Genetics and Genomics Commons^™

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …

High Connectivity In The Deepwater Snapper Pristipomoides Filamentosus (Lutjanidae) Across The Indo-Pacific With Isolation Of The Hawaiian Archipelago, Michelle R. Gaither, Shelley A. Jones, Christopher Kelley, Stephen J. Newman, Laurie Sorenson, Brian W. Bowen

Fisheries Research Articles

In the tropical Indo-Pacific, most phylogeographic studies have focused on the shallow-water taxa that inhabit reefs to approximately 30 m depth. Little is known about the large predatory fishes, primarily snappers (subfamily Etelinae) and groupers (subfamily Epinephelinae) that occur at 100–400 m. These long-lived, slow-growing species support fisheries across the Indo-Pacific, yet no comprehensive genetic surveys within this group have been conducted. Here we contribute the first range-wide survey of a deepwater Indo-Pacific snapper, Pristipomoides filamentosus, with special focus on Hawai'i. We applied mtDNA cytochrome b and 11 microsatellite loci to 26 samples (N = 1,222) collected across …

Reverse Protection Assay: A Tool To Analyze Transcriptional Rates From Individual Promoters, Yan O. Zubo, Victor V. Kusnetsov, Thomas Börner, Karsten Liere

Dartmouth Scholarship

Transcriptional activity of entire genes in chloroplasts is usually assayed by run-on analyses. To determine not only the overall intensity of transcription of a gene, but also the rate of transcription from a particular promoter, we created the Reverse RNase Protection Assay (RePro): in-organello run-on transcription coupled to RNase protection to define distinct transcript ends during transcription. We demonstrate successful application of RePro in plastid promoter analysis and transcript 3' end processing.

The Murine Caecal Microrna Signature Depends On The Presence Of The Endogenous Microbiota, Natasha Singh, Elize A. Shirdel, Levi Waldron, Regan-Heng Zhang, Igor Jurisica, Elena M. Comelli

Publications and Research

The intestinal messenger RNA expression signature is affected by the presence and compo-sition of the endogenous microbiota, with effects on host physiology. The intestine is also characterized by a distinctive micronome. However, it is not known if microbes also impact intestinal gene expression epigenetically. We investigated if the murine caecal microRNA expression signature depends on the presence of the microbiota, and the potential implica-tions of this interaction on intestinal barrier function. Three hundred and thirty four mi-croRNAs were detectable in the caecum of germ-free and conventional male mice and 16 were differentially expressed, with samples from the two groups clustering …

Fine Roots Of Aspen Clones In High Salt And Petroleum Hydrocarbon Pollution, Kim Yrjälä, Ivika Ostonen, Shinjini Mukherjee, Timo Sipila, Lu-Min Vaario, Pertti Pulkkinen

Aspen Bibliography

The quality of polluted soil can much be improved and the environmental risks reduced by use of phytoremediation. Harmful hydrocarbon compounds can be degraded through the activity of plant and its associated microbes. We previously showed that PAHs increase aromatic ring-cleavage gene diversity in rhizosphere of birch (Sipilä et al. 2008, Yrjälä et al. 2010a) and the rhizosphere of aspen harbors Burkholderia bacteria able to degrade aromatics (Yrjälä et al. 2010b). The results are promising for successful remediation of polluted soils with woody plants. The aim of our studies is to elucidate the response of the plant and the associated …

Modeling Protein Expression And Protein Signaling Pathways, Donatello Telesca, Peter Muller, Steven Kornblau, Marc Suchard, Yuan Ji

COBRA Preprint Series

High-throughput functional proteomic technologies provide a way to quantify the expression of proteins of interest. Statistical inference centers on identifying the activation state of proteins and their patterns of molecular interaction formalized as dependence structure. Inference on dependence structure is particularly important when proteins are selected because they are part of a common molecular pathway. In that case inference on dependence structure reveals properties of the underlying pathway. We propose a probability model that represents molecular interactions at the level of hidden binary latent variables that can be interpreted as indicators for active versus inactive states of the proteins. The …

Characterization Of A Novel Gef Kiaa1362, Emily Roach

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

A Study Of Correlations Between The Definition And Application Of The Gene Ontology, Yuji Mo

