Genetics and Genomics Commons^™

Whole-Genome Dna Methylation Status Associated With Clinical Ptsd Measures Of Oif/Oef Veterans., R Hammamieh, N Chakraborty, A Gautam, S Muhie, R Yang, D Donohue, R Kumar, B J Daigle, Y Zhang, D A Amara, S-A Miller, S Srinivasan, J Flory, R Yehuda, L Petzold, O M Wolkowitz, S H Mellon, L Hood, F J Doyle, C Marmar, M Jett

Articles, Abstracts, and Reports

Emerging knowledge suggests that post-traumatic stress disorder (PTSD) pathophysiology is linked to the patients' epigenetic changes, but comprehensive studies examining genome-wide methylation have not been performed. In this study, we examined genome-wide DNA methylation in peripheral whole blood in combat veterans with and without PTSD to ascertain differentially methylated probes. Discovery was initially made in a training sample comprising 48 male Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans with PTSD and 51 age/ethnicity/gender-matched combat-exposed PTSD-negative controls. Agilent whole-genome array detected ~5600 differentially methylated CpG islands (CpGI) annotated to ~2800 differently methylated genes (DMGs). The majority (84.5%) of these CpGIs …

Effect Assessment Of Tio2 Nanoparticles Exposure On Medicago By Monitoring Morphophysiology, Charles Towey

Mahurin Honors College Capstone Experience/Thesis Projects

In recent years titanium dioxide nanoparticles (TiO₂NPs) have been ingredients in everything from paints to cosmetics, and even in some kinds of food. This growth in use has resulted in a substantial increase in the amount of titanium released into the environment, which could have detrimental effects on nearby plant and animal life. Currently, the number of studies conducted on the effects of TiO₂NPs is quite small, especially when it comes to edible crops. Because of this lack of research data, this study has been designed to assess the effect of TiO₂ NPs exposure on …

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O⁶-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O⁶-alkylguanine and O⁴-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ω_ave. We found …

Odelay: A Large-Scale Method For Multi-Parameter Quantification Of Yeast Growth., Thurston Herricks, Fred D Mast, Song Li, John D Aitchison

Articles, Abstracts, and Reports

Growth phenotypes of microorganisms are a strong indicator of their underlying genetic fitness and can be segregated into 3 growth regimes: lag-phase, log-phase, and stationary-phase. Each growth phase can reveal different aspects of fitness that are related to various environmental and genetic conditions. High-resolution and quantitative measurements of all 3 phases of growth are generally difficult to obtain. Here we present a detailed method to characterize all 3 growth phases on solid media using an assay called One-cell Doubling Evaluation of Living Arrays of Yeast (ODELAY). ODELAY quantifies growth phenotypes of individual cells growing into colonies on solid media using …

Medical Genetics And Genomic Medicine In The United States Of America. Part 1: History, Demographics, Legislation, And Burden Of Disease., Carlos R Ferreira, Debra S Regier, Donald W Hadley, P Suzanne Hart, Maximilian Muenke

Pediatrics Faculty Publications

No abstract provided.

Consumer Knowledge, Perception And Attitudes Of Unlabeled Genetically Modified Foods Of An Educated Population In The State Of Kentucky, Aldious A. Waite

Masters Theses & Specialist Projects

Genetically modified (GM) foods technology is a novel idea for improving food and crop production, but the supposed health risk of GM foods, such as possible negative long-term health effects to humans, animals and the environment, have provoked the European Union to create assessment protocols to monitor and regulate the safety of GM foods and crops. This research investigates the perception and attitudes of unlabeled GM foods of the WKU faculty and staff. A survey was administered via WKU Qualtrics, and chi-square tests were performed to see how the benefits and disadvantages of GM foods may affect the purchasing decisions …

Praja Is Overexpressed In Glioblastoma And Contributes To Neural Precursor Development, Joshua Shin, Viveka Mishra, Eric Glasgow, Sobia Zaidi, Kazufumi Ohshiro, Lopa Mishra, Shuyun Rao, +Several Additional Authors

