Genetics and Genomics Commons^™

Relationship Of Global Dna Methylation With Cardiovascular Fitness And Body Composition, Michael Steele Jarrett

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: Global DNA Methylation (GDM), an epigenomic modification has been linked to the development of Cardiovascular Disease and its risk factors. Purpose: The purpose of this study was to determine if there is a significant correlation between GDM and cardiovascular fitness, as well as, measures of body composition. Methodology: 26 apparently healthy, adults (11 males) completed a physical activity and diet questionnaire, as well as, had a small blood sample (600μL) collected via finger prick for the determination of GDM. Body composition was assessed by means of a Dual-Energy X-ray Absorptiometry (DEXA) scan, while cardiovascular fitness was evaluated by the …

Physiologically-Based Pharmacokinetic Modeling For Predicting Caffeine/Theophylline-Ciprofloxacin Interactions, David M. Ng, Ali Navid

STAR Program Research Presentations

Dynamics of interactions between the drugs caffeine, theophylline, and ciprofloxacin are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drugs are distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body are reflected in the structure and functioning of the model. Multiple drugs can interact to increase or decrease their beneficial and/or undesired effects. This is important because some common substances, such as caffeine in coffee, soft drinks, and energy drinks, are actually drugs that affect the body. Ciprofloxacin is an inhibitor of caffeine and theophylline metabolism; such inhibition …

Prkca: Identification Of A Novel Downstream Target Of Wt1, Devin Jones

Dissertations and Theses (Open Access)

Wilms tumor is a childhood tumor of the kidney arising from the undifferentiated metanephric mesenchyme. Tumorigenesis is attributed to a number of genetic and epigenetic alterations. In 20% of Wilms tumors, Wilms tumor gene 1 (WT1) undergoes inactivating homozygous mutations causing loss of function of the zinc finger transcription factor it encodes. It is hypothesized that mutations in WT1 result in dysregulation of downstream target genes, leading to aberrant kidney development and/or Wilms tumor. These downstream target genes are largely unknown, and identification is important for further understanding Wilms tumor development. Heatmap data of human Wilms tumor protein …

Rna-Sequencing Applications: Gene Expression Quantification And Methylator Phenotype Identification, Guoshuai Cai

Dissertations and Theses (Open Access)

My dissertation focuses on two aspects of RNA sequencing technology. The first is the methodology for modeling the overdispersion inherent in RNA-seq data for differential expression analysis. This aspect is addressed in three sections. The second aspect is the application of RNA-seq data to identify the CpG island methylator phenotype (CIMP) by integrating datasets of mRNA expression level and DNA methylation status.

Section 1: The cost of DNA sequencing has reduced dramatically in the past decade. Consequently, genomic research increasingly depends on sequencing technology. However it remains elusive how the sequencing capacity influences the accuracy of mRNA expression measurement. We …

Reactin: Regulatory Activity Inference Of Transcription Factors Underlying Human Diseases With Application To Breast Cancer, Mingzhu Zhu, Chun-Chi Liu, Chao Cheng

Dartmouth Scholarship

Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs. Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between …

Association Study Of Common Genetic Variants And Hiv- 1 Acquisition In 6,300 Infected Cases And 7,200 Controls, Paul J. Mclaren, Cedric Coulonges, Stephan Ripke, Leonard H. Van Den Berg, Susan Buchbinder, Mary Carrington, Andrea Cossarizza, Judith Dalmau, Steven G. Deeks, Olivier Delaneau, Andrea De Luca, James J. Goedert, David W. Haas, Joshua T. Herbeck, Sekar Kathiresan, Gregory D. Kirk, Olivier Lambotte, Ma Luo, Simon Mallal, Danielle Van Manen, Javier Martinez-Picado, Florencia Pereyra, Francis A. Plummer, Guido Poli, Ying Qi, Pierre Rucart, Manj S. Sandhu, Patrick R. Shea, Hanneke Schuitemaker, Ioannis Theodorou, Fredrik Vannberg, Jan Veldink, Bruce D. Walker, Amy C. Weintrob, Cheryl Winkler, Steven M. Wolinsky, Amalio Telenti, David B. Goldstein, Paul I. W. De Bakker, Jean-Francois Zagury, Jacques Fellay

