Genetics and Genomics Commons^™

Distribution And Population Structure Of The Invasive Nitellopsis Obtusa (Desv. In Loisel.) J. Groves And Native Species Of Characeae In The Northeast U.S.A., Robin Sleith

Dissertations, Theses, and Capstone Projects

Freshwater ecosystems are some of the most biologically diverse environments on Earth. Billions of humans rely on functioning freshwater ecosystems for drinking water and many other services. These ecosystems are increasingly threatened by human impacts including nutrient pollution, invasive species, and climate change. Here I contribute four research chapters that investigate freshwater diversity and ecosystem threats using the Characeae, a family of freshwater green macroalgae, as a study system. Characeae are a diverse and ancient group with more than 500 extant species and a fossil history spanning at least 250 million years. These algae are macrophytes in freshwater ecosystems, and …

Activation Of The Bile Acid Pathway And No Observed Antimicrobial Peptide Sequences In The Skin Of A Poison Frog, Megan L. Civitello, Robert Denton, Michael A. Zasloff, John H. Malone

Biology Publications

The skin secretions of many frogs have genetically-encoded, endogenous antimicrobial peptides (AMPs). Other species, especially aposematic poison frogs, secrete exogenously derived alkaloids that serve as potent defense molecules. The origins of these defense systems are not clear, but a novel bileacid derived metabolite, tauromantellic acid, was recently discovered and shown to be endogenous in poison frogs (Mantella, Dendrobates, and Epipedobates). These observations raise questions about the evolutionary history of AMP genetic elements, the mechanism and function of tauromatellic acid production, and links between these systems. To understand the diversity and expression of AMPs among frogs, we assembled skin transcriptomes of …

A Phewas Study Of A Large Observational Epidemiological Cohort Of African Americans From The Regards Study, Xueyan Zhao, Xin Geng, Vinodh Srinivasasainagendra, Ninad Chaudhary, Suzanne Judd, Virginia Wadley, Orlando M. Gutiérrez, Henry Wang, Ethan M. Lange, Leslie A. Lange, Daniel Woo, Frederick W. Unverzagt, Monika Safford, Mary Cushman, Nita Limdi, Rakale Quarells, Donna K. Arnett, Marguerite R. Irvin, Degui Zhi

Epidemiology and Environmental Health Faculty Publications

Background: Cardiovascular disease, diabetes, and kidney disease are among the leading causes of death and disability worldwide. However, knowledge of genetic determinants of those diseases in African Americans remains limited.

Results: In our study, associations between 4956 GWAS catalog reported SNPs and 67 traits were examined among 7726 African Americans from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is focused on identifying factors that increase stroke risk. The prevalent and incident phenotypes studied included inflammation, kidney traits, cardiovascular traits and cognition. Our results validated 29 known associations, of which eight associations were reported for the …

Gene Co-Expression Networks Analysis Reveal Novel Molecular Endotypes In Alpha-1 Antitrypsin Deficiency, Jen-Hwa Chu, Wenlan Zang

Yale Day of Data

Rationale:Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction. The exact mechanism through which AATD leads to lung disease is incompletely understood.

Objectives: To investigate the effect of AAT genotype and augmentation therapy on bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) transcriptome, while examining the link between gene expression profiles, and clinical features of AATD.

Methods: We performed RNA-Seq on RNA extracted from BAL and PBMC on samples obtained from 89 AATD patients enrolled in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Differential …

Non-Invasive Analysis Of The Sputum Transcriptome Discriminates Clinical Phenotypes Of Asthma, Xiting Yan

Yale Day of Data

Whole transcriptome wide gene expression profiles in the sputum and circulation from 100 asthma patients were measured using the Affymetrix HuGene 1.0ST arrays. Unsupervised clustering analysis based on pathways from KEGG were used to identify TEA clusters of patients from the sputum gene expression profiles. The identified TEA clusters have significantly different pre-bronchodilator FEV1, bronchodilator responsiveness, exhaled nitric oxide levels, history of hospitalization for asthma and history of intubation. Evaluation of TEA clusters in children from Asthma BRIDGE cohort confirmed the identified differences in intubation and hospitalization. Furthermore, evaluation of the TH2 gene signatures suggested a much lower prevalence of …

A Novel Pathway-Based Distance Score Enhances Assessment Of Disease Heterogeneity In Gene Expression, Yunqing Liu, Xiting Yan

