Molecular Genetics Commons^™

Delayed Thrombus Resolution And Fibroproliferative Vascular Wound Healing From Deficiency Of Type Iii Collagen: A Paradoxical Mechanism For Tissue Fragility, Amy J. Reid

Dissertations and Theses (Open Access)

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1^+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury …

Small Interfering Rna-Mediated Translation Repression Alters Ribosome Sensitivity To Inhibition By Cycloheximide In Chlamydomonas Reinhardtii, Xinrong Ma

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

RNA interference (RNAi) is an evolutionarily conserved gene silencing mechanism in eukaryotes, with regulatory roles in a variety of biological processes, including cell cycle, cell differentiation, physiological and metabolic pathways, and stress responses. RNAi can function by transcriptional silencing, mRNA target cleavage, translation repression and/or DNA elimination. In this study, we used the unicellular green alga Chlamydomonas reinhardtii as a model system to study RNAi-mediated translation repression. We demonstrated that small RNAs (sRNAs) generated from exogenously introduced inverted repeat transgenes, with perfect complementarity to the 3’UTR of a target transcript, can inhibit protein synthesis, without or with only minimal mRNA …

Genetic Structure Of The Copperhead (Viperidae: Agkistrodon Contortrix Mokasen) At Its Most Northern Distribution, Brenna Aaren Levine

Graduate Theses and Dissertations

The focus of molecular studies in North American pitvipers has been on species that warrant conservation concern, such as Timber (Crotalus horridus) and Massasauga rattlesnakes (Sistrurus catenatus). Scant effort has been directed towards the molecular ecology of the Copperhead (Agkistrodon contortrix), other than to evaluate male reproduction in a laboratory setting and phylogenetic history. Thus, employing DNA-based molecular techniques to study the natural history of A. contortrix will broaden our knowledge of molecular ecology in North American pitvipers, and particularly in a non-threatened species that can serve as a surrogate for threatened and endangered …

Contributions Of Apolipoprotein E And Environmental Factors In Alzheimer’S Disease, Kelly C. Mcmullen

Senior Honors Theses

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder, which currently affects nearly 5.5 million people in the United States alone. Clinical features often exhibited in AD include memory loss, unusual behavior, personality changes, and impaired cognitive function. The primary molecular hallmarks of AD include deposits of senile plaques and neurofibrillary tangles in brain tissue. A myriad of risk factors are associated with the disease, but this review will focus on Apolipoprotein E polymorphisms and certain environmental factors. Understanding the role of Apolipoprotein E in AD pathology may aid in the development of certain drug therapies and possible cures for AD. …

Adenosine Triphosphate (Atp) Is A Candidate Signaling Molecule In The Mitochondria-To-Nucleus Retrograde Response Pathway, Feng Zhang, Tammy Pracheil, Janet Thornton, Zhengchang Liu

Biological Sciences Faculty Publications

Intracellular communication from the mitochondria to the nucleus is achieved via the retrograde response. In budding yeast, the retrograde response, also known as the RTG pathway, is regulated positively by Rtg1, Rtg2, Rtg3 and Grr1 and negatively by Mks1, Lst8 and two 14-3-3 proteins, Bmh1/2. Activation of retrograde signaling leads to activation of Rtg1/3, two basic helix-loop-helix leucine zipper transcription factors. Rtg1/3 activation requires Rtg2, a cytoplasmic protein with an N-terminal adenosine triphosphate (ATP) binding domain belonging to the actin/Hsp70/sugar kinase superfamily. The critical regulatory step of the retrograde response is the interaction between Rtg2 and Mks1. Rtg2 binds to …

Landscape Genetics Of Leaf-Toed Geckos In The Tropical Dry Forest Of Northern Mexico, Christopher Blair, Victor H. Jimenez-Arcos, Fausto R. Mendez De La Cruz, Robert W. Murphy

Publications and Research

Habitat fragmentation due to both natural and anthropogenic forces continues to threaten the evolution and maintenance of biological diversity. This is of particular concern in tropical regions that are experiencing elevated rates of habitat loss. Although less well-studied than tropical rain forests, tropical dry forests (TDF) contain an enormous diversity of species and continue to be threatened by anthropogenic activities including grazing and agriculture. However, little is known about the processes that shape genetic connectivity in species inhabiting TDF ecosystems. We adopt a landscape genetic approach to understanding functional connectivity for leaf-toed geckos (Phyllodactylus tuberculosus) at multiple sites …

Genome-Wide Analysis Reveals Selection For Important Traits In Domestic Horse Breeds, Jessica Lynn Petersen, James R. Mickelson, Aaron K. Rendahl, Stephanie K. Valberg, Lisa S. Andersson, Ernie Bailey, Danika L. Bannasch, Matthew M. Binns, Alexandre S. Borges, Pieter Brama, Artur Da Câmara Machado, Stefano Capomaccio, Katia Cappelli, E. Gus Cothran, Ottmar Distl, Laura Fox-Clipsham, Kathryn T. Graves, Gérard Guérin, Bianca Haase, Telhia Hasegawa, Karin Hemmann, Emmeline W. Hill, Tosso Leeb, Gabriella Lindgren, Hannes Lohi, Maria Susana Lopes, Beatrice A. Mcgivney, Sofia Mikko, Nicholas Orr, M. Cecilia T. Penedo, Richard J. Piercy, Marja Raekallio, Stefan Rieder, Knut H. Røed, June Swinburne, Teruaki Tozaki, Mark Vaudin, Claire M. Wade, Molly E. Mccue

