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Articles 1 - 14 of 14
Full-Text Articles in Genetics and Genomics
Mir319a Targeting Of Tcp4 Is Critical For Petal Growth And Development In Arabidopsis, Anwesha Nag, Stacey King, Thomas Jack
Mir319a Targeting Of Tcp4 Is Critical For Petal Growth And Development In Arabidopsis, Anwesha Nag, Stacey King, Thomas Jack
Dartmouth Scholarship
In a genetic screen in a drnl-2 background, we isolated a loss-of-function allele in miR319a (miR319a129). Previously, miR319a has been postulated to play a role in leaf development based on the dramatic curled-leaf phenotype of plants that ectopically express miR319a (jaw-D). miR319a129 mutants exhibit defects in petal and stamen development; petals are narrow and short, and stamens exhibit defects in anther development. The miR319a129 loss-of-function allele contains a single-base change in the middle of the encoded miRNA, which reduces the ability of miR319a to recognize targets. Analysis of the expression patterns of the …
Ceramide Kinase Regulates Phospholipase C And Phosphatidylinositol 4, 5, Bisphosphate In Phototransduction, Ujjaini Dasgupta, Takeshi Bamba, Salvatore Chiantia, Pusha Karim, Ahmad N. Abou Tayoun
Ceramide Kinase Regulates Phospholipase C And Phosphatidylinositol 4, 5, Bisphosphate In Phototransduction, Ujjaini Dasgupta, Takeshi Bamba, Salvatore Chiantia, Pusha Karim, Ahmad N. Abou Tayoun
Dartmouth Scholarship
Phosphoinositide-specific phospholipase C (PLC) is a central effector for many biological responses regulated by G-protein-coupled receptors including Drosophila phototransduction where light sensitive channels are activated downstream of NORPA, a PLCbeta homolog. Here we show that the sphingolipid biosynthetic enzyme, ceramide kinase, is a novel regulator of PLC signaling and photoreceptor homeostasis. A mutation in ceramide kinase specifically leads to proteolysis of NORPA, consequent loss of PLC activity, and failure in light signal transduction. The mutant photoreceptors also undergo activity-dependent degeneration. Furthermore, we show that a significant increase in ceramide, resulting from lack of ceramide kinase, perturbs the membrane microenvironment of …
Quantifying And Resolving Multiple Vector Transformants In S. Cerevisiae Plasmid Libraries, Thomas C. Scanlon, Elizabeth C. Gray, Karl E. Griswold
Quantifying And Resolving Multiple Vector Transformants In S. Cerevisiae Plasmid Libraries, Thomas C. Scanlon, Elizabeth C. Gray, Karl E. Griswold
Dartmouth Scholarship
In addition to providing the molecular machinery for transcription and translation, recombinant microbial expression hosts maintain the critical genotype-phenotype link that is essential for high throughput screening and recovery of proteins encoded by plasmid libraries. It is known that Escherichia coli cells can be simultaneously transformed with multiple unique plasmids and thusly complicate recombinant library screening experiments. As a result of their potential to yield misleading results, bacterial multiple vector transformants have been thoroughly characterized in previous model studies. In contrast to bacterial systems, there is little quantitative information available regarding multiple vector transformants in yeast. Saccharomyces cerevisiae is the …
Decreased Replication Origin Activity In Temporal Transition Regions, Zeqiang Guan, Christina M. Hughes, Settapong Kosiyatrakul, Paolo Norio, Ranjan Sen, Steven Fiering
Decreased Replication Origin Activity In Temporal Transition Regions, Zeqiang Guan, Christina M. Hughes, Settapong Kosiyatrakul, Paolo Norio, Ranjan Sen, Steven Fiering
Dartmouth Scholarship
In the mammalian genome, early- and late-replicating domains are often separated by temporal transition regions (TTRs) with novel properties and unknown functions. We identified a TTR in the mouse immunoglobulin heavy chain (Igh) locus, which contains replication origins that are silent in embryonic stem cells but activated during B cell development. To investigate which factors contribute to origin activation during B cell development, we systematically modified the genetic and epigenetic status of the endogenous Igh TTR and used a single-molecule approach to analyze DNA replication. Introduction of a transcription unit into the Igh TTR, activation of gene transcription, …
Spatially Uniform Relieff (Surf) For Computationally-Efficient Filtering Of Gene-Gene Interactions, Casey S. Greene, Nadia M. Penrod, Jeff Kiralis, Jason H. Moore
Spatially Uniform Relieff (Surf) For Computationally-Efficient Filtering Of Gene-Gene Interactions, Casey S. Greene, Nadia M. Penrod, Jeff Kiralis, Jason H. Moore
Dartmouth Scholarship
