Genetics and Genomics Commons^™

Genomic Analysis Of Factors Associated With Low Prevalence Of Antibiotic Resistance In Extraintestinal Pathogenic Escherichia Coli Sequence Type 95 Strains, Craig M. Stephens, Sheila Adams-Sapper, Manraj Sekhon, James R. Johnson, Lee W. Riley

Biology

Extraintestinal pathogenic Escherichia coli (ExPEC) strains belonging to multilocus sequence type 95 (ST95) are globally distributed and a common cause of infections in humans and domestic fowl. ST95 isolates generally show a lower prevalence of acquired antimicrobial resistance than other pandemic ExPEC lineages. We took a genomic approach to identify factors that may underlie reduced resistance. We fully assembled genomes for four ST95 isolates representing the four major fimH-based lineages within ST95 and also analyzed draft-level genomes from another 82 ST95 isolates, largely from the western United States. The fully assembled genomes of antibiotic-resistant isolates carried resistance genes exclusively on …

Pcr-Activated Cell Sorting As A General, Cultivation-Free Method For High-Throughput Identification And Enrichment Of Virus Hosts, Shaun W. Lim, Shea T. Lance, Kenneth M. Stedman, Adam R. Abate

Biology Faculty Publications and Presentations

Characterizing virus-host relationships is critical for understanding the impact of a virus on an ecosystem, but is challenging with existing techniques, particularly for uncultivable species. We present a general, cultivation-free approach for identifying phage-associated bacterial cells. Using PCR-activated cell sorting, we interrogate millions of individual bacteria for the presence of specific phage nucleic acids. If the nucleic acids are present, the bacteria are recovered via sorting and their genomes analyzed. This allows targeted recovery of all possible host species in a diverse population associated with a specific phage, and can be easily targeted to identify the hosts of different phages …

Crispr-Based Knockout Screening In Primary Neurons, Ben Callif

Master's Theses (2009 -)

Axon growth is coordinated by multiple interacting proteins that remain incompletely characterized. High content screening (HCS), in which manipulation of candidate genes is combined with rapid image analysis of phenotypic effects, has emerged as a powerful technique to identify key regulators of axon outgrowth. Here we explore the utility of a genome editing approach referred to as CRISPR (Clustered Regularly Interspersed Palindromic Repeats) for knockout screening in primary neurons. In the CRISPR approach a DNA-cleaving Cas enzyme is guided to genomic target sequences by user-created guide RNA (sgRNA), where it initiates a double-stranded break that ultimately results in frameshift mutation …

Phytohormone Signaling In Chlorella Sorokiniana: Perspectives On The Evolution Of Plant Cell-To-Cell Signaling, Maya Khasin

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

Cell-to-cell communication is a key aspect of microbial physiology and population dynamics, and a cornerstone in understanding the evolution of multicellularity. Quorum sensing in bacteria is a canonical example of microbial cell-to-cell signaling, in which bacteria use small molecule signals in order to monitor their population size and modulate their physiology accordingly. We propose that the evolution of plant hormone signaling arose in unicellular green algae, analogously to quorum sensing in bacteria, and that the complexity of these pathways required the recruitment of increasingly specific enzymes to increasingly sophisticated gene networks throughout the course of phytohormone signaling evolution. Using Chlorella …

Identifying Regulators From Multiple Types Of Biological Data In Cancer, Brittany Baur

Dissertations (1934 -)

Cancer genomes accumulate alterations that promote cancer cell proliferation and survival. Structural, genetic and epigenetic alterations that have a selective advantage for tumorigenesis affect key regulatory genes and microRNAs that in turn regulate the expression of many target genes. The goal of this dissertation is to leverage the alteration-rich landscape of cancer genomes to detect key regulatory genes and microRNAs. To this end, we designed a feature selection algorithm to identify DNA methylation signals around a gene that would highly predict its expression. We found that genes whose expression could be predicted by DNA methylation accurately were enriched in Gene …

A Novel Multi-Network Approach Reveals Tissue-Specific Cellular Modulators Of Fibrosis In Systemic Sclerosis, Jaclyn N. Taroni, Casey S. Greene, Viktor Martyanov, Tammara A. Wood

Dartmouth Scholarship

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology.We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast …

Discovery And Validation Of Information Theory-Based Transcription Factor And Cofactor Binding Site Motifs., Ruipeng Lu, Eliseos J Mucaki, Peter K Rogan

Biochemistry Publications

Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, …

P08. Unravelling Organelle Genome Evolution Architecture Using Rna-Sequencing Data, Matheus Sanita Lima, David Roy Smith

Western Research Forum

Background: Mitochondria genomes vary from 11 Mb to 6 kb, while plastids can vary from 1 Mb to 30 kb. Non-coding DNA accounts for most of this size variation, but the mechanistic and evolutionary reasons for that are still unknown. Next generation sequencing has generated unprecedented amounts of genomic and transcriptomic data that can be used for organelle genome evolution studies. However, most of these data is used only for the study of cell nucleus. Therefore, I decided to use these untapped data source to investigate the transcription of organelle genomes in plastid-bearing protists.

