Genetics and Genomics Commons^™

Characterizations Of Proteins Interacting With The Alpha Subunit Of Actin Capping Protein, Angelique Ducharme, Charity Zabel

Journal of Undergraduate Research at Minnesota State University, Mankato

Actin, a filamentous component of all cells, contributes to cell shape, cell motility and force transmission. Actin assembly and dynamics are regulated by a diverse array of regulatory proteins, including actin capping protein (CP). CP is a heterodimeric protein composed of two subunits, alpha (a) and beta (ß). Three isoforms of each subunit exist in eukaryotes. The ß isoforms have been shown to have distinct functions in vivo. The functions of the specific a isoforms have yet to be determined. Overall, the amino acid sequence of the a isoforms are highly conserved, sharing approximately 90% sequence identity. The region of …

Genome-Wide Dna Methylation Profiles In Progression To In Situ And Invasive Carcinoma Of The Breast With Impact On Gene Transcription And Prognosis, Thomas Fleischer, Arnoldo Frigessi, Kevin C. Johnson, Hege Edvardsen, Nizar Touleimat, Jovana Klajic, Margit Lh Riis, Vilde D. Haakensen, Fredrik Wärnberg, Bjørn Naume, Åslaug Helland, Anne-Lise Børresen-Dale, Jörg Tost, Brock C. Christensen, Vessela N. Kristensen

Dartmouth Scholarship

Background: Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Results: We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals …

Sma-Causing Missense Mutations In Survival Motor Neuron (Smn) Display A Wide Range Of Phenotypes When Modeled In Drosophila, Kavita Praveen, Ying Wen, Kelsey M. Gray, John J. Noto, Akash R. Patlolla, Gregory D. Van Duyne, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of …

Identification Of Snps In The Coding Region Of Human Mtdna, Cassidy Punt, Elizabeth Smalley

Journal of Undergraduate Research at Minnesota State University, Mankato

Two novel single nucleotide polymorphisms (SNPs) were discovered within the coding region of the NADH dehydrogenase subunit 2 gene of mitochondrial DNA (mtDNA). mtDNA is of particular importance in forensic analysis as well as in the study of the origin and dispersal of humans. Two segments of the coding region of human mtDNA, as well as the hyper-variable region 2 (HV 2) were selected and sequenced in order to determine if any previously unknown SNPs were present in our test subjects. Target regions were designed to include known SNPs; appropriate primers were developed using the OLIGO 6 Primer Analysis Software. …

Phenotypic Robustness And The Assortativity Signature Of Human Transcription Factor Networks, Dov A. Pechenick, Joshua L. Payne, Jason H. Moore

Dartmouth Scholarship

Many developmental, physiological, and behavioral processes depend on the precise expression of genes in space and time. Such spatiotemporal gene expression phenotypes arise from the binding of sequence-specific transcription factors (TFs) to DNA, and from the regulation of nearby genes that such binding causes. These nearby genes may themselves encode TFs, giving rise to a transcription factor network (TFN), wherein nodes represent TFs and directed edges denote regulatory interactions between TFs. Computational studies have linked several topological properties of TFNs - such as their degree distribution - with the robustness of a TFN's gene expression phenotype to genetic and environmental …

Biofilm Formation By Escherichia Coli Csga And Fima Mutants, Nicole Snyder, Sean Willaert

Journal of Undergraduate Research at Minnesota State University, Mankato

Biofilms are a structured community of bacterial cells enclosed in a self-produced polymeric matrix and adherent to an inert or living surface. These structures and the organisms that cause them can pose a very serious problem if they colonize on medical devices. This is because biofilms have the ability to communicate within the colony and with other organisms that might attach to the surface, acting like a community working together. Biofilms allow the organism to be resistant to harsh and unfavorable conditions allowing them to survive longer and spread. Several genes in Escherichia coli (E. coli) have been associated …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all phosphodiesterase …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all …

Regulation Of Mor By Different Abiotic Stresses In Arabidopsis Thaliana, Luke Stepan, Rucha Karve, Anjali Iyer-Pascuzzi

