Genetics and Genomics Commons^™

Hnrnpa2 Is A Novel Histone Acetyltransferase That Mediates Mitochondrial Stress-Induced Nuclear Gene Expression, Manti Guha, Satish Srinivasan, Kip Guja, Edison Mejia, Miguel Garcia-Diaz, F. Brad Johnson, Gordon Ruthel, Brett A. Kaufman, Eric F. Rappaport, M. Rebecca Glineburg, Ji-Kang Fang, Andres J. Klein-Szanto, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced …

Examination Of The Relevance Of Pi3k And Pten Pathway In Ustilago Maydis., Nathaniel Edward Dalton

Electronic Theses and Dissertations

Ustilago maydis is a fungal pathogen that is an obligate parasite on Zea mays (Corn) in order to undergo and complete its sexual life cycle. The cells grow as a haploid form until they meet a compatible partner and undergo a dimorphic switch from a budding yeast-like cell type to a filamentous dikaryon. Infection of the host plant is characterized by leaf chlorosis, anthocyanin content, and formation of large galls that develop on the stem, leaves, cobs, and flowers. Many signaling cascades such as MAPK and PKA are involved in the regulation of the infection lifecycle. The Phosphatidylinosotiol 3 Kinase/ …

Evolution In Light Of Mitonuclear Landscapes: An Examination Of Mitochondrial Replacement In Killifish (Fundulus Spp.), Stephen D. Flanagan

Dissertations

The mitochondria are responsible for the bulk of energy production in eukaryotes. They possess their own genome that works in conjunction with the nuclear genome to accomplish the extraordinarily important task of energy conversion. When species hybridize there will be a mismatch in evolutionary histories between these two genomes. The deleterious interactions of these genomes have been studied in great detail (i.e. hybrid breakdown). However, little work has been conducted to understand the population genetic, and morphological consequences of wide-ranging replacement. The Fundulus notatus complex is comprised of 3 species: F. notatus, F. olivaceus, and F. euryzonus. …

Exploration Of Dna Transfer In The Nyc Subway, Sannia K. Tauqeer

Student Theses

The ability to detect “touch” DNA has complicated the interpretation of DNA profiles in the field of forensics because it leads to the introduction of the concept of DNA transfer, persistence and background into casework. This project is geared towards understanding DNA transfer in the NYC subways and has relevance in groping and attempted sexual assault cases, where garments are submitted as evidence. The study involved 10 volunteers who were asked to wear a clean jacket during their trips on the subway for one week and the DNA from these jackets was collected, extracted, quantified, amplified and typed. The results …

Genetic Study Of Carotenoids In Maize Grain (Zea Mays L.), Oscar Rafael Espejel Venado

Open Access Theses

Pro-Vitamin A (proVA) carotenoids, which are converted into retinol (Vitamin A) in the human body, have been the subject of human nutrition studies and are a target for biofortification of staple crops. Historically, β-carotene has been the principal target for enhancing levels of proVA, yet there is recent interest in enhancing the proVA carotenoid β-cryptoxanthin. Studies have shown that β-cryptoxanthin has excellent bioavailability, and its use in maize may be nearly as effective as β-carotene in providing retinol. The primary aim of this study was to gain a better understanding of the genetic control of levels of β-cryptoxanthin, conversion of …

Improving And Elucidating Factors Regulating Black Walnut (Juglans Nigra L.) Clonal Propagation, Micah E. Stevens

Open Access Dissertations

Black walnut (Juglans nigra L.) is a fine hardwood tree species native to the central hardwood region of the United States. High-quality black walnut timber is highly desirable. Traded in both regional and global markets, it has been used for veneer, and the manufacture of high-end products such as cabinets, furniture, and gunstocks. As a result of its high economic value, black walnut has been commercially cultivated for many years, and breeding programs have generated superior timber genotypes with improved marketable traits. Once elite genotypes were developed, it was quickly recognized that black walnut was recalcitrant to clonal propagation …

Molecular Measurement Of Toxicity In Fish; Case Examples And Policy Implications, Jessica A. Freedman

