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Articles 1 - 16 of 16
Full-Text Articles in Genetics and Genomics
Chapter 11: Genome-Wide Association Studies, William S. Bush, Jason H. Moore
Chapter 11: Genome-Wide Association Studies, William S. Bush, Jason H. Moore
Dartmouth Scholarship
Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.
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 …
Characterization Of Xylan Utilization And Discovery Of A New Endoxylanase In Thermoanaerobacterium Saccharolyticum Through Targeted Gene Deletions, Kara K. Podkaminer, Adam M. Guss, Heather L. Trajano, David A. Hogsett, Lee R. Lynd
Characterization Of Xylan Utilization And Discovery Of A New Endoxylanase In Thermoanaerobacterium Saccharolyticum Through Targeted Gene Deletions, Kara K. Podkaminer, Adam M. Guss, Heather L. Trajano, David A. Hogsett, Lee R. Lynd
Dartmouth Scholarship
The economical production of fuels and commodity chemicals from lignocellulose requires the utilization of both the cellulose and hemicellulose fractions. Xylanase enzymes allow greater utilization of hemicellulose while also increasing cellulose hydrolysis. Recent metabolic engineering efforts have resulted in a strain of Thermoanaerobacterium saccharolyticum that can convert C5 and C6 sugars, as well as insoluble xylan, into ethanol at high yield. To better understand the process of xylan solubilization in this organism, a series of targeted deletions were constructed in the homoethanologenic T. saccharolyticum strain M0355 to characterize xylan hydrolysis and xylose utilization in this organism. While the deletion of …
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 …
Gene Ontology Analysis Of Pairwise Genetic Associations In Two Genome-Wide Studies Of Sporadic Als, Nora Chung Kim, Peter C. Andrews, Folkert W. Asselbergs, H Robert Frost, Scott M. Williams, Brent T. Harris, Cynthia Read, Kathleen D. Askland, Jason H. Moore
Gene Ontology Analysis Of Pairwise Genetic Associations In Two Genome-Wide Studies Of Sporadic Als, Nora Chung Kim, Peter C. Andrews, Folkert W. Asselbergs, H Robert Frost, Scott M. Williams, Brent T. Harris, Cynthia Read, Kathleen D. Askland, Jason H. Moore
Dartmouth Scholarship
It is increasingly clear that common human diseases have a complex genetic architecture characterized by both additive and nonadditive genetic effects. The goal of the present study was to determine whether patterns of both additive and nonadditive genetic associations aggregate in specific functional groups as defined by the Gene Ontology (GO).
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 …
Computational Design And Characterization Of A Temperature-Sensitive Plasmid Replicon For Gram Positive Thermophiles, Daniel G. Olson, Lee R. Lynd
Computational Design And Characterization Of A Temperature-Sensitive Plasmid Replicon For Gram Positive Thermophiles, Daniel G. Olson, Lee R. Lynd
Dartmouth Scholarship
Temperature-sensitive (Ts) plasmids are useful tools for genetic engineering, but there are currently none compatible with the gram positive, thermophilic, obligate anaerobe, Clostridium thermocellum. Traditional mutagenesis techniques yield Ts mutants at a low frequency, and therefore requires the development of high-throughput screening protocols, which are also not available for this organism. Recently there has been progress in the development of computer algorithms which can predict Ts mutations. Most plasmids currently used for genetic modification of C. thermocellum are based on the replicon of plasmid pNW33N, which replicates using the RepB replication protein. To address this problem, we set out …
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 …
Roles Of The Drosophila Sk Channel (Dsk) In Courtship Memory, Ahmad N. Abou Tayoun, Claudio Pikielny, Patrick J. Dolph
Roles Of The Drosophila Sk Channel (Dsk) In Courtship Memory, Ahmad N. Abou Tayoun, Claudio Pikielny, Patrick J. Dolph
Dartmouth Scholarship
A role for SK channels in synaptic plasticity has been very well-characterized. However, in the absence of simple genetic animal models, their role in behavioral memory remains elusive. Here, we take advantage of Drosophila melanogaster with its single SK gene (dSK) and well-established courtship memory assay to investigate the contribution of this channel to memory. Using two independent dSK alleles, a null mutation and a dominant negative subunit, we show that while dSK negatively regulates the acquisition of short-term memory 30 min after a short training session, it is required for normal long-term memory 24 h after extended …
Pf19 Encodes The P60 Catalytic Subunit Of Katanin And Is Required For Assembly Of The Flagellar Central Apparatus In Chlamydomonas, Erin E. Dymek, Elizabeth F. Smith
Pf19 Encodes The P60 Catalytic Subunit Of Katanin And Is Required For Assembly Of The Flagellar Central Apparatus In Chlamydomonas, Erin E. Dymek, Elizabeth F. Smith
Dartmouth Scholarship
For all eukaryotic cilia the basal bodies provide a template for the assembly of the doublet microtubules, and intraflagellar transport provides a mechanism for transport of axonemal components into the growing cilium. What is not known is how the central pair of microtubules is nucleated or how their associated polypeptides are assembled. Here we report that the Chlamydomonas pf19 mutation results in a single amino acid change within the p60 catalytic subunit of katanin, and that this mutation prevents microtubule severing activity. The pf19 mutant has paralyzed flagella that lack the central apparatus. Using a combination of mutant analysis, RNAi-mediated …
Heterogeneity In Mitochondrial Morphology And Membrane Potential Is Independent Of The Nuclear Division Cycle In Multinucleate Fungal Cells, John P. Gerstenberger, Patricia Occhipinti, Amy S. Gladfelter
Heterogeneity In Mitochondrial Morphology And Membrane Potential Is Independent Of The Nuclear Division Cycle In Multinucleate Fungal Cells, John P. Gerstenberger, Patricia Occhipinti, Amy S. Gladfelter
Dartmouth Scholarship
In the multinucleate filamentous fungus Ashbya gossypii, nuclei divide asynchronously in a common cytoplasm. We hypothesize that the division cycle machinery has a limited zone of influence in the cytoplasm to promote nuclear autonomy. Mitochondria in cultured mammalian cells undergo cell cycle-specific changes in morphology and membrane potential and therefore can serve as a reporter of the cell cycle state of the cytoplasm. To evaluate if the cell cycle state of nuclei in A. gossypii can influ
Complete Genome Sequence Of Clostridium Clariflavum Dsm 19732, Javier A. Izquierdo, Lynne Goodwin, Karen W. Davenport, Hazuki Teshima
Complete Genome Sequence Of Clostridium Clariflavum Dsm 19732, Javier A. Izquierdo, Lynne Goodwin, Karen W. Davenport, Hazuki Teshima
Dartmouth Scholarship
Clostridium clariflavum is a Cluster III Clostridium within the family Clostridiaceae isolated from thermophilic anaerobic sludge (Shiratori et al, 2009). This species is of interest because of its similarity to the model cellulolytic organism Clostridium thermocellum and for the ability of environmental isolates to break down cellulose and hemicellulose. Here we describe features of the 4,897,678 bp long genome and its annotation, consisting of 4,131 protein-coding and 98 RNA genes, for the type strain DSM 19732.