Genetics and Genomics Commons^™

Assessment Of Genetic And Education Recovery Plan Objectives For The Bog Turtle (Glyptemys Muhlenbergii), Cassie Marie Dresser

Doctoral Dissertations

Unprecedented declines in biodiversity are threatening the natural world as we know it. Without human intervention, two thousand species listed under the US Endangered Species Act are likely to disappear. Fortunately, these species receive federal protection and increased research effort is needed to create and satisfy the objectives outlined in the mandated Species Recovery Plan. In this dissertation, I address three conservation objectives outlined in the Recovery Plan for North America’s smallest and rarest turtle, the Bog Turtle (Glyptemys muhlenbergii): (1) investigate the potential genetic differentiation in southern portions of the species’ range, (2) investigate the genetic impacts …

Detection, Diversity, And Evolution Of Fungal Nitric Oxide Reductases (P450nor), Steven Adam Higgins

Doctoral Dissertations

Nitrous oxide (N₂O) is a gas responsible for significant ozone layer depletion and contributes to greenhouse effects in Earth’s atmosphere. N₂O is primarily generated by denitrification, whereby nitrate (NO_3-) or nitrite (NO_2-) is converted to gaseous N₂O or N2. Teragram quantities of N₂O are emitted annually from agricultural soils treated with nitrogenous fertilizers due to the activity of soil microbiota. Although bacteria and fungi harbor genes permitting denitrification, fungi lack NosZ, an enzyme responsible for reducing N₂O into inert N2 gas. Historically, scientists have linked fungi …

On The Construction And Interpretation Of Fitness Landscapes For Hiv: A Computational Perspective, Elizabeth Grace Johnson

Doctoral Dissertations

To identify vulnerable viral targets to incorporate into an immunogen, fitness landscapes for the viral proteome have been constructed. These landscapes describe the sum or synergistic replicative cost exacted on the virus for any combination of non-synonymous mutations. Here we attempt to assess the robustness of current computational methods for measuring the fitness cost of HIV polymorphisms in these landscapes. We also address in the following chapters assumptions and shortcomings that may underlie current landscape's uneven ability to predict fitness effects.

In the first chapter, I appraise the robustness of current frame-works that derive fitness costs from patient sequence data. …

Pro-Angiogenesis Therapy And Aging: A Mini-Review, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Apart from major illnesses and chronic afflictions, the elderly experience lesser ailments, such as muscle weakness, cold intolerance, and transient memory lapses. Physical signs in the aged include wrinkled skin and the slow healing of skin abrasions. These ailments and signs are grouped together because they may be due in part to an age-linked, waning microcirculation. A reduced capillary density (CD) throughout the body of aged people and animals has been reported in over 40 papers. The reduced CD is due in turn to declining levels of angiogenic growth factors (AGFs) throughout the body during old age, as documented in …

Production Of A Gonadotropin-Releasing Hormone 2 Receptor Knockdown (Gnrhr2 Kd) Swine Line., Amy T. Desaulniers, Rebecca Middleton, Ginger A. Mills, Clay A. Lents, Brett R. White

Department of Animal Science: Faculty Publications

Swine are the only livestock species that produce both the second mammalian isoform of gonadotropin-releasing hormone (GNRH2) and its receptor (GNRHR2). Previously, we reported that GNRH2 and GNRHR2 mediate LH-independent testosterone secretion from porcine testes. To further explore this ligand-receptor complex, a pig model with reduced GNRHR2 expression was developed. Small hairpin RNA sequences targeting porcine GNRHR2 were subcloned into a lentiviral-based vector, lentiviral particles were generated and microinjected into the perivitelline space of zygotes, and embryos were transferred into a recipient. One GNRHR2 knockdown (KD) female was born that subsequently produced 80 piglets from 6 litters with 46 hemizygous …

Aldehyde Dehydrogenase 1 (Aldh1) Isoform Expression And Potential Clinical Implications In Hepatocellular Carcinoma, Cheng Kun Yang, Xiang Kun Wang, Xi Wen Liao, Chuang Ye Han, Ting Dong Yu, Wei Qin, Guang Zhi Zhu, Hao Su, Long Yu, Xiao Guang Liu, Si Cong Lu, Zhi Wei Chen, Zhen Liu, Ke Tuan Huang, Zheng Tao Liu, Yu Liang, Jian Lu Huang, Kai Yin Xiao, Min Hao Peng, Cheryl Ann Winkle, Stephen J. O’Brien, Tao Peng

