Genetic Heterogeneity of Motor Neuropathies
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Targeted Genes and Methodology Details for Neuromuscular Genetic Panels
Targeted Genes and Methodology Details for Neuromuscular Genetic Panels Reference transcripts based on build GRCh37 (hg19) interrogated by Neuromuscular Genetic Panels Next-generation sequencing (NGS) and/or Sanger sequencing is performed Motor Neuron Disease Panel to test for the presence of a mutation in these genes. Gene GenBank Accession Number Regions of homology, high GC-rich content, and repetitive sequences may ALS2 NM_020919 not provide accurate sequence. Therefore, all reported alterations detected ANG NM_001145 by NGS are confirmed by an independent reference method based on laboratory developed criteria. However, this does not rule out the possibility CHMP2B NM_014043 of a false-negative result in these regions. ERBB4 NM_005235 Sanger sequencing is used to confirm alterations detected by NGS when FIG4 NM_014845 appropriate.(Unpublished Mayo method) FUS NM_004960 HNRNPA1 NM_031157 OPTN NM_021980 PFN1 NM_005022 SETX NM_015046 SIGMAR1 NM_005866 SOD1 NM_000454 SQSTM1 NM_003900 TARDBP NM_007375 UBQLN2 NM_013444 VAPB NM_004738 VCP NM_007126 ©2018 Mayo Foundation for Medical Education and Research Page 1 of 14 MC4091-83rev1018 Muscular Dystrophy Panel Muscular Dystrophy Panel Gene GenBank Accession Number Gene GenBank Accession Number ACTA1 NM_001100 LMNA NM_170707 ANO5 NM_213599 LPIN1 NM_145693 B3GALNT2 NM_152490 MATR3 NM_199189 B4GAT1 NM_006876 MYH2 NM_017534 BAG3 NM_004281 MYH7 NM_000257 BIN1 NM_139343 MYOT NM_006790 BVES NM_007073 NEB NM_004543 CAPN3 NM_000070 PLEC NM_000445 CAV3 NM_033337 POMGNT1 NM_017739 CAVIN1 NM_012232 POMGNT2 -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Epistasis-Driven Identification of SLC25A51 As a Regulator of Human
ARTICLE https://doi.org/10.1038/s41467-020-19871-x OPEN Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import Enrico Girardi 1, Gennaro Agrimi 2, Ulrich Goldmann 1, Giuseppe Fiume1, Sabrina Lindinger1, Vitaly Sedlyarov1, Ismet Srndic1, Bettina Gürtl1, Benedikt Agerer 1, Felix Kartnig1, Pasquale Scarcia 2, Maria Antonietta Di Noia2, Eva Liñeiro1, Manuele Rebsamen1, Tabea Wiedmer 1, Andreas Bergthaler1, ✉ Luigi Palmieri2,3 & Giulio Superti-Furga 1,4 1234567890():,; About a thousand genes in the human genome encode for membrane transporters. Among these, several solute carrier proteins (SLCs), representing the largest group of transporters, are still orphan and lack functional characterization. We reasoned that assessing genetic interactions among SLCs may be an efficient way to obtain functional information allowing their deorphanization. Here we describe a network of strong genetic interactions indicating a contribution to mitochondrial respiration and redox metabolism for SLC25A51/MCART1, an uncharacterized member of the SLC25 family of transporters. Through a combination of metabolomics, genomics and genetics approaches, we demonstrate a role for SLC25A51 as enabler of mitochondrial import of NAD, showcasing the potential of genetic interaction- driven functional gene deorphanization. 1 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria. 2 Laboratory of Biochemistry and Molecular Biology, Department of Biosciences, Biotechnologies and Biopharmaceutics, -
Pax6 Interactions with Chromatin and Identification of Its Novel Direct Target Genes in Lens and Forebrain
Pax6 Interactions with Chromatin and Identification of Its Novel Direct Target Genes in Lens and Forebrain Qing Xie1., Ying Yang1., Jie Huang4, Jovica Ninkovic5,6, Tessa Walcher5,6, Louise Wolf2, Ariel Vitenzon2, Deyou Zheng1,3, Magdalena Go¨ tz5,6, David C. Beebe4, Jiri Zavadil7¤, Ales Cvekl1,2* 1 The Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, United States of America, 2 The Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, New York, United States of America, 3 The Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, United States of America, 4 Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America, 5 Helmholtz Zentrum Munchen, Institute of Stem Cell Research, Ingolsta¨dter Landstraße 1, Neuherberg, Germany, 6 Institute of Physiology, Department of Physiological Genomics, Ludwig-Maximilians-University Munich, Munich Center for Integrated Protein Science CiPS, Munich, Germany, 7 Department of Pathology, New York University Langone Medical Center, New York, New York, United States