Genetics and Genomics Commons^™

Bayesian Methods For Network-Structured Genomics Data, Stefano Monni, Hongzhe Li

UPenn Biostatistics Working Papers

Graphs and networks are common ways of depicting information. In biology, many different processes are represented by graphs, such as regulatory networks, metabolic pathways and protein-protein interaction networks. This information provides useful supplement to the standard numerical genomic data such as microarray gene expression data. Effectively utilizing such an information can lead to a better identification of biologically relevant genomic features in the context of our prior biological knowledge. In this paper, we present a Bayesian variable selection procedure for network-structured covariates for both Gaussian linear and probit models. The key of our approach is the introduction of a Markov …

Crystal Structure Of A Virus-Encoded Putative Glycosyltransferase, Yi Xiang, Ulrich Baxa, Ying Zhang, Alasdair C. Steven, Gentry L. Lewis, James L. Van Etten, Michael G. Rossmann

James Van Etten Publications

The chloroviruses (family Phycodnaviridae), unlike most viruses, encode some, if not most, of the enzymes involved in the glycosylation of their structural proteins. Annotation of the gene product B736L from chlorovirus NY-2A suggests that it is a glycosyltransferase. The structure of the recombinantly expressed B736L protein was determined by X-ray crystallography to 2.3-Å resolution, and the protein was shown to have two nucleotide-binding folds like other glycosyltransferase type B enzymes. This is the second structure of a chlorovirus-encoded glycosyltransferase and the first structure of a chlorovirus type B enzyme to be determined. B736L is a retaining enzyme and belongs …

Tympanic Temperature In Confined Beef Cattle Exposed To Excessive Heat Load, Terry L. Mader, John B. Gaughan, Leslie J. Johnson, G. Leroy Hahn

Department of Animal Science: Faculty Publications

Angus crossbred yearling steers (n=168) were used to evaluate effects on performance and tympanic temperature (TT) of feeding additional potassium and sodium to steers exposed to excessive heat load (maximum daily ambient temperature exceeded 32°C for three consecutive days) during seasonal summer conditions. Steers were assigned one of four treatments: (1) control; (2) potassium supplemented (diet containing 2.10% KHCO3); (3) sodium supplemented (diet containing 1.10% NaCl); or (4) potassium and sodium supplemented (diet containing 2.10% KHCO3 and 1.10% NaCl). Overall, additional KHCO3 at the 2% level or NaCl at the 1% level did not improve performance or heat stress tolerance …

Functional Interplay Between Chromatin Remodeling Complexes Rsc, Swi/Snf And Iswi In Regulation Of Yeast Heat Shock Genes, Tamara Y. Erkina, Y. Zou, S. Freeling, V. I. Vorobyev, Alexander M. Erkine

Scholarship and Professional Work – COPHS

Chromatin remodeling is an essential part of transcription initiation. We show that at heat shock gene promoters functional interactions between individual ATP-dependent chromatin remodeling complexes play critical role in both nucleosome displacement and Pol II recruitment. Using HSP12, HSP82 and SSA4 gene promoters as reporters, we demonstrated that while inactivation of SNF2, a critical ATPase of the SWI/SNF complex, primarily affects the HSP12 promoter, depletion of STH1- a SNF2 homolog from the RSC complex reduces histone displacement and abolishes the Pol II recruitment at all three promoters. From these results, we conclude that redundancy between SWI/SNF and RSC complexes …

Meiotic Dna Re-Replication And The Recombination Checkpoint, Nicole Ann Najor

Wayne State University Dissertations

Progression through meiosis occurs through a strict sequence of events, so that one round of DNA replication precedes programmed recombination and two nuclear divisions. Cyclin dependent kinase 1 (Cdk1) is required for meiosis, and any disruption in its activity leads to meiotic defects. The Cdk1 inhibitor, Sic1, regulates the G1-S transition in the mitotic cell cycle and the analogous transition in meiosis. We have employed a form of Sic1, Sic1deltaP^HA, that is mutated at multiple phosphorylation sites and resistant to degradation. Meiosis specific expression of Sic1deltaP^HA disrupts Cdk1 activity and leads to significant accumulation of over replicated …

Feed Intake Of Sheep As Affected By Body Weight, Breed, Sex, And Feed Composition, R. M. Lewis, G. C. Emmans