Biology Faculty Articles

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the …

Elk (Cervus Elaphus) Seasonal Habitat Selection In A Heterogeneous Forest Structure, Jesse N. Popp, David N.C. Mcgeachy, Josef Hamr

Aspen Bibliography

Seasonal habitat selection by the reintroduced Burwash elk population, approximately 30 km south of Sudbury, Ontario, has been analysed in order to assist in the development of future management. Twenty-five adult females were radio-collared and tracked 1–3 times a week for 3 years. The most prominent patterns included selection of intolerant hardwood forests (trembling aspen, white birch, and balsam poplar) during all seasons, while Great Lakes-St. Lawrence pines (white and red pine dominated stands) were used less than expected based on availability for all seasons. The selection patterns are likely associated with seasonal climatic conditions and forage preferences. Because the …

Differential Regulation Of White-Opaque Switching By Individual Subunits Of Candida Albicans Mediator, Anda Zhang, Zhongle Liu, Lawrence C. Myers

Dartmouth Scholarship

The multisubunit eukaryotic Mediator complex integrates diverse positive and negative gene regulatory signals and transmits them to the core transcription machinery. Mutations in individual subunits within the complex can lead to decreased or increased transcription of certain subsets of genes, which are highly specific to the mutated subunit. Recent studies suggest a role for Mediator in epigenetic silencing. Using white-opaque morphological switching in Candida albicans as a model, we have shown that Mediator is required for the stability of both the epigenetic silenced (white) and active (opaque) states of the bistable transcription circuit driven by the master regulator Wor1. Individual …

Translating Dosage Compensation To Trisomy 21, Jun Jiang, Yuanchun Jing, Gregory J. Cost, Jen-Chieh Chiang, Heather J. Kolpa, Allison M. Cotton, Dawn M. Carone, Benjamin R. Carone, David A. Shivak, Dmitry Y. Guschin, Jocelynn R. Pearl, Edward J. Rebar, Meg Byron, Philip D. Gregory, Carolyn J. Brown, Fyodor D. Urnov, Lisa L. Hall, Jeanne B. Lawrence

College of Science & Mathematics Departmental Research

Down syndrome (DS) is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21 (Chr21). We tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST. Using genome editing with zinc finger nucleases, we targeted a large, inducible XIST transgene into the Chr21 DYRK1A locus, in DS pluripotent stem cells. XIST RNA coats Chr21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a “Chr21 Barr Body.” This provides a model to study human chromosome inactivation and creates a system …

Transcription Factor Binding Profiles Reveal Cyclic Expression Of Human Protein-Coding Genes And Non-Coding Rnas, Chao Cheng, Matthew Ung, Gavin D. Grant, Michael L. Whitfield

Dartmouth Scholarship

Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and …

The Rate And Effects Of Spontaneous Mutation On Fitness Traits In The Social Amoeba, Dictyostelium Discoideum, David W. Hall, Sara Fox, Jennie J. Kuzdzal-Fick, Joan E. Strassmann, David C. Queller

Biology Faculty Research

We performed a mutation accumulation (MA) experiment in the social amoeba Dictyostelium discoideum to estimate the rate and distribution of effects of spontaneous mutations affecting eight putative fitness traits. We found that the per-generation mutation rate for most fitness components is 0.0019 mutations per haploid genome per generation or larger. This rate is an order of magnitude higher than estimates for fitness components in the unicellular eukaryote Saccharomyces cerevisiae, even though the base-pair substitution rate is two orders of magnitude lower. The high rate of fitness-altering mutations observed in this species may be partially explained by a large mutational target …

Apolipoprotein E Mediates Attachment Of Clinical Hepatitis C Virus To Hepatocytes By Binding To Cell Surface Heparan Sulfate Proteoglycan Receptors, Jieyun Jiang, Xianfang Wu, Hengli Tang, Guangxiang Luo

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Our previous studies demonstrated that the cell culture-grown hepatitis C virus of genotype 2a (HCVcc) uses apolipoprotein E (apoE) to mediate its attachment to the surface of human hepatoma Huh-7.5 cells. ApoE mediates HCV attachment by binding to the cell surface heparan sulfate (HS) which is covalently attached to the core proteins of proteoglycans (HSPGs). In the present study, we further determined the physiological importance of apoE and HSPGs in the HCV attachment using a clinical HCV of genotype 1b (HCV1b) obtained from hepatitis C patients and human embryonic stem cell-differentiated hepatocyte-like cells (DHHs). DHHs were found to resemble primary …