of America Abstract Pax6 encodes a specific DNA-binding transcription factor that regulates the development of multiple organs, including the eye, brain and pancreas. Previous studies have shown that Pax6 regulates the entire process of ocular lens development. In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific populations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification in telencephalon. In the pancreas, Pax6 is essential for the differentiation of a-, b-andd-islet cells. To elucidate molecular roles of Pax6, chromatin immunoprecipitation experiments combined with high-density oligonucleotide array hybridizations (ChIP-chip) were performed using three distinct sources of chromatin (lens, forebrain and b-cells). -
Deciphering the Functional and Molecular Differences Between MTM1 and MTMR2 to Better Understand Two Neuromuscular Diseases Matthieu Raess
Deciphering the functional and molecular differences between MTM1 and MTMR2 to better understand two neuromuscular diseases Matthieu Raess To cite this version: Matthieu Raess. Deciphering the functional and molecular differences between MTM1 and MTMR2 to better understand two neuromuscular diseases. Genomics [q-bio.GN]. Université de Strasbourg, 2017. English. NNT : 2017STRAJ088. tel-03081300 HAL Id: tel-03081300 https://tel.archives-ouvertes.fr/tel-03081300 Submitted on 18 Dec 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE DES SCIENCES DE LA VIE ET DE LA SANTE (ED 414) Génétique Moléculaire, Génomique, Microbiologie (GMGM) – UMR 7156 & Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) UMR 7104 – INSERM U 964 THÈSE présentée par : Matthieu RAESS soutenue le : 13 octobre 2017 pour obtenir le grade de : Docteur de l’université de Strasbourg Discipline/ Spécialité : Aspects moléculaires et cellulaires de la biologie Deciphering the functional and molecular differences between MTM1 and MTMR2 to better understand two neuromuscular diseases. THÈSE dirigée par : Mme FRIANT Sylvie Directrice de recherche, Université de Strasbourg & Mme COWLING Belinda Chargée de recherche, Université de Strasbourg RAPPORTEURS : Mme BOLINO Alessandra Directrice de recherche, Institut San Raffaele de Milan M. -
Comparison of Human Solute Carriers
Comparison of human solute carriers Avner Schlessinger,1,2,3* Pa¨ r Matsson,1,2,3 James E. Shima,1,2,3,4 Ursula Pieper,1,2,3 Sook Wah Yee,1,2,3 Libusha Kelly,1,2,3,5 Leonard Apeltsin,1,2,3,5 Robert M. Stroud,6 Thomas E. Ferrin,1,2,3 Kathleen M. Giacomini,1,2,3 and Andrej Sali1,2,3* 1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California 2Department of Pharmaceutical Chemistry, University of California, San Francisco, California 3California Institute for Quantitative Biosciences, University of California, San Francisco, California 4Graduate Program in Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, California 5Graduate Program in Biological and Medical Informatics, University of California, San Francisco, California 6Department of Biochemistry and Biophysics, University of California, San Francisco, California Received 14 August 2009; Revised 10 December 2009; Accepted 14 December 2009 DOI: 10.1002/pro.320 Published online 5 January 2010 proteinscience.org Abstract: Solute carriers are eukaryotic membrane proteins that control the uptake and efflux of solutes, including essential cellular compounds, environmental toxins, and therapeutic drugs. Solute carriers can share similar structural features despite weak sequence similarities. Identification of sequence relationships among solute carriers is needed to enhance our ability to model individual carriers and to elucidate the molecular mechanisms of their substrate specificity and transport. Here, we describe a comprehensive comparison of solute carriers. We link the proteins using sensitive profile–profile alignments and two classification approaches, including similarity networks. The clusters are analyzed in view of substrate type, transport mode, organism conservation, and tissue specificity. -
Frontiersin.Org 1 April 2015 | Volume 9 | Article 123 Saunders Et Al