The Summer Undergraduate Research Fellowship (SURF) Symposium

The climate is changing and as a consequence the environment is becoming hotter and drier. How different plants will react to these changes is unknown. Identification of genes involved in stress tolerance can help predict plant-environment interactions and lead to stress tolerant plants. The MOR gene (Modulator Of Root ROS, ROS = Reactive Oxygen Species) in the model plant Arabidopsis thaliana encodes a transcription factor that may regulate stress responses, as mor mutants are drought tolerant. We hypothesized that MOR expression changes in response to different abiotic stress stimuli. We tested MOR expression in response to salt (NaCl), abscisic acid …

Development Of Transgenic North American White Ash (Fraxinus Americana) Expressing A Bacillus Thuringiensis Protein For Management Of The Emerald Ash Borer, Eric A. Dean, Paula M. Pijut Phd., Micah E. Stevens

The Summer Undergraduate Research Fellowship (SURF) Symposium

White ash (WA), Fraxinus americana, is an integral part of the hardwood forest ecosystem. Economically, WA provides wood for important products such as baseball bats, tool handles, and hardwood flooring. Ecologically WA provides cover and mast to support wildlife. The emerald ash borer (EAB) is a significant threat to all ash species because of a lack of native resistance in North American ash trees, its rapid spread, and the ineffectiveness and expense of control measures. EAB is a non-native beetle that consumes tree vascular tissue while in the larval stage. The development of an Agrobacterium-mediated transformation protocol may …

Imaging Luciferase-Expressing Viruses, Michael A. Barry, Shannon May, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Optical imaging of luciferage gene expression has become a powerful tool to track cells and viruses in vivo in small animal models. Luciferase imaging has been used to study the location of infection by replication-defective and replication-competent viruses and to track changes in the distribution of viruses in mouse models. This approach has also been used in oncolytic studies as a non-invasive means to monitor the growth and killing of tumor cells modified with luciferase genes. In this chapter, we describe the techniques used for luciferase imaging as have been applied to track replication-defective and replication-competent adenoviruses in mouse and …

Annotated Features Of Domestic Cat – Felis Catus Genome, Gaik Tamazian, Serguei Simonov, Pavel Dobrynin, Alexey Makunin, Anton Logachev, Aleksey Komissarov, Andrey Shevchenko, Vladimir Brukhin, Nikolay Cherkasov, Anton Svitin, Klaus-Peter Koepfli, Joan Pontius, Carlos A. Driscoll, Kevin Blackistone, Cristina Barr, David Goldman, Agostinho Antunes, Javier Quilez, Belen Lorente-Galdos, Can Alkan, Tomas Marques-Bonet, Marilyn Menotti-Raymond, Victor A. David, Kristina Narfstrom, Stephen J. O'Brien

Biology Faculty Articles

Background: Domestic cats enjoy an extensive veterinary medical surveillance which has described nearly 250 genetic diseases analogous to human disorders. Feline infectious agents offer powerful natural models of deadly human diseases, which include feline immunodeficiency virus, feline sarcoma virus and feline leukemia virus. A rich veterinary literature of feline disease pathogenesis and the demonstration of a highly conserved ancestral mammal genome organization make the cat genome annotation a highly informative resource that facilitates multifaceted research endeavors.

Findings: Here we report a preliminary annotation of the whole genome sequence of Cinnamon, a domestic cat living in Columbia (MO, USA), …

The Effects Of Sugar Consumption And Race On Satisfaction With Body Size And Weight, Diego Rubalcava

Undergraduate Research Conference

No abstract provided.

Global Population-Specific Variation In Mirna Associated With Cancer Risk And Clinical Biomarkers, Renata Rawlings-Goss, Michael Campbell, Sarah Tishkoff

Department of Biology Faculty Publications

Background: MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes.

Gene-Environment Interactions In Human Health: Case Studies And Strategies For Developing New Paradigms And Research Methodologies, Fatimah Linda Collier Jackson

Department of Biology Faculty Publications

THE SYNERGISTIC EFFECTS OF GENES AND THE ENVIRONMENT ON HEALTH ARE EXPLORED IN THREE CASE STUDIES: adult lactase persistence, autism spectrum disorders, and the metabolic syndrome, providing examples of the interactive complexities underlying these phenotypes. Since the phenotypes are the initial targets of evolutionary processes, understanding the specific environmental contexts of the genetic, epigenetic, and environmental changes associated with these phenotypes is essential in predicting their health implications. Robust databases must be developed on the local scale to deconstruct both the population substructure and the unique components of the environment that stimulate geographically specific changes in gene expression patterns. To …