Carcinogenic Adducts Induce Distinct Dna Polymerase Binding Orientations, Kyle B. Vrtis, Radoslaw P. Markiewicz, Louis J. Romano, David Rueda

Chemistry Faculty Research Publications

DNA polymerases must accurately replicate DNA to maintain genome integrity. Carcinogenic adducts, such as 2-aminofluorene (AF) and N-acetyl-2-aminofluorene (AAF), covalently bind DNA bases and promote mutagenesis near the adduct site. The mechanism by which carcinogenic adducts inhibit DNA synthesis and cause mutagenesis remains unclear. Here, we measure interactions between a DNA polymerase and carcinogenic DNA adducts in real-time by single-molecule fluorescence. We find the degree to which an adduct affects polymerase binding to the DNA depends on the adduct location with respect to the primer terminus, the adduct structure and the nucleotides present in the solution. Not only do the …

A Comprehensive And Integrative Reconstruction Of Evolutionary History For Anomura (Crustacea: Decapoda)., Heather D Bracken-Grissom, Maren E Cannon, Patricia Cabezas, Rodney M Feldmann, Carrie E Schweitzer, Shane T Ahyong, Darryl L Felder, Rafael Lemaitre, Keith A Crandall

Computational Biology Institute

BACKGROUND: The infraorder Anomura has long captivated the attention of evolutionary biologists due to its impressive morphological diversity and ecological adaptations. To date, 2500 extant species have been described but phylogenetic relationships at high taxonomic levels remain unresolved. Here, we reconstruct the evolutionary history-phylogeny, divergence times, character evolution and diversification-of this speciose clade. For this purpose, we sequenced two mitochondrial (16S and 12S) and three nuclear (H3, 18S and 28S) markers for 19 of the 20 extant families, using traditional Sanger and next-generation 454 sequencing methods. Molecular data were combined with 156 morphological characters in order to estimate the largest …

Phage Cluster Relationships Identified Through Single Gene Analysis., Kyle C Smith, Eduardo Castro-Nallar, Joshua Nb Fisher, Donald P Breakwell, Julianne H Grose, Sandra H Burnett

Computational Biology Institute

BACKGROUND: Phylogenetic comparison of bacteriophages requires whole genome approaches such as dotplot analysis, genome pairwise maps, and gene content analysis. Currently mycobacteriophages, a highly studied phage group, are categorized into related clusters based on the comparative analysis of whole genome sequences. With the recent explosion of phage isolation, a simple method for phage cluster prediction would facilitate analysis of crude or complex samples without whole genome isolation and sequencing. The hypothesis of this study was that mycobacteriophage-cluster prediction is possible using comparison of a single, ubiquitous, semi-conserved gene. Tape Measure Protein (TMP) was selected to test the hypothesis because it …

Using High-Fiber Diets To Limit Energy Intake In Developing Gilts: Effects On Puberty, Reproduction, Culling Rates, Lifetime Productivity, And Progeny Health And Growth, Phillip S. Miller, Rodger Johnson, Justin Bundy, Daniel Ciobanu

Department of Animal Science: Faculty Publications

A total of 182 gilts were used to evaluate the effects of limiting energy intake during development compared to traditional corn-soybean meal based diets using the addition of soybean hulls to reduce caloric intake with ad libitum access to feed. The gilt developmental period consisted of 110 days, from 120 to 230 days of age. Data collected during development included body weight, backfat, longissimus muscle area, and feed intake, every 2 weeks. Estrus detection was conducted on a daily basis until breeding. Females were maintained in the breeding groups for 4 parities (785 days of age), at which time data …

The Putative Role Of Resveratrol In Sirt-1 Mediated Modulation Of The Vitamin D Pathway, Angelika Dampf Stone, Shane F. Batie, G. Kerr Whitfield, Mark R. Haussler, Peter W. Jurutka

American Association for the Advancement of Science Pacific Conference

The nuclear vitamin D receptor (VDR) modulates gene transcription in 1,25-dihydroxyvitamin D (1,25D) target tissues such as kidney, colon, and bone. The 1,25D hormone is derived from vitamin D in the skin or from the diet, and binds to and activates the VDR. We have previously shown that resveratrol, an antioxidant found in the skin of red grapes, has the ability to activate the VDR signaling pathway. Moreover, cells treated with both resveratrol and 1,25D resulted in an additive or even synergistic stimulation of VDR-mediated transcription compared to cells treated with 1,25D alone. Based on these initial results, experiments were …

