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Articles 1 - 30 of 95
Full-Text Articles in Genetics and Genomics
A Longitudinal Cline Characterizes The Genetic Structure Of Human Populations In The Tibetan Plateau, Choongwon Jeong, Benjamin M. Peter, Buddha Basnyat, Maniraj Neupane, Geoff Childs, Sienna Craig, John Novembre, Anna Di Rienzo
A Longitudinal Cline Characterizes The Genetic Structure Of Human Populations In The Tibetan Plateau, Choongwon Jeong, Benjamin M. Peter, Buddha Basnyat, Maniraj Neupane, Geoff Childs, Sienna Craig, John Novembre, Anna Di Rienzo
Dartmouth Scholarship
Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their de- mography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with world- wide genetic variation data. We found a clear signal of genetic stratification across the east- west axis within Tibetan samples. Samples from more eastern locations …
Yeast Integral Membrane Proteins Apq12, Brl1, And Brr6 Form A Complex Important For Regulation Of Membrane Homeostasis And Nuclear Pore Complex Biogenesis, Museer A. Lone, Aaron E. Atkinson, Christine A. Hodge, Stéphanie Cottier, Fernando Martínez-Montañés, Shelley Maithel, Laurent Mène-Saffrané, Cole Cole, Roger Schneiter
Yeast Integral Membrane Proteins Apq12, Brl1, And Brr6 Form A Complex Important For Regulation Of Membrane Homeostasis And Nuclear Pore Complex Biogenesis, Museer A. Lone, Aaron E. Atkinson, Christine A. Hodge, Stéphanie Cottier, Fernando Martínez-Montañés, Shelley Maithel, Laurent Mène-Saffrané, Cole Cole, Roger Schneiter
Dartmouth Scholarship
Proper functioning of intracellular membranes is critical for many cellular processes. A key feature of membranes is their ability to adapt to changes in environmental conditions by adjusting their composition so as to maintain constant biophysical proper- ties, including fluidity and flexibility. Similar changes in the biophysical properties of membranes likely occur when intracellular processes, such as vesicle formation and fusion, require dramatic changes in membrane curvature. Similar modifications must also be made when nuclear pore complexes (NPCs) are constructed within the existing nuclear membrane, as occurs during in- terphase in all eukaryotes. Here we report on the role of …
Development Of The Crispr/Cas9 System For Targeted Gene Disruption In Aspergillus Fumigatus, Kevin Fuller, Shan Chen, Jennifer J. Loros, Jay C. Dunlap
Development Of The Crispr/Cas9 System For Targeted Gene Disruption In Aspergillus Fumigatus, Kevin Fuller, Shan Chen, Jennifer J. Loros, Jay C. Dunlap
Dartmouth Scholarship
Low rates of homologous recombination have broadly encumbered genetic studies in the fungal pathogen Aspergillus fumigatus. The CRISPR/Cas9 system of bacteria has recently been developed for targeted mutagenesis of eukaryotic genomes with high effi- ciency and, importantly, through a mechanism independent of homologous repair machinery. As this new technology has not been developed for use in A. fumigatus, we sought to test its feasibility for targeted gene disruption in this organism. As a proof of principle, we first demonstrated that CRISPR/Cas9 can indeed be used for high-efficiency (25 to 53%) targeting of the A. fu- migatus polyketide synthase gene (pksP), …
Polyq-Dependent Rna–Protein Assemblies Control Symmetry Breaking, Changhwan Lee, Patricia Occhipinti, Amy S. Gladfelter
Polyq-Dependent Rna–Protein Assemblies Control Symmetry Breaking, Changhwan Lee, Patricia Occhipinti, Amy S. Gladfelter
Dartmouth Scholarship
Dendritic growth in fungi and neurons requires that multiple axes of polarity are established and maintained within the same cytoplasm. We have discovered that transcripts encoding key polarity factors including a formin, Bni1, and a polarisome scaffold, Spa2, are nonrandomly clustered in the cytosol to initiate and maintain sites of polarized growth in the fungus Ashbya gossypii. This asymmetric distribution requires the mRNAs to interact with a polyQ-containing protein, Whi3, and a Pumilio protein with a low-complexity sequence, Puf2. Cells lacking Whi3 or Puf2 had severe defects in establishing new sites of polarity and failed to localize Bni1 protein. Interaction …
Biological Significance Of Photoreceptor Photocycle Length: Vivid Photocycle Governs The Dynamic Vivid-White Collar Complex Pool Mediating Photo-Adaptation And Response To Changes In Light Intensity, Arko Dasgupta, Chen-Hui Chen, Changhwan Lee, Amy S. Gladfelter, Jay C. Dunlap, Jennifer J. Loros
Biological Significance Of Photoreceptor Photocycle Length: Vivid Photocycle Governs The Dynamic Vivid-White Collar Complex Pool Mediating Photo-Adaptation And Response To Changes In Light Intensity, Arko Dasgupta, Chen-Hui Chen, Changhwan Lee, Amy S. Gladfelter, Jay C. Dunlap, Jennifer J. Loros
