Genetics and Genomics Commons^™

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 …

Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …

Conserved Noncoding Sequences Regulate Steady-State Mrna Levels In Arabidopsis Thaliana, Jacob Spangler

All Dissertations

Arabidopsis thaliana has undergone three whole genome duplications within its ancestry, and these events have dramatically affected its gene complement. Of the most recent whole genome duplication events (&alpha event), there remain 11,452 conserved noncoding sequences (CNSs) that have been retained proximal to &alpha duplicate gene pairs. As functional DNA elements are expected to diverge in sequence at a slower rate than nonfunctional DNA elements, the retained CNSs likely encode gene regulatory function. Within this dissertation I provide evidence for the regulatory role of CNSs within Arabidopsis thaliana. Using a collection of over 5,000 microarray RNA expression profiling datasets, I …

The Torsion Angle Of Random Walks, Mu He

Masters Theses & Specialist Projects

In this thesis, we study the expected mean of the torsion angle of an n-step
equilateral random walk in 3D. We consider the random walk is generated within a confining sphere or without a confining sphere: given three consecutive vectors ^→e₁ , ^→e₂ , and ^→e₃ of the random walk then the vectors ^→e₁ and ^→e₂ define a plane and the vectors ^→e₂ and ^→e₃ define a second plane. The angle between the two planes is called the torsion angle of the three vectors. Algorithms are …

Engaging Students In A Bioinformatics Activity To Introduce Gene Structure And Function, Barbara J. May

Biology Faculty Publications

Bioinformatics spans many fields of biological research and plays a vital role in mining and analyzing data. Therefore, there is an ever-increasing need for students to understand not only what can be learned from this data, but also how to use basic bioinformatics tools. This activity is designed to provide secondary and undergraduate biology students to a hands-on activity meant to explore and understand gene structure with the use of basic bioinformatic tools. Students are provided an “unknown” sequence from which they are asked to use a free online gene finder program to identify the gene. Students then predict the …

An Automatic Framework For Embryonic Localization Using Edges In A Scale Space, Zachary Bessinger

Masters Theses & Specialist Projects

Localization of Drosophila embryos in images is a fundamental step in an automatic computational system for the exploration of gene-gene interaction on Drosophila. Contour extraction of embryonic images is challenging due to many variations in embryonic images. In the thesis work, we develop a localization framework based on the analysis of connected components of edge pixels in a scale space. We propose criteria to select optimal scales for embryonic localization. Furthermore, we propose a scale mapping strategy to compress the range of a scale space in order to improve the efficiency of the localization framework. The effectiveness of the proposed …

Identification Of Genetic Determinants Of Metastasis And Clonal Relationships Between Primary And Metastatic Tumors, Gaurav Singhal

All Theses and Dissertations (ETDs)

No abstract provided.

Analysis Of The Chondroitinase Operon Of Flavobacterium Columnare, Erin L. Sorlien

Senior Honors Projects

Analysis of the chondroitinase operon of Flavobacterium columnare

Erin Sorlien

Major

Cell and Molecular Biology, Chemistry

Advisor

Dr. David R. Nelson

Date

May 2, 2013

Keywords

Flavobacterium columnare, columnaris disease, chondroitin AC lyase, complementation, csl operon

Abstract
Flavobacterium columnare, an opportunistic bacterial pathogen of fish, is the causative agent of columnaris disease (CD). The bacterium is a Gram-negative rod that exhibits gliding motility and avidly forms biofilms. CD affects both wild and cultured freshwater fish, and continues to cause large economic losses to the fish farming industry. According to an investigation conducted by the National Animal Health Monitoring System, CD …

Effects Of Ergot Alkaloids And Bovine Bodily Fluids On Cytochrome P450 Activity, Nicholas Scott Ezell

