From Gene Identification and Functional Characterization to Genome Editing Approaches for Inherited Retinal Disorders Elise Orhan Le Gac De Lansalut
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Program Nr: 1 from the 2004 ASHG Annual Meeting Mutations in A
Program Nr: 1 from the 2004 ASHG Annual Meeting Mutations in a novel member of the chromodomain gene family cause CHARGE syndrome. L.E.L.M. Vissers1, C.M.A. van Ravenswaaij1, R. Admiraal2, J.A. Hurst3, B.B.A. de Vries1, I.M. Janssen1, W.A. van der Vliet1, E.H.L.P.G. Huys1, P.J. de Jong4, B.C.J. Hamel1, E.F.P.M. Schoenmakers1, H.G. Brunner1, A. Geurts van Kessel1, J.A. Veltman1. 1) Dept Human Genetics, UMC Nijmegen, Nijmegen, Netherlands; 2) Dept Otorhinolaryngology, UMC Nijmegen, Nijmegen, Netherlands; 3) Dept Clinical Genetics, The Churchill Hospital, Oxford, United Kingdom; 4) Children's Hospital Oakland Research Institute, BACPAC Resources, Oakland, CA. CHARGE association denotes the non-random occurrence of ocular coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies and deafness (OMIM #214800). Almost all patients with CHARGE association are sporadic and its cause was unknown. We and others hypothesized that CHARGE association is due to a genomic microdeletion or to a mutation in a gene affecting early embryonic development. In this study array- based comparative genomic hybridization (array CGH) was used to screen patients with CHARGE association for submicroscopic DNA copy number alterations. De novo overlapping microdeletions in 8q12 were identified in two patients on a genome-wide 1 Mb resolution BAC array. A 2.3 Mb region of deletion overlap was defined using a tiling resolution chromosome 8 microarray. Sequence analysis of genes residing within this critical region revealed mutations in the CHD7 gene in 10 of the 17 CHARGE patients without microdeletions, including 7 heterozygous stop-codon mutations. -
1 Supporting Information for a Microrna Network Regulates
Supporting Information for A microRNA Network Regulates Expression and Biosynthesis of CFTR and CFTR-ΔF508 Shyam Ramachandrana,b, Philip H. Karpc, Peng Jiangc, Lynda S. Ostedgaardc, Amy E. Walza, John T. Fishere, Shaf Keshavjeeh, Kim A. Lennoxi, Ashley M. Jacobii, Scott D. Rosei, Mark A. Behlkei, Michael J. Welshb,c,d,g, Yi Xingb,c,f, Paul B. McCray Jr.a,b,c Author Affiliations: Department of Pediatricsa, Interdisciplinary Program in Geneticsb, Departments of Internal Medicinec, Molecular Physiology and Biophysicsd, Anatomy and Cell Biologye, Biomedical Engineeringf, Howard Hughes Medical Instituteg, Carver College of Medicine, University of Iowa, Iowa City, IA-52242 Division of Thoracic Surgeryh, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada-M5G 2C4 Integrated DNA Technologiesi, Coralville, IA-52241 To whom correspondence should be addressed: Email: [email protected] (M.J.W.); yi- [email protected] (Y.X.); Email: [email protected] (P.B.M.) This PDF file includes: Materials and Methods References Fig. S1. miR-138 regulates SIN3A in a dose-dependent and site-specific manner. Fig. S2. miR-138 regulates endogenous SIN3A protein expression. Fig. S3. miR-138 regulates endogenous CFTR protein expression in Calu-3 cells. Fig. S4. miR-138 regulates endogenous CFTR protein expression in primary human airway epithelia. Fig. S5. miR-138 regulates CFTR expression in HeLa cells. Fig. S6. miR-138 regulates CFTR expression in HEK293T cells. Fig. S7. HeLa cells exhibit CFTR channel activity. Fig. S8. miR-138 improves CFTR processing. Fig. S9. miR-138 improves CFTR-ΔF508 processing. Fig. S10. SIN3A inhibition yields partial rescue of Cl- transport in CF epithelia. -
Maria Barthmes, Andre Bazzone, Ulrich Thomas, Andrea Brüggemann, Michael George, Niels Fertig, Alison Obergrussberger