Multiplex Ssr-Pcr Analysis Of Genetic Diversity And Redundancy In The Philippine Rice (Oryza Sativa L.) Germplasm Collection, Jamaica L. Delos Reyes, Vivian A. Panes, Dindo A. Tabanao, Gabriel O. Romero

Biology Faculty Publications

Rice germplasm conservation is vital to ensuring the availability of a rich gene pool for future varietal improvement programs. However, with limited resources for gene banking, there is a need to identify and prioritize unique accessions in the PhilRice gene bank for maximum resource utilization. A robust and unequivocal way to identify duplicates is through multiplex SSR-PCR DNA fingerprinting. The present study established the optimal concentrations and reaction conditions for the successful amplification of PCR products using a multiplex panel composed of rice simple sequence repeat (SSR) markers, namely RM312, RM316, RM514 and RM171. The panel was then used to …

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.

Choline And Choline Metabolite Patterns And Associations In Blood And Milk During Lactation In Dairy Cows, Virginia M. Artegoitia, Jesse L. Foote, Federico M. Harte, Shawn R. Campagna, Michael J. De Veth

Department of Animal Science: Faculty Publications

Milk and dairy products are an important source of choline, a nutrient essential for human health. Infant formula derived from bovine milk contains a number of metabolic forms of choline, all contribute to the growth and development of the newborn. At present, little is known about the factors that influence the concentrations of choline metabolites in milk. The objectives of this study were to characterize and then evaluate associations for choline and its metabolites in blood and milk through the first 37 weeks of lactation in the dairy cow. Milk and blood samples from twelve Holstein cows were collected in …

Chlorovirus Pbcv-1 Encodes An Active Copper-Zinc Superoxide Dismutase, Ming Kang, Garry A. Duncan, Charles Kuszynski, George Oyler, Jiayin Zheng, Donald F. Becker, James L. Van Etten

James Van Etten Publications

Superoxide dismutases (SODs) are metalloproteins that protect organisms from toxic reactive oxygen species by catalyzing the conversion of superoxide anion to hydrogen peroxide and molecular oxygen. Chlorovirus PBCV-1 encodes a 187-amino-acid protein that resembles a Cu-Zn SOD with all of the conserved amino acid residues for binding copper and zinc (named cvSOD). cvSOD has an internal Met that results in a 165-amino-acid protein (named tcvSOD). Both cvSOD and tcvSOD recombinant proteins inhibited nitroblue tetrazolium reduction of superoxide anion generated in a xanthine-xanthine oxidase system in solution. tcvSOD was chosen for further characterization because it was easier to produce. Recombinant tcvSOD …

The Evolution Of Genomic Imprinting: Theories, Predictions And Empirical Tests, M M. Patten, L Ross, J P. Curley, David C. Queller, R Bonduriansky, J B. Wolf

Biology Faculty Research

The epigenetic phenomenon of genomic imprinting has motivated the development of numerous theories for its evolutionary origins and genomic distribution. In this review, we examine the three theories that have best withstood theoretical and empirical scrutiny. These are: Haig and colleagues’ kinship theory; Day and Bonduriansky’s sexual antagonism theory; and Wolf and Hager’s maternal–offspring coadaptation theory. These theories have fundamentally different perspectives on the adaptive significance of imprinting. The kinship theory views imprinting as a mechanism to change gene dosage, with imprinting evolving because of the differential effect that gene dosage has on the fitness of matrilineal and patrilineal relatives. …

Rna Interference As A Tool For The Functional Analysis Of Genes In The Colorado Potato Beetle, Leptinotarsa Decemlineata (Say), Ashley Danielle Yates

Department of Entomology: Dissertations, Theses, and Student Research

RNA interference (RNAi) is a naturally occurring phenomenon in eukaryotes in which a double-stranded RNA (dsRNA) suppresses the expression of a target gene. RNAi has markedly changed the way in which functional genetics studies are performed, especially in non-model organisms. In insects, the efficacy of RNAi is influenced by several factors, including the species and the methods of dsRNAs delivery.

