcitrant, with regenerative potential being confined to only several genotypes. The lack of elite, regenerable genotypes greatly restricts …

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

All Dissertations

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

All Dissertations

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

All Dissertations

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 …

Comparative Transcriptome Profiling Provides Insights Into Plant Salt Tolerance In Seashore Paspalum (Paspalum Vaginatum), Peipei Wu, Steven Cogill, Yijian Qiu, Zhigang Li, Man Zhou, Qian Hu, Zhihui Chang, Hong Luo, Rooksana E. Noorai, Xiaoxia Xia, Christopher Saski, Paul Raymer

Publications

Background

Seashore paspalum (Paspalum vaginatum), a halophytic warm-seasoned perennial grass, is tolerant of many environmental stresses, especially salt stress. To investigate molecular mechanisms underlying salinity tolerance in seashore paspalum, physiological characteristics and global transcription profiles of highly (Supreme) and moderately (Parish) salinity-tolerant cultivars under normal and salt stressed conditions were analyzed.

Results

Physiological characterization comparing highly (Supreme) and moderately (Parish) salinity-tolerant cultivars revealed that Supreme’s higher salinity tolerance is associated with higher Na+ and Ca2+ accumulation under normal conditions and further increase of Na+ under salt-treated conditions (400 mM NaCl), possibly by vacuolar sequestration. Moreover, K+ retention under …

Discovery Of Genomic Variations By Whole-Genome Resequencing Of The North American Araucana Chicken, Rooksana E. Noorai, Vijay Shankar, Nowlan H. Freese, Christopher M. Gregorski, Susan C. Chapman

Publications

Gallus gallus (chicken) is phenotypically diverse, with over 60 recognized breeds, among the myriad species within the Aves lineage. Domestic chickens have been under artificial selection by humans for thousands of years for agricultural purposes. The North American Araucana (NAA) breed arose as a cross between the Chilean “Collonocas” that laid blue eggs and was rumpless and the “Quetros” that had unusual tufts but with tail. NAAs were introduced from South America in the 1940s and have been kept as show birds by enthusiasts since then due to several distinctive traits: laying eggs with blue eggshells, characteristic ear-tufts, a pea …

Non-Enzymatic Roles Of Human Rad51 At Stalled Replication Forks, Jennifer M. Mason, Yuen-Ling Chan, Ralph W. Weichselbaum, Douglas K. Bishop

Publications

The central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, we use a separation-of-function allele of RAD51 that retains DNA binding, but not D-loop activity, to reveal mechanistic aspects of RAD51’s roles in the response to replication stress. Here, we find that cells lacking RAD51’s enzymatic activity protect replication forks from MRE11-dependent degradation, as expected from previous studies. Unexpectedly, we find that RAD51’s strand exchange activity is not required to convert stalled forks to a form that can be degraded by DNA2. Such conversion was shown previously to require replication …

Glucose Signaling Is Important For Nutrient Adaptation During Differentiation Of Pleomorphic African Trypanosomes, Yijian Qiu, Jillian E. Milanes, Jessica A. Jones, Rooksana E. Noorai, Vijay Shankar, James C. Morris

Publications

The African trypanosome has evolved mechanisms to adapt to changes in nutrient availability that occur during its life cycle. During transition from mammalian blood to insect vector gut, parasites experience a rapid reduction in environmental glucose. Here we describe how pleomorphic parasites respond to glucose depletion with a focus on parasite changes in energy metabolism and growth. Long slender bloodstream form parasites were rapidly killed as glucose concentrations fell, while short stumpy bloodstream form parasites persisted to differentiate into the insect-stage procyclic form parasite. The rate of differentiation was lower than that triggered by other cues but reached physiological rates …

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

All Dissertations

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 …

Cancer Cell Redirection Biomarker Discovery Using A Mutual Information Approach, Kimberly Roche, F. Alex Feltus, Jang Pyo Park, Marie-May Coissieux, Chenyan Chang, Vera B.S. Chan, Mohamed Bentires-Alj, Brian W. Booth

Publications

Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection …

A Leishmania Secretion System For The Expression Of Major Ampullate Spidroin Mimics, Todd A. Lyda, Elizabeth L. Wagner, Andre X. Bourg, Congyue Peng, Golnaz Najaf Tomaraei, Delphine Dean, Marian S. Kennedy, William R. Marcotte Jr.