Label-free analysis of Na+/Ca2+- exchanger (NCX) isolated from iPSC-derived cardiomyocytes Maria Barthmes, Andre Bazzone, Ulrich Thomas, Andrea Brüggemann, Michael George, Niels Fertig, Alison Obergrussberger Nanion Technologies GmbH, Ganghoferstr. 70A, 80339 Munich, Germany, contact: [email protected] Abstract Measuring NCX activity in human iPSC derived The Sodium-Calcium Exchangers (NCX) play an To drive the progress in pharmacological NCX cardiomyocytes important role in the cellular calcium research, new methods to measure NCX Human iPSC derived cardiomyocytes are being with high fluidic speed, the cells detached homeostasis under physiological and function are needed. At the current time, investigated as a model for cardiac safety again, but a sheet of the cell membrane pathological conditions. NCX has been of functional investigation of NCX range from assessment. To measure native NCX in these remains on the sensor. NCX currents can be interest as a pharmacological target for many patch-clamp, calcium flux assays, Langendorff- cardiomyocytes a cell based assay was evoked in these sheets. For a higher NCX signal years, in particular because clinical trials perfused hearts to studies in whole animals. We developed. Cardiomyocytes were detached female cardiomyocytes were used. This method involving inhibitors of the sodium-proton have developed an electrophysiological from the culture dish and added to the lipid enables the efficient investigation of the isolated exchanger, NHE, have delivered mixed results. method to investigate NCX function which is coated SSM sensor. Where the cell connected cardiac NCX current in a native membrane. Inhibition of the reversed mode of NCX is based on the solid supported membrane (SSM) with the lipid layer. -
Early-Stage Dynamics of Chloride Ion–Pumping Rhodopsin Revealed by a Femtosecond X-Ray Laser
Early-stage dynamics of chloride ion–pumping rhodopsin revealed by a femtosecond X-ray laser Ji-Hye Yuna,1, Xuanxuan Lib,c,1, Jianing Yued, Jae-Hyun Parka, Zeyu Jina, Chufeng Lie, Hao Hue, Yingchen Shib,c, Suraj Pandeyf, Sergio Carbajog, Sébastien Boutetg, Mark S. Hunterg, Mengning Liangg, Raymond G. Sierrag, Thomas J. Laneg, Liang Zhoud, Uwe Weierstalle, Nadia A. Zatsepine,h, Mio Ohkii, Jeremy R. H. Tamei, Sam-Yong Parki, John C. H. Spencee, Wenkai Zhangd, Marius Schmidtf,2, Weontae Leea,2, and Haiguang Liub,d,2 aDepartment of Biochemistry, College of Life Sciences and Biotechnology, Yonsei University, Seodaemun-gu, 120-749 Seoul, South Korea; bComplex Systems Division, Beijing Computational Science Research Center, Haidian, 100193 Beijing, People’s Republic of China; cDepartment of Engineering Physics, Tsinghua University, 100086 Beijing, People’s Republic of China; dDepartment of Physics, Beijing Normal University, Haidian, 100875 Beijing, People’s Republic of China; eDepartment of Physics, Arizona State University, Tempe, AZ 85287; fPhysics Department, University of Wisconsin, Milwaukee, Milwaukee, WI 53201; gLinac Coherent Light Source, Stanford Linear Accelerator Center National Accelerator Laboratory, Menlo Park, CA 94025; hDepartment of Chemistry and Physics, Australian Research Council Centre of Excellence in Advanced Molecular Imaging, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia; and iDrug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, 230-0045 Yokohama, Japan Edited by Nicholas K. Sauter, Lawrence Berkeley National Laboratory, Berkeley, CA, and accepted by Editorial Board Member Axel T. Brunger February 21, 2021 (received for review September 30, 2020) Chloride ion–pumping rhodopsin (ClR) in some marine bacteria uti- an acceptor aspartate (13–15). -
Subterranean Mammals Show Convergent Regression in Ocular Genes and Enhancers, Along with Adaptation to Tunneling
RESEARCH ARTICLE Subterranean mammals show convergent regression in ocular genes and enhancers, along with adaptation to tunneling Raghavendran Partha1, Bharesh K Chauhan2,3, Zelia Ferreira1, Joseph D Robinson4, Kira Lathrop2,3, Ken K Nischal2,3, Maria Chikina1*, Nathan L Clark1* 1Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, United States; 2UPMC Eye Center, Children’s Hospital of Pittsburgh, Pittsburgh, United States; 3Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, United States; 4Department of Molecular and Cell Biology, University of California, Berkeley, United States Abstract The underground environment imposes unique demands on life that have led subterranean species to evolve specialized traits, many of which evolved convergently. We studied convergence in evolutionary rate in subterranean mammals in order to associate phenotypic evolution with specific genetic regions. We identified a strong excess of vision- and skin-related genes that changed at accelerated rates in the subterranean environment due to relaxed