Genetics and Genomics Commons^™

Special Muscles, Annamaria C. Scaccia

Capstones

Special Muscles is a documentary that explores living with Duchenne muscular dystrophy, a fatal degenerative disease that weakens the muscles at an aggressive rate. The film will give an uncensored look at how one family copes with inevitability of the disease and their journey chasing a promising experimental cure.

Special Muscles follows 7-year-old Pietro Scarso and his family as they face the challenges, complications and promise of treating Pietro’s progressive muscle disorder. The film travels from New York to Los Angeles to Philadelphia to document the Scarso family’s race against time as Pietro undergoes a 96-week clinical trial for Eteplirsen, …

Elimination Of Chromosomal Island Spycim1 From Streptococcus Pyogenes Strain Sf370 Reverses The Mutator Phenotype And Alters Global Transcription, Christina Hendrickson, Chad W. Euler, Scott V. Nguyen, Maliha Rahman, Kimberly A. Mccullor, Catherine J. King, Vincent A. Fischetti, W. Michael Mcshan

Publications and Research

Streptococcus pyogenes chromosomal island M1 (SpyCIM1) integrates by site-specific recombination into the 5’ end of DNA mismatch repair (MMR) gene mutL in strain SF370SmR, blocking transcription of it and the downstream operon genes. During exponential growth, SpyCIM1 excises from the chromosome and replicates as an episome, restoring mutL transcription. This process is reversed in stationary phase with SpyCIM1 re-integrating into mutL, returning the cells to a mutator phenotype. Here we show that elimination of SpyCIM1 relieves this mutator phenotype. The downstream MMR operon genes, multidrug efflux pump lmrP, Holliday junction resolution helicase ruvA, and DNA base excision …

Molecular-Genetic And Behavioral Analysis Of The Functionality Of Patterning In The Trigeminal Neuraxis, Dana Bakalar

Dissertations, Theses, and Capstone Projects

A striking feature of the vibrissal representation in rodents is the presence; at brainstem (barrellettes), thalamic (barrelloids) and cortical levels (barrels) of a somatotopically organized pattern of neurons which is isomorphic, both morphologically and physiologically, to the pattern of vibrissae on the snout. The vibrissal system is required for several classes of behavior, including feeding and active vibrissal sensing, but the functional role of the patterning in these behaviors is unknown. We used two mutant animals lacking patterning in two areas of the vibrissal neuraxis to examine the functional role of patterning. We examined feeding behavior using a knockout of …

The Insulin/Igf Signaling Regulator Cytohesin/Grp-1 Modulates Sensitivity To Excitotoxicity In C. Elegans, Nazila Tehrani

Dissertations, Theses, and Capstone Projects

Excitotoxicity is a form of neurodegeneration that serves as the main underlying cause of brain damage in stroke/brain ischemia, and a contributing factor in a range of neurological diseases such as Epilepsy, ALS, Alzheimer, and Huntington's disease. In excitotoxicity, over-activation of glutamate receptors causes necrotic neuronal cell death. In spite of intense study of excitotoxicity, the molecular mechanisms that lead from glutamate receptor activation to necrotic death remain a mystery. Aging neurons are known to be more vulnerable to excitotoxicity and less likely to recover, but the underlying reasons for the increased cellular vulnerability are unknown. To gain insight into …

Dna Methylation Dynamics Of Germinal Center B Cells Are Mediated By Aid, Pilar M. Dominguez, Matt Teater, Nyasha Chambwe, Matthias Kormaksson, David Redmon, Jennifer Ishii, Bao Vuong, Jayanta Chaudhuri, Ari Melnick, Aparna Vasanthakumar, Lucy A. Godley, F. Nina Papavasiliou, Oliver Elemento, Rita Shaknovich

Publications and Research

Changes in DNA methylation are required for the formation of germinal centers (GCs), but the mechanisms of such changes are poorly understood. Activation-induced cytidine deaminase (AID) has been recently implicated in DNA demethylation through its deaminase activity coupled with DNA repair. We investigated the epigenetic function of AID in vivo in germinal center B cells (GCBs) isolated from wild-type (WT) and AID-deficient (Aicda^−/−) mice. We determined that the transit of B cells through the GC is associated with marked locus-specific loss of methylation and increased methylation diversity, both of which are lost in Aicda^−/− animals. Differentially …

Population Genetic Structure Of The Dwarf Seahorse (Hippocampus Zosterae) In Florida, Nathan Fedrizzi, Melanie L. J. Stiassny, J. T. Boehm, Eric R. Dougherty, George Amato, Martin Mendez

Publications and Research

The dwarf seahorse (Hippocampus zosterae) is widely distributed throughout near-shore habitats of the Gulf of Mexico and is of commercial significance in Florida, where it is harvested for the aquarium and curio trades. Despite its regional importance, the genetic structure of dwarf seahorse populations remains largely unknown. As an aid to ongoing conservation efforts, we employed three commonly applied mtDNA markers (ND4, DLoop and CO1) to investigate the genetic structuring of H. zosterae in Florida using samples collected throughout its range in the state. A total of 1450 bp provided sufficient resolution to delineate four populations of dwarf seahorses, as …

Transcriptome Sequencing And Annotation Of The Polychaete Hermodice Carunculata (Annelida, Amphinomidae), Shaadi Mehr, Aida Verdes, Rob Desalle, John S. Sparks, Vincent A. Pieribone, David F. Gruber

Publications and Research

Background: The amphinomid polychaete Hermodice carunculata is a cosmopolitan and ecologically important omnivore in coral reef ecosystems, preying on a diverse suite of reef organisms and potentially acting as a vector for coral disease. While amphinomids are a key group for determining the root of the Annelida, their phylogenetic position has been difficult to resolve, and their publically available genomic data was scarce.