Methods: I mapped the transcriptomes over …

The Mirnaome Of Catharanthus Roseus: Identification, Expression Analysis, And Potential Roles Of Micrornas In Regulation Of Terpenoid Indole Alkaloid Biosynthesis, Ethan M. Shen, Sanjay Kumar Singh, Jayadri S. Ghosh, Barunava Patra, Priyanka Paul, Ling Yuan, Sitakanta Pattanaik

Plant and Soil Sciences Faculty Publications

MicroRNAs (miRNAs) regulate numerous crucial biological processes in plants. However, information is limited on their involvement in the biosynthesis of specialized metabolites in plants, including Catharanthus roseus that produces a number of pharmaceutically valuable, bioactive terpenoid indole alkaloids (TIAs). Using small RNA-sequencing, we identified 181 conserved and 173 novel miRNAs (cro-miRNAs) in C. roseus seedlings. Genome-wide expression analysis revealed that a set of cro-miRNAs are differentially regulated in response to methyl jasmonate (MeJA). In silico target prediction identified 519 potential cro-miRNA targets that include several auxin response factors (ARFs). The presence of cleaved transcripts of miRNA-targeted ARFs in C. roseus …

Estimating The Probability Of Clonal Relatedness Of Pairs Of Tumors In Cancer Patients, Audrey Mauguen, Venkatraman E. Seshan, Irina Ostrovnaya, Colin B. Begg

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

Next generation sequencing panels are being used increasingly in cancer research to study tumor evolution. A specific statistical challenge is to compare the mutational profiles in different tumors from a patient to determine the strength of evidence that the tumors are clonally related, i.e. derived from a single, founder clonal cell. The presence of identical mutations in each tumor provides evidence of clonal relatedness, although the strength of evidence from a match is related to how commonly the mutation is seen in the tumor type under investigation. This evidence must be weighed against the evidence in favor of independent tumors …

An Assessment Of Potential False Positive E.Coli Pyroprints In The Cplop Database, Skyler A. Gordon

Master's Theses

The genetic information found in each species of organism is unique, and can be used as a tool to differentiate at the molecular level. This has caused rapid genotyping methods to become the cornerstone of a new area of research dependent on reading the genome as a form of identification. One of these specific identification methods, known as pyroprinting, relies on the small variation of DNA sequences within the same species to develop a unique, reproducible fingerprint. By simultaneously pyrosequencing multiple polymorphic loci within the ribosomal operons known as the intergenic transcribed spacers, a reproducible output is obtained, known as …

Penetrance Estimates For Incidental Genomic Findings In Acmg-59, James A. Diao

Yale Day of Data

The dropping costs and rising popularity of next-generation sequencing has introduced the possibility of personalizing medical treatments and screening for genetic diseases. Still, the clinical community’s understanding remains incomplete, with limited consensus on the proper interpretation for many genetic variants. Thus, the standard procedure when returning sequencing results has been to report findings only in genes related to the diagnostic indication, and not incidental findings in other genes. To balance the threat of false positives with the medical benefits of true findings, the American College on Medical Genetics and Genomics (ACMG) recommends an exception: that clinical sequencing laboratories seek and …

Familial Lung Cancer: A Brief History From The Earliest Work To The Most Recent Studies, Anthony Musolf, Claire Simpson, Mariza De Andrade, Diptasri Mandal, Colette Gaba, Ping Yang, Yafang Li

Dartmouth Scholarship

Lung cancer is the deadliest cancer in the United States, killing roughly one of four cancer patients in 2016. While it is well-established that lung cancer is caused primarily by environmental effects (particularly tobacco smoking), there is evidence for genetic susceptibility. Lung cancer has been shown to aggregate in families, and segregation analyses have hypothesized a major susceptibility locus for the disease. Genetic association studies have provided strong evidence for common risk variants of small-to-moderate effect. Rare and highly penetrant alleles have been identified by linkage studies, including on 6q23–25. Though not common, some germline mutations have also been identified …

