Genetics and Genomics Commons^™

Identifying Glioblastoma Gene Networks Based On Hypergeometric Test Analysis, Vasileios Stathias, Chiara Pastori, Tess Z. Griffin, Ricardo Komotar, Jennifer L. Clarke, Ming Zhang, Nagi G. Ayad

Department of Statistics: Faculty Publications

Patient specific therapy is emerging as an important possibility for many cancer patients. However, to identify such therapies it is essential to determine the genomic and transcriptional alterations present in one tumor relative to control samples. This presents a challenge since use of a single sample precludes many standard statistical analysis techniques. We reasoned that one means of addressing this issue is by comparing transcriptional changes in one tumor with those observed in a large cohort of patients analyzed by The Cancer Genome Atlas (TCGA). To test this directly, we devised a bioinformatics pipeline to identify differentially expressed genes in …

Evolutionary Genomics And Adaptive Evolution Of The Hedgehog Gene Family (Shh, Ihh And Dhh) In Vertebrates, Joana Pereira, Warren E. Johnson, Stephen J. O'Brien, Erich D. Jarvis, Guojie Zhang, M. Thomas P. Gilbert, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog – Shh; Indian hedgehog – Ihh; and Desert hedgehog – Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we …

Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett

Master's Theses

DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of …

Draft Genome Sequence Of New Bacillus Cereus Strain Tsu1, Hui Li, Suping Zhou, Terrance Johnson, Koen Vercruysse, Alexander J. Ropelewski, Theodore W. Thannhauser

Agricultural and Environmental Sciences Faculty Research

This paper reports the draft genome sequence of new Bacillus cereus strain tsu1, isolated on an agar-cellulose plate. The draft genome sequence is 5.81 Mb, revealing 5,673 coding sequences. It contains genes for cellulose-degradation and biosynthesis pathways of polyhydroxybutyrate (PHB) and 8 rRNA genes (5S, 16S, and 23S).

Comparative Population Genetics And Evolutionary History Of Two Commonly Misidentified Billfishes Of Management And Conservation Concern, Andrea M. Bernard, Mahmood S. Shivji, Eric Prince, Fabio H.V. Hazin, Freddy Arocha, Andres Domingo, Kevin A. Feldheim

Marine & Environmental Sciences Faculty Articles

Background:  Misidentifications between exploited species may lead to inaccuracies in population assessments, with potentially irreversible conservation ramifications if overexploitation of either species is occurring. A notable showcase is provided by the realization that the roundscale spearfish (Tetrapturus georgii), a recently validated species, has been historically misidentified as the morphologically very similar and severely overfished white marlin (Kajikia albida) (IUCN listing: Vulnerable). In effect, no information exists on the population status and evolutionary history of the enigmatic roundscale spearfish, a large, highly vagile and broadly distributed pelagic species. We provide the first population genetic evaluation of the …

Profile Of The Unfolded Protein Response In C. Elegans Depleted Of The Translational Chaperone, Nac., Caylin S. Murray

Masters Theses, 2010-2019

The function of a protein is a direct consequence of its final structure, which is achieved by protein-folding processes that generate a tertiary state through the juxtaposition of locally formed secondary structures. Because all cells need functional proteins to survive, each contains robust and redundant mechanisms that regulate the folding of newly forming proteins, and the refolding of misfolded proteins that are often generated during stress. Essential to these mechanisms, chaperones are proteins that aid in protein folding of nascent and misfolding protein without being incorporated in the final structure. One chaperone complex, the nascent polypeptide-associated complex (NAC), aids in …

Regulation Of Three Nitrogenase Gene Clusters In The Cyanobacterium Anabaena Variabilis Atcc 29413, Teresa Thiel, Brenda Pratte

Biology Department Faculty Works

The filamentous cyanobacterium Anabaena variabilis ATCC 29413 fixes nitrogen under aerobic conditions in specialized cells called heterocysts that form in response to an environmental deficiency in combined nitrogen. Nitrogen fixation is mediated by the enzyme nitrogenase, which is very sensitive to oxygen. Heterocysts are microxic cells that allow nitrogenase to function in a filament comprised primarily of vegetative cells that produce oxygen by photosynthesis. A. variabilis is unique among well-characterized cyanobacteria in that it has three nitrogenase gene clusters that encode different nitrogenases, which function under different environmental conditions. The nif1 genes encode a Mo-nitrogenase that functions only in heterocysts, …

