Life Sciences Commons^™

Genomic Analyses Of Paenibacillus Polymyxa Cr1, A Bacterium With Potential Applications In Biomass Degradation And Biofuel Production, Alexander W. Eastman

Electronic Thesis and Dissertation Repository

Lignin is a polyphenolic heteropolymer constituting between 18 to 35% of lignocellulose and is recognized as preventative of cellulosic biofuel commercialization. Paenibacillus polymyxa CR1 was isolated from naturally degrading corn stover and shown to produce alcohols using lignin as a sole carbon source. Genome sequencing and comparative genomics of P. polymyxa CR1 identified two homologs, a Dyp-type peroxidase and a laccase, which have previously been implicated in lignin metabolism in other bacteria. Knockout mutants of the identified genes displayed no growth deficiency and P. polymyxa CR1 is incapable of metabolizing common aromatic intermediates of lignin, suggesting the bacterium employs a …

Population Genomic Inference Of Ecology, Conservation, Evolution, And Demographic History Of Atlantic Seahorses And Pipefishes (Syngnathidae), Joel Thomas Boehm

Dissertations, Theses, and Capstone Projects

In the Atlantic Ocean powerful directional ocean currents can play a significant role in the formation and persistence of marine species. Syngnathidae fishes have a sparse fossil record, high morphological plasticity, and many of these species are difficult to observe in the wild, therefore they frequently lack life history information and the status of regional lineages and species designations are often obscure. In this dissertation I explore the ecology, evolution, and conservation of primarily Atlantic seahorses (Hippocampus) and pipefish (Syngnathus) in four core chapters, using differing genetic datasets ranging from mitochondrial DNA to genome-wide RAD sequences. Most Synganthids have the …

Genome-Scale Analyses Of Transcription And Transcriptional Regulation In Bacteria, Devon Marie Fitzgerald

Legacy Theses & Dissertations (2009 - 2024)

The textbook model of bacterial transcription regulation posits that promoters occur immediately upstream of genes and that transcription factors (TFs) modulate transcription through promoter-proximal binding. However, the recent application of unbiased genome-wide approaches, such as ChIP-seq and RNA-seq, has revealed a much more complex picture, including TF binding and transcription initiation occurring in unexpected locations. This dissertation describes the use of deep sequencing-based approaches to evaluate the genome-wide binding of transcription-related proteins and identify locations of transcription initiation. I have assessed the genome-wide binding of three Escherichia coli TFs and an alternative σ factor. Additionally, I have analyzed genome-wide patterns …

Characterizing The Fitness Landscapes Of Gut Symbionts In Defined Community And Diet Contexts, Meng Wu

Arts & Sciences Electronic Theses and Dissertations

A species' niche is the description of all the environmental conditions required to permit a population of that species to persist, including the effects of the population on those conditions. This definition includes the species' resource requirements, as well as stress tolerances and interactions with other species acting as competitors, predators, parasites, and mutualists. The human gut microbiota serves as a microbial `metabolic organ' tasked in part with the biotransformation of many components of our diet. Relatively little is known about the factors that allow members of the human gut microbiota to persist in a habitat that experiences marked changes …

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

Dissertations & 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 …

Blattabacterium Genome: Structure, Function, And Evolution, Austin Alleman

Biology Theses

Blattabacterium, an obligate bacterial endosymbiont, functions as a mechanism of nitrogen recycling and nutrient synthesis within the Order Blattaria (cockroaches). Through genome annotation and the application of bioinformatics, the function of Blattabacterium within the cockroach Nauphoeta cinerea was described. Results of analyses indicate that the Blattabacterium genome, comprised of ~620,000 base pairs and ~620 individual genes, is drastically reduced when compared Flavobacterium, Blattabacterium’s closest free-living relative. However, the Blattabacterium genome retained functionality vital to host survival and fecundity and functions as a source of additional nutrient biosynthesis within its host. Like other intracellular endosymbionts, the Blattabacterium genome has a G+C …

Small Rna Expression During Programmed Rearragement Of A Vertebrate Genome, Joseph R. Herdy Iii