A Comparative Genomic Analysis Of Putative Pathogenicity Genes In The Host-Specific Sibling Species Colletotrichum Graminicola And Colletotrichum Sublineola, Ester A. S. Buiate, Katia Viana Xavier, Neil Moore, Maria F. Torres, Mark L. Farman, Christopher L. Schardl, Lisa J. Vaillancourt

Plant Pathology Faculty Publications

Background: Colletotrichum graminicola and C. sublineola cause anthracnose leaf and stalk diseases of maize and sorghum, respectively. In spite of their close evolutionary relationship, the two species are completely host-specific. Host specificity is often attributed to pathogen virulence factors, including specialized secondary metabolites (SSM), and small-secreted protein (SSP) effectors. Genes relevant to these categories were manually annotated in two co-occurring, contemporaneous strains of C. graminicola and C. sublineola. A comparative genomic and phylogenetic analysis was performed to address the evolutionary relationships among these and other divergent gene families in the two strains.

Results: Inoculation of maize with C. sublineola …

Oncogenic Nelfe Enhances Myc-Induced Hepatocellular Carcinogenesis, Hien Dang, Atsushi Takai, Marshonna Forgues, Yosawat Pomyen, Haiwei Mou, Wen Xue, Debashish Ray, Kevn Ha, Quiad Morris, Timothy Hughes, Xin Wei Wang

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Mrub_1873, Mrub_1872, Mrub_1871 Genes Are Predicted Orthologs Of The B2285, B2284, And B2283 Genes Respectively, Found In Escherichia Coli Coding For Nadh Ubiquinone Oxidoreductase Complex Subunits E, F, And G., Hannah Lohmeier, Dr. Lori R. Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_1873, Mrub_1872, and Mrub_1871.We predict that Mrub_1873 (DNA coordinates 1933743..1934309 on the reverse strand), Mrub_1872 (DNA coordinates 1932430..1933746 on the reverse strand), and Mrub_1871 (DNA coordinates 1930055..1932421 on the reverse strand) are subunits of the NADH ubiquinone oxidoreductase complex (00190). The complex catalyzes both the transfer of protons across the cytoplasmic membrane and the transfer of electrons to ubiquinone during …

Mrub_2294, Mrub_2293, And Mrub_1942 Genes Are Orthologs Of E. Coli B2476, B1131, And B4006 Genes, Respectively, Lindsay Popp, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

No abstract provided.

Serine Biosynthesis And Glycine Biosynthesis/Degradation: Mrub_0173 Is Orthologous To E. Coli B2913 (Sera); Mrub_0125 Is Orthologous To E. Coli B4388 (Serb); Mrub_2910 Is Orthologous To E. Coli B2551 (Glya)., Megan M. Janssen, Dr. Lori R. Scott

Meiothermus ruber Genome Analysis Project

ABSTRACT. This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_0173, Mrub_0125, and Mrub_ 2910. We predict that Mrub_0173 encodes the enzyme phosphoglycerate dehydrogenase (DNA coordinates 152982 ... 154347), which is the 1st step of the serine biosynthesis pathway (KEGG map number 00680). It catalyzes the conversion of NAD+ + 3-phospho-D-glycerate → NADH H+ + 3-phospho-hydroxypyruvate. The E. coli K12 MG1655 ortholog is predicted to be b2913, which has …

Mrub_2642, Mrub_1054, And Mrub_1059 Genes Are Orthologs Of The Escherichia Coli Genes B2942, B0159, And B2687 Genes, Respectively, Which Code For Methionine Adenosyltransferase, Adenosylhomocysteine Nucleosidase, And S-Ribosylhomocysteine Lyase, Nicholas M. Orslini, Dr. Lori R. Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tools associated with the Guiding Education through Novel Investigation –Annotation Collaboration Toolkit (GENI-ACT) to predict gene function. We investigated the biological function of the genes Mrub_2642, Mrub_1054, and Mrub_1059.

We predict that Mrub_2642 encodes the enzyme methionine adenosyltransferase (DNA coordinates [2677251…2678426] on the reverse strand), the first step of the methionine degradation pathway (KEGG map number 00270). Methionine adenosyltransferase catalyzes the conversion of the substrates, ATP, L-methionine, and water, to yield the products S-adenosyl-L-methionine (SAM), inorganic phosphate, and diphosphate. Mrub_1054 encodes adenosylhomocysteine nucleosidase (DNA …

Mrub_1304, Mrub_2007 And Mrub_2006 Are Orthologs Of E. Coli B_3189, B_3972, And B_0091, Respectively Within The Peptidoglycan Biosynthesis Pathway, Mylaun E. Griffith, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

No abstract provided.