Evolution Of A Higher Intracellular Oxidizing Environment In Caenorhabditis Elegans Under Relaxed Selection, Joanna Joyner-Matos, Kiley A. Hicks, Dustin Cousins, Michelle Keller, Dee R. Denver, Charles F. Baer, Suzanne Estes

Biology Faculty Publications and Presentations

We explored the relationship between relaxed selection, oxidative stress, and spontaneous mutation in a set of mutationaccumulation (MA) lines of the nematode Caenorhabditis elegans and in their common ancestor. We measured steady-state levels of free radicals and oxidatively damaged guanosine nucleosides in the somatic tissues of five MA lines for which nuclear genome base substitution and GC-TA transversion frequencies are known. The two markers of oxidative stress are highly correlated and are elevated in the MA lines relative to the ancestor; point estimates of the per-generation rate of mutational decay (DM) of these measures of oxidative stress are similar to …

Archaeal Nucleosome Positioning In Vivo And In Vitro Is Directed By Primary Sequence Motifs, Narasimharao Nalabothula, Liqun Xi, Sucharita Bhattacharyya, Jonathan Widom, Ji-Ping Wang, John N. Reeve, Thomas J. Santangelo, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Background: Histone wrapping of DNA into nucleosomes almost certainly evolved in the Archaea, and predates Eukaryotes. In Eukaryotes, nucleosome positioning plays a central role in regulating gene expression and is directed by primary sequence motifs that together form a nucleosome positioning code. The experiments reported were undertaken to determine if archaeal histone assembly conforms to the nucleosome positioning code.

Results: Eukaryotic nucleosome positioning is favored and directed by phased helical repeats of AA/TT/AT/TA and CC/GG/CG/GC dinucleotides, and disfavored by longer AT-rich oligonucleotides. Deep sequencing of genomic DNA protected from micrococcal nuclease digestion by assembly into archaeal nucleosomes has established that …

Science Fiction And The Myth Of Trajectory Evolution, Jocelyn D. Pickreign

The Macalester Review

Stephen Jay Gould first proposed the idea of “iconographies of progress.” Today, one of the most prominent forms of progress iconography is the science fiction story. Science fiction as a genre frequently portrays evolution as a linear trajectory of increasing complexity, and in doing so, furthers a worldview that is not unlike the pre-Darwin understanding of human beings as both the center and the pinnacle of the natural world.

Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ²²). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …

Review Of "Translational Stem Cell Research: Issues Beyond The Debate On The Moral Status Of The Human Embryo" Edited By K. Hug And G. Hermerén, John B. Jenkins

Biology Faculty Works

No abstract provided.

The Genome Sequence Of The Most Widely Cultivated Cacao Type And Its Use To Identify Candidate Genes Regulating Pod Color, Juan C. Motamayor, Keithanne Mockaitis, Jeremy Schmutz, Niina Haiminen, Donald Livingstone Iii, Omar Cornejo, Seth Findley, Ping Zheng, Filippo Utro, Stefan Royaert, Christopher Saski

Publications

Background

Theobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders.

Results

We describe the sequencing and assembly of the genome of Theobroma cacao L. cultivar Matina

1-6. The genome of the Matina 1-6 cultivar is 445 Mbp, which is significantly larger than a sequenced Criollo cultivar, and more typical of other cultivars. The chromosome-scale assembly, version 1.1, contains 711 scaffolds covering 346.0 Mbp, with a contig N50 of 84.4 kbp, a scaffold N50 of …

Small Molecule Inhibitors Of Hpv16 E6, Chung-Hsiang Yuan

Loma Linda University Electronic Theses, Dissertations & Projects

High-risk human papillomaviruses (HR-HPVs) cause nearly all cases of cervical cancer. HPV 16 E6, one of two viral oncogenes, protects cells from apoptosis by binding to and accelerating the degradation of several apoptotic proteins, including caspase 8 and p53. We proposed that blocking the interactions between HPV E6 and its partners using small molecules had the potential to re-sensitize HPV+ cells to apoptosis. To test this prediction, we screened libraries of small molecules for candidates that could block E6/caspase 8 binding, and identified several candidates from different chemical classes. Testing hits for dose-dependency and specificity in vitro and for toxicity …