Department of Computer Electronics and Engineering: Dissertations, Theses, and Student Research

When using the Gene Ontology (GO), nucleotide and amino acid sequences are annotated by terms in a structured and controlled vocabulary organized into relational graphs. The usage of the vocabulary (GO terms) in the annotation of these sequences may diverge from the relations defined in the ontology. We measure the consistency of the use of GO terms by comparing GO's defined structure to the terms' application. To do this, we first use synthetic data with different characteristics to understand how these characteristics influence the correlation values determined by various similarity measures. Using these results as a baseline, we found that …

Afghan Genetic Mysteries, Bernard Dupaigne

Human Biology Open Access Pre-Prints

Letter To The Editor

The Y-Str Genetic Diversity Of An Idaho Basque Population, With Comparison To European Basques And Us Caucasians, Josu Zubizarreta, Michael C. Davis, Greg Hampikian

Human Biology Open Access Pre-Prints

Fifty unrelated Basque males from southwest Idaho were typed for the 17 Y-STR loci in the Yfiler multiplex kit (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, YGATA_H4.1 and DYS385a/b). A total of 42 haplotypes were identified, with no more than two individuals sharing a single haplotype. The haplotype diversity (HD) was 0.9935, and gene diversity (D) over loci was 0.457 ± 0.137. The Idaho Basque population was compared to the source population from the Basque autonomous region of Northern Spain and Southern France, as well as a US Caucasian population. The haplotype diversity …

Efficacy Of Genetically Modified Bt Toxins Against Insects With Different Genetic Mechanisms Of Resistance, Bruce E. Tabashnik, Fangneng P. Huang, Mukti N. Ghimire, B. Rogers Leonard, Blair D. Siegfried, Murugesan Rangasamy, Yajun Yang, Yidong Wu, Linda J. Gahan, David G. Heckel, Alejandro Bravo, Mario Soberón

Department of Entomology: Faculty Publications

Transgenic crops that produce Bacillus thuringiensis (Bt) toxins are grown widely for pest control, but insect adaptation can reduce their efficacy. The genetically modified Bt toxins Cry1AbMod and Cry1AcMod were designed to counter insect resistance to native Bt toxins Cry1Ab and Cry1Ac. Previous results suggested that the modified toxins would be effective only if resistance was linked with mutations in genes encoding toxin-binding cadherin proteins. Here we report evidence from five major crop pests refuting this hypothesis. Relative to native toxins, the potency of modified toxins was > 350-fold higher against resistant strains of Plutella xylostella and Ostrinia nubilalis …

A Population-Genetic Perspective On The Similarities And Differences Among Worldwide Human Populations, Noah A. Rosenberg

Human Biology Open Access Pre-Prints

Recent studies have produced a variety of advances in the investigation of genetic similarities and differences among human populations. Here, I pose a series of questions about human population- genetic similarities and differences, and I then answer these questions by numerical computation with a single shared population-genetic dataset. The collection of answers obtained provides an introductory perspective for understanding key results on the features of worldwide human genetic variation.

Integration Versus Apartheid In Post-Roman Britain: A Response To Thomas Et Al. (2008), John E. Pattison

Human Biology Open Access Pre-Prints

The genetic surveys of the population of Britain conducted by Weale et al. and Capelli et al. produced estimates of the Germani immigration into Britain during the early Anglo-Saxon period, c.430-c.730. These estimates are considerably higher than the estimates of archaeologists. A possible explanation suggested that an apartheid-like social system existed in the early Anglo-Saxon kingdoms resulting in the Germani breeding more quickly than the Britons. Thomas et al. attempted to model this suggestion and showed that it was a possible explanation if all Anglo-Saxon kingdoms had such a system for up to 400 yrs. I noted that their explanation …

Protein Trap Lines Of Drosophila To Demonstrate Spatio-Temporal Localization Of Proteins In An Undergraduate Lab, Oorvashi Roy Puli, Amit Singh