Medicine Faculty Publications

PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the …

Transcriptomic Differentiation Underlying Marine‐To‐Freshwater Transitions In The South American Silversides Odontesthes Argentinensis And O. Bonariensis (Atheriniformes), Lily Hughes, Gustavo Somoza, Bryan Nguyen, James Bernot, Mariano Gonzalez-Castro, Juan Martin Diaz De Astarloa, Guillermo Orti

Computational Biology Institute

Salinity gradients are critical habitat determinants for freshwater organisms. Silverside fishes in the genus Odontesthes have recently and repeatedly transitioned from marine to freshwater habitats, overcoming a strong ecological barrier. Genomic and transcriptomic changes involved in this kind of transition are only known for a few model species. We present new data and analyses of gene expression and microbiome composition in the gills of two closely related silverside species, marine O. argentinensis and freshwater O. bonariensis and find more than three thousand transcripts differentially expressed, with osmoregulatory/ion transport genes and immune genes showing very different expression patterns across species. Interspecific …

A Rapid Colorimetric Peptide Nucleic Acid Loop-Mediated Isothermal Amplification Assay For The Detection Of The Idh1 Mutation In Glioblastoma, Edward J. Raack

All NMU Master's Theses

The IDH1 mutation is an important diagnostic and prognostic biomarker used to characterize glioblastoma (GBM). Patients harboring the IDH1 mutation have improved overall survival following maximal resection. Knowledge of the IDH1 mutation status allows the surgeon to modify the surgical plan; however, no existing molecular test can provide this information intraoperatively. We designed a novel colorimetric peptide nucleic acid loop-mediated isothermal amplification (PNA-LAMP) method that rapidly detects the IDH1 R132H mutation in GBM. PNA-LAMP amplifies target DNA under isothermal conditions with high specificity and speed. The PNA prevents amplification of wild-type IDH1 DNA, while allowing amplification of the R132H variant …

Meta-Analysis Of Five Genome-Wide Association Studies Identifies Multiple New Loci Associated With Testicular Germ Cell Tumor., Zhaoming Wang, Katherine A Mcglynn, Ewa Rajpert-De Meyts, D Timothy Bishop, Charles C Chung, Marlene D Dalgaard, Mark H Greene, Ramneek Gupta, Tom Grotmol, Trine B Haugen, Robert Karlsson, Kevin Litchfield, Nandita Mitra, Kasper Nielsen, Louise C Pyle, Stephen M Schwartz, Vésteinn Thorsson, Saran Vardhanabhuti, Fredrik Wiklund, Clare Turnbull, Stephen J Chanock, Peter A Kanetsky, Katherine L Nathanson

Articles, Abstracts, and Reports

The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 × 10

Girk2 And Gababr1 Downregulate In Response To Ttx As Girk2, Gababr1, And Gababr2 Are Not Affected By Bc Treatment, Staci E. Hammer, Amanda Weiss, Hee Jung Chung

PRECS student projects

Homeostatic plasticity is the response neurons undergo to regulate changes in excitability levels and bring the cells back to homeostasis. Research on homeostatic plasticity at the molecular level can lead to improved treatments for neurological diseases such as epilepsy, Alzheimer's, and schizophrenia. The research featured in this poster looks at the response of GIRK (G protein-gated inwardly rectifying potassium) channels and GABAb (gamma-amniobutyric acid) receptors to neurotoxins, tetrodotoxin (TTX) or bicuculline (BC).

Prolonged activity blockade of 48 hour TTX treatment significantly reduced GABABR1 and GIRK2 expression. This supports the idea that because these two proteins inhibit action potentials, there will …

Thick Slice Clarity For Localization Of Novel Neuroactive Target Gene Products, Eva C. Ping, Michael C. Saul, Lisa Stubbs

PRECS student projects

This poster describes the Thick Slice CLARITY technique, an alternative to the whole tissue or whole body clarity technique. The CLARITY technique is a tissue clearing method allowing for both structural and molecular analysis of a tissue sample, but the method applied to whole tissue or body is very expensive and time consuming. Thick Slice CLARITY applies the same principles but to a 200 micrometer slice of brain tissue. This method, used in conjunction wit standard fluorescent staining methods and imaging via confocal microscopy, has allowed for the colocalization of GPR3 with neurons in the mouse striatum.