Dartmouth Scholarship
Most organisms on earth sense light through the use of chromophore-bearing photoreceptive proteins with distinct and characteristic photocycle lengths, yet the biological significance of this adduct decay length is neither understood nor has been tested. In the filamentous fungus Neurospora crassa VIVID (VVD) is a critical player in the process of photoadaptation, the attenuation of light-induced responses and the ability to maintain photosensitivity in response to changing light intensities. Detailed in vitro analysis of the photochemistry of the blue light sensing, FAD binding, LOV domain of VVD has revealed residues around the site of photo-adduct formation that influence the stability …
An Approach For Determining And Measuring Network Hierarchy Applied To Comparing The Phosphorylome And The Regulome, Chao Cheng, Erik Andrews, Koon-Kiu Yan, Matthew Ung, Daifeng Wang, Mark Gerstein
An Approach For Determining And Measuring Network Hierarchy Applied To Comparing The Phosphorylome And The Regulome, Chao Cheng, Erik Andrews, Koon-Kiu Yan, Matthew Ung, Daifeng Wang, Mark Gerstein
Dartmouth Scholarship
Many biological networks naturally form a hierarchy with a preponderance of downward information flow. In this study, we define a score to quantify the degree of hierarchy in a network and develop a simulated-annealing algorithm to maximize the hierarchical score globally over a network. We apply our algorithm to determine the hierarchical structure of the phosphorylome in detail and investigate the correlation between its hierarchy and kinase properties. We also compare it to the regulatory network, finding that the phosphorylome is more hierarchical than the regulome.
Spectral Gene Set Enrichment (Sgse), H Robert Frost, Zhigang Li, Jason H. Moore
Spectral Gene Set Enrichment (Sgse), H Robert Frost, Zhigang Li, Jason H. Moore
Dartmouth Scholarship
Gene set testing is typically performed in a supervised context to quantify the association between groups of genes and a clinical phenotype. In many cases, however, a gene set-based interpretation of genomic data is desired in the absence of a phenotype variable. Although methods exist for unsupervised gene set testing, they predominantly compute enrichment relative to clusters of the genomic variables with performance strongly dependent on the clustering algorithm and number of clusters. We propose a novel method, spectral gene set enrichment (SGSE), for unsupervised competitive testing of the association between gene sets and empirical data sources. SGSE first computes …
Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate Ncrnas, Andrew D. Kern, Daniel A. Barbash, Joshua Chang Mell, Daniel Hupalo, Amanda Jensen
Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate Ncrnas, Andrew D. Kern, Daniel A. Barbash, Joshua Chang Mell, Daniel Hupalo, Amanda Jensen
Dartmouth Scholarship
Eukaryotes contain short (∼80–200 bp) regions that have few or no substitutions among species that represent hundreds of millions of years of evolutionary divergence. These ultraconserved elements (UCEs) are candidates for containing essential functions, but their biological roles remain largely unknown. Here, we report the discovery and characterization of UCEs from 12 sequenced Drosophilaspecies. We identified 98 elements ≥80 bp long with very high conservation across the Drosophila phylogeny. Population genetic analyses reveal that these UCEs are not present in mutational cold spots. Instead we infer that they experience a level of selective constraint almost 10-fold higher compared with …
Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield
Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield
Dartmouth Scholarship
Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes …
Phenotypic Robustness And The Assortativity Signature Of Human Transcription Factor Networks, Dov A. Pechenick, Joshua L. Payne, Jason H. Moore
Phenotypic Robustness And The Assortativity Signature Of Human Transcription Factor Networks, Dov A. Pechenick, Joshua L. Payne, Jason H. Moore
Dartmouth Scholarship
Many developmental, physiological, and behavioral processes depend on the precise expression of genes in space and time. Such spatiotemporal gene expression phenotypes arise from the binding of sequence-specific transcription factors (TFs) to DNA, and from the regulation of nearby genes that such binding causes. These nearby genes may themselves encode TFs, giving rise to a transcription factor network (TFN), wherein nodes represent TFs and directed edges denote regulatory interactions between TFs. Computational studies have linked several topological properties of TFNs - such as their degree distribution - with the robustness of a TFN's gene expression phenotype to genetic and environmental …