Graduate Theses and Dissertations

This thesis evaluates the Promega^TM P450-Glo assay (Promega^TM V9800) as a tool for quantifying ergot alkaloid concentration. Current techniques used for detection of ergot alkaloids are slow and expensive, do not detect all ergot alkaloids, or are not effective on bovine bodily fluids. The first study was conducted to determine effects of commercial ergot alkaloids (n = 6; 0 - 400 μM) on the Promega^TM P450-Glo assay. Cytochrome P450 (CYP450) activity in assay had a differential response to each ergot alkaloid and concentration. As concentrations of ergotamine, dihydroergotamine, ergocornine, and ergocryptine increased CYP450 activity was inhibited (P …

Parentage Analysis And Conservation Genetics Educational Material For The Eastern Hellbender Salamander, Cryptobranchus Alleganiensis Alleganiensis, Sarah A. Chudyk

Master's Projects

Populations of the Eastern hellbender salamander, Cryptobranchus alleganiensis alleganiensis, are declining, making this a species of special concern in New York State and under consideration for Federal Endangered Species listing. As a result of this decline, the New York State Department of Environmental Conservation and the Buffalo Zoo initiated a headstarting program with an egg mass found in the Allegheny River drainage. The juveniles being raised by the Zoo will be released back into the watershed and so understanding the genetic diversity and parentage of these hellbenders will inform the reintroduction efforts. Furthermore, in order to determine how to …

Genetic Structure Of The Copperhead (Viperidae: Agkistrodon Contortrix Mokasen) At Its Most Northern Distribution, Brenna Aaren Levine

Graduate Theses and Dissertations

The focus of molecular studies in North American pitvipers has been on species that warrant conservation concern, such as Timber (Crotalus horridus) and Massasauga rattlesnakes (Sistrurus catenatus). Scant effort has been directed towards the molecular ecology of the Copperhead (Agkistrodon contortrix), other than to evaluate male reproduction in a laboratory setting and phylogenetic history. Thus, employing DNA-based molecular techniques to study the natural history of A. contortrix will broaden our knowledge of molecular ecology in North American pitvipers, and particularly in a non-threatened species that can serve as a surrogate for threatened and endangered …

Geometric Framework For Evaluating Rare Variant Tests Of Association, Keli Liu, Shannon Fast, Matthew Zawistowski, Nathan L. Tintle

Faculty Work Comprehensive List

The wave of next-generation sequencing data has arrived. However, many questions still remain about how to best analyze sequence data, particularly the contribution of rare genetic variants to human disease. Numerous statistical methods have been proposed to aggregate association signals across multiple rare variant sites in an effort to increase statistical power; however, the precise relation between the tests is often not well understood. We present a geometric representation for rare variant data in which rare allele counts in case and control samples are treated as vectors in Euclidean space. The geometric framework facilitates a rigorous classification of existing rare …

Optimal Methods For Using Posterior Probabilities In Association Testing, Keli Liu, Alexander Luedtke, Nathan L. Tintle

Faculty Work Comprehensive List

Objective: The use of haplotypes to impute the genotypes of unmeasured single nucleotide variants continues to rise in popularity. Simulation results suggest that the use of the dosage as a one-dimensional summary statistic of imputation posterior probabilities may be optimal both in terms of statistical power and computational efficiency; however, little theoretical understanding is available to explain and unify these simulation results. In our analysis, we provide a theoretical foundation for the use of the dosage as a one-dimensional summary statistic of genotype posterior probabilities from any technology. Methods: We analytically evaluate the dosage, mode and the more general set …

Genetic Imbalances In Endometriosis Detected By Oligonucleotide-Array Based Comparative Genomic Hybridization, Natalie Burke

Electronic Theses and Dissertations

Endometriosis is one of the most common gynecological diseases as it is thought to affect up to 15% of the female population. Characterized by the growth and proliferation of endometrial tissue outside of the uterine cavity, it is a complex condition with varying degrees of severity and can affect multiple regions of the body with symptoms ranging from a total lack of symptoms to debilitating pain and infertility. The most accepted theory of how endometriosis initiates is that of retrograde menstruation; however, approximately 90% of women with unobstructed fallopian tubes are thought to have some menstrual debris in the peritoneal …

Characterization Of Aebp2 Mutant Mice, Arundhati Bakshi

Honors Capstones

No abstract provided.

