Genetics and Genomics Commons^™

Cell Polarity Regulates Organ Growth Through The Hippo Pathway, Chiao-Lin Chen

Dissertations and Theses (Open Access)

Defects in apical-basal cell polarity and abnormal expression of cell polarity determinants are linked to human cancer. Loss of polarity is highly correlated with malignancy. In Drosophila, perturbation of apical-basal polarity, including overexpressing the apical determinant Crumbs, can lead to uncontrolled tissue growth. Cells mutant for the basolateral determinant scribble overproliferate and can form neoplastic tumors. Interestingly, scribble mutant clones that arise in wild-type tissues are eliminated and therefore do not manifest their tumorigenic potential. However, the mechanisms by which cell polarity coordinates with growth control pathways in developing organs to achieve appropriate organ size remain obscure.

To investigate …

Gene Discovery In Nonsyndromic Cleft Lip With Or Without Cleft Palate, Brett T. Chiquet

Dissertations and Theses (Open Access)

Nonsyndromic cleft lip with or without cleft palate (NSCLP), a common, complex orofacial birth defect that affects approximately 4,000 newborns each year in the United States, is caused by both genetic and environmental factors. Orofacial clefts affect the mouth and nose, causing severe deformity of the face, which require medical, dental and speech therapies. Despite having substantial genetic liability, less than 25% of the genetic contribute to NSCLP has been identified. The studies described in this thesis were performed to identify genes that contribute to NSCLP and to demonstrate the role of these genes in normal craniofacial development. Using genome …

Regulation Of Set1-Mediated Methylation Of Dam1, John A. Latham

Dissertations and Theses (Open Access)

Eukaryotic genomes exist within a dynamic structure named chromatin in which DNA is wrapped around an octamer of histones forming the nucleosome. Histones are modified by a range of posttranslational modifications including methylation, phosphorylation, and ubiquitination, which are integral to a range of DNA-templated processes including transcriptional regulation. A hallmark for transcriptional activity is methylation of histone H3 on lysine (K) 4 within active gene promoters. In S. cerevisiae, H3K4 methylation is mediated by Set1 within the COMPASS complex. Methylation requires prior ubiquitination of histone H2BK123 by the E2-E3 ligases Rad6 and Bre1, as well as the Paf1 transcriptional …

Prevalence Of Premature Ovarian Failure In Women With Tuberous Sclerosis, Emily Gabitzsch

Dissertations and Theses (Open Access)

Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor disorder characterized by hamartomas, or benign growths, in various organ systems. Inactivating mutations in either the TSC1 or the TSC2 gene cause most cases of TSC. Recently, the use of ovarian specific conditional knock-out mouse models has demonstrated a crucial role of the TSC genes in ovarian function. Mice with complete deletion of Tsc1 or Tsc2 showed accelerated ovarian follicle activation and subsequent premature follicular depletion, consistent with the human condition premature ovarian failure (POF). POF is defined in women as the cessation of menses before the age of 40 …

Expression And Regulation Of Human Cytochrome P450 4f Isoforms In Tissue Samples And Under Tnf-Alpha Challenges, Jordan C. Bell

Dissertations and Theses (Open Access)

CYP4F (Cytochrome P4504F) enzymes metabolize endogenous molecules including leukotrienes, prostaglandins and arachidonic acid. The involvement of these endogenous compounds in inflammation has led to the hypothesis that changes in the inflamed tissue environment may affect the expression of CYP4Fs during the pro-inflammatory state, which in turn may modulate inflammatory conditions during the anti-inflammatory state. We demonstrated that inflamed tissues have different levels of CYP4F isoform expression profiles in a number of human samples when compared to the average population. The CYP4F isoform expression levels change with the degree of inflammation present in tissue. Further investigation in cell culture studies revealed …

Molecular Evolution And Historical Biogeography Of New World Birds, Brian T. Smith