Yale Day of Data

Distance-based unsupervised clustering of gene expression data is commonly used to identify heterogeneity in biologic samples. However, high noise levels in gene expression data and the relatively high correlation between genes are often encountered, so traditional distances such as Euclidean distance may not be effective at discriminating the biological differences between samples. In this study, we developed a novel computational method to assess the biological differences based on pathways by assuming that ontologically defined biological pathways in biologically similar samples have similar behavior. Application of this distance score results in more accurate, robust, and biologically meaningful clustering results in both …

Mrub_3014 Is Orthologous To B2756, Samir Abdelkarim, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of the gene Mrub_3014, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system. We predict that Mrub_3014 (DNA coordinates 3054943..3055575) encodes CRISPR-associated protein Cse3/case which function as an endonuclease. Our hypothesis is supported by identical hits for Mrub_3014 and b2756 to the KEGG, Pfam, TIGRfam, CDD and PDB databases, as well as a low E-value for a pairwise NCBI BLAST comparison. Both protein products are predicted to be localized …

M. Ruber Mrub_3013 Is Orthologous To E. Coli B2755, Laura Butcher, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological function of gene Mrub_3013, which we hypothesize is orthologous to b2755 in E. coli K12 MG1655 (a.k.a. Cas1). We investigated the biological function of a gene with the M. ruber locus tag of Mrub_3013, which we hypothesize is a component of the CRISPR-Cas prokaryotic defense system in M. ruber. We predict that Mrub_3013 (DNA coordinates 3,053,978-3,054,940) encodes the protein Cas1 which as part of the CRISPR-Cas system, selects and cuts the foreign …

Mrub_3020, A Paralog Of Mrub_1489, Is Orthologous To E. Coli Casc (Locus Tag B2761), Alfred Dei-Ampeh, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the biological functions of two genes: mrub_3020 and mrub_1489. We make two hypotheses in this investigation: a) mrub_3020 is orthologous to the gene b2761 in E. coli K12 MG1655 (a.k.a. casC); b) mrub_1489 is a paralog of mrub_3020. We also predict that the two genes encode unique proteins: mrub_3020 with DNA coordinates 3060491…3063190 encodes a CRISPR – associated helicase (Cas3) that supports the Cascade complex of the CRISPR – Cas adaptive immune system …

Effects Of Temperature On Crispr/Cas System, Eddie Beckom, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses a collection of online bioinformatics tools to predict gene function. We investigated the effect of temperature on the complexity of CRISPR/Cas systems in bacterial organisms across temperature classifications. We predict that temperature extremes would result in CRISPR/Cas systems with multiple operons, repeating cas genes, and complex systems. CRISPR/Cas systems can be classified into three types with a number of subtypes based on the CRISPR-associated genes, cas genes, present in a given organism. Our hypothesis is supported by the presence of multiple operons in thermophilic organisms based on …

Comparative Analysis Of Four Dna Preparation Kits For Quercus Falcata, Palustris, And Rubra Dna Extractions And Subsequent Dna Sequencing, Devin Cummins, Timothy D. Trott

Research in Biology

In 2011, of the 8.7 million species of lif suspected to populate the globe only 1.2 million had been catalogued and it was estimated that 1,200 years would pass before the remainder were processed, allowing the possibility that some species would go extinct before they were even discovered (Mora, Tittensor, Adl, Simpson, & Worm, 2011). DNA barcoding may provide an answer to this problem. According to Hebert and Gregory, “DNA barcoding will accelerate the pace of species discovery by allowing taxonomists to rapidly sort specimens... by highlighting divergent taxa that may represent new species… and by making species identifications more …

Transcription Factor Binding Site Clusters Identify Target Genes With Similar Tissue-Wide Expression And Buffer Against Mutations., Peter Rogan, Ruipeng Lu

Biochemistry Publications

Background: The distribution and composition of cis-regulatory modules composed of transcription factor (TF) binding site (TFBS) clusters in promoters substantially determine gene expression patterns and TF targets. TF knockdown experiments have revealed that TF binding profiles and gene expression levels are correlated. We use TFBS features within accessible promoter intervals to predict genes with similar tissue-wide expression patterns and TF targets using Machine Learning (ML). Methods: Bray-Curtis Similarity was used to identify genes with correlated expression patterns across 53 tissues. TF targets from knockdown experiments were also analyzed by this approach to set up the ML framework. TFBSs were …