Mrub_0860, Mrub_0701 And Mrub_2285 Are Orthologous To E. Coli B2892, B2562 And B3863 Within The Recfor Pathway For Homologous Recombination, Bailey Englund, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

This project is part of the Meiothermus ruber genome analysis project, which uses the bioinformatics tool associated with the Guiding Education through Novel Investigation – Annotation Collaboration Toolkit (GENI-ACT) to predict the gene function. We investigated the biological function of the genes Mrub_0860, Mrub_0701,and Mrub_2285. We predicted that Mrub_0860 (DNA coordinates 842934..844868 on the forward strand) encodes for the enzyme single-stranded DNA-specific exonuclease, which is in the first step of homologous recombination via the RecFOR pathway (KEGG map number 03440). The E. coli K12 MG1655 ortholog is predicted to be b2892, which has the gene identifier …

Medical Genetics And Genomic Medicine In The United States. Part 2: Reproductive Genetics, Newborn Screening, Genetic Counseling, Training, And Registries, Debra S. Regier, Carlos Ferreira, Suzanne Hart, Donald Hadley, Maximilian Muenke

Pediatrics Faculty Publications

eview of genetics in the United States with emphasis on the prenatal, metabolic, genetic counseling, and training aspects of the field.

Detecting Discordance Enrichment Among A Series Of Two-Sample Genome-Wide Expression Data Sets, Yinglei Lai, Fanni Zhang, Tapan Nayak, Reza Modarres, Norman H. Lee, Timothy A. Mccaffrey

Epidemiology Faculty Publications

Background

With the current microarray and RNA-seq technologies, two-sample genome-wide expression data have been widely collected in biological and medical studies. The related differential expression analysis and gene set enrichment analysis have been frequently conducted. Integrative analysis can be conducted when multiple data sets are available. In practice, discordant molecular behaviors among a series of data sets can be of biological and clinical interest.

Methods

In this study, a statistical method is proposed for detecting discordance gene set enrichment. Our method is based on a two-level multivariate normal mixture model. It is statistically efficient with linearly increased parameter space when …

Metagomics: A Web-Based Tool For Peptide-Centric Functional And Taxonomic Analysis Of Metaproteomics Data, Michael Riffle, Damon H. May, Emma Timmins-Schiffman, Molly P. Mikan, Daniel Jaschob, William S. Noble, Brook L. Nunn

OES Faculty Publications

Metaproteomics is the characterization of all proteins being expressed by a community of organisms in a complex biological sample at a single point in time. Applications of metaproteomics range from the comparative analysis of environmental samples (such as ocean water and soil) to microbiome data from multicellular organisms (such as the human gut). Metaproteomics research is often focused on the quantitative functional makeup of the metaproteome and which organisms are making those proteins. That is: What are the functions of the currently expressed proteins? How much of the metaproteome is associated with those functions? And, which microorganisms are expressing the …

Improvement Of Milling And Nutritional Quality Characteristics Of Oats Through Genomic Selection, Sudha Neupane Adhikari

Electronic Theses and Dissertations

Oats can lower cholesterol, reduce risks of type-2 diabetes, and help prevent heart diseases when consumed daily. Therefore, it is important to evaluate and select breeding lines with desirable milling and nutritional quality traits. Genomic selection, which uses genotyping data to predict the breeding value of an individual, is a promising method to increase genetic gain by selecting for quality traits earlier in the line development process. In this study, we collected phenotypic data for three nutritional traits (protein, β- glucan, and fat content) and five milling quality traits (percent plumps, percent thins, percent plump groat, groat percent and thousand …

Differential Activity And Content Of High-Affinity Glutamate Transporters, Content Of Their Regulatory Proteins, And Capacity For Glutamine And Glutathione Synthesis In Tissues Of Finished Versus Growing Steers, Jing Huang