A Classification And Characterization Of Two-Locus, Pure, Strict, Epistatic Models For Simulation And Detection, Ryan J. Urbanowicz, Ambrose L. S. Granizo-Mackenzie, Jeff Kiralis, Jason H Moore
A Classification And Characterization Of Two-Locus, Pure, Strict, Epistatic Models For Simulation And Detection, Ryan J. Urbanowicz, Ambrose L. S. Granizo-Mackenzie, Jeff Kiralis, Jason H Moore
Dartmouth Scholarship
BackgroundThe statistical genetics phenomenon of epistasis is widely acknowledged to confound disease etiology. In order to evaluate strategies for detecting these complex multi-locus disease associations, simulation studies are required. The development of the GAMETES software for the generation of complex genetic models, has provided the means to randomly generate an architecturally diverse population of epistatic models that are both pure and strict, i.e. all n loci, but no fewer, are predictive of phenotype. Previous theoretical work characterizing complex genetic models has yet to examine pure, strict, epistasis which should be the most challenging to detect. This study addresses three goals: …
Structural Features Of The Pseudomonas Fluorescens Biofilm Adhesin Lapa Required For Lapg-Dependent Cleavage, Biofilm Formation, And Cell Surface Localization, Chelsea D. Boyd, T. Jarrod Smith, Sofiane El-Kirat-Chatel, Peter D. Newell, Yves F. Dufrêne, George A. O'Toole
Structural Features Of The Pseudomonas Fluorescens Biofilm Adhesin Lapa Required For Lapg-Dependent Cleavage, Biofilm Formation, And Cell Surface Localization, Chelsea D. Boyd, T. Jarrod Smith, Sofiane El-Kirat-Chatel, Peter D. Newell, Yves F. Dufrêne, George A. O'Toole
Dartmouth Scholarship
The localization of the LapA protein to the cell surface is a key step required by Pseudomonas fluorescens Pf0-1 to irreversibly attach to a surface and form a biofilm. LapA is a member of a diverse family of predicted bacterial adhesins, and although lacking a high degree of sequence similarity, family members do share common predicted domains. Here, using mutational analysis, we determine the significance of each domain feature of LapA in relation to its export and localization to the cell surface and function in biofilm formation. Our previous work showed that the N terminus of LapA is required for …
Methylation Of Leukocyte Dna And Ovarian Cancer: Relationships With Disease Status And Outcome, Brooke L. Fridley, Sebastian M. Armasu, Mine S. Cicek, Melissa C. Larson, Chen Wang, Stacey J. Winham, Kimberly R. Kalli, Devin C. Koestler
Methylation Of Leukocyte Dna And Ovarian Cancer: Relationships With Disease Status And Outcome, Brooke L. Fridley, Sebastian M. Armasu, Mine S. Cicek, Melissa C. Larson, Chen Wang, Stacey J. Winham, Kimberly R. Kalli, Devin C. Koestler
Dartmouth Scholarship
Genome-wide interrogation of DNA methylation (DNAm) in blood-derived leukocytes has become feasible with the advent of CpG genotyping arrays. In epithelial ovarian cancer (EOC), one report found substantial DNAm differences between cases and controls; however, many of these disease-associated CpGs were attributed to differences in white blood cell type distributions. We examined blood-based DNAm in 336 EOC cases and 398 controls; we included only high-quality CpG loci that did not show evidence of association with white blood cell type distributions to evaluate association with case status and overall survival.
Deletion Mutant Library For Investigation Of Functional Outputs Of Cyclic Diguanylate Metabolism In Pseudomonas Aeruginosa Pa14, Dae-Gon Ha, Megan E. Richman, George A. O'Toole
Deletion Mutant Library For Investigation Of Functional Outputs Of Cyclic Diguanylate Metabolism In Pseudomonas Aeruginosa Pa14, Dae-Gon Ha, Megan E. Richman, George A. O'Toole
Dartmouth Scholarship
We constructed a library of in-frame deletion mutants targeting each gene in Pseudomonas aeruginosa PA14 predicted to participate in cyclic di-GMP (c-di-GMP) metabolism (biosynthesis or degradation) to provide a toolkit to assist investigators studying c-di-GMP-mediated regulation by this microbe. We present phenotypic assessments of each mutant, including biofilm formation, exopolysaccharide (EPS) production, swimming motility, swarming motility, and twitch motility, as a means to initially characterize these mutants and to demonstrate the potential utility of this library.