Comparative Genome Analyses Reveal Distinct Structure In The Saltwater Crocodile Mhc., Weerachai Jaratlerdsiri, Janine Deakin, Ricardo M. Godinez, Xueyan Shan, Daniel G. Peterson, Sylvain Marthey, Eric Lyons, Fiona M. Mccarthy, Sally R. Isberg, Damien P. Higgins, Amanda Y. Chong, John St. John, Travis C. Glenn, David A. Ray, Jaime Gongora

CALS Publications

The major histocompatibility complex (MHC) is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III) containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians) are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus) and compared it with that of other taxa. We characterised genomic clusters …

The Birds Of Genome10k, Stephen J. O'Brien, David Haussler, Oliver A. Ryder

Biology Faculty Articles

Everyone loves the birds of the world. From their haunting songs and majesty of flight to dazzling plumage and mating rituals, bird watchers – both amateurs and professionals - have marveled for centuries at their considerable adaptations. Now, we are offered a special treat with the publication of a series of papers in dedicated issues of Science, Genome Biology and GigaScience (which also included pre-publication data release). These present the successful beginnings of an international interdisciplinary venture, the Avian Phylogenomics Project that lets us view, through a genomics lens, modern bird species and the evolutionary events that produced them.

The Unseen World: Environmental Microbial Sequencing And Identification Methods For Ecologists, Naupaka Zimmerman, Jacques Izard, Christian Klatt, Jizhong Zhou, Emma Aronson

Department of Food Science and Technology: Faculty Publications

Archaea, bacteria, microeukaryotes, and the viruses that infect them (collectively “microorganisms”) are foundational components of all ecosystems, inhabiting almost every imaginable environment and comprising the majority of the planet’s organismal and evolutionary diversity. Microorganisms play integral roles in ecosystem functioning; are important in the biogeochemical cycling of carbon (C), nitrogen (N), sulfur (S), phosphorus (P), and various metals (eg Barnard et al. 2005); and may be vital to ecosystem responses to large-scale climatic change. Rarely found alone, microorganisms often form complex communities that are dynamic in space and time. For these and other reasons, ecologists and environmental scientists have become …

Dprp: A Database Of Phenotype-Specific Regulatory Programs Derived From Transcription Factor Binding Data, David T. W. Tzeng, Yu-Ting Tseng, Matthew Ung, I-En Liao, Chun-Chi Liu, Chao Cheng

Dartmouth Scholarship

Gene expression profiling has been extensively used in the past decades, resulting in an enormous amount of expression data available in public databases. These data sets are informative in elucidating transcriptional regulation of genes underlying various biological and clinical conditions. However, it is usually difficult to identify transcription factors (TFs) responsible for gene expression changes directly from their own expression, as TF activity is often regulated at the posttranscriptional level. In recent years, technical advances have made it possible to systematically determine the target genes of TFs by ChIP-seq experiments. To identify the regulatory programs underlying gene expression profiles, we …

Meiotic Checkpoint Activation Promotes Anaphase Promoting Complex/Cyclosome Substrate Specificity And Ume6/Sin3/Rpd3-Independent Reduction In Emg Expression, Rebecca Lewandowski

Graduate School of Biomedical Sciences Theses and Dissertations

Complex differentiation pathways, such as yeast meiosis and sporulation, are initiated in response to cell type and external stimuli and are driven by changes in tightly regulated and temporally expressed transcriptional programs. These programs are monitored by checkpoint mechanisms that couple meiotic progression to transcriptional activity to ensure each stage is successfully completed prior to progression into the next phase. This work investigated transcriptional regulation controlling meiotic progression when cells sense an insult to genetic integrity. These studies revealed that the early meiotic gene (EMG) repressor Ume6p is degraded during meiotic checkpoint activation triggered by the deoxyribonucleotide reductase inhibitor and …

Review Of "The Pku Paradox: A Short History Of A Genetic Disease" By D. B. Paul And J. P. Brosco, John B. Jenkins

Biology Faculty Works

No abstract provided.

Mechanistic Investigations Of Pseudouridine Synthases : A Surprising Glycal Intermediate Lies On The Reaction Pathway., Govardhan Reddy Veerareddygari

Electronic Theses and Dissertations

Pseudouridine synthases (ΨSs) catalyze the isomerization of uridine (U) in RNA to pseudouridine (Ψ), which is the most common post-transcriptional modification in RNAs and is ubiquitous within all three domains of life. ΨSs are classified into six different families based on sequence alignments and have a universally conserved aspartic acid residue (‘conserved Asp’ for simplicity) that is absolutely essential for activity. RNA containing 5-fluorouridine ([F5U]RNA) has been used as a mechanistic probe. Upon incubation with [F5U]RNA, TruA and RluA get irreversibly inhibited and appear in a protein-RNA adduct band on denaturing PAGE gels, which is consistent with the ‘Michael mechanism’ …