Senior Honors Projects

Stormwater and oil are common urban contaminants that can be harmful to fish species. One way of recognizing exposed and impaired fish is by monitoring gene expression and gene induction. This study focused on the identification and validation of reference genes for measuring contaminant-induced changes in gene expression due to urban influence. In this study, reference genes (which are genes used to normalize data and remain consistent in varying exposures regardless of organism and tissue type) were established. Six genes were identified as reference genes (ef1a, wdtc1, mtm1, spop, rxrba and tuba1) from a longer list of potential …

Relationship Among Genetic And Physiological Biomarkers, And Horse Characteristics, Casey Orr

Graduate Theses and Dissertations

The objective of this study was to evaluate relationships among genetic and physiological biomarkers and phenotypic characteristics in horses. Three breeds (Quarter Horse, Thoroughbreds, Miniatures), and five genes of interest (leptin, ghrelin, cytochrome P450, glucocorticoid receptor, and lactate dehydrogenase) were the basis of the investigation. Genomic DNA was extracted from buffy coat samples of Quarter Horses (n = 21), Thoroughbreds (n = 26), and Miniatures (n = 34). Data were analyzed using MIXED MODEL procedures of SAS, with the main effects of breed and SNP genotype. Horse was the experimental unit, and dependent variables were classified as physical, cell differentials, …

Concomitant Targeting Of The Mtor/Mapk Pathways: Novel Therapeutic Strategy In Subsets Of Non-Small Cell Lung Cancer, Dennis Ruder

Dissertations and Theses (Open Access)

Over the last decade, a paradigm-shift in lung cancer therapy has evolved into targeted-driven medicinal approaches. However, patients frequently relapse and develop resistance to available therapies. Herein, we utilized genomic mutation data from advanced chemorefractory non-small cell lung cancer (NSCLC) patients enrolled in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-2) clinical trial to characterize novel actionable genomic alterations potentially of clinical relevance. We identified RICTOR alterations (mutations, amplifications) in 17% of lung adenocarcinomas and found RICTOR expression correlates to worse overall survival. There was enrichment of MAPK pathway genetic aberrations in key oncogenes (e.g. KRAS, BRAF, …

Exploring Molecular Mechanisms Of Paradoxical Activation In The Braf Kinase Dimers: Atomistic Simulations Of Conformational Dynamics And Modeling Of Allosteric Communication Networks And Signaling Pathways, Amanda Tse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The recent studies have revealed that most BRAF inhibitors can paradoxically induce kinase activation by promoting dimerization and enzyme transactivation. Despite rapidly growing number of structural and functional studies about the BRAF dimer complexes, the molecular basis of paradoxical activation phenomenon is poorly understood and remains largely hypothetical. In this work, we have explored the relationships between inhibitor binding, protein dynamics and allosteric signaling in the BRAF dimers using a network-centric approach. Using this theoretical framework, we have combined molecular dynamics simulations with coevolutionary analysis and modeling of the residue interaction networks to determine molecular determinants of paradoxical activation. We …

Broad-Sense Heritability And Genetic Gain For Powdery Mildew Resistance In Multiple Pseudo-F2 Populations Of Flowering Dogwoods (Cornus Florida L.), Lipi Parikh, Margaret T. Mmbaga, Srikanth Kodati, Matthew W. Blair, Dafeng Hui, Geoffrey Meru

Agricultural and Environmental Sciences Faculty Research

Powdery mildew caused by Erysiphe pulchra is one of the most destructive diseases of flowering dogwoods (Cornus florida L.). Control of powdery mildew relies heavily on chemical fungicides. Developing genetic resistance and planting powdery mildew resistant cultivars is a desirable long term control strategy for the disease. Information on inheritance characteristics associated with powdery mildew resistance in C. florida is needed to facilitate development of breeding strategies for a new generation of powdery mildew resistant cultivars. The objectives of this study were to determine broad-sense heritability, genetic gain and minimum number of effective genes associated with resistance to powdery mildew …

