Genetics and Genomics Commons^™

Intracellular Levels Of Centrin2, Xpc, & Hhr23b Increase After Dna Damage, Nicholas A. Rowland

Honors Capstones

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

U-Statistics-Based Tests For Multiple Genes In Genetic Association Studies, Zhi Wei, Mingyao Li Phd, Timothy Rebbeck, Hongzhe Li

UPenn Biostatistics Working Papers

Abstract: As our understanding of biological pathways and the genes that regulate these pathways increases, consideration of these biological pathways has become an increasingly important part of genetic and molecular epidemiology. Pathway-based genetic association studies often involve genotyping of variants in genes acting in certain biological pathways. Such pathway-based genetic association studies can potentially capture the highly heterogeneous nature of many complex traits, with multiple causative loci and multiple alleles at some of the causative loci. In this paper, we develop two nonparametric test statistics that consider simultaneously the effects of multiple markers. Our approach, which is based on data-adaptive …

Systems Approach Identifies An Organic Nitrogen-Responsive Gene Network That Is Regulated By The Master Clock Control Gene Cca1, Rodrigo A. Gutierrez, Trevor L. Stokes, Karen Thum, Xiaodong Xu, Mariana Obertello, Manpreet S. Katari, Milos Tanurdzic, Alexis Dean, Damion C. Nero, C Robertson Mcclung, Gloria M. Coruzzi

Dartmouth Scholarship

Understanding how nutrients affect gene expression will help us to understand the mechanisms controlling plant growth and development as a function of nutrient availability. Nitrate has been shown to serve as a signal for the control of gene expression in Arabidopsis. There is also evidence, on a gene-by-gene basis, that downstream products of nitrogen (N) assimilation such as glutamate (Glu) or glutamine (Gln) might serve as signals of organic N status that in turn regulate gene expression. To identify genome-wide responses to such organic N signals, Arabidopsis seedlings were transiently treated with ammonium nitrate in the presence or absence of …

Variation In Molybdenum Content Across Broadly Distributed Populations Of Arabidopsis Thaliana Is Controlled By A Mitochondrial Molybdenum Transporter (Mot1), Ivan Baxter, Balasubramaniam Muthukumar, Hyeong Cheol Park, Peter Buchner, Brett Lahner, John Danku, Keyan Zhao, Joohyun Lee, Malcolm J. Hawkesford, Mary Lou Guerinot, David E. Salt

Dartmouth Scholarship

Molybdenum (Mo) is an essential micronutrient for plants, serving as a cofactor for enzymes involved in nitrate assimilation, sulfite detoxification, abscisic acid biosynthesis, and purine degradation. Here we show that natural variation in shoot Mo content across 92 Arabidopsis thaliana accessions is controlled by variation in a mitochondrially localized transporter (Molybdenum Transporter 1 - MOT1) that belongs to the sulfate transporter superfamily. A deletion in the MOT1 promoter is strongly associated with low shoot Mo, occurring in seven of the accessions with the lowest shoot content of Mo. Consistent with the low Mo phenotype, MOT1 expression in low Mo accessions …

Micrornas And The Advent Of Vertebrate Morphological Complexity, Alysha M. Heimberg, Lorenzo F. Sempere, Vanessa N. Moy, Phillip C. J. Donoghue, Kevin J. Peterson

Dartmouth Scholarship

The causal basis of vertebrate complexity has been sought in genome duplication events (GDEs) that occurred during the emergence of vertebrates, but evidence beyond coincidence is wanting. MicroRNAs (miRNAs) have recently been identified as a viable causal factor in increasing organismal complexity through the action of these ≈22-nt noncoding RNAs in regulating gene expression. Because miRNAs are continuously being added to animalian genomes, and, once integrated into a gene regulatory network, are strongly conserved in primary sequence and rarely secondarily lost, their evolutionary history can be accurately reconstructed. Here, using a combination of Northern analyses and genomic searches, we show …

2c Dna Content Values In Amaranthus (Amaranthaceae) [Abstract], Donald B. Pratt, Shalini N. Jhangiani, Robert J. Wiggers

Faculty Publications

No abstract provided.