Molecular And Genomic Based Insights Into The Evolution Of Enterococcus Faecium From Commensal To Hospital-Adapted Pathogen, Jessica R. Galloway-Pena

Dissertations and Theses (Open Access)

The basis for the recent transition of Enterococcus faecium from a primarily commensal organism to one of the leading causes of hospital-acquired infections in the United States is not yet understood. To address this, the first part of my project assessed isolates from early outbreaks in the USA and South America using sequence analysis, colony hybridizations, and minimal inhibitory concentrations (MICs) which showed clinical isolates possess virulence and antibiotic resistance determinants that are less abundant or lacking in community isolates. I also revealed that the level of ampicillin resistance increased over time in clinical strains. By sequencing the pbp5 gene, …

The Natural And Orthogonal Interaction (Noia) Models For Quantitative Traits (Qts) And Complex Diseases, Feifei Xiao

Dissertations and Theses (Open Access)

My dissertation focuses on developing methods for gene-gene/environment interactions and imprinting effect detections for human complex diseases and quantitative traits. It includes three sections: (1) generalizing the Natural and Orthogonal interaction (NOIA) model for the coding technique originally developed for gene-gene (GxG) interaction and also to reduced models; (2) developing a novel statistical approach that allows for modeling gene-environment (GxE) interactions influencing disease risk, and (3) developing a statistical approach for modeling genetic variants displaying parent-of-origin effects (POEs), such as imprinting.

In the past decade, genetic researchers have identified a large number of causal variants for human genetic diseases and …

Knowledge And Expectations Of Support People In Prenatal Genetic Counseling Sessions, Michelle A. Mcdougle

Dissertations and Theses (Open Access)

Prenatal genetic counseling patients have the ability to choose from a myriad of screening and diagnostic testing options, each with intricacies and caveats regarding accuracy and timing. Decisions regarding such testing can be difficult and are often made on the same day that testing is performed. Therefore, it is reasonable to consider that the support people brought to an appointment may have a role in the decision-making process. We aimed to better define this potential role by examining the incoming knowledge and expectations of support people who attended prenatal genetic counseling appointments.

Support people were asked to complete a survey …

Mismatch Repair Deficient Tumors Lacking Known Sporadic Causes: Are They All Due To Lynch Syndrome?, Katherine M. Dempsey

Dissertations and Theses (Open Access)

BACKGROUND: Mismatch repair deficient (MMRD) colorectal (CRC) or endometrial (EC) cancers in the absence of MLH1 promoter hypermethylation and BRAF mutations are suggestive of Lynch syndrome (LS). Positive germline genetic test results confirm LS. It is unclear if individuals with MMRD tumors but no identified germline mutation or sporadic cause (MMRD+/germline-) have LS.

HYPOTHESIS: Since LS is hereditary, individuals with LS should have a stronger family history of LS-related cancers than individuals with sporadic tumors. We hypothesized that MMRD+/germline- CRC and/or EC patients would have less suggestive family histories than LS CRC and/or EC patients.

METHODS: 253 individuals with an …

Delayed Thrombus Resolution And Fibroproliferative Vascular Wound Healing From Deficiency Of Type Iii Collagen: A Paradoxical Mechanism For Tissue Fragility, Amy J. Reid

Dissertations and Theses (Open Access)

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1^+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury …

Small Interfering Rna-Mediated Translation Repression Alters Ribosome Sensitivity To Inhibition By Cycloheximide In Chlamydomonas Reinhardtii, Xinrong Ma

School of Biological Sciences: Dissertations, Theses, and Student Research

RNA interference (RNAi) is an evolutionarily conserved gene silencing mechanism in eukaryotes, with regulatory roles in a variety of biological processes, including cell cycle, cell differentiation, physiological and metabolic pathways, and stress responses. RNAi can function by transcriptional silencing, mRNA target cleavage, translation repression and/or DNA elimination. In this study, we used the unicellular green alga Chlamydomonas reinhardtii as a model system to study RNAi-mediated translation repression. We demonstrated that small RNAs (sRNAs) generated from exogenously introduced inverted repeat transgenes, with perfect complementarity to the 3’UTR of a target transcript, can inhibit protein synthesis, without or with only minimal mRNA …