Department of Animal Science: Faculty Publications

The hypotheses tested were that genetic size-scaling for mature BW (A, kg) would reduce variation in intake between kinds of sheep and that quadratic polynomials on u = BW/A with zero intercept would provide good descriptions of the relationship between scaled intake (SI, g/A0.73 d) and degree of maturity in BW (u) across feeds of differing quality. Both sexes of Suffolk sheep from 2 experimental lines (n = 225) and from 3 breed types (Suffolk, Scottish Blackface, and their cross; n = 149) were recorded weekly for ad libitum feed intake and BW; recording of intake was from weaning through, …

A Candidate Subspecies Discrimination System Involving A Vomeronasal Receptor Gene With Different Alleles Fixed In M. M. Domesticus And M. M. Musculus, Robert C. Karn, Janet M. Young, Christina M. Laukaitis

Scholarship and Professional Work - LAS

Assortative mating, a potentially efficient prezygotic reproductive barrier, may prevent loss of genetic potential by avoiding the production of unfit hybrids (i.e., because of hybrid infertility or hybrid breakdown) that occur at regions of secondary contact between incipient species. In the case of the mouse hybrid zone, where two subspecies of Mus musculus (M. m. domesticus and M. m. musculus) meet and exchange genes to a limited extent, assortative mating requires a means of subspecies recognition. We based the work reported here on the hypothesis that, if there is a pheromone sufficiently diverged between M. m. domesticus and …

Biochemical Profiling Of Histone Binding Selectivity Of The Yeast Bromodomain Family, Qiang Zhang, Suvobrata Chakravarty, Dario Ghersi, Lei Zeng, Alexander N. Plotnikov, Roberto Sanchez, Ming-Ming Zhou

Interdisciplinary Informatics Faculty Publications

Background: It has been shown that molecular interactions between site-specific chemical modifications such as acetylation and methylation on DNA-packing histones and conserved structural modules present in transcriptional proteins are closely associated with chromatin structural changes and gene activation. Unlike methyl-lysine that can interact with different protein modules including chromodomains, Tudor and MBT domains, as well as PHD fingers, acetyl-lysine (Kac) is known thus far to be recognized only by bromodomains. While histone lysine acetylation plays a crucial role in regulation of chromatin-mediated gene transcription, a high degree of sequence variation of the acetyl-lysine binding site in the bromodomains has …

Molecular Basis Of A Novel Adaptation To Hypoxic-Hypercapnia In A Strictly Fossorial Mole, Kevin L. Campbell, Jay F. Storz, Anthony V. Signore, Hideaki Moriyama, Kenneth C. Catania, Alexander P. Payson, Joseph Bonaventura, Jörg Stetefeld, Roy E. Weber

Jay F. Storz Publications

Background: Elevated blood O₂ affinity enhances survival at low O₂ pressures, and is perhaps the best known and most broadly accepted evolutionary adjustment of terrestrial vertebrates to environmental hypoxia. This phenotype arises by increasing the intrinsic O₂ affinity of the hemoglobin (Hb) molecule, by decreasing the intracellular concentration of allosteric effectors (e.g., 2,3-diphosphoglycerate; DPG), or by suppressing the sensitivity of Hb to these physiological cofactors.

Results: Here we report that strictly fossorial eastern moles (Scalopus aquaticus) have evolved a low O₂ affinity, DPG-insensitive Hb - contrary to expectations for a mammalian species that is …

The Role Of Cuticle, Fatty Acids, And Lipid Signaling In Plant Defense, Ye Xia

Theses and Dissertations--Plant Pathology

Systemic acquired resistance (SAR) is initiated upon recognition of specific microbial effectors by cognate plant resistance proteins and immunizes distal tissues of plants against secondary infections. SAR involves the generation of a mobile signal at the site of primary infection, which then translocates to and activates defense responses in the distal tissues via some unknown mechanism(s). This study shows that an ACYL CARRIER PROTEIN 4 (ACP4), GLABRA1 (GL1) and ACYL CARRIER BINDING PROTEINS (ACBP) are required for the processing of the mobile SAR signal in distal tissues of Arabidopsis. Although acp4, gl1 and acbp plants generate the mobile signal, …

Sex, Mixability, And Modularity, Adi Livnat, Christos Papadimitriou, Nicholas Pippenger, Marcus W. Feldman