constraint and adaptive evolution. We also demonstrate that ocular-specific transcriptional enhancers were convergently accelerated, whereas enhancers active outside the eye were not. Furthermore, several uncharacterized genes and regulatory sequences demonstrated convergence and thus constitute novel candidate sequences for congenital ocular disorders. The strong evidence of convergence in these species indicates that evolution in this environment is recurrent and predictable and can be used to gain insights into phenotype–genotype relationships. DOI: https://doi.org/10.7554/eLife.25884.001 *For correspondence: [email protected] (MC); [email protected] (NLC) Competing interests: The Introduction authors declare that no The subterranean habitat has been colonized by numerous animal species for its shelter and unique competing interests exist. -
Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights Froma Highly Derived Visual Phenotype Rui Borges Universidade Do Porto - Portugal
Nova Southeastern University NSUWorks Biology Faculty Articles Department of Biological Sciences 8-22-2019 Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights froma Highly Derived Visual Phenotype Rui Borges Universidade do Porto - Portugal Joao Fonseca Universidade do Porto - Portugal Cidalia Gomes Universidade do Porto - Portugal Warren E. Johnson Smithsonian Institution Stephen James O'Brien St. Petersburg State University - Russia; Nova Southeastern University, [email protected] See next page for additional authors Follow this and additional works at: https://nsuworks.nova.edu/cnso_bio_facarticles Part of the Biology Commons NSUWorks Citation Borges, Rui; Joao Fonseca; Cidalia Gomes; Warren E. Johnson; Stephen James O'Brien; Guojie Zhang; M. Thomas P. Gilbert; Erich D. Jarvis; and Agostinho Antunes. 2019. "Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights froma Highly Derived Visual Phenotype." Genome Biology and Evolution 11, (8): 2244-2255. doi:10.1093/gbe/evz111. This Article is brought to you for free and open access by the Department of Biological Sciences at NSUWorks. It has been accepted for inclusion in Biology Faculty Articles by an authorized administrator of NSUWorks. For more information, please contact [email protected]. Authors Rui Borges, Joao Fonseca, Cidalia Gomes, Warren E. Johnson, Stephen James O'Brien, Guojie Zhang, M. Thomas P. Gilbert, Erich D. Jarvis, and Agostinho Antunes This article is available at NSUWorks: https://nsuworks.nova.edu/cnso_bio_facarticles/982 GBE Avian Binocularity and Adaptation to Nocturnal Environments: Genomic Insights from a Highly Derived Visual Downloaded from https://academic.oup.com/gbe/article-abstract/11/8/2244/5544263 by Nova Southeastern University/HPD Library user on 16 September 2019 Phenotype Rui Borges1,2,Joao~ Fonseca1,Cidalia Gomes1, Warren E. -
Optogenetics and Its Application in Neural Degeneration and Regeneration
3/13/2018 Optogenetics and its application in neural degeneration and regeneration Neural Regen Res. 2017 Aug; 12(8): 1197–1209. PMCID: PMC5607808 doi: 10.4103/1673-5374.213532 Optogenetics and its application in neural degeneration and regeneration Josue D. Ordaz,1,2,3 Wei Wu,1,2,3 and Xiao-Ming Xu, M.D., Ph.D.1,2,3,4,* 1 Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA 2 Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, USA 3 Goodman Campbell Brain and Spine, Indianapolis, Indiana, USA 4 Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA * Correspondence to: Xiao-Ming Xu, [email protected]. Author contributions: JDO wrote the paper. JDO and WW were responsible for making figures and edited the paper. XMX reviewed and edited the paper. All authors participated in the conception of this study and approved the final version of this paper. Accepted 2017 Jul 11. Copyright : © Neural Regeneration Research This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. Abstract Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. -
University of London Thesis