Development And Characterization Of Microsatellite Markers For The Grain Amaranths [Abstract], Melanie A. Mallory, Rozaura V. Hall, Andrea R. Mcnabb, Donald B. Pratt, Eric N. Jellen, Peter J. Maughan

Faculty Publications

No abstract provided.

Different Requirements Of The Swi/Snf Complex For Robust Nucleosome Displacement At Promoters Of Heat Shock Factor And Msn2- And Msn4-Regulated Heat Shock Genes, Tamara Y. Erkina, P. A. Tschetter, Alexander M. Erkine

Scholarship and Professional Work – COPHS

The stress response in yeast cells is regulated by at least two classes of transcription activators—HSF and Msn2/4, which differentially affect promoter chromatin remodeling. We demonstrate that the deletion of SNF2, an ATPase activity-containing subunit of the chromatin remodeling SWI/SNF complex, eliminates histone displacement, RNA polymerase II recruitment, and heat shock factor (HSF) binding at the HSP12 promoter while delaying these processes at the HSP82 and SSA4 promoters. Out of the three promoters, the double deletion of MSN2 and MSN4 eliminates both chromatin remodeling and HSF binding only at the HSP12 promoter, suggesting that Msn2/4 activators are primary determinants of …

Gene Response Profiles For Daphnia Pulex Exposed To The Environmental Stressor Cadmium Reveals Novel Crustacean Metallothioneins, Joseph R. Shaw, John K. Colbourne, Jennifer C. Davey, Stephen P. Glaholt, Thomas H. Hampton, Celia Y. Chen, Carol L. Folt, Joshua W. Hamilton

Dartmouth Scholarship

Genomic research tools such as microarrays are proving to be important resources to study the complex regulation of genes that respond to environmental perturbations. A first generation cDNA microarray was developed for the environmental indicator species Daphnia pulex, to identify genes whose regulation is modulated following exposure to the metal stressor cadmium. Our experiments revealed interesting changes in gene transcription that suggest their biological roles and their potentially toxicological features in responding to this important environmental contaminant.

Genome-Wide Transcriptional Profiling Of The Cyclic Amp-Dependent Signaling Pathway During Morphogenic Transitions Of Candida Albicans, Yong-Sun Bahn, Matthew Molenda, Janet F. Staab, Courtney A. Lyman, Laura J. Gordon, Paula Sundstrom

Dartmouth Scholarship

Candida albicans is an opportunistic human fungal pathogen that causes systemic candidiasis as well as superficial mucosal candidiasis. In response to the host environment, C. albicans transitions between yeast and hyphal forms. In particular, hyphal growth is important in facilitating adhesion and invasion of host tissues, concomitant with the expression of various hypha-specific virulence factors. In previous work, we showed that the cyclic AMP (cAMP) signaling pathway plays a crucial role in morphogenic transitions and virulence of C. albicans by studying genes encoding adenylate cyclase-associated protein (CAP1) and high-affinity phosphodiesterase (PDE2) (Y. S. Bahn, J. Staab, and P. Sundstrom, Mol. …

Assessing Population Level Genetic Instability Via Moving Average, Samuel Mcdaniel, Rebecca Betensky, Tianxi Cai

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Hidden Spatial-Temporal Markov Random Field Model For Network-Based Analysis Of Time Course Gene Expression Data, Zhi Wei, Hongzhe Li

UPenn Biostatistics Working Papers

Microarray time course (MTC) gene expression data are commonly collected to study the dynamic nature of biological processes. One important problem is to identify genes that show different expression profiles over time and pathways that are perturbed during a given biological process. While methods are available to identify the genes with differential expression levels over time, there is a lack of methods that can incorporate the pathway information in identifying the pathways being modified/activated during a biological process. In this paper, we develop a hidden spatial-temporal Markov random field (hstMRF)-based method for identifying genes and subnetworks that are related to …

Role Of Actin Cytoskeletal Dynamics In Activation Of The Cyclic Amp Pathway And Hwp1 Gene Expression In Candida Albicans, Michael J. Wolyniak, Paula Sundstrom