How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos
How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos
Dartmouth Scholarship
Whole-genome profiling of gene expression is a powerful tool for identifying cancer-associated genes. Genes differentially expressed between normal and tumorous tissues are usually considered to be cancer associated. We recently demonstrated that the analysis of interindividual variation in gene expression can be useful for identifying cancer associated genes. The goal of this study was to identify the best microarray data–derived predictor of known cancer associated genes. We found that the traditional approach of identifying cancer genes—identifying differentially expressed genes—is not very efficient. The analysis of interindividual variation of gene expression in tumor samples identifies cancer-associated genes more effectively. The results …
Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold
Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold
Dartmouth Scholarship
Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can …
Trip/Nopo E3 Ubiquitin Ligase Promotes Ubiquitylation Of Dna Polymerase Η, Heather A. Wallace, Julie A. Merkle, Michael C. Yu, Taloa G. Berg, Ethan Lee, Giovanni Bosco, Laura A. Lee
Trip/Nopo E3 Ubiquitin Ligase Promotes Ubiquitylation Of Dna Polymerase Η, Heather A. Wallace, Julie A. Merkle, Michael C. Yu, Taloa G. Berg, Ethan Lee, Giovanni Bosco, Laura A. Lee
Dartmouth Scholarship
We previously identified a Drosophila maternal effect-lethal mutant named ‘no poles’ (nopo). Embryos from nopo females undergo mitotic arrest with barrel-shaped, acentrosomal spindles during the rapid cycles of syncytial embryogenesis because of activation of a Chk2-mediated DNA checkpoint. NOPO is the Drosophila homolog of human TNF receptor associated factor (TRAF)-interacting protein (TRIP), which has been implicated in TNF signaling. NOPO and TRIP contain RING domains closely resembling those of known E3 ubiquitin ligases. We herein sought to elucidate the mechanism by which TRIP/NOPO promotes genomic stability by performing a yeast two-hybrid screen to identify potential substrates/interactors. We identified members of …
Recurrent Tissue-Specific Mtdna Mutations Are Common In Humans, David C. Samuels, Chun Li, Bingshan Li, Zhuo Song, Eric Torstenson, Hayley Boyd Clay, Antonis Rokas, Tricia A. Thornton-Wells, Jason H. Moore, Tia M. Hughes, Robert D. Hoffman, Jonathan L. Haines, Deborah G. Murdock, Douglas P. Mortlock, Scott M. Williams
Recurrent Tissue-Specific Mtdna Mutations Are Common In Humans, David C. Samuels, Chun Li, Bingshan Li, Zhuo Song, Eric Torstenson, Hayley Boyd Clay, Antonis Rokas, Tricia A. Thornton-Wells, Jason H. Moore, Tia M. Hughes, Robert D. Hoffman, Jonathan L. Haines, Deborah G. Murdock, Douglas P. Mortlock, Scott M. Williams
Dartmouth Scholarship
Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in …
Differential Regulation Of White-Opaque Switching By Individual Subunits Of Candida Albicans Mediator, Anda Zhang, Zhongle Liu, Lawrence C. Myers
Differential Regulation Of White-Opaque Switching By Individual Subunits Of Candida Albicans Mediator, Anda Zhang, Zhongle Liu, Lawrence C. Myers
Dartmouth Scholarship
The multisubunit eukaryotic Mediator complex integrates diverse positive and negative gene regulatory signals and transmits them to the core transcription machinery. Mutations in individual subunits within the complex can lead to decreased or increased transcription of certain subsets of genes, which are highly specific to the mutated subunit. Recent studies suggest a role for Mediator in epigenetic silencing. Using white-opaque morphological switching in Candida albicans as a model, we have shown that Mediator is required for the stability of both the epigenetic silenced (white) and active (opaque) states of the bistable transcription circuit driven by the master regulator Wor1. Individual …
Key Genes For Modulating Information Flow Play A Temporal Role As Breast Tumor Coexpression Networks Are Dynamically Rewired By Letrozole, Nadia M. Penrod, Jason H. Moore
Key Genes For Modulating Information Flow Play A Temporal Role As Breast Tumor Coexpression Networks Are Dynamically Rewired By Letrozole, Nadia M. Penrod, Jason H. Moore
Dartmouth Scholarship