Theses and Dissertations--Biology

The sea lamprey (Petromyzon marinus) undergoes programmed genome rearrangements (PGRs) during embryogenesis that results in the deletion of ~0.5 Gb of germline DNA from the somatic lineage. The underlying mechanism of these rearrangements remains largely unknown. miRNAs (microRNAs) and piRNAs (PIWI interacting RNAs) are two classes of small noncoding RNAs that play important roles in early vertebrate development, including differentiation of cell lineages, modulation of signaling pathways, and clearing of maternal transcripts. Here, I utilized next generation sequencing to determine the temporal expression of miRNAs, piRNAs, and other small noncoding RNAs during the first five days of lamprey …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Methods For Integrative Analysis Of Genomic Data, Paul Manser

Theses and Dissertations

In recent years, the development of new genomic technologies has allowed for the investigation of many regulatory epigenetic marks besides expression levels, on a genome-wide scale. As the price for these technologies continues to decrease, study sizes will not only increase, but several different assays are beginning to be used for the same samples. It is therefore desirable to develop statistical methods to integrate multiple data types that can handle the increased computational burden of incorporating large data sets. Furthermore, it is important to develop sound quality control and normalization methods as technical errors can compound when integrating multiple genomic …

On The Origin Of Phenotypic Variation: Novel Technologies To Dissect Molecular Determinants Of Phenotype, Francesco Vallania

All Theses and Dissertations (ETDs)

This thesis describes the conception, design, and development of novel computational tools, theoretical models, and experimental techniques applied to the dissection of molecular factors underlying phenotypic variation. The first part of my work is focused on finding rare genetic variants in pooled DNA samples, leading to the development of a novel set of algorithms, SNPseeker and SPLINTER, applied to next-generation sequencing data. The second part of my work describes the creation of a reporter system for DNA methylation for the purpose of dissecting the genetic contribution of tissue-specific patterns of DNA methylation across the genome. Finally the last part of …

Resolving The Genetic Etiology Of Hypercholesterolemia In Familial Combined Hyperlipidemia, Mary A. Bamimore

Electronic Thesis and Dissertation Repository

Hypercholesterolemia is a classical risk factor for cardiovascular disease development. The genetic etiology of hypercholesterolemia in familial combined hyperlipidemia (FCH), one of the most common genetic dyslipidemias, is poorly understood. We aimed at understanding the genetic etiology of hypercholesterolemia in FCH.

Sequencing, genotyping and computational analyses were performed in a case-control setting to better understand the ‘nature’ aspect of hypercholesterolemia in FCH. My findings suggest that FCH more likely has a polygenic basis.

All my findings have shown that the genetic definition of a disease, especially relatively common diseases like FCH that have been previously considered to be monogenic, may …

Root Kinematics In Relation To Temperature And Genome Size In Wild And Domesticated Zea., Avery B. Cromwell

Master's Theses

We studied root kinematics in relation to temperature and genome size variation in teosinte (Zea mays subspecies parviglumis) and corn (Zea mays subspecies mays). Corn had significantly faster radicle growth than teosinte when grown at a constant temperature. Both species exhibited variation in seed size and for each species larger seeds had faster root growth. Genome size was not significantly correlated with faster radicle growth rates across multiple land races of corn. To examine temperature dependent growth in corn and teosinte, a germinated seedling was grown at multiple temperatures. Growth rates at these temperatures were used …

Characterization Of Uncultured, Human Oral Microbiota Using A Targeted, Single-Cell Genomics Approach, Alisha Gail Campbell

Doctoral Dissertations

Microbial communities associated with the human oral cavity are complex, and many oral microbes have yet to be cultured. These uncultured community members are of interest ecologically and phylogenetically, and a number of uncultured species have been positively correlated with oral diseases such as periodontitis. Thus, an approach was adapted to selectively separate single cells from mixed populations of oral bacteria and obtain genomic information for uncultured community members. A combination of fluorescent labeling, cell sorting with flow cytometry and multiple displacement amplification was used to obtain sufficient genomic material for whole-genome pyrosequencing.