Evolutionary Search For Models Of Planarian Regeneration Using Experimental Data, Marianna Viktorovna Budnikova

Boise State University Theses and Dissertations

The ability of science to produce experimental data greatly surpasses our current ability to effectively visualize, conceptualize, and integrate the vast volumes of available data into a unified understanding of how complex biological systems work. This inability is a hindrance to scientific progress, and is particularly daunting when one considers multidimensional and shape-based observations as in the field of regenerative biology. For example, for at least the last 200 years, scientists have been interested in the exceptional ability of Planaria to regenerate lost tissues from damage, and there is a large amount of experimental data available on this organism. However, …

Genetic Parameter Estimates And Breed Effects For Calving Difficulty And Birth Weight In A Multi-Breed Population, Cashley Ahlberg

Department of Animal Science: Dissertations, Theses, and Student Research

There are multiple breeds of beef cattle available to utilize in breeding systems to maximize production and economics. Calving difficulty (dystocia) is a significant cost to beef production and is more prevalent in first-calf heifers. The objectives of this study were to estimate genetic parameters and breed differences for calving difficulty and birth weight as a first step towards the development of across-breed adjustment factors for calving difficulty.

Two models were employed to analyze birth weight (BWT) and calving difficulty (CD) recorded on 4,579 first parity females from the Germplasm Evaluation program at the United States Meat Animal Research Center …

Suppression Of Neurodegenerative Symptoms Via Suppressor Of Levy Mutation In Drosophila Melanogaster, William Kaputa

Forensic Science Theses

Mutation of the levy gene on chromosome 2 of Drosophila melanogaster has previously been shown to cause temperature-induced paralysis and neurodegeneration. The Suppressor of levy mutation, Su(levy), also on chromosome 2, modulates the effects of the levy mutation and partly rescues the wild-type phenotype. The goal of this research was to determine if Su(levy) mutation alleviates the effects of neurodegeneration caused by mutations associated with Alzheimer’s and Parkinson’s diseases in humans. The mutant genes used were hLRRK2, α-Synuclein, DJ1-α, Pink, Parkin, and Aβ-42. To determine this, flies carrying the above-mentioned mutant genes were …

The Use Of Surface Cytokines As Biomarkers In B Cell Mediated Autoimmune Diseases, Abby Jones Weldon

Loma Linda University Electronic Theses, Dissertations & Projects

RA and SLE are B cell-mediated autoimmune diseases dominated by autoantibodies that affect over 1.5 million Americans. Together RA and SLE contribute to over 29 billion in healthcare costs, therefore due to the high financial burden and physical toll of these diseases on the population, there is a critical need to effectively and efficiently diagnose and treat RA and SLE patients. The aim of our studies was to identify biomarkers and drug targets to improve the identification and treatment of RA and SLE patients. As discussed above, APRIL, BAFF and TSLP have been implicated in the pathogenesis of RA and …

Identification Of Cell Signaling Pathway Regulated By Micrornas In Cancer Cells Using A Systems Biological Approach, Sangbae Kim

Dissertations and Theses (Open Access)

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression via imperfect binding of the miRNA to specific sites in the 3' untranslated region of the mRNAs. Because prediction of miRNA targets is an essential step for understanding the functional roles of miRNAs, many computational approaches have been developed to identify miRNA targets. However, identifying targets remains challenging due to the inherent limitation of current prediction approaches based on imperfect complementarity between miRNA and its target mRNAs. To overcome these current limitations, we developed a novel correlation-based approach that is sequence independence to predict functional targets of miRNAs by …