Control Of Neuroendocrine Cell Physiology By A Single Transcription Factor, Drosophila Basic Helix Loop Helix Regulator Dimmed, Tarik Hadzic

All Theses and Dissertations (ETDs)

Neuroendocrine cells feature a large capacity for the processing, accumulation and regulated release of bioactive peptides and peptide hormones. The ultrastructural correlate of this regulated secretory pathway is a specialized organelle, called a dense core vesicle: DCV). DCVs are typically larger than conventional, small synaptic vesicles. Past work has identified intrinsic DCV proteins: non-cargo proteins, like the processing enzyme, carboxypeptidase) or ancillary ones that play a role in DCV trafficking and exocytosis: like CAPS, the Ca2+-dependent activator protein for secretion). Currently, there is a lack of understanding of the developmental and physiological mechanisms that permit neurosecretory cells to coordinate and …

High Sine Rna Expression Correlates With Post-Transcriptional Downregulation Of Brca1, Maureen Peterson, Vicki Chandler, Giovanni Bosco

Dartmouth Scholarship

Short Interspersed Nuclear Elements (SINEs) are non-autonomous retrotransposons that comprise a large fraction of the human genome. SINEs are demethylated in human disease, but whether SINEs become transcriptionally induced and how the resulting transcripts may affect the expression of protein coding genes is unknown. Here, we show that downregulation of the mRNA of the tumor suppressor gene BRCA1 is associated with increased transcription of SINEs and production of sense and antisense SINE small RNAs. We find that BRCA1 mRNA is post-transcriptionally down-regulated in a Dicer and Drosha dependent manner and that expression of a SINE inverted repeat with sequence identity …

A Polyglot Approach To Bioinformatics Data Integration: Phylogenetic Analysis Of Hiv-1, Steven Reisman, Catherine Putonti, George K. Thiruvathukal, Konstantin Läufer

Computer Science: Faculty Publications and Other Works

RNA-interference has potential therapeutic use against HIV-1 by targeting highly-functional mRNA sequences that contribute to the virulence of the virus. Empirical work has shown that within cell lines, all of the HIV-1 genes are affected by RNAi-induced gene silencing. While promising, inherent in this treatment is the fact that RNAi sequences must be highly specific. HIV, however, mutates rapidly, leading to the evolution of viral escape mutants. In fact, such strains are under strong selection to include mutations within the targeted region, evading the RNAi therapy and thus increasing the virus’ fitness in the host. Taking a phylogenetic approach, we …

Characterization Of Resistance To The Cry1f Toxin From Bacillus Thuringiensis In Resistant Fall Armyworm, Spodoptera Frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) From Puerto Rico, Ana Maria Velez

Department of Entomology: Dissertations, Theses, and Student Research

Transgenic corn expressing Cry1F protein from Bacillus thuringiensis Berliner has been registered for Spodoptera frugiperda control since 2003. Unexpected damage to Cry1F corn was reported in 2006 in Puerto Rico and Cry1F resistance in S. frugiperda was documented. The inheritance of Cry1F resistance was characterized in a S. frugiperda resistant strain from Puerto Rico which displayed >387-fold resistance to Cry1F. Concentration-response bioassays of reciprocal crosses of resistant and susceptible parental populations indicated that resistance is recessive and autosomal. Bioassays of the backcross of the F₁ generation crossed with the resistant parental strain suggest that a single locus is responsible …

Conserved Structural Domains In Foxd4l1, A Neural Forkhead Box Transcription Factor, Are Required To Repress Or Activate Target Genes, Steven L. Klein, Karen M. Neilson, John Orban, Sergey Yaklichkin, Jennifer Hoffbauer, Kathy Mood, Ira O. Daar, Sally Ann Moody