Genes do not act in isolation but instead as part of complex regulatory networks. To understand how breast tumors adapt to the presence of the drug letrozole, at the molecular level, it is necessary to consider how the expression levels of genes in these networks change relative to one another. Using transcriptomic data generated from sequential tumor biopsy samples, taken at diagnosis, following 10-14 days and following 90 days of letrozole treatment, and a pairwise partial orrelation statistic, we build temporal gene coexpression networks. We characterize the structure of each network and identify genes that hold prominent positions for maintaining …
Atypical Glycolysis In Clostridium Thermocellum, Jilai Zhou, Daniel G. Olson, D. Aaron Argyros, Yu Deng, Walter M. Van Gulik, Johannes P. Van Dijken, Lee R. Lynd
Atypical Glycolysis In Clostridium Thermocellum, Jilai Zhou, Daniel G. Olson, D. Aaron Argyros, Yu Deng, Walter M. Van Gulik, Johannes P. Van Dijken, Lee R. Lynd
Dartmouth Scholarship
Cofactor specificities of glycolytic enzymes in Clostridium thermocellum were studied with cellobiose-grown cells from batch cultures. Intracellular glucose was phosphorylated by glucokinase using GTP rather than ATP. Although phosphofructokinase typically uses ATP as a phosphoryl donor, we found only pyrophosphate (PPi)-linked activity. Phosphoglycerate kinase used both GDP and ADP as phosphoryl acceptors. In agreement with the absence of a pyruvate kinase sequence in the C. thermocellum genome, no activity of this enzyme could be detected. Also, the annotated pyruvate phosphate dikinase (ppdk) is not crucial for the generation of pyruvate from phosphoenolpyruvate (PEP), as deletion of the ppdk gene did …
Candida Albicans Induces Arginine Biosynthetic Genes In Response To Host-Derived Reactive Oxygen Species, Claudia Jimenez-Lopez, John R. Collette, Kimberly M. Brothers, Kelly M. Shepardson, Robert A. Kramer
Candida Albicans Induces Arginine Biosynthetic Genes In Response To Host-Derived Reactive Oxygen Species, Claudia Jimenez-Lopez, John R. Collette, Kimberly M. Brothers, Kelly M. Shepardson, Robert A. Kramer
Dartmouth Scholarship
The interaction of Candida albicans with phagocytes of the host's innate immune system is highly dynamic, and its outcome directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation: translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during coculture with macrophages. Using single-cell reporters, we showed here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is …
Septin Phosphorylation And Coiled-Coil Domains Function In Cell And Septin Ring Morphology In The Filamentous Fungus Ashbya Gossypii, Rebecca A. Meseroll, Patricia Occhipinti, Amy S. Gladfelter
Septin Phosphorylation And Coiled-Coil Domains Function In Cell And Septin Ring Morphology In The Filamentous Fungus Ashbya Gossypii, Rebecca A. Meseroll, Patricia Occhipinti, Amy S. Gladfelter
Dartmouth Scholarship
Septins are a class of GTP-binding proteins conserved throughout many eukaryotes. Individual septin subunits associate with one another and assemble into heteromeric complexes that form filaments and higher-order structures in vivo. The mechanisms underlying the assembly and maintenance of higher-order structures in cells remain poorly understood. Septins in several organisms have been shown to be phosphorylated, although precisely how septin phosphorylation may be contributing to the formation of high-order septin structures is unknown. Four of the five septins expressed in the filamentous fungus, Ashbya gossypii, are phosphorylated, and we demonstrate here the diverse roles of these phosphorylation sites …
Gametes: A Fast, Direct Algorithm For Generating Pure, Strict, Epistatic Models With Random Architectures, Ryan J. Urbanowicz, Jeff Kiralis, Nicholas A. Sinnott-Armstrong, Tamra Heberling, Jonathan M. Fisher, Jason H. Moore
Gametes: A Fast, Direct Algorithm For Generating Pure, Strict, Epistatic Models With Random Architectures, Ryan J. Urbanowicz, Jeff Kiralis, Nicholas A. Sinnott-Armstrong, Tamra Heberling, Jonathan M. Fisher, Jason H. Moore
Dartmouth Scholarship
Background: Geneticists who look beyond single locus disease associations require additional strategies for the detection of complex multi-locus effects. Epistasis, a multi-locus masking effect, presents a particular challenge, and has been the target of bioinformatic development. Thorough evaluation of new algorithms calls for simulation studies in which known disease models are sought. To date, the best methods for generating simulated multi-locus epistatic models rely on genetic algorithms. However, such methods are computationally expensive, difficult to adapt to multiple objectives, and unlikely to yield models with a precise form of epistasis which we refer to as pure and strict. Purely and …