Comparative Genomics Reveals Insights Into Avian Genome Evolution And Adaptation, Guojie Zhang, Cai Li, Qiye Li, Bo Li, Dennis M. Larkin, Chul Lee, Jay F. Storz, Agostinho Antunes, Matthew J. Greenwold, Robert W. Meredith, Anders Ödeen, Jie Cui, Qi Zhou, Luohao Xu, Hailin Pan, Zongji Wang, Lijun Jin, Pei Zhang, Haofu Hu, Wei Yang, Jiang Hu, Jin Xiao, Zhikai Yang, Yang Liu, Qiaolin Xie, Hao Yu, Jinmin Lian, Ping Wen, Fang Zhang, Hui Li, Yongli Zeng, Zijun Xiong, Shiping Liu, Long Zhou, Zhiyong Huang, Na An, Jie Wang, Quimei Zheng, Yingqi Xiong, Guangbiao Wang, Bo Wang, Jingjing Wang, Yu Fan, Rute R. Da Fonseca, Alonzo Alfaro-Núñez, Mikkel Schubert, Ludovic Orlando, Tobias Mourier, Jason T. Howard, Ganeshkumar Ganapathy, Andreas Pfenning, Osceola Whitney, Miriam V. Rivas, Erina Hara, Julia Smith, Marta Farré, Jitendra Narayan, Gancho Slavov, Michael N. Romanov, Rui Borges, João Paulo Machado, Imran Khan, Mark S. Springer, John Gatesy, Federico G. Hoffmann, Juan C. Opazo, Olle Håstad, Roger H. Sawyer, Heebal Kim, Kyu-Won Kim, Hyeon Jeong Kim, Seoae Cho, Ning Li, Yinhua Huang, Michael W. Bruford, Xiangjiang Zhan, Andrew Dixon, Mads F. Bertelsen, Elizabeth Derryberry, Wesley Warren, Richard K. Wilson, Shengbin Li, David A. Ray, Richard E. Green, Stephen J. O'Brien, Darren Griffin, Warren E. Johnson, David Haussler, Oliver A. Ryder, Eske Willerslev, Gary R. Graves, Per Alström, Jon Fjeldså, David P. Mindell, Scott V. Edwards, Edward L. Braun, Carsten Rahbek, David W. Burt, Peter Houde, Yong Zhang, Huanming Yang, Jian Wang, Avian Genome Consortium, Erich D. Jarvis, M. Thomas P. Gilbert, Jun Wang

Jay F. Storz Publications

Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses …

Genetic Structure Of Yellow Perch Populations In Coastal Areas Of Eastern Lake Michigan, Jessica N. Wesolek

Masters Theses

Genetic population substructure is often overlooked because of discontinuities between management and actual population structure as in the case of yellow perch, an ecologically and economically important indigenous fish species in the Laurentian Great Lakes. A knowledge gaps pertaining to the natural history of yellow perch relates to the biological connectivity between nearshore Lake Michigan and drowned river mouth (DRM) lakes, where it remains unclear whether resident yellow perch from Lake Michigan use DRM lakes for spawning or whether DRM lakes contribute to nearshore yellow perch populations in Lake Michigan. I used DNA fingerprinting (genotyping) to explore biological connectivity between …

Genetic Dissection Of Neuromuscular Diseases Affecting Domestic Dogs, Caitlin Rinz

All Dissertations

The domestic dog, Canis familiaris, has a unique population structure that lends itself to the study of hereditary diseases. Purebred dogs populations are genetically isolated and as a result are affected by more than 400 naturally occurring diseases, many of which have human counterparts. In the last 15 years, dogs have emerged as a model for the study of human hereditary diseases, fueling the development of resources including a 7.6X coverage reference genome and single nucleotide polymorphism (SNP) genotyping arrays.

Congenital myasthenic syndrome (CMS) is a neuromuscular disorder of both humans and dogs in which transmission across the neuromuscular …

Gene Electro Transfer Of Plasmid Encoding Vascular Endothelial Growth Factor For Enhanced Expression And Perfusion In The Ischemic Swine Heart, Barbara Y. Hargrave, Robert Strange Jr., Sagar Navare, Michael Stratton, Niculina Burcus, Len Murray, Cathryn Lundberg, Anna A. Bulysheva, Fanying Li, Richard Heller

Bioelectrics Publications

Myocardial ischemia can damage heart muscle and reduce the heart's pumping efficiency. This study used an ischemic swine heart model to investigate the potential for gene electro transfer of a plasmid encoding vascular endothelial growth factor for improving perfusion and, thus, for reducing cardiomyopathy following acute coronary syndrome. Plasmid expression was significantly greater in gene electro transfer treated tissue compared to injection of plasmid encoding vascular endothelial growth factor alone. Higher gene expression was also seen in ischemic versus non-ischemic groups with parameters 20 Volts (p

Angelman Syndrome, Stephanie Sorbara (Class Of 2015)

Biology Undergraduate Publications

Angelman Syndrome (AS) is a neurogenetic disorder that is classically characterized by excessive laughter and a happy demeanor. Aggression, sleep disorders and epilepsy are other phenotypes associated with this disorder as well. Both happy and aggressive demeanors have been expressed in five different consumers at The Kennedy Center, a site which offers programs and services to individuals with varying disabilities. Research proposes several different genetic mechanisms responsible for the development of AS, each of which impact the function of the UBE3A gene located in the 15q11-13 region on chromosome 15. Additionally, from an evolutionary perspective, Emotion Signaling Theory and Kinship …

The Conservation Genetics Of Two Emydid Turtles: Emydoidea Blandingii And Malaclemys Terrapin, Charlotte Lizana Petre