Department of Animal Science: Faculty Publications

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F_ST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were …

Characterization And Distribution Of Novel Non-Ltr Retroelements Driving High Telomere Rflp Diversity In Clonal Lines Of Magnaporthe Oryzae, John H. Starnes

Theses and Dissertations--Plant Pathology

The filamentous ascomycete fungus Magnaporthe oryzae is a pathogen of over 50 genera of grasses. Two important diseases it can cause are gray leaf spot in Lolium perenne (perennial ryegrass) and blast in Oryza sativa (rice). The telomeres of M. oryzae isolates causing gray leaf spot are highly variable, and can spontaneously change during fungal culture. In this dissertation, it is shown that a rice-infecting isolate is much more stable at the telomeres than an isolate from gray leaf spot. To determine the molecular basis of telomere instability several gray leaf spot isolates telomeres were cloned, which revealed two non-LTR …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

Overexpression/Silencing Of Selected Soybean Genes Alters Resistance To Pathogens, Mohamed H. El-Habbak

Theses and Dissertations--Plant Pathology

Plant diseases remain a major obstruction to meeting the world’s increased demand for soybean oil and protein. Reducing the losses caused by diseases in order to improve crop production is a high priority for agricultural research. The need for novel strategies for plant disease control cannot be overstated. In the present study, selected defense-related genes were silenced and/or overexpressed in soybean using a virus-based vector and the resultant plants were tested for their responses to pathogens. The first part of the study focused on Rps1k (Resistance to Phytophthora sojae) gene. The two conserved domains encoding ‘P-Loop NTPase’ and ‘PLN03210’ …

Mechanisms Of Nitrogenous Waste Excretion During The Complex Life Cycle Of The Sea Lamprey (Petromyzon Marinus), James M. Neal Mr.

Theses and Dissertations (Comprehensive)

Sea lampreys (Petromyzon marinus) are a phylogenetically ancient jawless fish, with a multi-staged life cycle characterized by a prolonged suspension-feeding larval stage, which is followed by metamorphosis into parasitic lampreys that feed on the protein-rich blood of fishes. The switch from a nutrient poor to protein-rich diet in the sea lamprey is associated with an increased capacity to deaminate excess amino acids and to excrete ammonia and urea following metamorphosis. The focus of this thesis was to determine if changes in nitrogenous waste transporter protein abundance facilitate ammonia and urea excretion during different stages of the sea lamprey …

The Tick Genus Amblyomma In Africa: Phylogeny And Mutilocus Dna Barcoding, Omobolanle Kushimo

College of Graduate Studies: Theses & Dissertations

The tick genus Amblyomma includes approximately 130 species, 28 of which are found on the African continent and/ or in Madagascar. In order to understand the evolutionary phylogeography of the genus, it is necessary to gain a better understanding of the relationships between African taxa. Therefore, the main goals of this work were to, (1) reconstruct the phylogenetic relationships of the African Amblyomma available to us and (2) test markers for their usefulness as barcoding tools to link unknown immature specimens to their corresponding adults. The mitochondrial gene markers used in this study (12SrDNA and COI) did not resolve the …

Mitochondrial Dna Instability In Cells Lacking Aconitase Correlates With Iron Citrate Toxicity, Muhammad A. Farooq, Tammy M. Pracheil, Zhejun Dong, Fei Xiao, Zhengchang Liu

Biological Sciences Faculty Publications

Aconitase, the second enzyme of the tricarboxylic acid cycle encoded by ACO1 in the budding yeast Saccharomyces cerevisiae, catalyzes the conversion of citrate to isocitrate. aco1 Delta results in mitochondrial DNA (mtDNA) instability. It has been proposed that Aco1 binds to mtDNA and mediates its maintenance. Here we propose an alternative mechanism to account for mtDNA loss in aco1 Delta mutant cells. We found that aco1 Delta activated the RTG pathway, resulting in increased expression of genes encoding citrate synthase. By deleting RTG1, RTG3, or genes encoding citrate synthase, mtDNA instability was prevented in aco1 Delta mutant …

Characterization Of G-Patch Motif Contribution To Prp43 Function In The Pre-Messenger Rna Splicing And Ribosomal Rna Biogenesis Pathways, Daipayan Banerjee