Crystal Structure Of Yersinia Pestis Virulence Factor Yfea Reveals Two Polyspecific Metal-Binding Sites, Christopher D. Radka, Lawrence J. Delucas, Landon S. Wilson, Matthew B. Lawrenz, Robert D. Perry, Stephen G. Aller

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Gram-negative bacteria use siderophores, outer membrane receptors, inner membrane transporters and substrate-binding proteins (SBPs) to transport transition metals through the periplasm. The SBPs share a similar protein fold that has undergone significant structural evolution to communicate with a variety of differentially regulated transporters in the cell. In Yersinia pestis, the causative agent of plague, YfeA (YPO2439, y1897), an SBP, is important for full virulence during mammalian infection. To better understand the role of YfeA in infection, crystal structures were determined under several environmental conditions with respect to transition-metal levels. Energy-dispersive X-ray spectroscopy and anomalous X-ray scattering data show that …

The Mzidentml Data Standard Version 1.2, Supporting Advances In Proteome Informatics., Juan Antonio Vizcaíno, Gerhard Mayer, Simon Perkins, Harald Barsnes, Marc Vaudel, Yasset Perez-Riverol, Tobias Ternent, Julian Uszkoreit, Martin Eisenacher, Lutz Fischer, Juri Rappsilber, Eugen Netz, Mathias Walzer, Oliver Kohlbacher, Alexander Leitner, Robert J Chalkley, Fawaz Ghali, Salvador Martínez-Bartolomé, Eric W Deutsch, Andrew R Jones

Articles, Abstracts, and Reports

The first stable version of the Proteomics Standards Initiative mzIdentML open data standard (version 1.1) was published in 2012-capturing the outputs of peptide and protein identification software. In the intervening years, the standard has become well-supported in both commercial and open software, as well as a submission and download format for public repositories. Here we report a new release of mzIdentML (version 1.2) that is required to keep pace with emerging practice in proteome informatics. New features have been added to support: (1) scores associated with localization of modifications on peptides; (2) statistics performed at the level of peptides; (3) …

Functional Analysis Of Microrna Pathway Genes In The Somatic Gonad And Germ Cells During Ovulation In C. Elegans, Carmela Rios

Dissertations (1934 -)

MicroRNAs (miRNAs) are post-­transcriptional regulators of gene expression that play critical roles in animal development and physiology, though functions for most miRNAs remain unknown. Worms with reduced miRNA biogenesis due to loss of Drosha or Pasha/DGCR8 activity are sterile and fail to ovulate, indicating that miRNAs are required for the process of oocyte maturation and ovulation. Starting with this penetrant sterile phenotype and using new strains created to perform tissue-­specific RNAi, we characterize the roles of the C. elegans Pasha, pash-­1, and two miRNA-­specific Argonautes, alg-­1 and alg-­2, in somatic gonad cells and in germ cells in the regulation of …

Analysis Of Population Structure In A California Newt (Taricha Torosa) Metapopulation, Jessica Vincent

Mahurin Honors College Capstone Experience/Thesis Projects

As anthropogenic influences take an ever-increasing toll on the environment, understanding how environmental change affects species is paramount. Concern regarding decline in amphibian populations has spurred research examining the effects of habitat change on the dynamics of populations at landscape levels. One important goal is to understand how gene flow among populations is affected by changes in habitat. Biologists need to consider the relationship between gene flow and habitat alterations so that movements among individual breeding ponds can be maintained over time, reducing risk of local extinction events. This study focuses on patterns of gene flow among thirteen populations of …

An Approach To Identify Mycobacteriophage Diversity Prior To Dna Sequencing, Charles Gregory