Results: We performed deep transcriptome sequencing (Illumina HiSeq) and profiling on Hermodice carunculata collected in the Western Atlantic Ocean. We focused this study on 58,454 predicted Open Reading Frames (ORFs) of genes longer than 200 amino acids …

Phylogenomic Identification Of Regulatory Sequences In Bacteria: An Analysis Of Statistical Power And An Application To Borrelia Burgdorferi Sensu Lato, Che I. Martin, Tika Y. Sukarna, Saymon Akther, Girish Ramrattan, Pedro Pagan, Lia Di, Emmanuel F. Mongodin, Claire M. Fraser, Steven E. Schutzer, Benjamin J. Luft, Sherwood R. Casjens, Wei-Gang Qiu

Publications and Research

Phylogenomic footprinting is an approach for ab initio identification of genome-wide regulatory elements in bacterial species based on sequence conservation. The statistical power of the phylogenomic approach depends on the degree of sequence conservation, the length of regulatory elements, and the level of phylogenetic divergence among genomes. Building on an earlier model, we propose a binomial model that uses synonymous tree lengths as neutral expectations for determining the statistical significance of conserved intergenic spacer (IGS) sequences. Simulations show that the binomial model is robust to variations in the value of evolutionary parameters, including base frequencies and the transition-to-transversion ratio. We …

Associations Between Host Gene Expression, The Mucosal Microbiome, And Clinical Outcome In The Pelvic Pouch Of Patients With Inflammatory Bowel Disease, Xochitl C. Morgan, Boyko Kabakchiev, Levi Waldron, Andrea D. Tyler, Timothy L. Tickle, Raquel Milgrom, Joanne M. Stempak, Dirk Gevers, Ramnik J. Xavier, Mark S. Silverberg, Curtis Huttenhower

Publications and Research

Background: Pouchitis is common after ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC). Similar to inflammatory bowel disease (IBD), both host genetics and the microbiota are implicated in its pathogenesis. We use the IPAA model of IBD to associate mucosal host gene expression with mucosal microbiomes and clinical outcomes. We analyze host transcriptomic data and 16S rRNA gene sequencing data from paired biopsies from IPAA patients with UC and familial adenomatous polyposis. To achieve power for a genome-wide microbiome-transcriptome association study, we use principal component analysis for transcript and clade reduction, and identify significant co-variation between clades and transcripts. …

Historical And Contemporary Demography Of Leaf-Toed Geckos (Phyllodactylidae: Phyllodactylus) In The Mexican Dry Forest, Christopher Blair, Victor H. Jiménez Arcos, Fausto R. Méndez De La Cruz, Robert W. Murphy

Publications and Research

Disentangling the relative influence of historical versus contemporary processes shaping the spatial distribution of genetic variation is critical if we are to effectively mitigate key biodiversity issues. We utilize a comprehensive approach based on different molecular marker types and analytical methods to understand the demographic consequences of recent habitat fragmentation in a spatially explicit context. We focus our efforts on native leaf-toed geckos (Phyllodactylus tuberculosus saxatilis) throughout fragmented habitat in the tropical dry forest of northern Mexico as recent evidence suggests that geographic ranges for these geckos may be much smaller than currently realized. However, no data are …

Improved Evidence-Based Genome-Scale Metabolic Models For Maize Leaf, Embryo, And Endosperm, Samuel M. D. Seaver, Louis M. T. Bradbury, Océane Frelin, Raphy Zarecki, Eytan Ruppin, Andrew D. Hanson, Christopher S. Henry

Publications and Research

There is a growing demand for genome-scale metabolic reconstructions for plants, fueled by the need to understand the metabolic basis of crop yield and by progress in genome and transcriptome sequencing. Methods are also required to enable the interpretation of plant transcriptome data to study how cellular metabolic activity varies under different growth conditions or even within different organs, tissues, and developmental stages. Such methods depend extensively on the accuracy with which genes have been mapped to the biochemical reactions in the plant metabolic pathways. Errors in these mappings lead to metabolic reconstructions with an inflated number of reactions and …

High-Throughput Comparison, Functional Annotation, And Metabolic Modeling Of Plant Genomes Using The Plantseed Resource, Samuel M. D. Seaver, Svetlana Gerdes, Océane Frelin, Claudia Lerma-Ortiz, Louis M. T. Bradbury, Rémi Zallot, Ghulam Hasnain, Thomas D. Niehaus, Basma El Yacoubi, Shiran Pasternak, Robert Olson, Gordon Pusch, Ross Overbeek, Valérie De Crécy-Lagarde, Doreen Ware, Andrew D. Hanson, Christopher S. Henry

Publications and Research

There is a growing demand for genome-scale metabolic reconstructions for plants, fueled by the need to understand the metabolic basis of crop yield and by progress in genome and transcriptome sequencing. Methods are also required to enable the interpretation of plant transcriptome data to study how cellular metabolic activity varies under different growth conditions or even within different organs, tissues, and developmental stages. Such methods depend extensively on the accuracy with which genes have been mapped to the biochemical reactions in the plant metabolic pathways. Errors in these mappings lead to metabolic reconstructions with an inflated number of reactions and …