Forms Of Supplemental Selenium In Vitamin-Mineral Mixes Differentially Affect Serological And Hepatic Parameters Of Growing Beef Steers Grazing Endophyte-Infected Tall Fescue, Yang Jia

Theses and Dissertations--Animal and Food Sciences

Consumption of endophyte-infected tall fescue results in a syndrome of negatively altered physiological systems, collectively known as fescue toxicosis. Another challenge to endophyte-infected tall fescue -based beef cattle operations is that the soils often are selenium (Se) poor, necessitating the need to provide supplemental Se. To test the general hypothesis that different forms of supplemental Se would ameliorate the negative effects of fescue toxicosis, predominately-Angus steers (BW = 183 ± 34 kg) were randomly selected from herds of fall-calving cows grazing an endophyte-infected tall fescue pasture and consuming vitamin-mineral mixes that contained 35 ppm Se as sodium selenite (ISe), SELPLEX …

Effects Of Suv39h1 And Suv420h1/H2 On Programmed Genome Rearrangement In Petromyzon Marinus, Claire A. Scott

Oswald Research and Creativity Competition

The sea lamprey (Petromyzon marinus), diverged from the vertebrate lineage roughly 550 million years ago, prior to the evolution of several major morphological features such as jaws and paired fins/appendages. Lamprey therefore provides a comparative perspective that can be used to study the evolution of differences in genome regulation, including epigenetics and programmed genome rearrangement (PGR). Programmed genome rearrangement is a unique regulatory mechanism wherein specific genes are effectively turned off by completely eliminating their sequences from the genome. Through PGR, lamprey delete approximately 20% of their genome from all somatic cells, with these specific sequences being only …

Effects Of A Systemic High Urea Concentration On The Endometrial And Embryonic Transcriptomes Of The Mare, Yatta Linhares Boakari

Theses and Dissertations--Veterinary Science

Pregnancy loss remains a major source of economic cost to the equine industry. Frequently, the exact causes of pregnancy loss remain unknown. It has been shown, in other species, that increased dietary protein leading to elevated blood urea nitrogen concentrations (BUN) can be a factor in decreased survival of the early embryo. Our studies provided novel information regarding the effects of elevated BUN on endometrium and embryos from mares as well as insights on changes in their gene expression. Our first objective was to develop an experimental model to elevate BUN during diestrus using intravenous urea infusion. We analyzed the …

Computational Tools For The Dynamic Categorization And Augmented Utilization Of The Gene Ontology, Eugene Waverly Hinderer Iii

Theses and Dissertations--Molecular and Cellular Biochemistry

Ontologies provide an organization of language, in the form of a network or graph, which is amenable to computational analysis while remaining human-readable. Although they are used in a variety of disciplines, ontologies in the biomedical field, such as Gene Ontology, are of interest for their role in organizing terminology used to describe—among other concepts—the functions, locations, and processes of genes and gene-products. Due to the consistency and level of automation that ontologies provide for such annotations, methods for finding enriched biological terminology from a set of differentially identified genes in a tissue or cell sample have been developed to …

Multigenerational Genomic And Epigenetic Effects Of Manufactured Silver Nanomaterials In Caenorhabditis Elegans, Anye Wamucho

Theses and Dissertations--Toxicology and Cancer Biology

There has been an increase in the incorporation of silver nanomaterials into consumer products due to their antimicrobial properties. Therefore there is potential for silver nanoparticles (Ag-NPs) to leach out into the environment during different life-cycle stages of these nanomaterial-containing products. Concern about the toxicity of Ag-NPs has led to investigations into their toxic effects on a variety of organisms mainly using acute and sub-chronic, single-generation exposures. The focus of this project was to understand the effects of long-term continuous multigenerational exposure to AgNO₃ and Ag-NPs in both pristine and environmentally transformed forms, on the model organism, Caenorhabditis elegans …

Impact Of Industrial Biocides On Bacterial Isolates From Hydraulic Fracturing Produced Water, Waad Ahmed Aljohani