Master's Theses

Conservation of turtles is complicated by their sensitivity to habitat degradation and overexploitation. I used microsatellites and standard population genetic analyses to explore genetic diversity, population structure, paternity and demographic history in two emydid turtles that are currently experiencing threats to their survival. The Blanding’s turtle, Emydoidea blandingii, has experienced habitat fragmentation throughout its range, and this study focuses on a population in Massachusetts where hatchlings from one population are being translocated to establish a new population. I found evidence of multiple paternity within clutches and found no significant reduction in genetic diversity when comparing the source population and …

Antibacterial Gene Transfer Across The Tree Of Life, Jason A. Metcalf, Lisa J. Funkhouser-Jones, Kristen A. Brileya, Anna-Louise Reysenbach, Seth R. Bordenstein

Biology Faculty Publications and Presentations

Though horizontal gene transfer (HGT) is widespread, genes and taxa experience biased rates of transferability. Curiously, independent transmission of homologous DNA to archaea, bacteria, eukaryotes, and viruses is extremely rare and often defies ecological and functional explanations. Here, we demonstrate that a bacterial lysozyme family integrated independently in all domains of life across diverse environments, generating the only glycosyl hydrolase 25 muramidases in plants and archaea. During coculture of a hydrothermal vent archaeon with a bacterial competitor, muramidase transcription is upregulated. Moreover, recombinant lysozyme exhibits broad-spectrum antibacterial action in a dose-dependent manner. Similar to bacterial transfer of antibiotic resistance genes, …

An Active Role For The Ribosome In Determining The Fate Of Oxidized Mrna, Carrie L. Simms, Benjamin H. Hudson, John W. Mosior, Ali S. Rangwala, Hani S. Zaher

Biology Faculty Research

Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle to the translational apparatus; however, the effects of damaged mRNA on the speed and accuracy of the decoding process and their interplay with quality-control processes are not known. Here, we systematically explore the effects of oxidative damage on the decoding process using a well-defined bacterial in vitro translation system. We find that the oxidative lesion 8-oxoguanosine (8-oxoG) reduces the rate of peptide-bond formation by more than three orders of magnitude independent of its position within the codon. Interestingly, 8-oxoG had little effect on the fidelity …

In Vivo Identification Of Eugenol-Responsive And Muscone-Responsive Mouse Odorant Receptors, Timothy S. Mcclintock, Kaylin Adipietro, William B. Titlow, Patrick Breheny, Andreas Walz, Peter Mombaerts, Hiroaki Matsunami

Physiology Faculty Publications

Our understanding of mammalian olfactory coding has been impeded by the paucity of information about the odorant receptors (ORs) that respond to a given odorant ligand in awake, freely behaving animals. Identifying the ORs that respond in vivo to a given odorant ligand from among the ∼1100 ORs in mice is intrinsically challenging but critical for our understanding of olfactory coding at the periphery. Here, we report an in vivo assay that is based on a novel gene-targeted mouse strain, S100a5-tauGFP, in which a fluorescent reporter selectively marks olfactory sensory neurons that have been activated recently in vivo. Because each …

Testing Gene-Environment Interactions In The Presence Of Measurement Error, Chongzhi Di, Li Hsu, Charles Kooperberg, Alex Reiner, Ross Prentice

UW Biostatistics Working Paper Series

Complex diseases result from an interplay between genetic and environmental risk factors, and it is of great interest to study the gene-environment interaction (GxE) to understand the etiology of complex diseases. Recent developments in genetics field allows one to study GxE systematically. However, one difficulty with GxE arises from the fact that environmental exposures are often measured with error. In this paper, we focus on testing GxE when the environmental exposure E is subject to measurement error. Surprisingly, contrast to the well-established results that the naive test ignoring measurement error is valid in testing the main effects, we find that …

A Comparison Of The Caulobacter Na1000 And K31 Genomes Reveals Extensive Genome Rearrangements And Differences In Metabolic Potential, Craig Stephens, Kurt Ash, Theta Brown, Tynetta Watford, Latia E. Scott, Bert Ely

Biology

The genus Caulobacter is found in a variety of habitats and is known for its abilityto thrive in low-nutrient conditions. K31 is a novel Caulobacter isolate that has the ability to tolerate copper and chlorophenols, and can grow at 48Cwith a doubling time of 40 h. K31 contains a 5.5 Mb chromosome that codes for more than 5500 proteins and two large plasmids (234 and 178 kb) thatcode for 438 additional proteins. A comparison of the K31 and the Caulobactercrescentus NA1000 genomes revealed extensive rearrangements of gene order,suggesting that the genomes had been randomly scrambled. However, a careful analysis revealed …