Dartmouth Scholarship

Changes in gene expression during reversible bud-hypha transitions of the opportunistic fungal pathogen Candida albicans permit adaptation to environmental conditions that are critical for proliferation in host tissues. Our previous work has shown that the hypha-specific adhesin gene HWP1 is up-regulated by the cyclic AMP (cAMP) signaling pathway. However, little is known about the potential influences of determinants of cell morphology on HWP1 gene expression. We found that blocking hypha formation with cytochalasin A, which destabilizes actin filaments, and with latrunculin A, which sequesters actin monomers, led to a loss of HWP1 gene expression. In contrast, high levels of HWP1 …

Fully Codon-Optimized Luciferase Uncovers Novel Temperature Characteristics Of The Neurospora Clock, Van D. Gooch, Arun Mehra, Luis F. Larrondo, Julie Fox, Melissa Touroutoutoudis, Jennifer J. Loros, Jay C. Dunlap

Dartmouth Scholarship

We report the complete reconstruction of the firefly luciferase gene, fully codon optimized for expression in Neurospora crassa. This reporter enhances light output by approximately 4 log orders over that with previously available versions, now producing light that is visible to the naked eye and sufficient for monitoring the activities of many poorly expressed genes. Time lapse photography of strains growing in race tubes, in which the frq or eas/ccg-2 promoter is used to drive luciferase, shows the highest levels of luciferase activity near the growth front and newly formed conidial bands. Further, we have established a sorbose medium colony …

Sheep Updates 2007 - Part 2, Ian Mcfarland, Catherine Stockman, Anne Barnes, David Pethick, Jenny Davis, Brett Thompson, Ron Leng, Sally Pieruzzini, Elizabeth Jackson, Mohammed Quaddus, Nazrul Islam, John Stanton, Melanie Dowling

Sheep Updates

This session covers six papers from different authors:

CONCURRENT SESSIONS

FINISHING LAMB AND BEEF

1. Precision Feedlot Lamb, Ian McFarland, Department of Agriculture and Food, Western Australia

2. Feeding sheep under high heat load did not decrease intake of feedlot rations, Catherine Stockman, Department of Agriculture and Food, Western Australia & Murdoch University, Anne Barnes, Murdoch University David Pethick, Murdoch University

3. Taking the stress out of fifishing lambs and cattle - EasyFeed solutions, Jenny Davis, Brett Thomson, Milne AgriGroup, Welshpool WA, Ron Leng, Emeritus Professor, University of New England, Armidale, NSW

WOOL

4. DAFWA …

A Novel Ensemble Learning Method For De Novo Computational Identification Of Dna Binding Sites, Arijit Chakravarty, Jonathan M. Carlson, Radhika S. Khetani, Robert H H. Gross

Dartmouth Scholarship

Despite the diversity of motif representations and search algorithms, the de novo computational identification of transcription factor binding sites remains constrained by the limited accuracy of existing algorithms and the need for user-specified input parameters that describe the motif being sought.ResultsWe present a novel ensemble learning method, SCOPE, that is based on the assumption that transcription factor binding sites belong to one of three broad classes of motifs: non-degenerate, degenerate and gapped motifs. SCOPE employs a unified scoring metric to combine the results from three motif finding algorithms each aimed at the discovery of one of these classes of motifs. …

Assessment Of A Cgh-Based Genetic Instability, David A. Engler, Yiping Shen, J F. Gusella, Rebecca A. Betensky

Harvard University Biostatistics Working Paper Series

No abstract provided.

Survival Analysis With Large Dimensional Covariates: An Application In Microarray Studies, David A. Engler, Yi Li

Harvard University Biostatistics Working Paper Series

Use of microarray technology often leads to high-dimensional and low- sample size data settings. Over the past several years, a variety of novel approaches have been proposed for variable selection in this context. However, only a small number of these have been adapted for time-to-event data where censoring is present. Among standard variable selection methods shown both to have good predictive accuracy and to be computationally efficient is the elastic net penalization approach. In this paper, adaptation of the elastic net approach is presented for variable selection both under the Cox proportional hazards model and under an accelerated failure time …

Regulation Of Meiotic Cohesion And Chromosome Core Morphogenesis During Pachytene In Drosophila Oocytes, Radhika S. Khetani, Sharon E. Bickel