The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is a pest of the plant family Solanaceae. RNAi in the CPB is of interest for potential use in insect management and as a tool to study the interaction with host plants. …

General Approaches For Combining Multiple Rare Variant Associate Tests Provide Improved Power Across A Wider Range Of Genetic Architecture, Nathan L. Tintle, Brian Greco, Allison Hainline, Keli Liu, Jaron Arbet, Alejandra Benitez, Kelsey Grinde

Faculty Work Comprehensive List

In the wake of the widespread availability of genome sequencing data made possible by way of nextgeneration technologies, a flood of gene‐based rare variant tests have been proposed. Most methods claim superior power against particular genetic architectures. However, an important practical issue remains for the applied researcher—namely, which test should be used for a particular association study which may consider multiple genes and/or multiple phenotypes. Recently, tests have been proposed which combine individual tests to minimize power loss while improving the robustness to a wide range of genetic architectures. In our analysis, we propose an expansion of these approaches, by …

Potential Roles Of Peroxidases In Caenorhabditis Elegans Innate Immunity, George R. Tiller, George R. Tiller

Dissertations and Theses (Open Access)

The production of ROS (reactive oxygen species) in response to pathogen detection is a rapid, nonspecific response that is evolutionarily conserved from nematodes to humans. ROS serve as direct and indirect effectors of innate and adaptive immunity. In Caenorhabditis elegans, a ROS burst is observed during infection and is mediated by the dual oxidase BLI-3, which produces H₂O₂. RNAi (RNA interference) to reduce the amount of BLI-3 results in a significant increase in susceptibility to pathogens, suggesting BLI-3 has a role in the immune response. However, H₂O₂ by itself is not a …

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations and Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Development Of Chimeric Type Iv Secretion Systems For Transfer Of Heterologous Substrates Across The Gram-Negative Cell Envelope, Trista M. Berry

Dissertations and Theses (Open Access)

Many bacteria use Type IV Secretion Systems (T4SSs) to aid in pathogenesis by translocating virulence factors across the cell envelope and into eukaryotic cells. These systems are structurally and functionally diverse, but are often compared to the archetypal VirB/VirD4 T4SS of Agrobacterium tumefaciens. This system is composed of the VirD4 type IV coupling protein (T4CP) and 11 VirB subunits (VirB1-11) that assemble as the secretion channel and an extracellular pilus. The T4CP is an inner membrane ATPase that interacts with T4SS substrates and the secretion channel, and is thought to link substrates with the secretion channel and possibly energize …

Utilizing Haplotypes For Sensitive Snp Array-Based Discovery Of Somatic Chromosomal Mutations, Selina M. Vattathil

Dissertations and Theses (Open Access)

Somatic copy-number (CN) gains and losses and copy-neutral loss of heterozygosity (CNLOH) frequently occur in tumors and play a major role in the progression of disease by altering gene dosage and unmasking deleterious recessive variants. Characterizing these mutations in an individual tumor sample is therefore critical for research on the relationship of specific mutations to disease outcome and for clinical decision-making based on mutations with known impact. A pervasive hindrance to sensitive detection of these mutations is genetic heterogeneity and high levels of contaminating normal cells in tumor samples, which limit the fraction of cells carrying informative mutations. The method …

Genomic Characterization Of Polyps In Familial Adenomatous Polyposis Patients And Identification Of Candidate Chemopreventive Drugs, Francis A. San Lucas

Dissertations and Theses (Open Access)

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by APC germline mutations and the development of hundreds to thousands of premalignant adenomas in the gastrointestinal tract at a young age. If left untreated, these patients inevitably develop colon cancer (CRC) and small bowel tumors. We performed exome sequencing of samples from 12 FAP patients to characterize adenomas and to identify candidate genes of adenoma development that may serve as potential targets for chemoprevention drug development. From each patient, a blood and at least one polyp were sequenced with a total of 25 polyps analyzed. In some cases, normal …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations and Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

Development Of A Molecular Gram-Stain Assay For The Diagnosis Of Blood Stream Infections Associated With Sepsis, Douglas Bryan Litwin

Dissertations and Theses (Open Access)

Sepsis is a serious medical condition resulting from the severe dysregulation of the immune response that is generally triggered by infection. It affects more than 1.1 million Americans, has an average mortality rate of 30%, and is estimated to cost $24.3 billion annually. Currently, blood culture followed by Gram-stain analysis is the gold standard for diagnosing bacterial infections associated with sepsis. This method generates a high rate of false negative results and, in general, requires 20 to 48 hr to provide results. Both of these problems are related to the requirement that the bacterial pathogens grow under defined laboratory conditions. …

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Graduate Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important …