Biology Faculty Articles

Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was …

Optimizing A Method For Simultaneous Recovery Of Proteins And Dna From Fingerprints, Steven Kranes

Student Theses

DNA testing on touched objects is a valuable tool in forensic investigations, but DNA is usually present in low amounts, causing poor STR typing results. For touch DNA evidence, there is a clear need for additional individualization, especially for highly probative samples. This could be achieved by testing genetically variable proteins. The goal of this project was to develop a DNA/protein co-extraction method to facilitate DNA and protein testing on the same evidence item. Existing DNA extraction methods were carefully adjusted to allow for downstream mass spectrometry analysis. Initial experiments on saliva and fingerprints placed on glass suggested that trypsin …

Chaperoning Ef Hands That Shape Calcium Response: Ncald, Hpca And S100b, Jingyi Zhang

Graduate School of Biomedical Sciences Theses and Dissertations

All organisms have an internal clock with a defined period between repetitions of activities. The period for circadian clock in human is 24.5 hours, while in mouse and rat, it is 23.5 hours. However, all organisms are forced to be in synchronization with their environment. A major environmental force that resets the internal clock to 24 hours is light. This phenomenon is defined as “light entrainment” or “phase-setting”. It is unclear how this entrainment process occurs. Studies from this laboratory indicate a role for two neuronal calcium sensor proteins: Neurocalcin  (NCALD) and S100B. For these two genes, mRNA as …

Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz

Graduate School of Biomedical Sciences Theses and Dissertations

Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …

Ion Channel Signaling Influences Cellular Proliferation And Phagocyte Activity During Axolotl Tail Regeneration, Brandon M. Franklin, S. Randal Voss, Jeffrey L. Osborn

Biology Faculty Publications

Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, K_V2.1, K_V2.2, L-type CaV channels and H/K ATPases) or completely (GlyR, GABA_AR, K_V1.5 and SERCA pumps) inhibited tail regeneration. Partial inhibition of tail regeneration by blocking the calcium activated chloride channels, anoctamin1&2, was associated with a reduction of cellular proliferation in …

Impact Of Home Visit Capacity On Genetic Association Studies Of Late-Onset Alzheimer's Disease, David W. Fardo, Laura E. Gibbons, Shubhabrata Mukherjee, M. Maria Glymour, Wayne Mccormick, Susan M. Mccurry, James D. Bowen, Eric B. Larson, Paul K. Crane

Biostatistics Faculty Publications

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer's disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits.

METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators.

RESULTS …

Clinical And Experimental Studies Of A Novel P525r Fus Mutation In Amyotrophic Lateral Sclerosis, Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St. Clair, Edward J. Kasarskis, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models.

Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same …

Expression Profiling Of Non-Coding Rna By Environmental Interactions In Innate Immunity, Jacob R. Longfellow

Electronic Theses and Dissertations

Cystic fibrosis (CF) is a genetic disorder that affects 30,000 people in the United States and currently has no cure. Although CF affects all of the body’s systems, it is largely characterized as a lung disease. CF is caused by a mutation in both copies of the gene for cystic fibrosis transmembrane conductance regulator (CFTR). A mutation in the CFTR gene leads to improper movement of chloride ions and water into the airways, which dysregulates the airway surface liquid volume and composition. Individuals with CF are prone to lung infections due to inefficient bacterial clearance and by the age of …

Identifying Three-Way Gene Interactions From Microarray Data Using Kolmogorov-Smirnov And Cross-Match Tests, Shubhashree Khadka

Graduate Theses and Dissertations

Human gene network is much more complex than just pairwise interaction among the genes. Zhang et al. [6] extracted microarray data from International Genomics Consortium (IGC), and presented the detection of three-way gene interactions in their paper using Fisher’s z-transformation test. Three-way gene interactions are closer than pairwise correlations in representing the complex gene structures. Additionally, it was more tractable than assessing four or more gene interactions. In this paper, we are simulating different models where Fisher’s test might not be as effective. Zhang et al.’s approach utilized Pearson’s correlation coefficients and involved detection of linear interactions only. Since gene …

Comprehensive Assessments Of The Genetic Determinants In Salmonella Typhimurium For Fitness Under Host Stressors: Oxidative Stress And Iron Restriction, Sardar Abdullah