Publications

Spider major ampullate silk fibers have been shown to display a unique combination of relatively high fracture strength and toughness compared to other fibers and show potential for tissue engineering scaffolds. While it is not possible to mass produce native spider silks, the potential ability to produce fibers from recombinant spider silk fibers could allow for an increased innovation rate within tissue engineering and regenerative medicine. In this pilot study, we improved upon a prior fabrication route by both changing the expression host and additives to the fiber pulling precursor solution to improve the performance of fibers. The new expression …

Beyond The Mhc: A Canine Model Of Dermatomyositis Shows A Complex Pattern Of Genetic Risk Involving Novel Loci, Jacquelyn M. Evans, Rooksana E. Noorai, Kate L. Tsai, Alison N. Starr-Moss, Cody M. Hill, Kendall J. Anderson, Thomas R. Famula, Leigh Anne Clark

Publications

Juvenile dermatomyositis (JDM) is a chronic inflammatory myopathy and vasculopathy driven by genetic and environmental influences. Here, we investigated the genetic underpinnings of an analogous, spontaneous disease of dogs also termed dermatomyositis (DMS). As in JDM, we observed a significant association with a haplotype of the major histocompatibility complex (MHC) (DLA-DRB1*002:01/-DQA1*009:01/-DQB1*001:01), particularly in homozygosity (P-val = 0.0001). However, the high incidence of the haplotype among healthy dogs indicated that additional genetic risk factors are likely involved in disease progression. We conducted genome-wide association studies in two modern breeds having common …

Ectopic Expression Of A Cyanobacterial Flavodoxin In Creeping Bentgrass Impacts Plant Development And Confers Broad Abiotic Stress Tolerance, Zhigang Li, Shuangrong Yuan, Haiyan Jia, Fangyuan Gao, Qian Hu, Dongfa Sun, Hong Luo

Publications

Flavodoxin (Fld) plays a pivotal role in photosynthetic microorganisms as an alternative electron carrier flavoprotein under adverse environmental conditions. Cyanobacterial Fld has been demonstrated to be able to substitute ferredoxin (Fd) of higher plants in most electron transfer processes under stressful conditions. We have explored the potential of Fld for use in improving plant stress response in creeping bentgrass (Agrostis stolonifera L.). Overexpression of Fld altered plant growth and development. Most significantly, transgenic (TG) plants exhibited drastically enhanced performance under oxidative, drought and heat stress as well as nitrogen (N) starvation, which was associated with higher water retention and …

The Β-Isoform Of Bccip Promotes Adp Release From The Rad51 Presynaptic Filament And Enhances Homologous Dna Pairing, Andrew A. Kelso, Steven D. Goodson, Leah E. Watts, Leanna L. Ledford, Sarah M. Waldvogel, J. Nathaniel Diehl, Shivani B. Shah, Amanda F. Say, Julie D. White, Michael G. Sehorn

Publications

Homologous recombination (HR) is a template-driven repair pathway that mends DNA double-stranded breaks (DSBs), and thus helps to maintain genome stability. The RAD51 recombinase facilitates DNA joint formation during HR, but to accomplish this task, RAD51 must be loaded onto the single-stranded DNA. DSS1, a candidate gene for split hand/split foot syndrome, provides the ability to recognize RPA-coated ssDNA to the tumor suppressor BRCA2, which is complexed with RAD51. Together BRCA2-DSS1 displace RPA and load RAD51 onto the ssDNA. In addition, the BRCA2 interacting protein BCCIP normally colocalizes with chromatin bound BRCA2, and upon DSB induction, RAD51 colocalizes with BRCA2-BCCIP …