Nemo-Like Kinase (Nlk) Is A Pathological Signaling Effector In The Mouse Heart, Ruijie Liu

Peer Reviewed Articles

Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice. NLK transgenic mice demonstrated baseline cardiac hypertrophy, dilation, interstitial fibrosis, apoptosis and progression towards heart failure in response to two surgery-induced …

Causal Effect Estimation In Sequencing Studies: A Bayesian Method To Account For Confounder Adjustment Uncertainty, Chi Wang, Jinpeng Liu, David W. Fardo

Biostatistics Faculty Publications

Estimating the causal effect of a single nucleotide variant (SNV) on clinical phenotypes is of interest in many genetic studies. The effect estimation may be confounded by other SNVs as a result of linkage disequilibrium as well as demographic and clinical characteristics. Because a large number of these other variables, which we call potential confounders, are collected, it is challenging to select and adjust for the variables that truly confound the causal effect. The Bayesian adjustment for confounding (BAC) method has been proposed as a general method to estimate the average causal effect in the presence of a large number …

Phylogeny, Systematics And Biogeography Of Short-Tailed Opossums (Didelphidae: Monodelphis), Silvia E. Pavan

Dissertations, Theses, and Capstone Projects

Short-tailed opossums (genus Monodelphis) comprise the most species-rich genus of New World marsupials, with 25 currently recognized species. Monodelphis comprise small, terrestrial species collectively widespread in South America, which makes the group potentially informative about biogeographic processes that have shaped the continental fauna. The genus exhibits striking variation in several phenotypic characters, notably pelage coloration, behavior, and reproductive strategies. This diversity is unique among Neotropical marsupials, and makes the group particularly interesting to investigate the evolution and the adaptive significance of phenotypic trait variation. Despite this potential, missing knowledge on phylogeny and basic taxonomy precludes broader studies on evolution …

Weighted-Samgsr: Combining Significance Analysis Of Microarray-Gene Set Reduction Algorithm With Pathway Topology-Based Weights To Select Relevant Genes, Suyan Tian, Howard H. Chang, Chi Wang

Biostatistics Faculty Publications

Background: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method.

Methods: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to …

Parallel Mutations Result In A Wide Range Of Cooperation And Community Consequences In A Two-Species Bacterial Consortium, Sarah Douglas, Lon Chubiz, William Harcombe, F. Ytreberg, Christopher Marx

Biology Department Faculty Works

Multi-species microbial communities play a critical role in human health, industry, and waste remediation. Recently, the evolution of synthetic consortia in the laboratory has enabled adaptation to be addressed in the context of interacting species. Using an engineered bacterial consortium, we repeatedly evolved cooperative genotypes and examined both the predictability of evolution and the phenotypes that determine community dynamics. Eight Salmonella enterica serovar Typhimurium strains evolved methionine excretion sufficient to support growth of an Escherichia coli methionine auxotroph, from whom they required excreted growth substrates. Non-synonymous mutations in metA, encoding homoserine trans-succinylase (HTS), were detected in each evolved S. enterica …

221 Newborn-Screened Neonates With Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency: Findings From The Inborn Errors Of Metabolism Collaborative, K Bentler, S Zhai, S Elsbecker, G Arnold, B Burton, J Vockley, C Cameron, S Hiner, M Edick, S Berry, J Thomas, M Dodge, R Singh, S Lakshman, David Kronn, Inborn Errors Of Metabolism Collaborative

NYMC Faculty Publications

Introduction: There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods: Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism-Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results: The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcamitine (C8) value on first newborn screen was 11.2 …

Review Of "A Primer Of Human Genetics" By G. Gibson, John B. Jenkins

Biology Faculty Works

No abstract provided.