Dissertations, Master's Theses and Master's Reports

Biocides are antimicrobial compounds that are designed to kill diverse groups of microbes in an untargeted fashion. Glutaraldehyde and DBNPA are commonly used to manage microbial growth in different industries. It is possible that biocide use may result in the development of bacterial resistance. However, resistance to DBNPA is believed to be limited under normal use conditions. We isolated a number of bacteria from produced water from a hydraulically fractured site in West Texas. We then tested the ability of these isolates to resist Glutaraldehyde and DBNPA. In this study, we found that these isolates have varying resistance to these …

Latent Growth Model Approach To Characterize Maternal Prenatal Dna Methylation Trajectories, Dana Lapato

Theses and Dissertations

Background. DNA methylation (DNAm) is a removable chemical modification to the DNA sequence intimately associated with genomic stability, cellular identity, and gene expression. DNAm patterning reflects joint contributions from genetic, environmental, and behavioral factors. As such, differences in DNAm patterns may explain interindividual variability in risk liability for complex traits like major depression (MD). Hundreds of significant DNAm loci have been identified using cross-sectional association studies. This dissertation builds on that foundational work to explore novel statistical approaches for longitudinal DNAm analyses. Methods. Repeated measures of genome-wide DNAm and social and environmental determinants of health were collected up to six …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Testing For Cryptic Diversity And Inference Of Population Structure In The Cosmopolitan Hoplonemertean Emplectonema Gracile (Nemertea), Paul L. Delaney Iv

Theses and Dissertations

Emplectonema gracile (Johnston 1837) is a hoplonemertean of marine intertidal hard-bottom communities and is distributed throughout the Northern Hemisphere. Although possessing a planktonic larval stage in its life history, the range of such cosmopolitan marine invertebrate species is often explained by cryptic speciation and anthropogenic transport. The purpose of this study is to test for possible cryptic species using mtDNA markers (COI and 16S rDNA) and to investigate population structure in E. gracile over a portion of its geographic range using mtDNA markers and ddRADseq nuclear SNP data. The results of both phylogenetic- and tree-based species delimitation revealed that E. …

Association Genetics And Local Adaptation Of Populus Trichocarpa Torr. & Gray, Hari Bahadur Chhetri

Graduate Theses, Dissertations, and Problem Reports (ETD)

A major goal in plant science is overcoming the recalcitrance of plant biomass to cellulose extraction, to enable efficient production of cellulosic biofuel. We have started to understand the genetic basis of some important traits such as cell wall chemistry, but we do not know anything about the key structural and functional traits such as wood anatomy that greatly affect plant biomass recalcitrance. Furthermore, biofuel feedstocks have to be adapted to varied environmental conditions to ensure high productivity in plantations, but little is known about the molecular mechanisms underlying local adaptation. With the advancement in sequencing and genotyping technologies, association …

Genomic Inference Of Inbreeding In Alexander Archipelago Wolves (Canis Lupus Ligoni) On Prince Of Wales Island, Southeast Alaska, Katherine Emily Zarn

Graduate Student Theses, Dissertations, & Professional Papers

Habitat loss and climate change are increasingly resulting in reduction and fragmentation of wildlife populations. Populations that have experienced fragmentation and decreases in abundance are at heightened risk of inbreeding due to reduced opportunities to mate with unrelated conspecifics. Prolonged or extensive inbreeding can result in inbreeding depression via the exposure of deleterious alleles in long runs of homozygosity. Alexander Archipelago wolves (Canis lupus ligoni) on Prince of Wales Island (POW) in Southeast Alaska are a small, isolated population of conservation concern that have experienced habitat loss and high harvest rates, and present an ideal system in which …

Effects Of Commercial Formulations Of Glyphosate On Saccharomyces Cerevisiae, Apoorva Ravi Shankar

Graduate Theses, Dissertations, and Problem Reports (ETD)

Commercial formulations of glyphosate are among the most extensively used herbicides around the world. The active ingredient, glyphosate, targets the aromatic amino acid pathway. This pathway is absent in mammals, resulting in low toxicity. Different formulations contain varying adjuvants and surfactants, whose synergistic effects are yet to be extensively studied at the cellular level. In this study, I tested multiple commercial formulations that showed a variation in growth phenotype among different yeast strains. To gain a better understanding of response and resistance mechanisms at the genome and transcriptome level, I carried out an in-lab evolution study, along with a transcriptome …