All HMC Faculty Publications and Research

The assumption that different genetic elements can make separate contributions to the same quantitative trait was originally made in order to reconcile biometry and Mendelism and ever since has been used in population genetics, specifically for the trait of fitness. Here we show that sex is responsible for the existence of separate genetic effects on fitness and, more generally, for the existence of a hierarchy of genetic evolutionary modules. Using the tools developed in the process, we also demonstrate that in terms of their fitness effects, separation and fusion of genes are associated with the increase and decrease of the …

Detection, Validation, And Downstream Analysis Of Allelic Variation In Gene Expression, Daniel C. Ciobanu, Lu Engle, Khyobeni Mozhui, Xusheng Wang, Manjunatha Jagalur, John A. Morris, William L. Taylor, Klaus Dietz, Perikles Simon, Robert W. Williams

Department of Animal Science: Faculty Publications

Common sequence variants within a gene often generate important differences in expression of corresponding mRNAs. This high level of local (allelic) control—or cis modulation—rivals that produced by gene targeting, but expression is titrated finely over a range of levels. We are interested in exploiting this allelic variation to study gene function and downstream consequences of differences in expression dosage. We have used several bioinformatics and molecular approaches to estimate error rates in the discovery of cis modulation and to analyze some of the biological and technical confounds that contribute to the variation in gene expression profiling. Our analysis of SNPs …

Strain Differences In Stress Responsivity Are Associated With Divergent Amygdala Gene Expression And Glutamate-Mediated Neuronal Excitability, Khyobeni Mozhui, Rose-Marie Karlsson, Thomas L. Kash, Jessica Ihne, Maxine Norcross, Sachin Patel, Mollee R. Farrell, Elizabeth E. Hill, Carolyn Graybeal, Kathryn P. Martin, Marguerite Camp, Paul J. Fitzgerald, Daniel C. Ciobanu, Rolf Sprengel, Masayoshi Mishina, Cara L. Wellman, Danny G. Winder, Robert W. Williams, Andrew Holmes

Department of Animal Science: Faculty Publications

Stress is a major risk factor for numerous neuropsychiatric diseases. However, susceptibility to stress and the qualitative nature of stress effects on behavior differ markedly among individuals. This is partly because of the moderating influence of genetic factors. Inbred mouse strains provide a relatively stable and restricted range of genetic and environmental variability that is valuable for disentangling gene–stress interactions. Here, we screened a panel of inbred strains for anxiety- and depression-related phenotypes at baseline (trait) and after exposure to repeated restraint. Two strains, DBA/2J and C57BL/6J, differed in trait and restraint-induced anxiety-related

behavior (dark/light exploration, elevated plus maze). Gene …

Srebp Pathway Genes As Candidate Markers In Country Ham Production, Benedicte Renaville, Kimberly L. Glenn, Benny E. Mote, Bin Fan, Kenneth J. Stalder, Max F. Rothschild

Department of Animal Science: Faculty Publications

Country hams are dry-cured products from the Southeastern region of the USA. This high value product requires quality fresh meat to avoid later processing problems. The marker SREBF1 is a transcription factor involved in the regulation of fatty acid synthesis and antioxidative enzyme transcription. The SREBF1 gene and its regulators, SCAP and MBTPS1, were investigated for associations with several meat quality traits in country hams. After single nucleotide polymorphism (SNP) identification, PCR-RFLP tests were designed for one polymorphism in each of the three investigated genes. Meat quality and physical traits were collected on 299 fresh hams. Significant associations were …

The Role Of Ledgf/P75 In Transcriptional Regulation, Jeffrey Ryan Kugelman

Open Access Theses & Dissertations

The Lens Epithelial Derived Growth Factor p75 (LEDGF/p75) is a chromatin bound protein whose cellular function is not yet clearly known. A role in transcriptional regulation had been previously proposed based on its interaction with the basal transcriptional machinery and on its effects on the expression of genes involved in the cellular response to environmental stresses. To further elucidate the function of LEDGF/p75, we conducted a global and unbiased evaluation of the role of this protein in gene expression. To that aim, we performed a microarray analysis of cellular gene expression in cells that are severely depleted of LEDGF/p75. To …

Plasmid Injection And Application Of Electric Pulses Alter Endogenous Mrna And Protein Expression In B16.F10 Mouse Melanomas, L. C. Heller, Y. L. Cruz, B. Ferraro, H. Yang, R. Heller