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

All Dissertations

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

All Dissertations

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

All Dissertations

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 …

Heterologous Expression Of A Rice Mir395 Gene In Nicotiana Tabacum Impairs Sulfate Homeostasis, Ning Yuan, Shuangrong Yuan, Zhigang Li, Dayong Li, Qian Hu, Hong Luo

Publications

Sulfur participates in many important mechanisms and pathways of plant development. The most common source of sulfur in soil –SO₄²⁻– is absorbed into root tissue and distributed into aerial part through vasculature system, where it is reduced into sulfite and finally sulfide within the subcellular organs such as chloroplasts and mitochondria and used for cysteine and methionine biosynthesis. MicroRNAs are involved in many regulation pathways by repressing the expression of their target genes. MiR395 family in Arabidopsis thaliana has been reported to be an important regulator involved in sulfate transport and assimilation, and a high-affinity sulphate transporter …

Heterologous Expression Of A Rice Mir395 Gene In Nicotiana Tabacum Impairs Sulfate Homeostasis, Ning Yuan, Shuangrong Yuan, Zhigang Li, Dayong Li, Hong Luo

Publications

Sulfur participates in many important mechanisms and pathways of plant development. The most common source of sulfur in soil –SO42−– is absorbed into root tissue and distributed into aerial part through vasculature system, where it is reduced into sulfite and finally sulfide within the subcellular organs such as chloroplasts and mitochondria and used for cysteine and methionine biosynthesis. MicroRNAs are involved in many regulation pathways by repressing the expression of their target genes. MiR395 family in Arabidopsis thaliana has been reported to be an important regulator involved in sulfate transport and assimilation, and a high-affinity sulphate transporter and three ATP …

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

All Dissertations

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

All Dissertations

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

All Dissertations

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 …

Gene Discovery And Differential Expression Analysis Of Humoral Immune Response Elements In Female Culicoides Sonorensis (Diptera: Ceratopogonidae), Naya Nayduch, Matthew B. Lee, Christopher Saski

Publications

Female Culicoides sonorensis midges (Diptera: Ceratopogonidae) are vectors of pathogens that impact livestock and wildlife in the United States. Little is known about their biology on a molecular-genetic level, including components of their immune system. Because the insect immune response is involved with important processes such as gut microbial homeostasis and vector competence, our aims were to identify components of the midge innate immune system and examine their expression profiles in response to diet across time.

The Reference Transcriptome Of The Adult Female Biting Midge (Culicoides Sonorensis) And Differential Gene Expression Profiling During Teneral, Blood, And Sucrose Feeding Conditions, Dana Nayduch, Matthew B. Lee, Christopher Saski

Publications

Unlike other important vectors such as mosquitoes and sandflies, genetic and genomic tools for Culicoides biting midges are lacking, despite the fact that they vector a large number of arboviruses and other pathogens impacting humans and domestic animals world-wide. In North America, female Culicoides sonorensis midges are important vectors of bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV), orbiviruses that cause significant disease in livestock and wildlife. Libraries of tissue-specific transcripts expressed in response to feeding and oral orbivirus challenge in C. sonorensis have previously been reported, but extensive genome-wide expression profiling in the midge has not. Here, we …

Mapping Quantitative Trait Loci Associated With Alternaria Leaf Blight Resistance And Elemental Sulfur Tolerance In Melon, James Daley

All Theses

Melon (Cucumis melo L.) production is significantly affected by Alternaria leaf blight, caused by Alternaria cucumerina. Fungicide application is the primary control method; however, this could be mitigated through the increased use of resistant varieties. USDA-ARS breeding line MR-1 has been shown to have a high level of resistance to Alternaria cucumerina. However, molecular markers linked MR-1 Alternaria resistance have yet to be identified. In order in identify QTL associated with Alternaria resistance MR-1 x Ananas Yokneum (AY) derived recombinant inbred lines (RILs) were phenotyped using a modified wounded-leaf assay. Elemental sulfur is an effective fungicide for several foliar pathogens …