The first targets were from uncultured oral …

Detection Of Bacterial Retroelements Using Genomics, Sen Mu

Electronic Theses and Dissertations

The reverse flow of genetic information can occur when a special DNA polymerase called Reverse Transcriptase (RT) copies the genetic information in an RNA molecule back into a complementary DNA. One type of RT encoding gene found in bacteria is called a retron element. Recent bacterial genome sequencing projects have revealed many examples of retron RT genes. This gene assignment is based on comparison with a few known retron RT proteins. However, RT proteins are highly diverse in their amino acid sequences, and thus the assigned identity of these RT proteins as retrons in genome databases is questionable. One way …

Family Cancer History And Pedigrees As A Public Health Intervention For Promoting Health And Preventing Prostate Cancer In African American Men, Holisa Wharton

All Dissertations

ABSTRACT
Prostate cancer is the most common cancer diagnosed in men and the second leading cause of cancer death among men in the United States. African-American men have substantially higher prostate cancer incidence and mortality than European-American men. It is unclear whether this incidence is due to acquired DNA changes (sporadic cancer) or if germline Mendelian genetics/genomics (inherited cancer) is the source of this health disparity. To explore this cause, the focus of this dissertation paper is family health history and hereditary prostate cancer. A family history tool is the most commonly used predictive instrument for hereditary prostate cancer. The …

Elucidating The Igfbp2 Signaling Pathway In Glioma Development And Progression, Kristen M. Holmes

Dissertations & Theses (Open Access)

Diffuse gliomas are highly lethal central nervous system malignancies which, unfortunately, are the most common primary brain tumor and also the least responsive to the very few therapeutic modalities currently available to treat them. IGFBP2 is a newly recognized oncogene that is operative in multiple cancer types, including glioma, and shows promise for a targeted therapeutic approach. Elevated IGFBP2 expression is present in high-grade glioma and correlates with poor survival. We have previously demonstrated that IGFBP2 induces glioma development and progression in a spontaneous glioma mouse model, which highlighted its significance and potential for future therapy. However, we did not …

Uses Of Genomic Predictions In Commercial Beef Cattle Operations, Matt Miller

Dairy Science

This paper aimed to achieve two different objectives. The first objective of this study was to identify and explain the genetic gain achieved in commercial beef cattle operations with the use of genomic predictions versus the use of visual appraisal and EPDs. The second goal of this paper was to develop a method to easily explain genomic predictions and their practical applications on commercial beef operations to a lay audience, specifically to ranchers. In order to accomplish these objectives, I evaluated three of the most common selection methods used by producers today. These included visual appraisal, expected progeny differences (EPDs), …

Genetics And Genomics Of Complex Diseases;Mouse Atherosclerosis Modifier Genes And Human Gene Expression After Bariatric Surgery, Stela Z. Berisha

ETD Archive

The overall goal of our research was to study and identify genes involved in the development of complex diseases in mice and humans through integrative genetic/genomic approaches. Two complex diseases were the focus of research, atherosclerosis and type 2 diabetes. Mouse models of atherosclerosis, in which the genetic background and the environment can be controlled for, were used to identify and validate atherosclerosis modifier genes. We studied an atherosclerosis quantitative trait locus (QTL) on the distal end of chromosome 5, called Ath24, and generated interval-specific congenic mice on the atherosclerosis resistant AKR and susceptible DBA/2 apoE-deficient strains. To date we …

Bridging Functional Genomics And Toxicogenomics Through Dna Microarrays In A Fish Model, Shuzhao Li

Dissertations

In a case study of finding gene expression signatures for environmental stressors in Cyprinodon variegatus, this dissertation examines several important issues of applying DNA microarray technology to fish toxicogenomics. The most relevant disciplines, fish toxicogenomics and computational systems biology are reviewed in Chapter 1. Chapter 2 reviews major aspects of DNA microarray technology.

On DNA microarrays, even for probes that target the same transcript, large variations are seen in the probe signals. These variations are partly dependent and partly independent on probe sequences. Chapter 3 estimates the sequence independent variation by combining experimental and computational approaches. Chapter 4 and …

Cis-Regulatory Sequence And Co-Regulatory Transcription Factor Functions In Erα-Mediated Transcriptional Repression, Richard Leroy Smith

Theses and Dissertations

Estrogens exert numerous actions throughout the human body, targeting healthy tissue while also enhancing the proliferative capacity of breast cancers. Estrogen signaling is mediated by the estrogen receptor (ER), which binds DNA and ultimately affects the expression of adjacent genes. Current understanding of ER-mediated transcriptional regulation is mostly limited to genes whose transcript levels increase following estrogen exposure, though recent studies demonstrate that direct down-regulation of estrogen-responsive genes is also a significant feature of ER action. We hypothesized that differences in cis-regulatory DNA was a factor in determining target gene expression and performed computational and experimental studies to test this …