REFERENCE ONLY UNIVERSITY OF LONDON THESIS Degree pWvO Y e a r Name of Author ^ COPYRIGHT This is a thesis accepted for a Higher Degree of the University of London. It is an unpublished typescript and the copyright is held by the author. All persons consulting the thesis must read and abide by the Copyright Declaration below. COPYRIGHT DECLARATION I recognise that the copyright of the above-described thesis rests with the author and that no quotation from it or information derived from it may be published without the prior written consent of the author. LOANS Theses may not be lent to individuals, but the Senate House Library may lend a copy to approved libraries within the United Kingdom, for consultation solely on the premises of those libraries. Application should be made to: Inter-Library Loans, Senate House Library, Senate House, Malet Street, London WC1E 7HU. REPRODUCTION University of London theses may not be reproduced without explicit written permission from the Senate House Library. Enquiries should be addressed to the Theses Section of the Library. Regulations concerning reproduction vary according to the date of acceptance of the thesis and are listed below as guidelines. A. Before 1962. Permission granted only upon the prior written consent of the author. (The Senate House Library will provide addresses where possible). B. 1962 - 1974. In many cases the author has agreed to permit copying upon completion of a Copyright Declaration. C. 1975 - 1988. Most theses may be copied upon completion of a Copyright Declaration. D. 1989 onwards. Most theses may be copied. This thesis comes within category D. -
The Alter Retina: Alternative Splicing of Retinal Genes in Health and Disease
International Journal of Molecular Sciences Review The Alter Retina: Alternative Splicing of Retinal Genes in Health and Disease Izarbe Aísa-Marín 1,2 , Rocío García-Arroyo 1,3 , Serena Mirra 1,2 and Gemma Marfany 1,2,3,* 1 Departament of Genetics, Microbiology and Statistics, Avda. Diagonal 643, Universitat de Barcelona, 08028 Barcelona, Spain; [email protected] (I.A.-M.); [email protected] (R.G.-A.); [email protected] (S.M.) 2 Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Universitat de Barcelona, 08028 Barcelona, Spain 3 Institute of Biomedicine (IBUB, IBUB-IRSJD), Universitat de Barcelona, 08028 Barcelona, Spain * Correspondence: [email protected] Abstract: Alternative splicing of mRNA is an essential mechanism to regulate and increase the diversity of the transcriptome and proteome. Alternative splicing frequently occurs in a tissue- or time-specific manner, contributing to differential gene expression between cell types during development. Neural tissues present extremely complex splicing programs and display the highest number of alternative splicing events. As an extension of the central nervous system, the retina constitutes an excellent system to illustrate the high diversity of neural transcripts. The retina expresses retinal specific splicing factors and produces a large number of alternative transcripts, including exclusive tissue-specific exons, which require an exquisite regulation. In fact, a current challenge in the genetic diagnosis of inherited retinal diseases stems from the lack of information regarding alternative splicing of retinal genes, as a considerable percentage of mutations alter splicing Citation: Aísa-Marín, I.; or the relative production of alternative transcripts. Modulation of alternative splicing in the retina García-Arroyo, R.; Mirra, S.; Marfany, is also instrumental in the design of novel therapeutic approaches for retinal dystrophies, since it G. -
Gene Expression in the Mouse Eye: an Online Resource for Genetics Using 103 Strains of Mice
Molecular Vision 2009; 15:1730-1763 <http://www.molvis.org/molvis/v15/a185> © 2009 Molecular Vision Received 3 September 2008 | Accepted 25 August 2009 | Published 31 August 2009 Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice Eldon E. Geisert,1 Lu Lu,2 Natalie E. Freeman-Anderson,1 Justin P. Templeton,1 Mohamed Nassr,1 Xusheng Wang,2 Weikuan Gu,3 Yan Jiao,3 Robert W. Williams2 (First two authors contributed equally to this work) 1Department of Ophthalmology and Center for Vision Research, Memphis, TN; 2Department of Anatomy and Neurobiology and Center for Integrative and Translational Genomics, Memphis, TN; 3Department of Orthopedics, University of Tennessee Health Science Center, Memphis, TN Purpose: Individual differences in patterns of gene expression account for much of the diversity of ocular phenotypes and variation in disease risk. We examined the causes of expression differences, and in their linkage to sequence variants, functional differences, and ocular pathophysiology. Methods: mRNAs from young adult eyes were hybridized to oligomer microarrays (Affymetrix M430v2). Data were embedded in GeneNetwork with millions of single nucleotide polymorphisms, custom array annotation, and information on complementary cellular, functional, and behavioral traits. The data include male and female samples from 28 common strains, 68 BXD recombinant inbred lines, as well as several mutants and knockouts. Results: We provide a fully integrated resource to map, graph, analyze, and test causes and correlations of differences in gene expression in the eye. Covariance in mRNA expression can be used to infer gene function, extract signatures for different cells or tissues, to define molecular networks, and to map quantitative trait loci that produce expression differences. -
The Role of Chx10 in the Development of the Vertebrate Retina
T h e r o l e o f c h x io in t h e development OF THE VERTEBRATE RETINA Adam David Rutherford A thesis submitted for the degree of Doctor of Philosophy University College London University of London, 2001 Developmental Biology Unit Institute of Child Health and Department of Biology University College London 30 Guilford St London, WC1N 1EH ProQuest Number: U642609 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U642609 Published by ProQuest LLC(2015). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 A b s t r a c t The role of Chx10 in the development of the vertebrate retina Complex interactions between intrinsic and extrinsic factors regulate the development of the retina from multipotential progenitor cells to the highly organised, mature tissue. Many genes are known to be essential to this process. Chx10 is a homeodomain transcription factor that is essential for the development of the retina and eye in many vertebrate species. Based on previous work embracing ChxW gene expression patterns and the analysis of the mutant mouse , which has a null mutation in ChxW, the established roles of Chx10 in eye development include promotion of cellular proliferation in the neuroblastic retina, specification of bipolar interneurons in the differentiating retina, and maintenance of bipolar cells in the mature retina. -
Ligand-Specific Transcriptional Mechanisms Underlie Aryl Hydrocarbon Receptor-Mediated Developmental Toxicity of Oxygenated Pahs
Ligand-specific transcriptional mechanisms underlie aryl hydrocarbon receptor-mediated developmental toxicity of oxygenated PAHs Goodale, B.C.* †, La Du, J. *, Tilton, S.C.* ‡, Sullivan, C.M.* §, Bisson, W.H. *, Waters, K.M. ‡ and Tanguay, R.L.* *Department of Environmental and Molecular Toxicology, the Environmental Health Sciences Center, Oregon State University, Corvallis, OR, 97330 †Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, 604 Remsen Bldg., Hanover, NH 03755 ‡Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99354 §Center for Genome Research and Biocomputing, Oregon State University, Corvallis, OR, 97330 Corresponding author: Robert Tanguay, Ph.D., Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97330. Email: [email protected] Abstract Polycyclic aromatic hydrocarbons (PAHs) are priority environmental contaminants that exhibit mutagenic, carcinogenic, proinflammatory and teratogenic properties. Oxygen-substituted PAHs (OPAHs) are formed during combustion processes and via phototoxidation and biological degradation of parent (unsubstituted) PAHs. Despite their prevalence both in contaminated industrial sites and in urban air, OPAH mechanisms of action in biological systems are relatively understudied. Like parent PAHs, OPAHs exert structure-dependent mutagenic activities and activation of the aryl hydrocarbon receptor (AHR) and cytochrome p450 metabolic pathway (CYP1A). Four-ring OPAHs 1,9-benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) cause morphological aberrations and induce markers of oxidative stress in developing zebrafish with similar potency, but only 7,12-B[a]AQ induces robust Cyp1a protein expression. We investigated the role of the AHR in mediating the toxicity of BEZO and 7,12-B[a]AQ, and found that knockdown of AHR2 rescued developmental effects caused by both compounds.