ORIGINAL RESEARCH published: 28 April 2015 doi: 10.3389/fnins.2015.00123 Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study Norman R. Saunders 1*, Katarzyna M. Dziegielewska 1, Kjeld Møllgård 2, Mark D. Habgood 1, Matthew J. Wakefield 3, Helen Lindsay 4, Nathalie Stratzielle 5, Jean-Francois Ghersi-Egea 5 and Shane A. Liddelow 1, 6 1 Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, VIC, Australia, 2 Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark, 3 Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia, 4 Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland, 5 Lyon Neuroscience Research Center, INSERM U1028, Centre National de la Recherche Scientifique UMR5292, Université Lyon 1, Lyon, France, 6 Department of Neurobiology, Stanford University, Stanford, CA, USA The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq Edited by: Joana A. Palha, was performed at embryonic day (E) 15 and adult with additional data obtained at University of Minho, Portugal intermediate ages from microarray analysis. The largest represented functional group Reviewed by: in the embryo was amino acid transporters (twelve) with expression levels 2–98 times Fernanda Marques, University of Minho, Portugal greater than in the adult. In contrast, in the adult only six amino acid transporters Hanspeter Herzel, were up-regulated compared to the embryo and at more modest enrichment levels Humboldt University, Germany (<5-fold enrichment above E15). -
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Vesterlund et al. BMC Developmental Biology 2011, 11:30 http://www.biomedcentral.com/1471-213X/11/30 RESEARCHARTICLE Open Access The zebrafish transcriptome during early development Liselotte Vesterlund1,2*, Hong Jiao1,2, Per Unneberg1, Outi Hovatta3 and Juha Kere1,2,4 Abstract Background: The transition from fertilized egg to embryo is accompanied by a multitude of changes in gene expression, and the transcriptional events that underlie these processes have not yet been fully characterized. In this study RNA-Seq is used to compare the transcription profiles of four early developmental stages in zebrafish (Danio rerio) on a global scale. Results: An average of 79 M total reads were detected from the different stages. Out of the total number of reads 65% - 73% reads were successfully mapped and 36% - 44% out of those were uniquely mapped. The total number of detected unique gene transcripts was 11187, of which 10096 were present at 1-cell stage. The largest number of common transcripts was observed between 1-cell stage and 16-cell stage. An enrichment of gene transcripts with molecular functions of DNA binding, protein folding and processing as well as metal ion binding was observed with progression of development. The sequence data (accession number ERP000635) is available at the European Nucleotide Archive. Conclusion: Clustering of expression profiles shows that a majority of the detected gene transcripts are present at steady levels, and thus a minority of the gene transcripts clusters as increasing or decreasing in expression over the four investigated developmental stages. The three earliest developmental stages were similar when comparing highly expressed genes, whereas the 50% epiboly stage differed from the other three stages in the identity of highly expressed genes, number of uniquely expressed genes and enrichment of GO molecular functions. -
Lipid Phosphatases Identified by Screening a Mouse Phosphatase Shrna Library Regulate T-Cell Differentiation and Protein Kinase
Lipid phosphatases identified by screening a mouse PNAS PLUS phosphatase shRNA library regulate T-cell differentiation and Protein kinase B AKT signaling Liying Guoa, Craig Martensb, Daniel Brunob, Stephen F. Porcellab, Hidehiro Yamanea, Stephane M. Caucheteuxa, Jinfang Zhuc, and William E. Paula,1 aCytokine Biology Unit, cMolecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and bGenomics Unit, Research Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840 Contributed by William E. Paul, March 27, 2013 (sent for review December 18, 2012) Screening a complete mouse phosphatase lentiviral shRNA library production (10, 11). Conversely, constitutive expression of active using high-throughput sequencing revealed several phosphatases AKT leads to increased proliferation and enhanced Th1/Th2 cy- that regulate CD4 T-cell differentiation. We concentrated on two lipid tokine production (12). phosphatases, the myotubularin-related protein (MTMR)9 and -7. The amount of PI[3,4,5]P3 and the level of AKT activation are Silencing MTMR9 by shRNA or siRNA resulted in enhanced T-helper tightly controlled by several mechanisms, including breakdown of (Th)1 differentiation and increased Th1 protein kinase B (PKB)/AKT PI[3,4,5]P3, down-regulation of the amount and activity of PI3K, phosphorylation while silencing MTMR7 caused increased Th2 and and the dephosphorylation of AKT (13). PTEN is a major negative Th17 differentiation and increased AKT phosphorylation in these regulator of PI[3,4,5]P3. It removes the 3-phosphate from the cells. -