Biology Faculty Publications

The objective of this teaching note is to generate a laboratory exercise, which allows students to get a hands-on experience of a cell biology technique. The short duration of the laboratory classes is the biggest challenge with the development of a cell biology lab for an undergraduate curriculum. Therefore, it is necessary to design a laboratory exercise that enables the students to carry out cell biological assays in the desired time. This laboratory exercise focuses on tracking protein expression levels along a spatial (space) and temporal (time) axis in developing Drosophila melanogaster organ primordium. Here we use the protein trap …

Global And Specific Controls Of Protein Synthesis In Hibernators, Peipei Pan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Mammalian hibernation is a highly dynamic physiological process that is composed of a series of torpor bouts, wherein hibernators oscillate between periods of torpor and interbout arousal. Although normally vital to homeostasis, many energetically consumptive processes such as translation or protein synthesis are virtually ceased during hibernation. Earlier studies indicated that protein synthesis had fallen to almost negligible levels. Cap-dependent initiation of translation is well regulated by eukaryotic translation initiation factor 4E (eIF4E) and its binding partner eIF4E-binding protein 1 (4E-BP1) when hibernators cycle in and out the torpor state. Herein, I investigated well-characterized regulatory mechanisms of global and specific …

Quantitative Comparison Of Cis-Regulatory Element (Cre) Activities In Transgenic Drosophila Melanogaster, William A. Rogers, Thomas M. Williams

Biology Faculty Publications

Gene expression patterns are specified by cis-regulatory element (CRE) sequences, which are also called enhancers or cis-regulatory modules. A typical CRE possesses an arrangement of binding sites for several transcription factor proteins that confer a regulatory logic specifying when, where, and at what level the regulated gene(s) is expressed. The full set of CREs within an animal genome encodes the organism′s program for development¹, and empirical as well as theoretical studies indicate that mutations in CREs played a prominent role in morphological evolution^2-4. Moreover, human genome wide association studies indicate that genetic variation in CREs …

The Incidence Of Plexiform Lesion Formation In Lines Divergently Selected For Ascites, James Grant Mason

Graduate Theses and Dissertations

Complex Vascular Lesions, (CVL) are a common vascular change associated with idiopathicpulmonary arterial hypertension (IPAH). CVL have been characterized in studies using animal models involving, but not limited to, Sprague-Dawley rats and poultry (Abe et al., 2010; Wideman et al., 2011).IPAH has been documented in poultry although no connection has been made with CVLs. The current study characterizes CVL in the lungs from broilers derived from lines divergently selected for 15 generations for ascites susceptibility under conditions of simulated high altitude. The ascites RES and SUS lines were sampled for CVL incidence over time. Both lines were reared in a …

Identification Of Factors Involved In Dna Methylation Of Cpg-Island-Promoters, Yan Zhang

Dissertations and Theses (Open Access)

Repression of many tumor suppressor genes (TSGs) in cancer is mediated by aberrantly increased DNA methylation levels at promoter CpG islands (CGI). About one-fourth of empirically defined human promoters are surrounded by or contain clustered repetitive elements. It was previously observed that a sharp transition of methylation occurs between highly methylated repetitive elements (SINE or LINE) and unmethylated CGI-promoters (e.g. P16, VHL, CDH and RIL) in normal tissues. The functions that lead to increased CGI methylation in cancer remain poorly understood. We propose that CGI-promoters contain cis-elements for triggering de novo DNA methylation. In the first part of our project, …

Contribution Of Ectodomain Mutations In Epidermal Growth Factor Receptor To Signaling In Glioblastoma Multiforme, Marta L. Rojas

Dissertations and Theses (Open Access)

CONTRIBUTION OF ECTODOMAIN MUTATIONS IN EPIDERMAL GROWTH FACTOR RECEPTOR TO SIGNALING IN GLIOBLASTOMA MULTIFORME

Publication No._________

Marta Rojas, M.S.

Supervisory Professor: Oliver Bögler, Ph.D.

The Cancer Genome Atlas (TCGA) has conducted a comprehensive analysis of a large tumor cohort and has cataloged genetic alterations involving primary sequence variations and copy number aberrations of genes involved in key signaling pathways in glioblastoma (GBM). This dataset revealed missense ectodomain point mutations in epidermal growth factor receptor (EGFR), but the biological and clinical significance of these mutations is not well defined in the context of gliomas.