UNLV Theses, Dissertations, Professional Papers, and Capstones

Deciphering the patterns of how biodiversity has evolved across time and space has remained a fundamental objective for biologists for the last 200 years. Researchers are faced with the challenge of interpreting the complexity of evolutionary patterns that have been generated over the deep history of the Earth. The advancement of DNA sequencing technology has yielded a new and powerful genetic toolkit that has allowed biologists to address novel evolutionary questions. For my dissertation research, I used molecular genetics and a statistical framework to study the evolution and historical biogeography of birds distributed in North and South America. My dissertation …

Depicting Simultaneously Similarity, Diversity, Ancestry, And Admixture?, Peter J. Taylor

Working Papers on Science in a Changing World

Can any depiction of genetic relationships among humans allow simultaneously for similarity, diversity, ancestry, and admixture (i.e., groups that had split mixing again)? I asked this question while puzzling over the messages conveyed by diagrams from the work of Tishkoff and collaborators on genetic variation among humans in and out of Africa. In this talk I present explorations of alternative depictions of human genetic variation keeping my initial question in mind. By the end I will have prepared the ground for an assertion that the very methodology of generating and depicting human ancestry privileges a racialized view of human diversity.

Elevated Expression Of Squamous Cell Carcinoma Antigen (Scca) Is Associated With Human Breast Carcinoma, Joseph M. Catanzaro, Jennifer L. Guerriero, Jingxuan Liu, Namratha Sheshadri, John J. Chen, Wei-Xing Zhong

Department of Molecular Genetics and Microbiology Faculty Publications

Squamous cell carcinoma antigen (SCCA) belongs to the serine protease inhibitor (Serpin) family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC) in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360) and normal breast epithelium (n = 124). SCCA expression was scored on a tiered scale (0-3) independently by two evaluators blind to the patient's clinical status. SCCA expression was observed in …

Oral Presentation: Plant Genes And Drought Tolerance, Norris Lam

Festival of Communities: UG Symposium (Posters)

Research has shown that a gene from C3 xerophyte Larrea tridentata (creosote bush), LtWRKY21, is involved in pathways governing creosote bush’s high tolerance to environmental stress. By understanding the way in which creosote bush adapts to drought, crop plants can be engineered to be more drought tolerant during times of imminent global climate change. To study the underlying mechanisms of creosote bush drought response, the LtWRKY21 gene was mobilized into the model organism Arabidopsis thaliana. Chlorophyll degradation, cellular electrolyte leakage, and water content in leaves will serve as indicators of drought tolerance in LtWRKY21-transgenic A. thaliana after treatment in chemically …

Stationary Phase Mutagenesis In Bacillus Subtilisis Independent Of Genome Replication, Mark Upchurch, Holly Martin, Eduardo Robleto

Festival of Communities: UG Symposium (Posters)

Stationary phase mutagenesis is defined as cellular mechanisms that produce genetic diversity in cells experiencing conditions of stress. These processes are associated with many biological phenomena, including those that produce the formation of cancers in animal cells and other degenerative diseases. Also, these mechanisms are associated with the accumulation of beneficial mutations in bacteria, but follow stochastic processes and are controlled by genetic factors. The current models explaining the generation of stress-induced mutations are predicated on the formation of DNA replication intermediates that are formed during the repair of damaged DNA or during DNA replication and transcription encounters. Here we …

Screening Synteny Blocks In Pairwise Genome Comparisons Through Integer Programming, Haibao Tang, Eric Lyons, Brent S. Pedersen, James C. Schnable, Andrew H. Paterson, Michael Freeling

Department of Agronomy and Horticulture: Faculty Publications

Background:

It is difficult to accurately interpret chromosomal correspondences such as true orthology and paralogy due to significant divergence of genomes from a common ancestor. Analyses are particularly problematic among lineages that have repeatedly experienced whole genome duplication (WGD) events. To compare multiple “subgenomes” derived from genome duplications, we need to relax the traditional requirements of “one-to-one” syntenic matchings of genomic regions in order to reflect “one-to-many” or more generally “many-to-many” matchings. However this relaxation may result in the identification of synteny blocks that are derived from ancient shared WGDs that are not of interest. For many downstream analyses, we …

Generation, Cloning, And Expression Of Full-Length Human Evc Gene, Trey Polvadore

Undergraduate Research Conference

No abstract provided.