Theses and Dissertations--Animal and Food Sciences

Improvement of feeding regimens for production animals has been hindered by a lack of fundamental knowledge about how the capacity to regulate nutrient absorption across cell membranes affects the function of nutrient metabolizing enzymes. The objective is to determine if the activities and protein content of system X^-_AG glutamate transporter, its regulatory protein (GTRAP3-18 and ARL6IP1), glutamine synthetase (GS) and glutathione (GSH) content, changes in liver (Experiment 1), longissimus dorsi (LM) and subcutaneous adipose tissue (SF) (Experiment 2) as beef steers transitioned from predominantly-lean (growing) to -lipid (finished) tissue accretion phases. In liver (Experiment 1), system X^{- …}

Evolution Of Molt Phenology In Dwarf Hamsters, Zachary Clare-Salzler

Graduate Student Theses, Dissertations, & Professional Papers

Environmental seasonality presents many challenges for survival. In response, organisms from across the tree of life exhibit adaptive phenology, which can facilitate survival from season to season. In particular, many species are white in the winter and brown in the summer where winter snow cover alters the visual environment. There is an extensive body of literature describing the physiological and cellular regulation of this trait in the Siberian dwarf hamster (Phodopus sungorus), but there are major shortcomings in our understanding concerning the evolution and molecular regulation of mammalian skin phenology. Notably, little is known about the genetic basis …

Characterization Of A Large Vertebrate Genome And Homomorphic Sex Chromosomes In The Axolotl, Ambystoma Mexicanum, Melissa Keinath

Theses and Dissertations--Biology

Changes in the structure, content and morphology of chromosomes accumulate over evolutionary time and contribute to cell, developmental and organismal biology. The axolotl (Ambystoma mexicanum) is an important model for studying these changes because: 1) it provides important phylogenetic perspective for reconstructing the evolution of vertebrate genomes and amphibian karyotypes, 2) its genome has evolved to a large size (~10X larger than human) but has maintained gene orders, and 3) it possesses potentially young sex chromosomes that have not undergone extensive differentiation in the structure that is typical of many other vertebrate sex chromosomes (e.g. mammalian XY chromosomes …

Complete Genome Sequences Of Cluster A Mycobacteriophages Bobswaget, Fred313, Kady, Lokk, Myradee, Stagni, And Stepmih, Kristen A. Butela, Susan M. R. Gurney, Heather L. Hendrickson, Janine M. Leblanc-Straceski, Anastasia M. Zimmerman, Stephanie B. Conant, Nikki E. Freed, Olin K. Silander, Joshua J. Thomson, Charlotte A. Berkes, Cristina Bertolez, Courtney G. Davies, Amber Elinsky, Alison J. Hanlon, Juliette Nersesyan, Payal Patel, John Sherwood, Tiffany Tieu Ngo, Kathryn A. Wisniewski, Kathrine Yacoo, Paul M. Arendse, Nathan W. Bowlen, Jasmina Cunmulaj, Julie L. Downs, Charlee A. Ferrenberg, Alexandra E. Gassman, Cody E. R. Gilligan, Emily Gorkiewicz, Christopher Harness, Anthony Huffman, Christina Jones, Anna Julien, Alexis E. Kupic, Sayonara F. Latu, Thomas J. Manning, Danielle Maxwell, Merrimack College Sea-Phages Annotators 2016, Catherine E. Meyer, Madeleine Reardon, Matthew Slaughter, Royce Swasey, Rebecca I. Tennent, Victoria Torres, Tamia Waller, Rachel M. Worcester, Brooke L. Yost, Steven G. Cresawn, Rebecca A. Garlena, Deborah Jacobs-Sera, Welkin H. Pope, Daniel A. Russell, Graham F. Hatfull, Jacob D. Kagey

Biology Faculty Publications

Seven mycobacteriophages from distinct geographical locations were isolated, using Mycobacterium smegmatis mc2155 as the host, and then purified and sequenced. All of the genomes are related to cluster A mycobacteriophages, BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to that subcluster.

Evolutionary Linkage Of Mimetic And Non-Mimetic Color Traits In A Coral Snake Mimicry Complex, John D. Curlis Jr

College of Graduate Studies: Theses & Dissertations

Color polymorphism in aposematic mimicry systems is a perplexing phenomenon for evolutionary biologists, as theoretically the benefits of converging on a model phenotype should constrain the evolution of phenotypic diversity in these systems (i.e., color polymorphism should not occur). Nevertheless, color polymorphism in mimicry systems is prevalent throughout many taxa. In some of these systems, the evolution of color polymorphism results in the existence of non-mimetic morphs, such as those that are cryptic. The case of ground snakes (Sonora semiannulata) is unique in that color polymorphism encompasses both mimetic and cryptic morphs, as well as individual mimetic and …