Bioelectrics Publications

The application of electric pulses to tissues causes cell membrane destabilization, allowing exogenous molecules to enter the cells. This delivery technique can be used for plasmid gene therapy. Reporter gene expression after plasmid delivery with eight representative published protocols was compared in B16.F10 mouse melanoma tumors. This expression varied significantly based on the pulse parameters utilized for delivery. To observe the possible influence of plasmid injection and/or pulse application on endogenous gene expression, levels of stress-related mRNAs 4 and 24 h after delivery were determined by PCR array. Increases in mRNA levels for several inflammatory chemokines and cytokines were observed …

Electroporation-Mediated Delivery Of A Naked Dna Plasmid Expressing Vegf To The Porcine Heart Enhances Protein Expression, W. G. Marshall Jr., B. A. Boone, J. D. Burgos, S. I. Gografe, M. K. Baldwin, M. L. Danielson, M. J. Larson, D. R. Caretto, Y. Cruz, B. Ferraro, L. C. Heller, K. E. Ugen, M. J. Jaroszeski, R. Heller

Bioelectrics Publications

Gene therapy is an attractive method for the treatment of cardiovascular disease. However, using current strategies, induction of gene expression at therapeutic levels is often inefficient. In this study, we show a novel electroporation (EP) method to enhance the delivery of a plasmid expressing an angiogenic growth factor (vascular endothelial growth factor, VEGF), which is a molecule previously documented to stimulate revascularization in coronary artery disease. DNA expression plasmids were delivered in vivo to the porcine heart with or without coadministered EP to determine the potential effect of electrically mediated delivery. The results showed that plasmid delivery through EP significantly …

Microarray Analysis Of Paramecium Bursaria Chlorella Virus 1 Transcription, Giane M. Yanai-Balser, Garry A. Duncan, James D. Eudy, Dong Wang, Xiao Li, Irina V. Agarkova, David D. Dunigan, James L. Van Etten

James Van Etten Publications

Paramecium bursaria chlorella virus 1 (PBCV-1), a member of the family Phycodnaviridae, is a large doublestranded DNA, plaque-forming virus that infects the unicellular green alga Chlorella sp. strain NC64A. The 330-kb PBCV-1 genome is predicted to encode 365 proteins and 11 tRNAs. To monitor global transcription during PBCV-1 replication, a microarray containing 50-mer probes to the PBCV-1 365 protein-encoding genes (CDSs) was constructed. Competitive hybridization experiments were conducted by using cDNAs from poly(A)- containing RNAs obtained from cells at seven time points after virus infection. The results led to the following conclusions: (i) the PBCV-1 replication cycle is temporally …

The Differential Roles Of D-Pax2 Variants In Regulating Drosophila Eye And Bristle Development, Colin J. O’Shea

Honors Theses

The ability to appropriately interact with the environment is crucial to an organism’s survival. The establishment of functional sensory systems, such as the bristles and eyes in Drosophila, is a critical event during the development of the organism. The transcription factor D Pax2 is involved in the differentiation of the shaft and glial cells in the developing bristle (Kavaler et al., Dev, 126:2261-2272, 1999) and of the cone and primary pigment cells in the developing eye (Fu and Noll, Genes Dev, 11:389-405, 1997). How D-Pax2 contributes to distinct differentiative pathways in different cell types is not known. Recent work by …

Development Of Protocols For Tissue Culture And Mutagenesis In Two Variegated Sansevieria Sp., Irmawati Akma Abdul Hapiz

Student Works (2010-2019)

Studies were conducted to develop the tissue culture protocol and mutagenesis through Gamma ray irradiation for two variegated Sansevieria species known as Sansevieria trifasciata var. Laurentii (goldband Sansevieria) and Sansevieria trifasciata var. Hahnii (birdnest Sansevieria). Seven combinations of BAP and NAA were chosen which are represented by letter A= 1.00 mg/I BAP, B = 1.00 mg/I BAP + 0.25 mg/I NAA, C = 2.00 mg/I BAP + 0.50 mg/I NAA, D = 2.00 mg/I BAP + 1.00 mg/I NAA, E = 3.00 mg/I BAP + 1.00 mg/I NAA, F = 4.00 mg/I BAP + 1.00 mg/I NAA and G = …