Insights Into Mrnp Biogenesis Provided By New Genetic Interactions Among Export And Transcription Factors, Francisco Estruch, Christine Hodge, Natalia Gómez-Navarro, Lorena Peiró-Chova, Catherine V. Heath, Charles N. Cole
Insights Into Mrnp Biogenesis Provided By New Genetic Interactions Among Export And Transcription Factors, Francisco Estruch, Christine Hodge, Natalia Gómez-Navarro, Lorena Peiró-Chova, Catherine V. Heath, Charles N. Cole
Dartmouth Scholarship
The various steps of mRNP biogenesis (transcription, processing and export) are interconnected. It has been shown that the transcription machinery plays a pivotal role in mRNP assembly, since several mRNA export factors are recruited during transcription and physically interact with components of the transcription machinery. Although the shuttling DEAD-box protein Dbp5p is concentrated on the cytoplasmic fibrils of the NPC, previous studies demonstrated that it interacts physically and genetically with factors involved in transcription initiation. We investigated the effect of mutations affecting various components of the transcription initiation apparatus on the phenotypes of mRNA export mutant strains. Our results show …
Farnesol And Cyclic Amp Signaling Effects On The Hypha-To-Yeast Transition In Candida Albicans, Allia K. Lindsay, Aurélie Deveau, Amy E. Piispanen, Deborah A. Hogan
Farnesol And Cyclic Amp Signaling Effects On The Hypha-To-Yeast Transition In Candida Albicans, Allia K. Lindsay, Aurélie Deveau, Amy E. Piispanen, Deborah A. Hogan
Dartmouth Scholarship
Candida albicans, a fungal pathogen of humans, regulates its morphology in response to many environmental cues and this morphological plasticity contributes to virulence. Farnesol, an autoregulatory molecule produced by C. albicans, inhibits the induction of hyphal growth by inhibiting adenylate cyclase (Cyr1). The role of farnesol and Cyr1 in controlling the maintenance of hyphal growth has been less clear. Here, we demonstrate that preformed hyphae transition to growth as yeast in response to farnesol and that strains with increased cyclic AMP (cAMP) signaling exhibit more resistance to farnesol. Exogenous farnesol did not induce the hypha-to-yeast transition in mutants …
Condensin Ii Promotes The Formation Of Chromosome Territories By Inducing Axial Compaction Of Polyploid Interphase Chromosomes, Christopher R. R. Bauer, Tom A. Hartl, Giovanni Bosco
Condensin Ii Promotes The Formation Of Chromosome Territories By Inducing Axial Compaction Of Polyploid Interphase Chromosomes, Christopher R. R. Bauer, Tom A. Hartl, Giovanni Bosco
Dartmouth Scholarship
The eukaryotic nucleus is both spatially and functionally partitioned. This organization contributes to the maintenance, expression, and transmission of genetic information. Though our ability to probe the physical structure of the genome within the nucleus has improved substantially in recent years, relatively little is known about the factors that regulate its organization or the mechanisms through which specific organizational states are achieved. Here, we show that Drosophila melanogaster Condensin II induces axial compaction of interphase chromosomes, globally disrupts interchromosomal interactions, and promotes the dispersal of peri-centric heterochromatin. These Condensin II activities compartmentalize the nucleus into discrete chromosome territories and indicate …
Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen
Two Boundaries Separate Borrelia Burgdorferi Populations In North America, Gabriele Margos, Jean I. Tsao, Santiago Castillo-Ramirez, Yvette A. Girard, Anne G. Hoen
Dartmouth Scholarship
Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s …
Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit
Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit
Dartmouth Scholarship
There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.
The Tlo Proteins Are Stoichiometric Components Of Candida Albicans Mediator Anchored Via The Med3 Subunit, Anda Zhang, Kostadin O. Petrov, Emily R. Hyun, Zhongle Liu, Scott A. Gerber, Lawrence C. Myers
The Tlo Proteins Are Stoichiometric Components Of Candida Albicans Mediator Anchored Via The Med3 Subunit, Anda Zhang, Kostadin O. Petrov, Emily R. Hyun, Zhongle Liu, Scott A. Gerber, Lawrence C. Myers
Dartmouth Scholarship
The amplification of the TLO (for telomere-associated) genes in Candida albicans, compared to its less pathogenic, close relative Candida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex from C. albicans (caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo …