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 …

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 …

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 …

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 …

Comparative Analysis Of Prostate Cancer Gene Regulatory Networks Via Hub Type Variation, Pegah Khosravi, Vahid H. Gazestani, Mohammad Akbarzadeh, Samira Mirkhalaf, Mehdi Sadeghi, Bahram Goliaei

Publications and Research

Background

Prostate cancer is one of the most widespread cancers in men and is fundamentally a genetic disease. Identifying regulators in cancer using novel systems biology approaches will potentially lead to new insight into this disease. It was sought to address this by inferring gene regulatory networks (GRNs). Moreover, dynamical analysis of GRNs can explain how regulators change among different conditions, such as cancer subtypes.

Methods

In our approach, independent gene regulatory networks from each prostate state were reconstructed using one of the current state-of-art reverse engineering approaches. Next, crucial genes involved in this cancer were highlighted by analyzing each …

Revisiting The Vanishing Refuge Model Of Diversification, Robert Damasceno, Maria L. Strangas, Ana C. Carnaval, Miguel T. Rodrigues, Craig Moritz

Publications and Research

Much of the debate around speciation and historical biogeography has focused on the role of stabilizing selection on the physiological (abiotic) niche, emphasizing how isolation and vicariance, when associated with niche conservatism, may drive tropical speciation. Yet, recent re-emphasis on the ecological dimensions of speciation points to a more prominent role of divergent selection in driving genetic, phenotypic, and niche divergence. The vanishing refuge model (VRM), first described by Vanzolini and Williams (1981), describes a process of diversification through climate-driven habitat fragmentation and exposure to new environments, integrating both vicariance and divergent selection. This model suggests that dynamic climates and …

Long-Term Cre-Mediated Retrograde Tagging Of Neurons Using A Novel Recombinant Pseudorabies Virus, Hysell V. Oviedo, Hassasna K. Oyibo, Petr Znamenskiy, Lynn W. Enquist, Anthony M. Zador

Publications and Research

Brain regions contain diverse populations of neurons that project to different long-range targets. The study of these subpopulations in circuit function and behavior requires a toolkit to characterize and manipulate their activity in vivo. We have developed a novel set of reagents based on Pseudorabies Virus (PRV) for efficient and long-term genetic tagging of neurons based on their projection targets. By deleting IE180, the master transcriptional regulator in the PRV genome, we have produced a mutant virus capable of infection and transgene expression in neurons but unable to replicate in or spread from those neurons. IE180-null mutants showed no cytotoxicity, …

Collective Behaviour Without Collective Order In Wild Swarms Of Midges, Alessandro Attanasi, Andrea Cavagna, Lorenzo Del Castello, Irene Giardina, Stefania Melillo, Leonardo Parisi, Oliver Pohl, Bruno Rossaro, Edward Shen, Edmondo Silvestri, Massimilano Viale

Publications and Research

Collective behaviour is a widespread phenomenon in biology, cutting through a huge span of scales, from cell colonies up to bird flocks and fish schools. The most prominent trait of collective behaviour is the emergence of global order: individuals synchronize their states, giving the stunning impression that the group behaves as one. In many biological systems, though, it is unclear whether global order is present. A paradigmatic case is that of insect swarms, whose erratic movements seem to suggest that group formation is a mere epiphenomenon of the independent interaction of each individual with an external landmark. In these cases, …

Early Back-To-Africa Migration Into The Horn Of Africa, Jason A. Hodgson, Connie J. Mulligan, Ali Al-Meeri, Ryan L. Raaum

Publications and Research

Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive of earlier episodes of admixture. To investigate this further, we generated new genome-wide SNP data for a Yemeni population sample and merged these new data with published genome-wide genetic data from the HOA and a broad selection of surrounding populations. We used multidimensional scaling and ADMIXTURE methods in an exploratory data analysis to develop hypotheses …

Multilocus Coalescent Analyses Reveal The Demographic History Of Mouse Lemur Sister Species., Christopher Blair, Kellie L. Heckman, Amy L. Russell, Anne D. Yoder

Publications and Research

Debate continues as to whether allopatric speciation or peripatric speciation through a founder effect is the predominant force driving evolution in vertebrates. The mouse lemurs of Madagascar are a system in which evolution has generated a large number of species over a relatively recent time frame. Here, we examine speciation patterns in a pair of sister species of mouse lemur, Microcebus murinus and M. griseorufus. These two species have ranges that are disparately proportioned in size, with M. murinus showing a much more extensive range that marginally overlaps that of M. griseorufus. Given that these two species are …

Genome-Wide Methylation Analyses In Glioblastoma Multiforme, Rose K. Lai, Yanwen Chen, Xiaowei Guan, Darryl Nousome, Charu Sharma, Peter Canoll, Jeffrey Bruce, Andrew E. Sloan, Etty Cortes, Jean-Paul Vonsattel, Tao Su, Lissette Delgado-Cruzata, Irina Gurvich, Regina M. Santella, Quinn Ostrom, Annette Lee, Peter Gregersen, Jill Barnholtz-Sloan

Publications and Research

Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM). Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in both the discovery …

Phylogeny And Population Genetics Of The Endangered Dwarf Bear-Poppy, Arctomecon Humilis Coville (Papaveraceae) Using Microsatellite Markers, Joshua Simpson

Dissertations, Theses, and Capstone Projects

The genus Arctomecon (Papaveraceae) is comprised of three narrowly endemic rare species that are largely restricted to gypsum soils of the eastern Mojave Desert. The small, remaining populations of these species have become increasingly isolated by urban development and habitat fragmentation. Arctomecon humilis is federally listed as endangered due to its limited distribution within a ~15 km radius of an actively expanding city. Organizations involved with land management and conservation have called for greater insight into the genetic variation and population structure of the remaining subpopulations as they make important decisions regarding where to focus their efforts and resources.

The …

Fast Quantitative Real-Time Pcr-Based Screening For Common Chromosomal Aneuploidies In Mouse Embryonic Stem Cells, Charlotte D'Hulst, Irena Parvanova, Delia Tomoiaga, Maria L. Sapar, Paul Feinstein

Publications and Research

Chromosomal integrity has been known for many years to affect the ability of mouse embryonic stem cells (mESCs) to contribute to the germline of chimeric mice. Abnormal chromosomes are generally detected by standard cytogenetic karyotyping. However, this method is expensive, time consuming, and often omitted prior to blastocyst injection, consequently reducing the frequency of mESC-derived offspring. Here, we show a fast, accurate, and inexpensive screen for identifying the two most common aneuploidies (Trisomy 8 and loss of chromosome Y) in genetically manipulated mESCs using quantitative real-time PCR (qPCR). Screening against these two aneuploidies significantly increases the fraction of normal mESC …

Myc-Dependent Genome Instability And Lifespan In Drosophila, Christina Greer, Moonsook Lee, Maaike Westerhof, Brandon Milholland, Rebecca Spokony, Jan Vijg, Julie Secombe

Publications and Research

The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs). In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence …

Signatures Of Rapid Evolution In Urban And Rural Transcriptomes Of White-Footed Mice (Peromyscus Leucopus) In The New York Metropolitan Area, Stephen Edward Harris, Jason Munshi-South, Craig Oberfell, Rachel O'Neill

Publications and Research

Urbanization is a major cause of ecological degradation around the world, and human settlement in large cities is accelerating. New York City (NYC) is one of the oldest and most urbanized cities in North America, but still maintains 20% vegetation cover and substantial populations of some native wildlife. The white-footed mouse, Peromyscus leucopus, is a common resident of NYC’s forest fragments and an emerging model system for examining the evolutionary consequences of urbanization. In this study, we developed transcriptomic resources for urban P. leucopus to examine evolutionary changes in protein-coding regions for an exemplar “urban adapter.” We used Roche 454 …

Genome-Wide Analyses Of Shavenbaby Target Genes Reveals Distinct Features Of Enhancer Organization, Delphine Menoret, Marc Santolini, Isabelle Fernandes, Rebecca Spokony, Jennifer Zanet, Ignacio Gonzalez, Yvan Latapie, Pierre Ferrer, Hervé Rouault, Kevin P. White, Philippe Besse, Vincent Hakim, Stein Aerts, Francois Payre, Serge Plaza

Publications and Research

Background: Developmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes.

Results: We defined a sizeable set of genes downstream of Svb and used in vivo assays to delineate 14 enhancers driving their specific expression in trichome …

Landscape Genetics Of Leaf-Toed Geckos In The Tropical Dry Forest Of Northern Mexico, Christopher Blair, Victor H. Jimenez-Arcos, Fausto R. Mendez De La Cruz, Robert W. Murphy

Publications and Research

Habitat fragmentation due to both natural and anthropogenic forces continues to threaten the evolution and maintenance of biological diversity. This is of particular concern in tropical regions that are experiencing elevated rates of habitat loss. Although less well-studied than tropical rain forests, tropical dry forests (TDF) contain an enormous diversity of species and continue to be threatened by anthropogenic activities including grazing and agriculture. However, little is known about the processes that shape genetic connectivity in species inhabiting TDF ecosystems. We adopt a landscape genetic approach to understanding functional connectivity for leaf-toed geckos (Phyllodactylus tuberculosus) at multiple sites …

Ecological Genetics Of Chinese Rhesus Macaque In Response To Mountain Building: All Things Are Not Equal, Shan-Jin Wu, Jing Luo, Qing-Qing Li, Yan-Qin Wang, Robert E. Murphy, Christopher Blair, Shi-Fang Wu, Bi-Song Yue, Ya-Ping Zhang

Publications and Research

Pliocene uplifting of the Qinghai-Tibetan Plateau (QTP) and Quaternary glaciation may have impacted the Asian biota more than any other events. Little is documented with respect to how the geological and climatological events influenced speciation as well as spatial and genetic structuring, especially in vertebrate endotherms. Macaca mulatta is the most widely distributed non-human primate. It may be the most suitable model to test hypotheses regarding the genetic consequences of orogenesis on an endotherm.

Sceloporus Clarkii—Nocturnal Foraging, Christopher Blair, Noberto Martinez-Mendez, Rafael A. Lara-Resendiz

Publications and Research

No abstract provided.

Genetics Answers Questions And Raises More, Aldemaro Romero Jr.

Publications and Research

No abstract provided.

Dynamic Gene Expression In The Human Cerebral Cortex Distinguishes Children From Adults, Kirstin N. Sterner, Amy Weckle, Harry T. Chugani, Adi L. Tarca, Chet C. Sherwood, Patrick R. Hof, Christopher W. Kuzawa, Amy M. Boddy, Asad Abbas, Ryan L. Raaum, Lucie Grégoire, Leonard Lipovich, Lawrence I. Grossman, Monica Uddin, Morris Goodman, Derek E. Wildman

Publications and Research

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR>0). Moreover, genes known to …

Pre-Whaling Genetic Diversity And Population Ecology In Eastern Pacific Gray Whales: Insights From Ancient Dna And Stable Isotopes, S Elizabeth Alter, Seth D. Newsome, Stephen R. Palumbi

Publications and Research

Commercial whaling decimated many whale populations, including the eastern Pacific gray whale, but little is known about how population dynamics or ecology differed prior to these removals. Of particular interest is the possibility of a large population decline prior to whaling, as such a decline could explain the ,5-fold difference between genetic estimates of prior abundance and estimates based on historical records. We analyzed genetic (mitochondrial control region) and isotopic information from modern and prehistoric gray whales using serial coalescent simulations and Bayesian skyline analyses to test for a pre-whaling decline and to examine prehistoric genetic diversity, population dynamics and …