Theses and Dissertations--Biology

The DExD/H-box protein Prp43 is essential for two biological processes: nucleoplasmic pre-mRNA splicing and nucleolar rRNA maturation. The biological basis for the temporal and spatial regulation of Prp43 remains elusive. The Spp382/Ntr1, Sqs1/Pfa1 and Pxr1/Gno1 G-patch proteins bind to and activate the Prp43 DExD/H box-helicase in pre-mRNA splicing (Spp382) and rRNA processing (Sqs1, Pxr1). These Prp43-interacting proteins each contain the G-patch domain, a conserved sequence of ~48 amino acids that includes 6 highly conserved glycine (G) residues. Five annotated G-patch proteins in baker’s yeast (i.e., Spp382, Pxr1, Spp2, Sqs1 and Ylr271) and with the possible exception of the uncharacterized Ylr271 …

Malnutrition In Sickle Cell Anemia: Implications For Infection, Growth And Maturation, Hyacinth I. Hyacinth, Oluwatoyosi A. Adekeye, Christopher S. Yilgwan

Journal of Social, Behavioral, and Health Sciences

Sickle cell anemia (SCA) is a genetic disease that affects mostly individuals of African and/or Hispanic descent, with the majority of cases in sub-Saharan Africa. Individuals with this disease show slowed growth, delayed sexual maturity, and poor immunologic function. These complications could partly be explained by the state of undernutrition associated with the disease. Proposed mechanism of undernutrition include protein hypermetabolism, decreased dietary intake possibly from interleukin-6-related appetite suppression, increased cardiac energy demand/expenditure, and increased red cell turnover. All the above mechanisms manifest as increased resting energy expenditure. Nutritional intervention utilizing single or multiple nutrient supplementation has led to improved …

Dna-Binding Site Recognition By Bhlh And Mads-Domain Transcription Factors, Joshua R. Werkman

Theses and Dissertations--Plant and Soil Sciences

Herewithin, two transcription factor (TF) regulatory complexes were investigated. A bHLH–MYB–WDR (BMW) DNA-binding complex from maize was the first complex to be studied. R, a maize bHLH involved in the activation of genes in the anthocyanin pathway, had been characterized to indirectly bind DNA despite the presence of a functional DNA-binding domain. Findings presented here reveal that this is only partially correct. Direct DNA-binding by R was found to be dependent upon two distinct dimerization domains that function as a switch. This switch-like mechanism allows R to be repurposed for the activation of promoters of differing cis-element structure.

The …

Localization And Mutational Analysis Of The Nuclear And Aggregation-Prone Ime4 Protein In Saccharomyces Cerevisiae, Patricia M. Dehon

LSU New Orleans Theses and Dissertations

In Saccharomyces cerevisiae, Ime4 is a protein that is induced during meiosis and has a primary role in regulating sporulation in starving diploids. One function of Ime4 is methylation of adenosine residues within mRNA transcripts. Recent studies have shown Ime4 to be induced in haploids during the mating response, although its role in mating has not been determined. In this report, I identify the subcellular localization of Ime4 during the mating response through treatment with alpha factor. A plasmid containing IME4-GFP under the control of the medium strength promoter CYC1 was created in order to express the protein in a …

Identifying Genetic Variants And Characterizing Their Role In Clubfoot, Katelyn S. Weymouth

Dissertations and Theses (Open Access)

Clubfoot is a common, complex birth defect affecting 4,000 newborns in the United States and 135,000 world-wide each year. The clubfoot deformity is characterized by inward and rigid downward displacement of one or both feet, along with persistent calf muscle hypoplasia. Despite strong evidence for a genetic liability, there is a limited understanding of the genetic and environmental factors contributing to the etiology of clubfoot. The studies described in this dissertation were performed to identify variants and/or genes associated with clubfoot. Genome-wide linkage scan performed on ten multiplex clubfoot families identified seven new chromosomal regions that provide new areas to …

Fancm And Faap24 Maintain Genomic Stability Through Cooperative And Unique Functions, Yucai Wang

Dissertations and Theses (Open Access)

Fanconi anemia (FA) is a rare recessive genetic disease with an array of clinical manifestations including multiple congenital abnormalities, progressive bone marrow failure and profound cancer susceptibility. A hallmark of cells derived from FA patients is hypersensitivity to DNA interstrand crosslinking agents such as mitomycin C (MMC) and cisplatin, suggesting that FA- and FA-associated proteins play important roles in protecting cells from DNA interstrand crosslink (ICL) damage. Two genes involved in the FA pathway, FANCM and FAAP24, are of particular interest because they contain DNA interacting domains. However, there are no definitive patient mutations for these two genes, and the …

Genetic Interactions Of Factors That Regulate Alternative Rna Splicing In The Male Germ Line Of Drosophila, Shanzhi Wang

Dissertations and Theses (Open Access)

Alternative RNA splicing is a critical process that contributes variety to protein functions, and further controls cell differentiation and normal development. Although it is known that most eukaryotic genes produce multiple transcripts in which splice site selection is regulated, how RNA binding proteins cooperate to activate and repress specific splice sites is still poorly understood. In addition how the regulation of alternative splicing affects germ cell development is also not well known. In this study, Drosophila Transformer 2 (Tra2) was used as a model to explore both the mechanism of its repressive function on its own pre-mRNA splicing, and the …