Genome-wide association studies are becoming the de facto standard in the genetic analysis of common human diseases. Given the complexity and robustness of biological networks such diseases are unlikely to be the result of single points of failure but instead likely arise from the joint failure of two or more interacting components. The hope in genome-wide screens is that these points of failure can be linked to single nucleotide polymorphisms (SNPs) which confer disease susceptibility. Detecting interacting variants that lead to disease in the absence of single-gene effects is difficult however, and methods to exhaustively analyze sets of these variants …
Genetic Population Structure Analysis In New Hampshire Reveals Eastern European Ancestry, Chantel D. Sloan, Angeline D. Andrew, Eric J. Duell, Scott M. Williams, Margaret R. Karagas, Jason H. Moore
Genetic Population Structure Analysis In New Hampshire Reveals Eastern European Ancestry, Chantel D. Sloan, Angeline D. Andrew, Eric J. Duell, Scott M. Williams, Margaret R. Karagas, Jason H. Moore
Dartmouth Scholarship
Genetic structure due to ancestry has been well documented among many divergent human populations. However, the ability to associate ancestry with genetic substructure without using supervised clustering has not been explored in more presumably homogeneous and admixed US populations. The goal of this study was to determine if genetic structure could be detected in a United States population from a single state where the individuals have mixed European ancestry. Using Bayesian clustering with a set of 960 single nucleotide polymorphisms (SNPs) we found evidence of population stratification in 864 individuals from New Hampshire that can be used to differentiate the …
Microbial Nad Metabolism: Lessons From Comparative Genomics, Francesca Gazzaniga, Rebecca Stebbins, Sheila Z. Chang, Mark A. Mcpeek, Charles Brenner
Microbial Nad Metabolism: Lessons From Comparative Genomics, Francesca Gazzaniga, Rebecca Stebbins, Sheila Z. Chang, Mark A. Mcpeek, Charles Brenner
Dartmouth Scholarship
NAD is a coenzyme for redox reactions and a substrate of NAD-consuming enzymes, including ADP-ribose transferases, Sir2-related protein lysine deacetylases, and bacterial DNA ligases. Microorganisms that synthesize NAD from as few as one to as many as five of the six identified biosynthetic precursors have been identified. De novo NAD synthesis from aspartate or tryptophan is neither universal nor strictly aerobic. Salvage NAD synthesis from nicotinamide, nicotinic acid, nicotinamide riboside, and nicotinic acid riboside occurs via modules of different genes. Nicotinamide salvage genes nadV and pncA, found in distinct bacteria, appear to have spread throughout the tree of life …
Failure To Replicate A Genetic Association May Provide Important Clues About Genetic Architecture, Casey S. Greene, Nadia M. Penrod, Scott M. Williams, Jason H. Moore
Failure To Replicate A Genetic Association May Provide Important Clues About Genetic Architecture, Casey S. Greene, Nadia M. Penrod, Scott M. Williams, Jason H. Moore
Dartmouth Scholarship
Replication has become the gold standard for assessing statistical results from genome-wide association studies. Unfortunately this replication requirement may cause real genetic effects to be missed. A real result can fail to replicate for numerous reasons including inadequate sample size or variability in phenotype definitions across independent samples. In genome-wide association studies the allele frequencies of polymorphisms may differ due to sampling error or population differences. We hypothesize that some statistically significant independent genetic effects may fail to replicate in an independent dataset when allele frequencies differ and the functional polymorphism interacts with one or more other functional polymorphisms. To …
Minimum Criteria For Dna Damage-Induced Phase Advances In Circadian Rhythms, Christian I. Hong, Judit Zámborszky, Attila Csikász-Nagy
Minimum Criteria For Dna Damage-Induced Phase Advances In Circadian Rhythms, Christian I. Hong, Judit Zámborszky, Attila Csikász-Nagy
Dartmouth Scholarship
Robust oscillatory behaviors are common features of circadian and cell cycle rhythms. These cyclic processes, however, behave distinctively in terms of their periods and phases in response to external influences such as light, temperature, nutrients, etc. Nevertheless, several links have been found between these two oscillators. Cell division cycles gated by the circadian clock have been observed since the late 1950s. On the other hand, ionizing radiation (IR) treatments cause cells to undergo a DNA damage response, which leads to phase shifts (mostly advances) in circadian rhythms. Circadian gating of the cell cycle can be attributed to the cell cycle …