Mahurin Honors College Capstone Experience/Thesis Projects

Over 6,869 Mycobacteriophages have been isolated and purified. Of these, 1,367 genomes have been sequenced at the DNA level and more are added each year through the SEA-PHAGES program. Sequenced mycobacteriophages are grouped into clusters based on a 50% or greater nucleotide identity. The number and breadth of these clusters represents the diversity present in the environment. Each year, as new phages are discovered by students in the SEA-PHAGES program, the question arises, “Which isolates should we sequence?” In order to sequence phages that represent the greatest possible diversity, and thus broaden under-represented clusters and identify new singletons, we need …

Validating Candidate Congenital Heart Disease Genes In Drosophila., Jun-Yi Zhu, Yulong Fu, Adam Richman, Zhe Han

Pediatrics Faculty Publications

Genomic sequencing efforts can implicate large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system to validate candidate gene association with pathology is therefore useful. We present such a system employing Drosophila to validate candidate congenital heart disease (CHD) genes. The protocols exploit comprehensive libraries of UAS-GeneX-RNAi fly strains that when crossed into a 4×Hand-Gal4 genetic background afford highly efficient cardiac-specific knockdown of endogenous fly orthologs of human genes. A panel of quantitative assays evaluates phenotypic severity across multiple cardiac parameters. These include developmental lethality, larva and adult heart morphology, …

Genome-Wide Association Study Of Borderline Personality Disorder Reveals Genetic Overlap With Bipolar Disorder, Major Depression And Schizophrenia, S. H. Witt, F. Streit, M. Jungkunz, J. Frank, Ney Alliey Rodriguez

School of Medicine Publications

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Sivasai Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Selected Works Temporary Series

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Departmental Papers (Biology)

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

A Linkage Map For The Newt Notophthalmus Viridescens: Insights In Vertebrate Genome And Chromosome Evolution, Melissa C. Keinath, S. Randal Voss, Panagiotis A. Tsonis, Jeramiah J. Smith

Biology Faculty Publications

Genetic linkage maps are fundamental resources that enable diverse genetic and genomic approaches, including quantitative trait locus (QTL) analyses and comparative studies of genome evolution. It is straightforward to build linkage maps for species that are amenable to laboratory culture and genetic crossing designs, and that have relatively small genomes and few chromosomes. It is more difficult to generate linkage maps for species that do not meet these criteria. Here, we introduce a method to rapidly build linkage maps for salamanders, which are known for their enormous genome sizes. As proof of principle, we developed a linkage map with thousands …

Epigenetics Of Host-Pathogen Interactions: The Effect Of Acetosyringone On Ti Plasmid Methylation Patterns In Agrobacterium Tumefaciens C58, Genevieve Roberts

Honors Projects

The plant pathogen Agrobacterium tumefaciens C58 can transfer a portion of its tumor-inducing (Ti) plasmid to plant hosts in response to the plant wound signals, including Acetosyringone. The portion transferred is aptly titled Transfer DNA (T-DNA) which encode genes involved in tumor production and biosynthesis of a unique bacterial food source called opines that provide an advantage to the inducing Agrobacterium. The Ti plasmid contains a number of genes, including the virulence region that enables T-DNA transfer. Epigenetics investigates how chemical modifications to DNA that don’t alter sequence are used to control gene expression (for example, genes involved in pathogen …

Rnaseq Analysis Of The Drosophila Response To The Entomopathogenic Nematode Steinernema., Shruti Yadav, Sean Daugherty, Amol Carl Shetty, Ioannis Eleftherianos

Computational Biology Institute

Drosophila melanogaster is an outstanding model to study the molecular and functional basis of host-pathogen interactions. Currently, our knowledge of microbial infections in D. melanogaster is well understood; however, the response of flies to nematode infections is still in its infancy. Here, we have used the potent parasitic nematode Steinernema carpocapsae, which lives in mutualism with its endosymbiotic bacteria Xenorhabdus nematophila, to examine the transcriptomic basis of the interaction between D. melanogaster and entomopathogenic nematodes. We have employed next-generation RNA sequencing (RNAseq) to investigate the transcriptomic profile of D. melanogaster larvae in response to infection by S. carpocapsae symbiotic (carrying …