Characterization, Development And Multiplexing Of Microsatellite Markers In Three Commercially Exploited Reef Fish And Their Application For Stock Identification, Laura Taillebois, Christine Dudgeon, Safia Maher, David Crook, Thor Saunders, Diane P. Barton, Jonathan A. Taylor, David J. Welch, Stephen J. Newman, Michael J. Travers, Richard J. Saunders, Jennifer Ovenden

Fisheries Research Articles

Thirty-four microsatellite loci were isolated from three reef fish species; golden snapper Lutjanus johnii, blackspotted croaker Protonibea diacanthus and grass emperor Lethrinus laticaudis using a next generation sequencing approach. Both IonTorrent single reads and Illumina MiSeq paired-end reads were used, with the latter demonstrating a higher quality of reads than the IonTorrent. From the 1–1.5 million raw reads per species, we successfully obtained 10–13 polymorphic loci for each species, which satisfied stringent design criteria. We developed multiplex panels for the amplification of the golden snapper and the blackspotted croaker loci, as well as post-amplification pooling panels for the grass …

Population Dynamics And Genetic Differentiation Of The Threatened Freshwater Mussel Species Fusconaia Askewi, Fusconaia Lananensis, And Pleurobema Riddellii, Edith D. Plants-Paris

Biology Theses

North America has the most diverse freshwater mussel fauna in the world with approximately 300 species; unfortunately, extinction rates for freshwater mussels rivals the rates of many other groups of organisms. Population-level natural life history data is essential in the management of species of conservation concern, yet basic information about freshwater mussel life-history and demographic traits are unknown for many species. To further complicate matters, taxonomic uncertainty exists among some members of the group. The work detailed herein had two goals: to gain further understanding of the taxonomic relationship between Fusconaia lananensis and F. askewi by sequencing genes that had …

Study Of The Structure-Related Functions Of Eukaryotic Primase-Pol Alpha Complex During Replication, Yinbo Zhang

Theses & Dissertations

During eukaryotic replication primase•polymerase α (prim•polα) complex synthesizes de novo chimeric primers composed of about 10 nt RNA and 20 nt DNA, which are subsequently extended by main replicative DNA polymerases (pol), polε and polδ, on leading and lagging strands, respectively. It is estimated that prim•polα initiates more than 10 millions of lagging strand Okazaki fragments in human genome in each replication cycle. A concerted action of the two active sites, RNA pol and DNA pol, is required to ensure the efficient priming. A remarkable feature of the prim•polα complex is the “programmed” synthesis of the chimeric primer, where the …

Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of generally aggressive lymphoid malignancies, accounting for 10-15% of all non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) represents approximately 20% of all PTCLs and is recognized as a distinct entity. Accurate diagnosis and classification of PTCL remain challenging. With the exception of ALK+ ALCL, patients with PTCL generally have a poor prognosis with standard chemotherapy and even with the availability of many novel drugs, including HDAC inhibitor (romidepsin and belinostat), gemcitabine, and bortezomib. Therefore, deciphering the pathogenesis of this group of diseases is needed to identify novel treatable targets for better therapeutic intervention. …

Genetic Landscape Of Pediatric Myelodysplastic Syndromes, Jennifer E. Grove

Theses & Dissertations

Myelodysplastic syndromes (MDS) are acquired heterogeneous hematopoietic clonal disorders primarily seen in the adult and elderly populations that presents a variety of cellular morphologies in cell lineages, varying prognoses, and differences in overall survival (OS) between individual patients. The occurrence of MDS in the pediatric and young adult population, or those between the ages of 0 and 29, is slowly on the rise. Pediatric and elderly cases exhibit diverse cytogenetic findings with differences in OS. The characterization of the genetic landscape of pediatric MDS is limited and most studies detailing genetic changes have been conducted in adult MDS cases. In …

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR Program Research Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few …

Vascular Endothelial Growth Factor-A Gene Electrotransfer Promotes Angiogenesis In A Porcine Model Of Cardiac Ischemia, Anna A. Bulysheva, Barbara Hargrave, Nina Burcus, Cathryn G. Lundberg, Len Murray, Richard Heller

Bioelectrics Publications

This study aimed to assess safety and therapeutic potential of gene electrotransfer (GET) as a method for delivery of plasmid encoding vascular endothelial growth factor A (VEGF-A) to ischemic myocardium in a porcine model. Myocardial ischemia was induced by surgically occluding the left anterior descending coronary artery in swine. GET following plasmid encoding VEGF-A injection was performed at four sites in the ischemic region. Control groups either received injections of the plasmid without electrotransfer or injections of the saline vehicle. Animals were monitored for 7 weeks and the hearts were evaluated for angiogenesis, myocardial infarct size and left ventricular contractility. …

