Genetics and Genomics Commons^™

Reverse Recruitment: Activation Of Yeast Genes At The Nuclear Periphery, Terry Marvin Haley

Dissertations

The regulation of genes at the nuclear periphery is an evolutionarily conserved phenomenon in eukaryotes. The reverse-recruitment model of transcriptional activation postulates that genes are activated by moving to and contacting transcription machinery located at subnuclear structures. In Saccharomyces cerevisiae it has been reported that this platform for gene regulation may reside at the nuclear periphery. To test this hypothesis, I utilized a GFP-gene tagging technique, which uses LacI-GFP to visualize a tandem array of its DNA-binding sequence, to monitor localization ofSUC2 and GALL I found that both genes preferentially localized to the nuclear periphery when transcriptionally active. By developing …

Insight Into The Origins Of The Rumex Acetosa Sex Chromosomes And Mechanisms Causing Dimorphism, Samuel Forrest

All Dissertations

Sex conferring chromosomes are subject to rapid change throughout evolution. Y-chromosomes (male determining) are subject to extensive chromatin remodeling and higher mutation rates than the autosomes being that recombination with the X chromosome is inhibited in many regions. The non-recombining regions comprise varying proportions of Y chromosomes from species to species and they are subject to mutation acquisition including both deletions and insertions. Recently it has been shown that these insertion mutations include repetitive DNA such as satellite DNA sequences (satDNA) and transposable elements. It is thought that Y chromosomes go through many rounds of expansion and contraction throughout evolution …

Evidence For Contrasting Modes Of Selection At Interacting Globin Genes In The European Rabbit (Oryctolagus Cuniculus), R. Campos, Jay F. Storz, N. Ferrand

Jay F. Storz Publications

In hybrid zones between genetically differentiated populations, variation in locus-specific rates of introgression may reflect adaptation to different environments or adaptation to different genetic backgrounds. The European rabbit, Oryctolagus cuniculus, is well-suited to studies of such hybrid zone dynamics because it is composed of two genetically divergent subspecies that hybridize in a zone of secondary contact in central Iberia. A species-wide survey of allozyme variation revealed a broad range of locus-specific divergence levels (F_ST ranged from 0 to 0.54, mean F_ST = 0.16). Interestingly, the two loci that fell at opposite ends of the distribution of …

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 …

Incorporation Of Genetic Pathway Information Into Analysis Of Multivariate Gene Expression Data, Zhi Wei, Jane E. Minturn, Eric Rappaport, Garrett Brodeur, Hongzhe Li

UPenn Biostatistics Working Papers

Abstract: Multivariate microarray gene expression data are commonly collected to study the genomic responses under ordered conditions such as over increasing/decreasing dose levels or over time during biological processes. One important question from such multivariate gene expression experiments is to identify genes that show different expression patterns over treatment dosages or over time and pathways that are perturbed during a given biological process. In this paper, we develop a hidden Markov random field model for multivariate expression data in order to identify genes and subnetworks that are related to biological processes, where the dependency of the differential expression patterns of …

Likelihood Estimation Of Conjugacy Relationships In Linear Models With Applications To High-Throughput Genomics, Brian S. Caffo, Liu Dongmei, Robert Scharpf, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

In the simultaneous estimation of a large number of related quantities, multilevel models provide a formal mechanism for efficiently making use of the ensemble of information for deriving individual estimates. In this article we investigate the ability of the likelihood to identify the relationship between signal and noise in multilevel linear mixed models. Specifically, we consider the ability of the likelihood to diagnose conjugacy or independence between the signals and noises. Our work was motivated by the analysis of data from high-throughput experiments in genomics. The proposed model leads to a more flexible family. However, we further demonstrate that adequately …

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 …

Gene Rearrangement Analysis And Ancestral Order Inference From Chloroplast Genomes With Inverted Repeat, Feng Yue, Liying Cui, Claude W. Depamphilis, Bernard M.E. Moret, Jijun Tang

Faculty Publications

Background
Genome evolution is shaped not only by nucleotide substitutions, but also by structural changes including gene and genome duplications, insertions, deletions and gene order rearrangements. The most popular methods for reconstructing phylogeny from genome rearrangements include GRAPPA and MGR. However these methods are limited to cases where equal gene content or few deletions can be assumed. Since conserved duplicated regions are present in many chloroplast genomes, the inference of inverted repeats is needed in chloroplast phylogeny analysis and ancestral genome reconstruction.