In our study, we focused on understanding …

Role Of The Gcn5 Histone Acetyltransferase In Spinocerebellar Ataxia Type 7 And In Immature Neurons, Yi Chun Chen

Dissertations and Theses (Open Access)

Spinocerebellar Ataxia type 7 (SCA7) is a neurodegenerative disease caused by expansion of a CAG repeat encoding a polyglutamine tract in ATXN7, a component of the SAGA histone acetyltransferase (HAT) complex. Previous studies provided conflicting evidence regarding the effects of polyQ-ATXN7 on the activity of Gcn5, the HAT catalytic subunit of SAGA. Here I showed that reducing Gcn5 expression accelerates both cerebellar and retinal degeneration in a mouse model of SCA7. Deletion of Gcn5 in Purkinje cells in mice expressing wild type Atxn7, however, causes only mild ataxia and does not lead to the early lethality observed in SCA7 mice. …

Msh1 Influence On Plant Mitochondrial Genome Recombination And Phenotype In Tobacco, Peibei Sun

School of Biological Sciences: Dissertations, Theses, and Student Research

Plant mitochondrial genomes are composed of unusually complex structures, due to active recombination at numerous repeated sequences in the genome. The maintenance of mitochondrial genome stability is under the control of identifiable nuclear genes. In plants, three nuclear genes (MSH1, RECA3 and OSB1) have been shown to participate in recombination surveillance and the suppression of illegitimate recombination in mitochondria. Disruption of these loci in Arabidopsis results in reproducible mitochondrial genome rearrangements. We demonstrated that repeat-mediated de novo recombination was also enhanced in both Arabidopsis and tobacco during passage through in vitro culture. Furthermore, in vitro conditions led …

Exploring The Effects Of Hypoxia On Sulfate Reducing Anaerobes, Annaliese K. Jones

Senior Honors Projects

Exploring the Effects of Hypoxia on Sulfate Reducing Anaerobes

Annaliese K. Jones

Sponsor: Bethany Jenkins, Cell and Molecular Biology

As a student about to graduate with a degree in Biological Sciences, I find myself faced with the need to find my own independent research interests and scientific voice. As a result of my interests in the fields of both microbiology and ecology, I am drawn to questions surrounding the role and behavior of microorganisms in the environment. With climate change being an issue capturing the attention of a large portion of the scientific community, I have chosen to focus my …

Ethnic Disparity In 21-Hydroxylase Gene Mutations Identified In Pakistani Congenital Adrenal Hyperplasia Patient, Aysha Habib Khan, Muniba Aban, Jamal Raza, Naeem Ul Haq, Abdul Jabbar, Tariq Moatter

Department of Pathology and Laboratory Medicine

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2). We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH.

Methods: A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay.

Results: Overall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females …

Planning Combinatorial Disulfide Cross-Links For Protein Fold Determination, Fei Xiong, Alan M Friedman, Chris Bailey-Kellogg

Dartmouth Scholarship

Fold recognition techniques take advantage of the limited number of overall structural organizations, and have become increasingly effective at identifying the fold of a given target sequence. However, in the absence of sufficient sequence identity, it remains difficult for fold recognition methods to always select the correct model. While a native-like model is often among a pool of highly ranked models, it is not necessarily the highest-ranked one, and the model rankings depend sensitively on the scoring function used. Structure elucidation methods can then be employed to decide among the models based on relatively rapid biochemical/biophysical experiments.