Chromosome-End Knockoff Strategy To Reshape Alkaloid Profiles Of A Fungal Endophyte, Simona Florea, Timothy D. Phillips, Daniel G. Panaccione, Mark L. Farman, Christopher L. Schardl

Plant Pathology Faculty Publications

Molecular genetic techniques to precisely eliminate genes in asexual filamentous fungi require the introduction of a marker gene into the target genome. We developed a novel strategy to eliminate genes or gene clusters located in subterminal regions of chromosomes, and then eliminate the marker gene and vector backbone used in the transformation procedure. Because many toxin gene clusters are subterminal, this method is particularly suited to generating nontoxic fungal strains. We tested this technique on Epichloë coenophiala, a seed-transmissible symbiotic fungus (endophyte) of the important forage grass, tall fescue (Lolium arundinaceum). The endophyte is necessary for maximal …

Characterization Of Broiler Lines Divergently Selected For Breast Muscle Color, Sara Katherine Orlowski

Graduate Theses and Dissertations

An increase in the consumption of poultry has generated an increase in demand for higher yielding broilers. This has led to an increase in atypical meat and issues with appearance. Color is a direct result of a pH decline as meat goes through rigor mortis with meat generally becoming lighter. If the pH declines too rapidly or too slowly, meat quality can suffer. Physical properties of meat can be altered by pH. A fast pH decline results in pale meat with decreased tenderness. A slow pH decline can result in darker meat with a reduced shelf-life. With a known relationship …

Development Of Genomic Resources For The Evaluation Of Red Snapper, An Emerging Species Candidate For Marine Aquaculture And Stock Enhancement, Adrienne Elise Norrell

Master's Theses

The northern red snapper (Lutjanus campechanus) is a highly targeted reef fish candidate for marine aquaculture and stock enhancement in the southern United States. This work aimed to develop genomic resources for the genetic management of aquaculture programs and to investigate population structure using high-throughput sequencing technologies. Eighty-four new microsatellite markers were developed through screening of Illumina paired-end sequencing reads. Microsatellite loci and Single Nucleotide Polymorphisms (SNPs) generated through Restriction Site Associated DNA (RAD) sequencing were assayed in 5 outbred full-sib families to construct a high-density linkage map of the red snapper genome. The map consists of 7,964 …

The Role Of Mfd In Stationary-Phase Oxidative Damage Repair In Bacillus Subtilis, Katelyn E. Porter

UNLV Theses, Dissertations, Professional Papers, and Capstones

Since the 1950’s it has been shown that bacterial cells accumulate mutations even in non- dividing conditions, but how this type of mutation occurs is still highly debated. In Bacillus subtilis, Mfd, a precursor of the nucleotide excision repair (NER) system, mediates the formation of mutations in stationary-phase or non-replicating cells. In growing cells, Mfd recruits repair when RNA polymerase is stalled during transcription; it then recruits proteins from NER to repair damage. Here, we examine the hypothesis that Mfd mediates the formation of mutations by interacting with cellular components that repair reactive oxygen species (ROS), a natural byproduct of …

Elucidating The Genetic Cause To Ascites Syndrome In Broiler Chickens Utilizing Multi-Generational Genome Wide Association Studies, Katy Tarrant

Graduate Theses and Dissertations

Ascites syndrome in broiler chickens has developed into a source of economic loss in the last three decades. Intensive selective pressure, and implementation of flock management practices, has successfully reduced ascites frequency, but has not eliminated its occurrence. For this reason, it is imperative to better understand the genetic cause to ascites in broiler chickens. Previous studies of this magnitude have been attempted, but, thus far, a consensus of genomic associations have not been made. This collection of studies was aimed at identifying and interpreting genomic and genetic associations to ascites phenotype specific to a broiler line representative of a …