Results
We extend GRAPPA and develop a new method GRAPPA-IR to handle chloroplast genomes. A test of GRAPPA-IR …

Identifying Selected Regions From Heterozygosity And Divergence Using A Light-Coverage Genomic Dataset From Two Human Populations, T. K. Oleksyk, Kai Zhao, Francisco M. De La Vega, Dennis A. Gilbert, Stephen J. O'Brien, Michael W. Smith

Biology Faculty Articles

When a selective sweep occurs in the chromosomal region around a target gene in two populations that have recently separated, it produces three dramatic genomic consequences: 1) decreased multi-locus heterozygosity in the region; 2) elevated or diminished genetic divergence (F_ST) of multiple polymorphic variants adjacent to the selected locus between the divergent populations, due to the alternative fixation of alleles; and 3) a consequent regional increase in the variance of F_ST (S²F_ST) for the same clustered variants, due to the increased alternative fixation of alleles in the loci surrounding the selection target. In …

Functions, Structure, And Read-Through Alternative Splicing Of Feline Apobec3 Genes, Carsten Munk, Thomas W. Beck, Jorg Zielonka, Agnes Hotz-Wagenblatt, Sarah Chareza, Marion Battenberg, Jens Thielebein, Klaus Cichutek, Ignacio G. Bravo, Stephen J. O'Brien, Martin Lochelt, Naoya Yuhki

Biology Faculty Articles

Background:

Over the past years a variety of host restriction genes have been identified in human and mammals that modulate retrovirus infectivity, replication, assembly, and/or cross-species transmission. Among these host-encoded restriction factors, the APOBEC3 (A3; apolipoprotein B mRNA-editing catalytic polypeptide 3) proteins are potent inhibitors of retroviruses and retrotransposons. While primates encode seven of these genes (A3A to A3H), rodents carry only a single A3 gene.

Results:

Here we identified and characterized several A3 genes in the genome of domestic cat (Felis catus) by analyzing the genomic A3 locus. The cat genome presents one A3H gene and three …

The Adaptive Evolution Of The Mammalian Mitochondrial Genome, Rute R. Da Fonseca, Warren E. Johnson, Stephen J. O'Brien, Maria J. Ramos, Agostinho Antunes

Biology Faculty Articles

Background

The mitochondria produce up to 95% of a eukaryotic cell's energy through oxidative phosphorylation. The proteins involved in this vital process are under high functional constraints. However, metabolic requirements vary across species, potentially modifying selective pressures. We evaluate the adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental mammalian species by assessing amino acid sequence variation and exploring the functional implications of observed variation in secondary and tertiary protein structures.

Results

Wide variation in the properties of amino acids were observed at functionally important regions of cytochrome b in species with more-specialized metabolic requirements (such as adaptation to …

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 …

Empirical Null And False Discovery Rate Inference For Exponential Families, Armin Schwartzman

Harvard University Biostatistics Working Paper Series

No abstract provided.

Effect Of Thyroid Hormone Concentration On The Transcriptional Response Underlying Induced Metamorphosis In The Mexican Axolotl (Ambystoma), Robert B. Page, Stephen R. Voss, Amy K. Samuels, Jeramiah J. Smith, Srikrishna Putta, Christopher K. Beachy

Biology Faculty Publications

Background

Thyroid hormones (TH) induce gene expression programs that orchestrate amphibian metamorphosis. In contrast to anurans, many salamanders do not undergo metamorphosis in nature. However, they can be induced to undergo metamorphosis via exposure to thyroxine (T₄). We induced metamorphosis in juvenile Mexican axolotls (Ambystoma mexicanum) using 5 and 50 nM T₄, collected epidermal tissue from the head at four time points (Days 0, 2, 12, 28), and used microarray analysis to quantify mRNA abundances.

Results

Individuals reared in the higher T₄ concentration initiated morphological and transcriptional changes earlier and completed metamorphosis by …

Effect Of Thyroid Hormone Concentration On The Transcriptional Response Underlying Induced Metamorphosis In The Mexican Axolotl (Ambystoma), Robert B. Page, Stephen R. Voss, Amy K. Samuels, Jeramiah J. Smith, Srikrishna Putta, Christopher K. Beachy

Biology Faculty Publications

BACKGROUND: Thyroid hormones (TH) induce gene expression programs that orchestrate amphibian metamorphosis. In contrast to anurans, many salamanders do not undergo metamorphosis in nature. However, they can be induced to undergo metamorphosis via exposure to thyroxine (T4). We induced metamorphosis in juvenile Mexican axolotls (Ambystoma mexicanum) using 5 and 50 nM T4, collected epidermal tissue from the head at four time points (Days 0, 2, 12, 28), and used microarray analysis to quantify mRNA abundances.