Dartmouth Scholarship

During meiosis, cohesion between sister chromatids is required for normal levels of homologous recombination, maintenance of chiasmata and accurate chromosome segregation during both divisions. In Drosophila, null mutations in the ord gene abolish meiotic cohesion, although how ORD protein promotes cohesion has remained elusive. We show that SMC subunits of the cohesin complex colocalize with ORD at centromeres of ovarian germ-line cells. In addition, cohesin SMCs and ORD are visible along the length of meiotic chromosomes during pachytene and remain associated with chromosome cores following DNase I digestion. In flies lacking ORD activity, cohesin SMCs fail to accumulate at oocyte …

Coordinated Regulation Of Myc Trans-Activation Targets By Polycomb And The Trithorax Group Protein Ash1, Julie M. Goodliffe, Michael D. Cole, Eric Wieschaus

Dartmouth Scholarship

The Myc oncoprotein is a transcriptional regulator whose function is essential for normal development. Myc is capable of binding to 10% of the mammalian genome, and it is unclear how a developing embryo controls the DNA binding of its abundant Myc proteins in order to avoid Myc's potential for inducing tumorigenesis.To identify chromatin binding proteins with a potential role in controlling Myc activity, we established a genetic assay for dMyc activity in Drosophila. We conducted a genome-wide screen using this assay, and identified the Trithorax Group protein Ash1 as a modifier of dMyc activity. Ash1 is a histone methyltransferase known …

A 368-Base-Pair Cis-Acting Hwp1 Promoter Region, Hcr, Of Candida Albicans Confers Hypha-Specific Gene Regulation And Binds Architectural Transcription Factors Nhp6 And Gcf1p, Samin Kim, Michael J. Wolyniak, Janet F. Staab, Paula Sundstrom

Dartmouth Scholarship

To elucidate the molecular mechanisms controlling the expression of the hypha-specific adhesin gene HWP1 of Candida albicans, its promoter was dissected and analyzed using a green fluorescent protein reporter gene. A 368-bp region, the HWP1 control region (HCR), was critical for activation under hypha-inducing conditions and conferred developmental regulation to a heterologous ENO1 promoter. A more distal region of the promoter served to amplify the level of promoter activation. Using gel mobility shift assays, a 249-bp subregion of HCR, HCRa, was found to bind at least four proteins from crude extracts of yeasts and hyphae with differing binding patterns dependent …

Statistical Evaluation Of Evidence For Clonal Allelic Alterations In Array-Cgh Experiments, Colin B. Begg, Kevin Eng, Adam Olshen, E S. Venkatraman

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

In recent years numerous investigators have conducted genetic studies of pairs of tumor specimens from the same patient to determine whether the tumors share a clonal origin. These studies have the potential to be of considerable clinical significance, especially in clinical settings where the distinction of a new primary cancer and metastatic spread of a previous cancer would lead to radically different indications for treatment. Studies of clonality have typically involved comparison of the patterns of somatic mutations in the tumors at candidate genetic loci to see if the patterns are sufficiently similar to indicate a clonal origin. More recently, …

Sequential Quantitative Trait Locus Mapping In Experimental Crosses, Jaya M. Satagopan, Saunak Sen, Gary A. Churchill

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

The etiology of complex diseases is heterogeneous. The presence of risk alleles in one or more genetic loci affects the function of a variety of intermediate biological pathways, resulting in the overt expression of disease. Hence, there is an increasing focus on identifying the genetic basis of disease by sytematically studying phenotypic traits pertaining to the underlying biological functions. In this paper we focus on identifying genetic loci linked to quantitative phenotypic traits in experimental crosses. Such genetic mapping methods often use a one stage design by genotyping all the markers of interest on the available subjects. A genome scan …

Multiple Diseases In Carrier Probability Estimation: Accounting For Surviving All Cancers Other Than Breast And Ovary In Brcapro, Hormuzd A. Katki, Amanda Blackford, Sining Chen, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

Mendelian models can predict who carries an inherited deleterious mutation of known disease genes based on family history. For example, the BRCAPRO model is commonly used to identify families who carry mutations of BRCA1 and BRCA2, based on familial breast and ovarian cancers. These models incorporate the age of diagnosis of diseases in relatives and current age or age of death. We develop a rigorous foundation for handling multiple diseases with censoring. We prove that any disease unrelated to mutations can be excluded from the model, unless it is sufficiently common and dependent on a mutation-related disease time. Furthermore, if …