Diseases Caused by Mutations in Mitochondrial Carrier Genes SLC25: a Review
1 SUPPLEMENTARY MATERIAL TO: Diseases caused by mutations in mitochondrial carrier genes SLC25: a review Authors: Ferdinando Palmieri1,*, Pasquale Scarcia1 and Magnus Monné1,2,* Affiliations: 1Department of Biosciences, Biotechnologies and Biopharmaceutics, Laboratory of Biochemistry and Molecular Biology, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy, 2Department of Sciences, University of Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy *Corresponding authors: F. Palmieri (Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via E. Orabona 4, 70125 Bari, Italy, 0039- 0805443323, [email protected]) and M. Monné (Department of Sciences, University of Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy, [email protected]). Table S1. Disease-causing mutations in mitochondrial carriers. For each gene/carrier the mutations are listed in the following order: first the nonsense, deletion/insertion and splicing mutations, and afterwards the missense mutations. Mitochondrial Disease-associated Mutation effect in Homo- / References carrier mutation the protein (or Hetero- problem in zygous splicing) patients SLC25A1, CIC c.18_24dup p.Ala9Profs*82 2/1 (1) (2) c.517_526del p.Arg173Glyfs*2 1/1 (1) (3) c.648_655del p.Met218Serfs*25 0/1 (3) c.768C > G p.Tyr256* 0/1 (1) Position in c.821C > T p.Ala274Ilefs*24 2/4 (1) Fig. 2 10 c.82G > A p.Ala28Thr 0/1 (3) 22 c.119T > A p.Ile40Asn 0/1 (3) 27 c.134C > T p.Pro45Leu 0/2 (1)(2) 29 c.139G > A p.Glu47Lys 1/0 (3) 55 c.205G > T p.Asp69Tyr -
The SLC25 Carrier Family: Important Transport Proteins in Mitochondrial Physiology and Pathology
University of Groningen The SLC25 Carrier Family Kunji, Edmund R S; King, Martin S; Ruprecht, Jonathan J; Thangaratnarajah, Chancievan Published in: Physiology DOI: 10.1152/physiol.00009.2020 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2020 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Kunji, E. R. S., King, M. S., Ruprecht, J. J., & Thangaratnarajah, C. (2020). The SLC25 Carrier Family: Important Transport Proteins in Mitochondrial Physiology and Pathology. Physiology, 35(5), 302-327. https://doi.org/10.1152/physiol.00009.2020 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. -
For Peer Review 19 Rafael Pulido1,2, Andrew W
Human Molecular Genetics PTPs emerge as PIPs: protein tyrosine phosphatases with lipid-phosphatase activities in human disease Journal: Human Molecular Genetics Manuscript ID: Draft Manuscript ForType: 4 Invited Peer Review Article Review Date Submitted by the Author: n/a Complete List of Authors: Pulido, Rafael; Biocruces Health Research Institute, Molecular Signaling and Cancer Stoker, Andrew; Institute of Child Health, University College London, Neural Development Unit Hendriks, Wiljan; Radboud University Nijmegen Medical Centre, Department of Cell Biology Key Words: phosphatase, phosphorylation, hereditary disease, cancer Page 1 of 28 Human Molecular Genetics 1 2 3 4 5 6 7 8 9 10 PTPs emerge as PIPs: protein tyrosine phosphatases with lipid‐ 11 12 phosphatase activities in human disease 13 14 15 16 17 18 For Peer Review 19 Rafael Pulido1,2, Andrew W. Stoker3, Wiljan J.A.J. Hendriks4 20 21 22 23 1BioCruces Health Research Institute, 48903 Barakaldo, Spain 24 25 2 26 IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain 27 28 3Neural Development Unit, Institute of Child Health, University College London, WC1N 1EH 29 30 London, UK 31 32 4Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud 33 University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands 34 35 36 37 38 Correspondence to: 39 40 Rafael Pulido; Biocruces Health Research Institute; Plaza Cruces s/n, 48903 Barakaldo, Spain. 41 Email: [email protected] 42 43 Wiljan J.A.J. Hendriks; Nijmegen Centre for Molecular Life Sciences, Radboud University 44 Nijmegen Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands. 45 Email: [email protected] 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 Human Molecular Genetics Page 2 of 28 1 2 3 Abstract 4 5 Protein tyrosine phosphatases (PTPs) constitute a family of key homeostatic regulators, with 6 7 wide implications on physiology and disease.