RESULTS: Individuals reared in the higher T4 concentration initiated morphological and transcriptional changes earlier and completed metamorphosis by Day 28. In contrast, initiation of metamorphosis …

High-Throughput Genotyping With The Goldengate Assay In The Complex Genome Of Soybean, David L. Hyten, Qijian Song, Ik-Young Choi, Mun-Sup Yoon, James E. Specht, Lakshimi Matukumalli, Randall L. Nelson, Randy C. Shoemaker, Nevin D. Young, Perry B. Cregan

Department of Agronomy and Horticulture: Faculty Publications

Large numbers of single nucleotide polymorphism (SNP) markers are now available for a number of crop species. However, the high-throughput methods for multiplexing SNP assays are untested in complex genomes, such as soybean, that have a high proportion of paralogous genes. The Illumina GoldenGate assay is capable of multiplexing from 96 to 1,536 SNPs in a single reaction over a 3-day period. We tested the GoldenGate assay in soybean to determine the success rate of converting verified SNPs into working assays. A custom 384-SNP GoldenGate assay was designed using SNPs that had been discovered through the resequencing of five diverse …

Genomic Evidence For Independent Origins Of Β-Like Globin Genes In Monotremes And Therian Mammals, Juan C. Opazo, Federico G. Hoffmann, Jay F. Storz

Jay F. Storz Publications

Phylogenetic reconstructions of the β-globin gene family in vertebrates have revealed that developmentally regulated systems of hemoglobin synthesis have been reinvented multiple times in independent lineages. For example, the functional differentiation of embryonic and adult β-like globin genes occurred independently in birds and mammals. In both taxa, the embryonic β-globin gene is exclusively expressed in primitive erythroid cells derived from the yolk sac. However, the “ε-globin” gene in birds is not orthologous to the ε-globin gene in mammals, because they are independently derived from lineage-specific duplications of a proto β-globin gene. Here, we report evidence that the early and late …

Genomic Organization, Sequence Divergence, And Recombination Of Feline Immunodeficiency Virus From Lions In The Wild, Jill Pecon-Slattery, Carrie L. Mccracken, Jennifer L. Troyer, Sue Vandewoude, Melody E. Roelke, Kerry Sondgeroth, Christiaan Winterbach, Stephen J. O'Brien

Biology Faculty Articles

Background

Feline immunodeficiency virus (FIV) naturally infects multiple species of cat and is related to human immunodeficiency virus in humans. FIV infection causes AIDS-like disease and mortality in the domestic cat (Felis catus) and serves as a natural model for HIV infection in humans. In African lions (Panthera leo) and other exotic felid species, disease etiology introduced by FIV infection are less clear, but recent studies indicate that FIV causes moderate to severe CD4 depletion.

Results

In this study, comparative genomic methods are used to evaluate the full proviral genome of two geographically distinct FIV subtypes …

Genetic Characterization Of Feline Leukemia Virus From Florida Panthers, Meredith Brown, Mark W. Cunningham, Alfred L. Roca, Jennifer L. Troyer, Warren E. Johnson, Stephen J. O'Brien

Biology Faculty Articles

From 2002 through 2005, an outbreak of feline leukemia virus (FeLV) occurred in Florida panthers (Puma concolor coryi). Clinical signs included lymphadenopathy, anemia, septicemia, and weight loss; 5 panthers died. Not associated with FeLV outcome were the genetic heritage of the panthers (pure Florida vs. Texas/Florida crosses) and co-infection with feline immunodeficiency virus. Genetic analysis of panther FeLV, designated FeLV-Pco, determined that the outbreak likely came from 1 cross-species transmission from a domestic cat. The FeLV-Pco virus was closely related to the domestic cat exogenous FeLV-A subgroup in lacking recombinant segments derived from endogenous FeLV. FeLV-Pco sequences were …

Historic Genetic Structuring And Paraphyly Within The Great-Tailed Grackle, Jeffrey M. Dacosta, Walter Wehtje, John Klicka

Ornithology Program (HRC)

The Great-tailed Grackle (Quiscalus mexicanus) and Boat-tailed Grackle (Q. major) are sister species that have expanded their ranges during historical times. This expansion has created an area of sympatry between these species in Texas and Louisiana, and between distinctive Great-tailed Grackle subspecies in the southwestern United States and northern Mexico. We investigated the evolutionary histories of both species using mitochondrial DNA sequence data and modern phylogenetic methods. Our results reveal genetic structure within Great-tailed, but not Boat-tailed Grackles. Great-tailed Grackles are separated into two clades, but range expansion in the north has led to secondary contact …

Adenomatous Polyposis Coli Is Present Near The Minimal Level Required For Accurate Graded Responses To The Wingless Morphogen, Hassina Benchabane, Edward G. Hughes, Carter M. Takacs, Jason R. Baird, Yashi Ahmed