Graduate Theses and Dissertations

Salmonella is an intracellular pathogen that infects a wide range of hosts. The infected host utilizes reactive oxygen species (ROS) and iron-restriction to eliminate the pathogen. We used proteogenomics to determine the candidate genes and proteins that have a role in resistance of S. Typhimurium to H2O2. For Tn-seq, a highly saturated Tn5 library was grown in vitro under either 2.5 (H2O2L) or 3.5 mM H2O2 (H2O2H). We identified two sets of overlapping genes that are required for resistance of S. Typhimurium to H2O2L and H2O2H, and the results were validated via phenotypic evaluation of 50 selected mutants. The enriched …

Functional Consequences Of Rna Exosome Complex Alteration By Conformational Changes And Cofactor Binding, Jaeil Han

Dissertations & Theses (Open Access)

The RNA exosome is an essential 3’-5 ribonuclease that processes or degrades a variety of RNA species in eukaryotes. It is composed of nine structural cores and one catalytic subunit, Rrp44. Structural studies captured two different conformations of Rrp44, Rrp44^ch (channel) and Rrp44^da (direct-access). The Rrp44^ch appears to recruit RNA substrates from the central channel formed by the core subunits, while the substrate is directly recruited to Rrp44^da bypassing the central channel. Although in vivo function of the Rrp44^ch-exosome is extensively studied, the function or even the presence of the Rrp44^da-exosome in …

Genome Wide Association And Next Generation Sequencing Approaches To Map Determinants Of Ascites In Broiler Chickens, Shatovisha Dey

Graduate Theses and Dissertations

These studies have investigated different candidate genomic regions for their contributions to ascites in broilers. Ascites syndrome is a manifestation of idiopathic pulmonary arteriole hypertension that concerns the poultry industry worldwide. Investigations have demonstrated the disease to be genetically regulated and to exhibit moderate to high heritabilities. Although previous studies have indicated a few chromosomes to be involved with ascites, no genes have been identified to date with direct links to the disease. This dissertation presents a collection of studies that determine the genomic and genetic interactions for regions on chromosome 2 and 9 for ascites phenotypes in broiler chickens. …

Retrotransposons Are The Major Contributors To The Expansion Of The Drosophila Ananassae Muller F Element, Wilson Leung, Martin G. Burg, Spencer M. Batten, Lindsay M. Corbeill, Erica Enoch, Jesse J. Ensign, Mary E. Franks, Breanna Haiker, Judith A. Ingles, Lyndsay D. Kirkland, Josha M. Lorenz-Guertin, Jordan Matthews, Cody M. Mittig, Nicholaus Monsma, Katherine J. Olson, Guillermo Perez-Aragon, Alen Ramic, Jordan R. Ramirez, Christopher Scheiber, Patrick A. Schneider, Devon E. Schultz, Matthew Simon, Eric Spencer, Adam C. Wernette, Maxine E. Wykle, Elizabeth Zavala-Arellano, Mitchell J. Mcdonald, Kristine Ostby, Peter Wendland

Peer Reviewed Articles

The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) …

Molecular And Pathological Analyses Of Three New Mouse Mutations That Affect Ear Development And Function, Cong Tian

Electronic Theses and Dissertations

This dissertation presents three new mouse models that help to study the functions of Enpp1, Atp6v1b1, and Tbx1 for ear development and function. asj (aging with stiffened joints) carries a missense mutation in the mouse Enpp1 gene. Enpp1 encodes the enzyme ENPP1 that regulate soft-tissue calcification and bone mineralization, and is associated with generalized arterial calcification of infancy and hypophosphatemic rickets in human patients. asj mutant mice show severe middle ear infection and tissue calcification, which provide a new mouse model to study otitis media and tympanoscleorosis. Atp6v1b1 encode a protein that is a subunit of the V-ATPase …

New Insights Into The Role Of Antimicrobials Of Xenorhabdus In Interspecies Competition, Kristin Jean Ciezki

Theses and Dissertations

Xenorhabdus spp. are symbionts of entomopathogenic nematodes and pathogens of susceptible insects. The nematodes penetrate the insect midgut to enter the hemocoel where Xenorhabdus bacteria are released, transitioning to their pathogenic stage. During nematode invasion microbes from the insect gut translocate into the hemocoel. In addition, different species of nematodes carrying specific strains of Xenorhabdus can invade a single insect. Xenorhabdus spp thereby engage in competition with both related strains and nonrelated gut microbes. In complex media Xenorhabdus spp produce diverse antimicrobial compounds whose functions in biological systems remain poorly understood. R-type bacteriocins are contractile phage-tail-like structures that are bactericidal …