Power Boosting In Genome-Wide Studies Via Methods For Multivariate Outcomes, Mary J. Emond

UW Biostatistics Working Paper Series

Whole-genome studies are becoming a mainstay of biomedical research. Examples include expression array experiments, comparative genomic hybridization analyses and large case-control studies for detecting polymorphism/disease associations. The tactic of applying a regression model to every locus to obtain test statistics is useful in such studies. However, this approach ignores potential correlation structure in the data that could be used to gain power, particularly when a Bonferroni correction is applied to adjust for multiple testing. In this article, we propose using regression techniques for misspecified multivariate outcomes to increase statistical power over independence-based modeling at each locus. Even when the outcome …

The Yeast Orthologue Of Grasp65 Forms A Complex With A Coiled-Coil Protein That Contributes To Er To Golgi Traffic, Rudy Behnia, Francis A. Barr, John J. Flanagan, Charles Barlowe, Sean Munro

Dartmouth Scholarship

The mammalian Golgi protein GRASP65 is required in assays that reconstitute cisternal stacking and vesicle tethering. Attached to membranes by an N-terminal myristoyl group, it recruits the coiled-coil protein GM130. The relevance of this system to budding yeasts has been unclear, as they lack an obvious orthologue of GM130, and their only GRASP65 relative (Grh1) lacks a myristoylation site and has even been suggested to act in a mitotic checkpoint. In this study, we show that Grh1 has an N-terminal amphipathic helix that is N-terminally acetylated and mediates association with the cis-Golgi. We find that Grh1 forms a complex with …

Following Temperature Stress, Export Of Heat Shock Mrna Occurs Efficiently In Cells With Mutations In Genes Normally Important For Mrna Export, Christiane Rollenhagen, Christine A. Hodge, Charles N. Cole

Dartmouth Scholarship

Heat shock leads to accumulation of polyadenylated RNA in nuclei of Saccharomyces cerevisiae cells, transcriptional induction of heat shock genes, and efficient export of polyadenylated heat shock mRNAs. These studies were conducted to examine the requirements for export of mRNA following heat shock. We used in situ hybridization to detect SSA4 mRNA (encoding Hsp70) and flow cytometry to measure the amount of Ssa4p-green fluorescent protein (GFP) produced following heat shock. Npl3p and Yra1p are mRNA-binding proteins recruited to nascent mRNAs and are essential for proper mRNA biogenesis and export. Heat shock mRNA was exported efficiently in temperature-sensitive npl3, yra1 …

Use Of Hidden Markov Models For Qtl Mapping, Karl W. Broman

Johns Hopkins University, Dept. of Biostatistics Working Papers

An important aspect of the QTL mapping problem is the treatment of missing genotype data. If complete genotype data were available, QTL mapping would reduce to the problem of model selection in linear regression. However, in the consideration of loci in the intervals between the available genetic markers, genotype data is inherently missing. Even at the typed genetic markers, genotype data is seldom complete, as a result of failures in the genotyping assays or for the sake of economy (for example, in the case of selective genotyping, where only individuals with extreme phenotypes are genotyped). We discuss the use of …

Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh

Harvard University Biostatistics Working Paper Series

No abstract provided.

Limited Functional Redundancy And Oscillation Of Cyclins In Multinucleated Ashbya Gossypii Fungal Cells, A. Katrin Hungerbuehler, Peter Philippsen, Amy S. Gladfelter

Dartmouth Scholarship

Cyclin protein behavior has not been systematically investigated in multinucleated cells with asynchronous mitoses. Cyclins are canonical oscillating cell cycle proteins, but it is unclear how fluctuating protein gradients can be established in multinucleated cells where nuclei in different stages of the division cycle share the cytoplasm. Previous work in A. gossypii, a filamentous fungus in which nuclei divide asynchronously in a common cytoplasm, demonstrated that one G1 and one B-type cyclin do not fluctuate in abundance across the division cycle. We have undertaken a comprehensive analysis of all G1 and B-type cyclins in A. gossypii to determine whether …