Dartmouth Scholarship

The mechanisms by which the Wingless (Wg) morphogen modulates the activity of the transcriptional activator Armadillo (Arm) to elicit precise, concentration-dependent cellular responses remain uncertain. Arm is targeted for proteolysis by the Axin/Adenomatous polyposis coli (Apc1 and Apc2)/Zeste-white 3 destruction complex, and Wg-dependent inactivation of destruction complex activity is crucial to trigger Arm signaling. In the prevailing model for Wg transduction, only Axin levels limit destruction complex activity, whereas Apc is present in vast excess. To test this model, we reduced Apc activity to different degrees, and analyzed the effects on three concentration-dependent responses to Arm signaling that specify distinct …

Comparative Secretome Analysis Suggests Low Plant Cell Wall Degrading Capacity In Frankia Symbionts, Juliana E. Mastronunzio, Louis S. Tisa, Philippe Normand, David R. Benson

Molecular, Cellular & Biomedical Sciences

Background: Frankia sp. strains, the nitrogen-fixing facultative endosymbionts of actinorhizal plants, have long been proposed to secrete hydrolytic enzymes such as cellulases, pectinases, and proteases that may contribute to plant root penetration and formation of symbiotic root nodules. These or other secreted proteins might logically be involved in the as yet unknown Molecular interactions between Frankia and their host plants. We compared the genome-based secretomes of three Frankia strains representing diverse host specificities. Signal peptide detection algorithms were used to predict the individual secretomes of each strain, and the set of secreted proteins shared among the strains, termed the core …

Assessing The Role Of Multi-Protein Complexes In Determining Phenotype, Nolwenn Le Meur, Robert Gentleman

Bioconductor Project Working Papers

Understanding regulatory mechanisms in complex biological systems is an important challenge, in particular to understand disease mechanisms, and to discover new therapies and drugs. In this paper, we consider the important question of cellular regulation of phenotype. Using single gene deletion data, we address the problem of linking a phenotype to underlying functional roles in the organism and provide a sound computational and statistical paradigm that can be extended to address more complex experimental settings such as multiple deletions. We apply the proposed approaches to publicly available data sets to demonstrate strong evidence for the involvement of multi-protein complexes in …

Design And Analysis Issues In Genome-Wide Somatic Mutation Studies Of Cancer, Giovanni Parmigiani, Simina Boca, Jimmy Lin, Kenneth W. Kinzler, Victor E. Velculescu, Bert Vogelstein

Johns Hopkins University, Dept. of Biostatistics Working Papers

The availability of the human genome sequence and progress in sequencing and bioinformatic technologies have enabled genome-wide investigation of somatic mu- tations in human cancers. This article briefly reviews challenges arising in the statistical analysis of mutational data of this kind. A first challenge is that of designing studies that efficiently allocate sequencing resources. We show that this can be addressed by two-stage designs, and demonstrate via simulations that even relatively small studies can produce lists of candidate cancer genes that are highly informative for future research efforts. A second challenge is to distinguish mutated genes that are selected for …

Differential Role Of Nadp+ And Nadph In The Activity And Structure Of Gdp-D-Mannose 4,6-Dehydratase From Two Chlorella Viruses, Floriana Fruscione, Laura Sturla, Garry Duncan, James L. Van Etten, Paola Valbuzzi, Antonio De Flora, Eleonopra Di Zanni, Michela Tonetti

James Van Etten Publications

GDP-D-mannose 4,6-dehydratase (GMD) is a key enzyme involved in the synthesis of 6-deoxyhexoses in prokaryotes and eukaryotes. Paramecium bursaria chlorella virus-1 (PBCV-1) encodes a functional GMD, which is unique among characterized GMDs because it also has a strong stereospecific NADPH-dependent reductase activity leading to GDP-D-rhamnose formation (Tonetti, M., Zanardi, D., Gurnon, J., Fruscione, F., Armirotti, A., Damonte, G., Sturla, L., De Flora, A., and Van Etten, J.L. (2003) J. Biol. Chem. 278, 21559–21565). In the present study we characterized a recombinant GMD encoded by another chlorella virus, Acanthocystis turfacea chlorella virus 1 (ATCV-1), demonstrating that it has the expected dehydratase …

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.

The Dynamic Evolutionary History Of The Bananaquit (Coereba Flaveola) In The Caribbean Revealed By A Multigene Analysis, Eva Bellemain, Eldredge Bermingham, Robert Ricklefs

Biology Department Faculty Works

BackgroundThe bananaquit (Coereba flaveola) is a small nectivorous and frugivorous emberizine bird (order Passeriformes) that is an abundant resident throughout the Caribbean region. We used multi-gene analyses to investigate the evolutionary history of this species throughout its distribution in the West Indies and in South and Middle America. We sequenced six mitochondrial genes (3744 base pairs) and three nuclear genes (2049 base pairs) for forty-four bananaquits and three outgroup species. We infer the ancestral area of the present-day bananaquit populations, report on the species' phylogenetic, biogeographic and evolutionary history, and propose scenarios for its diversification and range expansion.ResultsPhylogenetic concordance between …