Viability Of Alternative Genetic Improvement Strategies Using Whole Genome Selection On Commercial Dairy Operations, Levi W.M. Gassaway

Master's Theses

The objective of this thesis was to determine the viability of alternative genetic improvement strategies (GIS). Each alternative GIS combined the use of whole genome selection (WGS) with common reproductive methods (non-sexed semen artificial insemination (AI), sexed semen AI, embryo transfer utilizing non-sexed semen AI) that can be found on a commercial dairy operation. The viability of each GIS was determined using a discounted gene flow model, designed with parameters of a typical western dairy operation, to evaluate the following variables: reproductive method, selection intensity, accuracy of prediction and female age-class. Of the GIS investigated, a heifer-based strategy that used …

Lipid Uptake And Metabolism In The Parasitic Protozoan Giardia Lamblia., Mayte Yichoy

Open Access Theses & Dissertations

Giardia lamblia is a protozoan parasite that causes various intestinal syndromes, and it is a common cause of water-borne illness worldwide, both in developed and developing countries. Giardia attaches to the mucosal epithelia of the duodenum below the bile duct, where it is exposed to bile salts and dietary lipids. G. lamblia is unable to synthesize lipids de novo and must therefore scavenge necessary lipids from its extracellular environment and remodel them as needed. However, the current lipidomic analysis (presented in this Dissertation) has revealed that while the Giardia lipidome is rich in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG), …

A Locus-Based Paradigm For Generating Systems Biological Inferences From Large Scale Functional Genomics Datasets, Ajish Dominic George

Legacy Theses & Dissertations (2009 - 2024)

Genomics data is growing at a exponential rate. The ability to integrate new results with existing knowledge about genomic biology is rapidly becoming the limiting factor as there no universal language with which to describe genomic functional elements. To integrate and compare new and existing genomic data, we define our basic functional unit of a genome to be a locus -- a set of positional coordinates along any genome with an arbitrary amount of functional annotations attached. The locus concept enables addressing genomic elements and annotations at any level of granularity from entire swaths of chromosomes to single base-positions. We …

The Family Fuselloviridae : Diversity And Replication Of A Hyperthermic Virus Infecting The Archaeon Genus Sulfolobus, Adam Joseph Clore

Dissertations and Theses

The virus family Fuselloviridae infects the hyperthermophilic and acidophilic Crenarchaeon genus Sulfolobus and has been isolated from terrestrial hotsprings worldwide. Two previously uncharacterized Fuselloviruses, SSV-13 and SSV-L1, were isolated and sequenced and are compared to the five fully sequenced viruses presently in the public databases. Conserved promoters in all viruses and similar putative origins of replication suggest that these viruses use a transcriptional and genomic replication program similar to the relatively well-characterized SSV1. Pairwise comparisons of conserved genes in the seven virus genomes show that, like its host Sulfolobus, these viruses' genetic divergence correlates with geographic separation. Genome rearrangements, horizontal …

Bioinformatics Tool Development And Sequence Analysis Of Rosaceae Family Expressed Sequence Tags, Margaret Staton

All Dissertations

BACKGROUND: An international community of researchers has generated a significant number of Expressed Sequence Tags (ESTs) for the Rosaceae, an economically important plant family that includes most temperate fruits such as apple, cherry, peach, and strawberry as well as other commercially valuable members. ESTs are fragments of expressed genes that can be used for gene discovery, developing markers for mapping and cultivar improvement via marker assisted selection. Efficient dissemination and integration of this data is best facilitated through a centralized and curated database with associated sequence analysis tools.

DESCRIPTION: The Genome Database for Rosaceae (GDR) was initiated to provide a …

Comparing Clustering Algorithms For Use With Genomic And Proteomic Data, Rebecca A. Olson

Theses and Dissertations

The Human Genome Project and related projects have resulted in the development of a number of new experimental and analytic tools for use in genomic and proteomic research. In the area of toxicogenomics, researchers are concerned with how genes react to exposure to certain chemicals. The United States Air Force is interested in the effect of exposure to mission-essential chemicals. Although military personnel may come into contact with chemicals such as hydrazine, risk assessment is usually very limited. On the genomic level, risk assessment is a multi-stop and multi-disciplinary process. The process begins with an experiment that exposes cells to …