Bcl11b And Combinatorial Resolution Of Cell Fate In The T-Cell Gene Regulatory Network., William J R Longabaugh, Weihua Zeng, Jingli A Zhang, Hiroyuki Hosokawa, Camden S Jansen, Long Li, Maile Romero-Wolf, Pentao Liu, Hao Yuan Kueh, Ali Mortazavi, Ellen V Rothenberg

Articles, Abstracts, and Reports

T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein. However, the role of lineage commitment factor Bcl11b has been unclear. We use self-organizing maps on 63 RNA-seq datasets from normal and perturbed T-cell development to identify functional targets of Bcl11b during commitment …

Rumen Fluid Metabolomics Analysis Associated With Feed Efficiency On Crossbred Steers, Virginia M. Artegoitia, Andrew P. Cassady, Ronald M. Lewis, Harvey C. Freetly

Department of Animal Science: Faculty Publications

The rumen has a central role in the efficiency of digestion in ruminants. To identify potential differences in rumen function that lead to differences in average daily gain (ADG), rumen fluid metabolomic analysis by LC-MS and multivariate/univariate statistical analysis were used to identify differences in rumen metabolites. Individual feed intake and body-weight was measured on 144 steers during 105 d on a high concentrate ration. Eight steers with the greatest ADG and 8 steers with the least-ADG with dry matter intake near the population average were selected. Blood and rumen fluid was collected from the 16 steers 26 d before …

Naturally-Derived Molecular Ensembles In Medicine, Materials Science And Evolutionary Biology: An Interdisciplinary Study, Silvio Panettieri

Dissertations, Theses, and Capstone Projects

The first chapter will introduce the work carried out in collaboration with the Govind laboratory at CCNY. Our quest was set forth to investigate the intimate relationship lying between chronic inflammation and tumor development. For at least the last fifteen years much research has been conducted on this topic; yet, the level of complexity arising from exceedingly interwoven biochemical pathways in mammals has resulted in slow advancements in this field. This is why we resorted to a simple yet powerful immunogenetic model organism, the fruit fly Drosophila melanogaster, in combination with the administration of the most common anti-inflammatory drug, …

The Recycling Gtpase, Rab-10, Regulates Autophagy Flux In Caenorhabditis Elegans, Nicholas J. Palmisano

Dissertations, Theses, and Capstone Projects

Autophagy and endocytosis are two cellular pathways that are vital to cell growth and homeostasis. Autophagy is a dynamic and catabolic process involving the formation of a double-membrane vesicle called the autophagosome, which engulfs long-lived proteins and damaged organelles. Endocytosis involves the uptake of extracellular material into the cell through the formation of intracellular vesicles termed endosomes. Although both endocytosis and autophagy are interconnected processes, the extent to which endocytic proteins and/or compartments contribute to autophagy, and how these endocytic components do so, is still unknown. To improve our understanding of the connections that exist between autophagy and endocytosis, we …

Lichen Conservation In Eastern North America: Population Genomics, Climate Change, And Translocations, Jessica Allen

Dissertations, Theses, and Capstone Projects

Conservation biology is a scientific discipline that draws on methods from diverse fields to address specific conservation concerns and inform conservation actions. This field is overwhelmingly focused on charismatic animals and vascular plants, often ignoring other diverse and ecologically important groups. This trend is slowly changing in some ways; for example, increasing number of fungal species are being added to the IUCN Red-List. However, a strong taxonomic bias still exists. Here I contribute four research chapters to further the conservation of lichens, one group of frequently overlooked organisms. I address specific conservation concerns in eastern North America using modern methods. …

Body Size Regulation Via Bmp Signaling In Caenorhabditis Elegans, Uday Madaan

Dissertations, Theses, and Capstone Projects

The body size of an organism can be a crucial determinant of access to nutrition, reproductive success and overall survival in the wild. However, how body size of an individual is determined is incompletely understood. Body size is a complex trait determined by multiple pathways and genes, making it difficult to understand the role of individual genes and pathways in determining overall size. In Caenorhabditis elegans, a homolog of Bone Morphogenetic Proteins (BMP) is a major regulator of body size; functional loss of DBL-1 leads to a small body size. Due to a drastic change in body size in dbl-1 …