Assessing Methods For Assigning Snps To Genes In Gene-Based Tests Of Association Using Common Variants, Ashley Petersen, Carolina Alvarez, Scott Declaire, Nathan L. Tintle

Faculty Work Comprehensive List

Gene-based tests of association are frequently applied to common SNPs (MAF>5%) as an alternative to single-marker tests. In this analysis we conduct a variety of simulation studies applied to five popular gene-based tests investigating general trends related to their performance in realistic situations. In particular, we focus on the impact of non-causal SNPs and a variety of LD structures on the behavior of these tests. Ultimately, we find that non-causal SNPs can significantly impact the power of all gene-based tests. On average, we find that the “noise” from 6–12 non-causal SNPs will cancel out the “signal” of one causal …

Dna From Feces And Museum Specimens Confirms A First State Record Bird, Alec R. Lindsay Ph. D., Skye C. Haas

Faculty Works

In October 2005, a vagrant kingbird (Aves: Tyrannus sp.) appeared in Michigan’s Upper Peninsula, nearly 2000 km from the northern limit of its usual range. Using mitochondrial DNA obtained from a fecal sample deposited by the bird and mitochondrial DNA isolated from museum reference specimens, the species iden- tity of this bird was definitively confirmed as a Tropical Kingbird (T. melancholicus) rather than a Couch’s Kingbird (T. couchii). This is the first time DNA evidence has been used to establish a state bird record, and one of the few studies of any type to successfully use avian feces for DNA …

Investigating Potential Target Genes Of The Rfx Transcription Factor Daf-19 In Caenorhabditis Elegans, He Zhang

Lawrence University Honors Projects

Neurodegenerative diseases, such as Alzheimer’s disease, are characterized by an age-related decrease in the synaptic activity of the patient’s brain. Previous research suggested that a RFX transcription factor DAF-19 in the nematode Caenorhabditis elegans (C. elegans) may be involved in the maintenance of synaptic protein levels. Particularly, worms that were DAF-19A/B defective showed reduced synaptic activities when compared to their age-matched controls.

This study investigated the role of DAF-19A/B isoforms in the C. elegans nervous system. Three genes, F46G11.3, F57B10.9, and F58E2.3 were selected as potential downstream targets of DAF-19A/B based on their potential neuronal expression. …

Machine Learning And Genome Annotation: A Match Meant To Be?, Kevin Y. Yip, Chao Cheng, Mark Gerstein

Dartmouth Scholarship

By its very nature, genomics produces large, high-dimensional datasets that are well suited to analysis by machine learning approaches. Here, we explain some key aspects of machine learning that make it useful for genome annotation, with illustrative examples from ENCODE.

Occurrence And Genetic Diversity Of Lemon Sharks (Negaprion Brevirostris) At A Nursery Ground At The Chandeleur Islands, Louisiana., Jonathan F. Mckenzie

LSU New Orleans Theses and Dissertations

Anecdotal evidence suggested that immature lemon sharks (Negaprion brevirostris) occur at the Chandeleur Islands in southeastern Louisiana. From May 2009 to August 2011, the Nekton Research Laboratory at the University of New Orleans regularly sampled habitats at the Chandeleur Islands to confirm the presence of immature individuals of this species. During these efforts, 147 immature lemon sharks (neonates, young-of-the-year, and juveniles) were collected. Each shark was PIT tagged and a tissue sample was taken for genetic analyses. Sizes ranged from 56 – 177 cm total length. Sharks showed a preference for sandy substrate and smaller individuals showed significant preference …

An Alternative Ribozyme For The Rna Hypercycle, Ishak Elkhal

Student Research Symposium

In the quest to forward understanding of the prebiotic world (specifically, the RNA World Hypothesis), one of the most interesting paradigms to consider is the potential for cooperative networks that may have driven molecular evolution forward. Such a network may exist as an RNA hypercycle, as proposed by Eigen (1977). Much progress has been made towards an RNA hypercycle-like system, especially using the Azoarcus ribozyme system demonstrated by Vaidya et al. (2012). The current work is dedicated to constructing a second model as a cooperative RNA network, utilizing a group I intron from Coxiella burnetii (Cbu1917). The intron was constructed …