Charles Darwin: Evolutionary Theory & The Theatre, Katrina Tarson

Undergraduate Research Conference

No abstract provided.

The Importance Of The Set2 Gene In The Virulence Of Candida Albicans, Molly Marchel

Honors Capstones

Capstone submitted as a graduation requirement for BSU Honors Program.

Molecular Correlates Of Social Dominance: A Novel Role For Ependymin In Aggression, Lynne U. Sneddon, Rupert Schmidt, Yongxiang Fang, Andrew R. Cossins

Ethology Collection

Theoretical and empirical studies have sought to explain the formation and maintenance of social relationships within groups. The resulting dominance hierarchies have significant fitness and survival consequences dependent upon social status. We hypothesised that each position or rank within a group has a distinctive brain gene expression profile that correlates with behavioural phenotype. Furthermore, transitions in rank position should determine which genes shift in expression concurrent with the new dominance status. We used a custom cDNA microarray to profile brain transcript expression in a model species, the rainbow trout, which forms tractable linear hierarchies. Dominant, subdominant and submissive individuals had …

A Myriad Of Misunderstanding Standing: Decoding Judicial Review For Gene Patents, Jenny L. Maxey

West Virginia Law Review

No abstract provided.

Copyright For Engineered Dna: An Idea Whose Time Has Come?, Christopher M. Holman

West Virginia Law Review

The rapidly emerging field of synthetic biology has tremendous potential to address some of the most compelling challenges facing our planet by providing clean renewable energy, nutri- tionally-enhanced and environmentally friendly agricultural products, and revolutionary new life-saving cures. However, leaders in the synthetic biology movement have voiced concern that biotechnology's current patent-centric approach to intellec- tual property is in many ways ill-suited to meet the challenge of synthetic biology, threatening to impede follow-on innovation and open access technology. For years, copyright and patent protection for computer software have existed side-by-side, the two forms of intellectual property complementing one another. Numerous …

Preliminary Analysis Of An Agent-Based Model For A Tick-Borne Disease, Holly Gaff

Biological Sciences Faculty Publications

Ticks have a unique life history including a distinct set of life stages and a single blood meal per life stage. This makes tick-host interactions more complex from a mathematical perspective. In addition, any model of these interactions must involve a significant degree of stochasticity on the individual tick level. In an attempt to quantify these relationships, I have developed an individual-based model of the interactions between ticks and their hosts as well as the transmission of tick-borne disease between the two populations. The results from this model are compared with those from previously published differential equation based population models. …

Draft Genome Of The Red Harvester Ant Pogonomyrmex Barbatus, Chris R. Smith, Christopher D. Smith, Hugh M. Robertson, Martin Helmkampf, Aleksey Zimin, Mark Yandall, Carson Holt, Hao Hu, Ehab Abouheif, Richard Benton, Elizabeth Cash, Vincent Croset, Cameron R. Currie, Eran Elhaik, Christine G. Elsik, Marie-Julie Favé, Vilaiwan Fernandes, Joshua D. Gibson, Dan Graur, Wulfila Gronenberg, Kirk J. Grubbs, Darren E. Hagen, Ana Sofia Ibarraran Viniegra, Brian R. Johnson, Reed M. Johnson, Abderrahman Khila, Jay W. Kim, Kaitlyn A, Mathis, Monica C. Munoz-Torres, Marguerite C. Murphy, Julie A. Mustard, Rin Nakamura, Oliver Niehuis, Surabhi Nigam, Rick P. Overson, Jennifer E. Placek, Rajendhran Rajakumar, Justin T. Reese, Garret Suen, Shu Tao, Candice W. Torres, Neil D. Tsutsui, Lumi Viljakainen, Florian Wolschin, Jürgen Gadau