Anatomy and Regenerative Biology Faculty Publications

FoxD4L1 is a forkhead transcription factor that expands the neural ectoderm by down-regulating genes that promote the onset of neural differentiation and up-regulating genes that maintain proliferative neural precursors in an immature state. We previously demonstrated that binding of Grg4 to an Eh-1 motif enhances the ability of FoxD4L1 to down-regulate target neural genes but does not account for all of its repressive activity. Herein we analyzed the protein sequence for additional interaction motifs and secondary structure. Eight conserved motifs were identified in the C-terminal region of fish and frog proteins. Extending the analysis to mammals identified a high scoring …

Contributions Of Apolipoprotein E And Environmental Factors In Alzheimer’S Disease, Kelly C. Mcmullen

Senior Honors Theses

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder, which currently affects nearly 5.5 million people in the United States alone. Clinical features often exhibited in AD include memory loss, unusual behavior, personality changes, and impaired cognitive function. The primary molecular hallmarks of AD include deposits of senile plaques and neurofibrillary tangles in brain tissue. A myriad of risk factors are associated with the disease, but this review will focus on Apolipoprotein E polymorphisms and certain environmental factors. Understanding the role of Apolipoprotein E in AD pathology may aid in the development of certain drug therapies and possible cures for AD. …

Functional Annotation And Comparative Analysis Of A Zygopteran Transcriptome, Alexander G. Shanku, Mark A. Mcpeek, Andrew D. Kern

Dartmouth Scholarship

In this paper we present a de novo assembly of the transcriptome of the damselfly (Enallagma hageni) through the use of 454 pyrosequencing. E. hageni is a member of the suborder Zygoptera, in the order Odonata, and Odonata organisms form the basal lineage of the winged insects (Pterygota). To date, sequence data used in phylogenetic analysis of Enallagma species have been derived from either mitochondrial DNA or ribosomal nuclear DNA. This Enallagma transcriptome contained 31,661 contigs that were assembled and translated into 14,813 individual open reading frames. Using these data, we constructed an extensive dataset of 634 orthologous nuclear protein-encoding …

Patterns Of Gene Expression From Human Costal Cartilage In Relation To The Chest Wall Deformity Pectus Carinatum, Janna E. Grubbs

Biological Sciences Theses & Dissertations

Cartilage deformities within the human chest wall, specifically pectus excavatum (PE) and pectus carinatum (PC) are common (1/400-1/1000) and yet, despite their clinical significance, are some of the least studied disorders pertaining to cartilage [1]. The costal cartilage connecting "false ribs" 8-10 to the sternum is often abnormally grown and can lead to formation of a severely sunken "funnel" chest (PE) or push outwards to form a "pigeon" chest (PC). Both conditions can have impact on the diaphragm, heart, lungs, and psychological function. An established ratio of PE and PC in males to females is 4:1, indicating a sex-linked male …

The Advertisement Calls And Distribution Of Two Sympatric Species Of Chiasmocleis (Méhely 1904) (Anura, Microhylidae, Gastrophryninae) From The Atlantic Forest, Mauricio C. Florani, Caio Vinicus De Mira Mendes, Iuri Ribeiro Dias, Danilo Silva Ruas, João Fillipe Riva Tonini, Rafael O. De Sá

Biology Faculty Publications

The advertisement calls of Chiasmocleis cordeiroi and C. crucis are described for populations from the municipalities of Igrapiúna and Camacan, respectively, state of Bahia, Brazil. Both calls consist of multipulsed notes produced in series. Differences between the two calls are: dominant frequency, higher in C. cordeiroi (range 4500–4898 Hz; C. crucis range 4069–4435 Hz); note rate, higher in C. cordeiroi (range 6.20–7.46 s/note; C. crucis range 5.17–5.59 s/note); pulse rate, higher in C. cordeiroi (151.82–194.83 s/note; C. crucis range 125.30– 142.12 s/note); and the structure of the modulation patterns of the notes. Moreover, the advertisement calls of C. crucis and …