Correcting The Site Frequency Spectrum For Divergence-Based Ascertainment, Andrew D. Kern
Correcting The Site Frequency Spectrum For Divergence-Based Ascertainment, Andrew D. Kern
Dartmouth Scholarship
Comparative genomics based on sequenced referenced genomes is essential to hypothesis generation and testing within population genetics. However, selection of candidate regions for further study on the basis of elevated or depressed divergence between species leads to a divergence-based ascertainment bias in the site frequency spectrum within selected candidate loci. Here, a method to correct this problem is developed that obtains maximum-likelihood estimates of the unascertained allele frequency distribution using numerical optimization. I show how divergence-based ascertainment may mimic the effects of natural selection and offer correction formulae for performing proper estimation into the strength of selection in candidate regions …
The C. Elegans Snail Homolog Ces-1 Can Activate Gene Expression In Vivo And Share Targets With Bhlh Transcription Factors, John S. Reece-Hoyes, Bart Deplancke, M. Inmaculada Barrasa, Julia Hatzold, Ryan B. Smit, H Efsun Arda, Patricia A. Pope, Jeb Gaudet, Barbara Conradt, Albertga J.M. Walhout
The C. Elegans Snail Homolog Ces-1 Can Activate Gene Expression In Vivo And Share Targets With Bhlh Transcription Factors, John S. Reece-Hoyes, Bart Deplancke, M. Inmaculada Barrasa, Julia Hatzold, Ryan B. Smit, H Efsun Arda, Patricia A. Pope, Jeb Gaudet, Barbara Conradt, Albertga J.M. Walhout
Dartmouth Scholarship
Snail-type transcription factors (TFs) are found in numerous metazoan organisms and function in a plethora of cellular and developmental processes including mesoderm and neuronal development, apoptosis and cancer. So far, Snail-type TFs are exclusively known as transcriptional repressors. They repress gene expression by recruiting transcriptional co-repressors and/or by preventing DNA binding of activators from the basic helix-loop-helix (bHLH) family of TFs to CAGGTG E-box sequences. Here we report that the Caenorhabditis elegans Snail-type TF CES-1 can activate transcription in vivo. Moreover, we provide results that suggest that CES-1 can share its binding site with bHLH TFs, in different tissues, …
Multifactor Dimensionality Reduction Analysis Identifies Specific Nucleotide Patterns Promoting Genetic Polymorphisms, Eric Arehart, Scott Gleim, Bill White, John Hwa, Jason H. Moore
Multifactor Dimensionality Reduction Analysis Identifies Specific Nucleotide Patterns Promoting Genetic Polymorphisms, Eric Arehart, Scott Gleim, Bill White, John Hwa, Jason H. Moore
Dartmouth Scholarship
The fidelity of DNA replication serves as the nidus for both genetic evolution and genomic instability fostering disease. Single nucleotide polymorphisms (SNPs) constitute greater than 80% of the genetic variation between individuals. A new theory regarding DNA replication fidelity has emerged in which selectivity is governed by base-pair geometry through interactions between the selected nucleotide, the complementary strand, and the polymerase active site. We hypothesize that specific nucleotide combinations in the flanking regions of SNP fragments are associated with mutation.
Efficient Gene Replacements In Toxoplasma Gondii Strains Deficient For Nonhomologous End Joining, Barbara A. Fox, Jessica G. Ristuccia, Jason P. Gigley, David J. Bzik
Efficient Gene Replacements In Toxoplasma Gondii Strains Deficient For Nonhomologous End Joining, Barbara A. Fox, Jessica G. Ristuccia, Jason P. Gigley, David J. Bzik
Dartmouth Scholarship
A high frequency of nonhomologous recombination has hampered gene targeting approaches in the model apicomplexan parasite Toxoplasma gondii. To address whether the nonhomologous end-joining (NHEJ) DNA repair pathway could be disrupted in this obligate intracellular parasite, putative KU proteins were identified and a predicted KU80 gene was deleted. The efficiency of gene targeting via double-crossover homologous recombination at several genetic loci was found to be greater than 97% of the total transformants in KU80 knockouts. Gene replacement efficiency was markedly increased (300- to 400-fold) in KU80 knockouts compared to wild-type strains. Target DNA flanks of only approximately 500 bp were …
Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon
Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon
Dartmouth Scholarship
Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show that the internalized rhodopsin is not degraded in the lysosome but instead accumulates in the late endosomes. Using mutants that are defective in late endosome to lysosome trafficking, we were able to show that rhodopsin accumulates …