Understanding The Impacts Of Current And Future Environmental Variation On Central African Amphibian Biodiversity, Courtney A. Miller

LSU New Orleans Theses and Dissertations

Global climate change is projected to impact multiple levels of biodiversity by imposing strong selection pressures on existing populations, triggering shifts in species distributions, and reorganizing entire communities. The Lower Guineo-Congolian region in central Africa, a reservoir for amphibian diversity, is predicted to be severely affected by future climate change through rising temperatures and greater variability in rainfall. Geospatial modelling can be used to assess how environmental variation shapes patterns of biological variation – from the genomic to the community level – and use these associations to predict patterns of biological change across space and time. The overall goal of …

Power In Pairs: Assessing The Statistical Value Of Paired Samples In Tests For Differential Expression, John R. Stevens, Jennifer S. Herrick, Roger K. Wolff, Martha L. Slattery

Mathematics and Statistics Faculty Publications

Background: When genomics researchers design a high-throughput study to test for differential expression, some biological systems and research questions provide opportunities to use paired samples from subjects, and researchers can plan for a certain proportion of subjects to have paired samples. We consider the effect of this paired samples proportion on the statistical power of the study, using characteristics of both count (RNA-Seq) and continuous (microarray) expression data from a colorectal cancer study.

Results: We demonstrate that a higher proportion of subjects with paired samples yields higher statistical power, for various total numbers of samples, and for various strengths of …

Physella Acuta, Comparative Immunology And Evolutionary Aspects Of Gastropod Immune Function, Jonathan H. Schultz

Biology ETDs

Gastropod immunobiology has benefitted from investigations focused on the planorbid snail Biomphalaria glabrata, intermediate host for the human parasite Schistosoma mansoni. Though such concentrated efforts have elucidated fascinating aspects of invertebrate immunity, they have not provided full knowledge regarding the evolution of immune function among other gastropod species. This dissertation presents the importance of making strategic choices regarding which organisms to select for comparative immunology. Herein, the choice was made to investigate the immunobiology of Physella acuta, a freshwater snail species of the Physidae, a sister family to Planorbidae to which B. glabrata belongs. Benefiting greatly from …

Genetic Evolution And Prognostic Determinants Of Pancreatic Cancer On Longitudinal Liquid Biopsies, Vincent Bernard

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest 5-year survival rates amongst solid tumors. As early detection of PDAC is unusual and typically incidental, most patients present with locally advanced and metastatic disease where effective therapeutic strategies remain a significant unmet need. Specifically, surrogate biomarkers for tumor monitoring of PDAC may lead to improved elucidation of clinical actionability and prognostic potential. On the other hand, tumor tissue is rarely sampled in patients presenting with de novo or recurrent metastatic PDAC, apart from a fine needle aspiration or a core needle biopsy performed for diagnosis. This precludes the opportunity for …

Improving Dbnsfp, Mingyao Lu

Dissertations and Theses (Open Access)

IMPROVING dbNSFP

Mingyao Lu, B.S.

Advisory Professor: Xiaoming Liu, Ph.D.

The analysis and interpretation of DNA variation are very important for the Whole Exome studies (WES). Genome research has focused on single nucleotide variants (SNVs). Since indels are as important as SNVs, especially indels in coding regions are often candidates of disease-causing variants, thus, it is necessary to expand the focus to include indel mutations.

The goal of my project is to provide an automatic annotation pipeline to the WES based disease studies project by extending the dbNSFP with a tool for automated indel annotation and deleteriousness prediction. The current …

Genome Wide Association Studies For Identification Of Markers Linked To Sucrose Traits In Sugarcane, Nathanael Darrell Fickett

LSU Doctoral Dissertations

Sugarcane, being a complex aneu-polyploid, poses unique challenges to fine mapping of quantitative trait loci (QTL) controlling agronomic traits of interest. Genome-wide association studies (GWAS) could be a better alternative to identify molecular markers associated with specific traits due to high linkage disequilibrium in sugarcane. In the first study, marker-trait associations (MTAs) were evaluated for three sucrose traits, Brix, total recoverable sugar (TRS), and percent sucrose on 48 elite and historic Louisiana breeding clones using 1,062 alleles. These sucrose traits were highly correlated (P-value < 0.0001) at >0.96. TASSEL 5.1 and JMP Genomics 8.0 were compared with eight models run in each program. …