Department of Entomology: Faculty Publications

We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome was sequenced using 454 pyrosequencing, and the current assembly and annotation were completed in less than 1 y. Analyses of conserved gene groups (more than 1,200 manually annotated genes to date) suggest a high-quality assembly and annotation comparable to recently sequenced insect genomes using Sanger sequencing. The red harvester ant is a model for studying reproductive division of labor, phenotypic plasticity, and sociogenomics. Although the genome of P. barbatus is similar to other sequenced hymenopterans (Apis mellifera and Nasonia vitripennis) in …

Blended Biogeography-Based Optimization For Constrained Optimization, Haiping Ma, Daniel J. Simon

Electrical and Computer Engineering Faculty Publications

Biogeography-based optimization (BBO) is a new evolutionary optimization method that is based on the science of biogeography. We propose two extensions to BBO. First, we propose a blended migration operator. Benchmark results show that blended BBO outperforms standard BBO. Second, we employ blended BBO to solve constrained optimization problems. Constraints are handled by modifying the BBO immigration and emigration procedures. The approach that we use does not require any additional tuning parameters beyond those that are required for unconstrained problems. The constrained blended BBO algorithm is compared with solutions based on a stud genetic algorithm (SGA) and standard particle swarm …

Drafting Human Ancestry: What Does The Neanderthal Genome Tell Us About Hominid Evolution? Commentary On Green Et Al. (2010), Michael Hofreiter

Human Biology

Ten years after the first draft versions of the human genome were
announced, technical progress in both DNA sequencing and ancient DNA
analyses has allowed a research team around Ed Green and Svante Pa¨a¨bo to
complete this task from infinitely more difficult hominid samples: a few
pieces of bone originating from our closest, albeit extinct, relatives, the
Neanderthals. Pulling the Neanderthal sequences out of a sea of contaminating
environmental DNA impregnating the bones and at the same time
avoiding the problems of contamination with modern human DNA is in itself
a remarkable accomplishment. However, the crucial question in the long …

In Vitro Amplification Of Misfolded Prion Protein Using Lysate Of Cultured Cells, Charles E. Mays, Jihyun Yeom, Hae-Eun Kang, Jifeng Bian, Vadim Khaychuk, Younghwan Kim, Jason C Bartz, Glenn C Telling, Chongsuk Ryou

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Protein misfolding cyclic amplification (PMCA) recapitulates the prion protein (PrP) conversion process under cell-free conditions. PMCA was initially established with brain material and then with further simplified constituents such as partially purified and recombinant PrP. However, availability of brain material from some species or brain material from animals with certain mutations or polymorphisms within the PrP gene is often limited. Moreover, preparation of native PrP from mammalian cells and tissues, as well as recombinant PrP from bacterial cells, involves time-consuming purification steps. To establish a convenient and versatile PMCA procedure unrestricted to the availability of substrate sources, we attempted to …

Evolution Of A Major Drug Metabolizing Enzyme Defect In The Domestic Cat And Other Felidae: Phylogenetic Timing And The Role Of Hypercarnivory, Binu Shrestha, J. Michael Reed, Philip T. Starks, Gretchen E. Kaufman, Jared V. Goldstone, Melody E. Roelke, Stephen J. O'Brien, Klaus-Peter Koepfli, Laurence Frank, Michael H. Court

Biology Faculty Articles

The domestic cat (Felis catus) shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT) 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional …

A Molecular Phylogeny Of Living Primates, Polina L. Perelman, Warren E. Johnson, Christian Roos, Hector Seuanez, Julie E. Horvath, Miguel A. M. Moreira, Bailey Kessing, J. U. Pontius, Melody E. Roelke, Yves Rumpler, Maria P. C. Schneider, Artur Silva, Stephen J. O'Brien, Jill Pecon-Slattery

Biology Faculty Articles

Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb) from 186 primates representing 61 (~90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate …

Advances And Future Challenges In Adenoviral Vector Pharmacology And Targeting, Reeti Khare, Christopher Y. Chen, Eric A. Weaver, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multifaceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral “sinks” must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology …

Leaf Number Indicates Salt Tolerance Of Young Seedling Families Of European Aspen (Populus Tremula L.) Growing In Different Soils, Lu-Min Vaario, Kim Yrjälä, Matti Rousi, Timo Sipila, Pertti Pulkkinen

Aspen Bibliography

Soil salinity limits plant productivity and quality. We evaluated the response of 12 aspen (Populus tremula) families to salt stress in two different soils irrigated for 4-weeks with 0, 80 or 160 mM saline solution. Easily measurable characteristics such as shoot height, leaf number, dry mass as well as the distribution of sodium (Na+) ions were measured in 5-month-old aspen seedlings raised in controlled greenhouse conditions on two different soils. Growth among families varied significantly, and the interaction between family and soil type was significant. From 2–5 months, leaf number correlated with that of the first month and salin-ity tolerance. …

Genes Identified By Visible Mutant Phenotypes Show Increased Bias Toward One Of Two Subgenomes Of Maize, James C. Schnable, Michael Freeling

Department of Agronomy and Horticulture: Faculty Publications

Not all genes are created equal. Despite being supported by sequence conservation and expression data, knockout homozygotes of many genes show no visible effects, at least under laboratory conditions. We have identified a set of maize (Zea mays L.) genes which have been the subject of a disproportionate share of publications recorded at MaizeGDB. We manually anchored these ‘‘classical’’ maize genes to gene models in the B73 reference genome, and identified syntenic orthologs in other grass genomes. In addition to proofing the most recent version 2 maize gene models, we show that a subset of these genes, those that …

Dose–Sensitivity, Conserved Non-Coding Sequences, And Duplicate Gene Retention Through Multiple Tetraploidies In The Grasses, James C. Schnable, Brent S. Pedersen, Sabarinath Subramaniam, Michael Freeling

Department of Agronomy and Horticulture: Faculty Publications

Whole genome duplications, or tetraploidies, are an important source of increased gene content. Following whole genome duplication, duplicate copies of many genes are lost from the genome. This loss of genes is biased both in the classes of genes deleted and the subgenome from which they are lost. Many or all classes are genes preferentially retained as duplicate copies are engaged in dose sensitive protein–protein interactions, such that deletion of any one duplicate upsets the status quo of subunit concentrations, and presumably lowers fitness as a result. Transcription factors are also preferentially retained following every whole genome duplications studied. This …

Isolation By Distance Explains Genetic Structure Of Buggy Creek Virus, A Bird-Associated Arbovirus, Abinash Padhi, Amy T. Moore, Mary Bomberger Brown, Jerome E. Foster, Martin Pfeffer, Charles R. Brown

School of Natural Resources: Faculty Publications

Many of the arthropod-borne viruses (arboviruses) show extensive genetic variability and are widely distributed over large geographic areas. Understanding how virus genetic structure varies in space may yield insight into how these pathogens are adapted to and dispersed by different hosts or vectors, the relative importance of mutation, drift, or selection in generating genetic variability, and where and when epidemics or epizootics are most likely to occur. However, because most arboviruses tend to be sampled opportunistically and often cannot be isolated in large numbers at a given locale, surprisingly little is known about their spatial genetic structure on the local …

Systematic Assessment Of Accuracy Of Comparative Model Of Proteins Belonging To Different Structural Fold Classes, Subrata Chakrabarty, Dario Ghersi, Roberto Sanchez

Interdisciplinary Informatics Faculty Publications

In the absence of experimental structures, comparative modeling continues to be the chosen method for retrieving structural information on target proteins. However, models lack the accuracy of experimental structures. Alignment error and structural divergence (between target and template) influence model accuracy the most. Here, we examine the potential additional impact of backbone geometry, as our previous studies have suggested that the structural class (all-α, αβ, all-β) of a protein may influence the accuracy of its model. In the twilight zone (sequence identity ≤ 30%) and at a similar level of target-template divergence, the accuracy of protein models does indeed follow …