Additive Functions In Boolean Models Of Gene Regulatory Network Modules, Christian Darabos, Ferdinando Ferdinando Di Cunto, Marco Tomassini, Jason H. Moore

Dartmouth Scholarship

Gene-on-gene regulations are key components of every living organism. Dynamical abstract models of genetic regulatory networks help explain the genome’s evolvability and robustness. These properties can be attributed to the structural topology of the graph formed by genes, as vertices, and regulatory interactions, as edges. Moreover, the actual gene interaction of each gene is believed to play a key role in the stability of the structure. With advances in biology, some effort was deployed to develop update functions in Boolean models that include recent knowledge. We combine real-life gene interaction networks with novel update functions in a Boolean model. We …

Mitochondrial Dna Analysis By Denaturing High-Performance Liquid Chromatography For The Characterization And Separation Of Mixtures In Forensic Samples, Richard Kristinsson

Electronic Theses and Dissertations

A mixture of different mtDNA molecules in a single sample is a significant obstacle to the successful use of standard methods of mtDNA analysis (i.e., dideoxy dye-terminator sequencing). Forensic analysts often encounter either naturally occurring mixtures (e.g., heteroplasmy) or situational mixtures typically arising from a combination of body fluids from separate individuals. The ability to accurately resolve and interpret these types of samples in a timely and cost efficient manner would substantially increase the power of mtDNA analysis and potentially provide valuable investigative information by allowing its use in cases where the current approach is limited or fails. Therefore, this …

Species D Adenoviruses As Oncolytics Against B-Cell Cancers, Christopher Y. Chen, Julien S. Senac, Eric A. Weaver, Shannon M. May, Diane F. Jelinek, Philip Greipp, Thomas Witzig, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Purpose: Oncolytic viruses are self-amplifying anticancer agents that make use of the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has been extensively tested against solid cancers, but less so against B-cell cancers because these cells do not generally express the coxsackie and adenoviral receptor (CAR). To determine whether other adenoviruses might have better potency, we "mined" the adenovirus virome of 55 serotypes for viruses that could kill B-cell cancers.

Experimental Design: Fifteen adenoviruses selected to represent Ad species B, C, D, E, and F were tested in vitro against cell lines and primary patient B-cell cancers …

Molecular Systematics Of The Middle American Genus Hypopachus (Anura: Microhylidae), Eli Greenbaum, Eric N. Smith, Rafael O. De Sá

Biology Faculty Publications

We present the first phylogenetic study on the widespread Middle American microhylid frog genus Hypopachus. Partial sequences of mitochondrial (12S and 16S ribosomal RNA) and nuclear (rhodopsin) genes (1275 bp total) were analyzed from 43 samples of Hypopachus, three currently recognized species of Gastrophryne, and seven arthroleptid, brevicipitid and microhylid outgroup taxa. Maximum parsimony (PAUP), maximum likelihood (RAxML) and Bayesian inference (MrBayes) optimality criteria were used for phylogenetic analyses, and BEAST was used to estimate divergence dates of major clades. Population-level analyses were conducted with the programs NETWORK and Arlequin. Results confirm the placement of Hypopachus …

The Nuclear Pore Complex Mediates Binding Of The Mig1 Repressor To Target Promoters, Nayan J. Sarma, Thomas D. Buford, Terry Haley, Kellie Barbara-Haley, George M. Santangelo, Kristine A. Willis

Faculty Publications

All eukaryotic cells alter their transcriptional program in response to the sugar glucose. In Saccharomyces cerevisiae, the best-studied downstream effector of this response is the glucose-regulated repressor Mig1. We show here that nuclear pore complexes also contribute to glucose-regulated gene expression. NPCs participate in glucose-responsive repression by physically interacting with Mig1 and mediating its function independently of nucleocytoplasmic transport. Surprisingly, despite its abundant presence in the nucleus of glucose-grown nup120Δ or nup133Δ cells, Mig1 has lost its ability to interact with target promoters. The glucose repression defect in the absence of these nuclear pore components therefore appears …

Assessing The Impact Of Non-Differential Genotyping Errors On Rare Variant Tests Of Association, Scott Powers, Shyam Gopalakrishnan, Nathan L. Tintle

Faculty Work Comprehensive List

Background/Aims: We aim to quantify the effect of non-differential genotyping errors on the power of rare variant tests and identify those situations when genotyping errors are most harmful. Methods: We simulated genotype and phenotype data for a range of sample sizes, minor allele frequencies, disease relative risks and numbers of rare variants. Genotype errors were then simulated using five different error models covering a wide range of error rates. Results: Even at very low error rates, misclassifying a common homozygote as a heterozygote translates into a substantial loss of power, a result that is exacerbated even further as the minor …