VAMP4 (NM 003762) Human Recombinant Protein Product Data

Total Page:16

File Type:pdf, Size:1020Kb

VAMP4 (NM 003762) Human Recombinant Protein Product Data OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP302734 VAMP4 (NM_003762) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Recombinant protein of human vesicle-associated membrane protein 4 (VAMP4) Species: Human Expression Host: HEK293T Tag: C-Myc/DDK Predicted MW: 16.2 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25 mM Tris.HCl, pH 7.3, 100 mM glycine, 10% glycerol Preparation: Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. Storage: Store at -80°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_003753 Locus ID: 8674 UniProt ID: O75379, Q6IAZ3 RefSeq Size: 5155 Cytogenetics: 1q24.3 RefSeq ORF: 363 Synonyms: VAMP-4; VAMP24 Summary: Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. This protein may play a role in trans-Golgi network-to-endosome transport. [provided by RefSeq, Jul 2008] This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 VAMP4 (NM_003762) Human Recombinant Protein – TP302734 Protein Families: Transmembrane Protein Pathways: SNARE interactions in vesicular transport Product images: Coomassie blue staining of purified VAMP4 protein (Cat# TP302734). The protein was produced from HEK293T cells transfected with VAMP4 cDNA clone (Cat# [RC202734]) using MegaTran 2.0 (Cat# [TT210002]). This product is to be used for laboratory only. Not for diagnostic or therapeutic use. ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 2 / 2.
Recommended publications
  • The Endocytic Membrane Trafficking Pathway Plays a Major Role
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Liverpool Repository RESEARCH ARTICLE The Endocytic Membrane Trafficking Pathway Plays a Major Role in the Risk of Parkinson’s Disease Sara Bandres-Ciga, PhD,1,2 Sara Saez-Atienzar, PhD,3 Luis Bonet-Ponce, PhD,4 Kimberley Billingsley, MSc,1,5,6 Dan Vitale, MSc,7 Cornelis Blauwendraat, PhD,1 Jesse Raphael Gibbs, PhD,7 Lasse Pihlstrøm, MD, PhD,8 Ziv Gan-Or, MD, PhD,9,10 The International Parkinson’s Disease Genomics Consortium (IPDGC), Mark R. Cookson, PhD,4 Mike A. Nalls, PhD,1,11 and Andrew B. Singleton, PhD1* 1Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 2Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain 3Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 4Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 5Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom 6Department of Pathophysiology, University of Tartu, Tartu, Estonia 7Computational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA 8Department of Neurology, Oslo University Hospital, Oslo, Norway 9Department of Neurology and Neurosurgery, Department of Human Genetics, McGill University, Montréal, Quebec, Canada 10Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada 11Data Tecnica International, Glen Echo, Maryland, USA ABSTRACT studies, summary-data based Mendelian randomization Background: PD is a complex polygenic disorder.
    [Show full text]
  • 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.
    [Show full text]
  • Miz1 Is Required to Maintain Autophagic Flux
    ARTICLE Received 3 Apr 2013 | Accepted 3 Sep 2013 | Published 3 Oct 2013 DOI: 10.1038/ncomms3535 Miz1 is required to maintain autophagic flux Elmar Wolf1,*, Anneli Gebhardt1,*, Daisuke Kawauchi2, Susanne Walz1, Bjo¨rn von Eyss1, Nicole Wagner3, Christoph Renninger3, Georg Krohne1, Esther Asan3, Martine F. Roussel2 & Martin Eilers1,4 Miz1 is a zinc finger protein that regulates the expression of cell cycle inhibitors as part of a complex with Myc. Cell cycle-independent functions of Miz1 are poorly understood. Here we use a Nestin-Cre transgene to delete an essential domain of Miz1 in the central nervous system (Miz1DPOZNes). Miz1DPOZNes mice display cerebellar neurodegeneration characterized by the progressive loss of Purkinje cells. Chromatin immunoprecipitation sequencing and biochemical analyses show that Miz1 activates transcription upon binding to a non-palin- dromic sequence present in core promoters. Target genes of Miz1 encode regulators of autophagy and proteins involved in vesicular transport that are required for autophagy. Miz1DPOZ neuronal progenitors and fibroblasts show reduced autophagic flux. Consistently, polyubiquitinated proteins and p62/Sqtm1 accumulate in the cerebella of Miz1DPOZNes mice, characteristic features of defective autophagy. Our data suggest that Miz1 may link cell growth and ribosome biogenesis to the transcriptional regulation of vesicular transport and autophagy. 1 Theodor Boveri Institute, Biocenter, University of Wu¨rzburg, Am Hubland, 97074 Wu¨rzburg, Germany. 2 Department of Tumor Cell Biology, MS#350, Danny Thomas Research Center, 5006C, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA. 3 Institute for Anatomy and Cell Biology, University of Wu¨rzburg, Koellikerstrasse 6, 97070 Wu¨rzburg, Germany. 4 Comprehensive Cancer Center Mainfranken, Josef-Schneider-Strasse 6, 97080 Wu¨rzburg, Germany.
    [Show full text]
  • Structural Basis for the Interaction of the Golgi-Associated Retrograde Protein Complex with the T-SNARE Syntaxin 6
    Structure Short Article Structural Basis for the Interaction of the Golgi-Associated Retrograde Protein Complex with the t-SNARE Syntaxin 6 Guillermo Abascal-Palacios,1,4 Christina Schindler,2,4 Adriana L. Rojas,1 Juan S. Bonifacino,2,* and Aitor Hierro1,3,* 1Structural Biology Unit, CIC bioGUNE, Bizkaia Technology Park, 48160 Derio, Spain 2Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA 3IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain 4These authors contributed equally to this work *Correspondence: [email protected] (J.S.B.), [email protected] (A.H.) http://dx.doi.org/10.1016/j.str.2013.06.025 SUMMARY (1) capture of transport vesicles in the vicinity of the target organ- elle, and (2) regulation of the fusion event through actions on the The Golgi-Associated Retrograde Protein (GARP) SNAREs. The Golgi-Associated Retrograde Protein (GARP) (also complex is a tethering factor involved in the fusion known as VFT) complex promotes fusion of retrograde transport of endosome-derived transport vesicles to the vesicles derived from endosomes with the trans-Golgi network trans-Golgi network through interaction with compo- (TGN), a critical step for transmembrane proteins that cycle nents of the Syntaxin 6/Syntaxin 16/Vti1a/VAMP4 between these organelles (Bonifacino and Hierro, 2011). GARP SNARE complex. The mechanisms by which GARP is conserved from yeast to humans and consists of four subunits named Vps51 (Ang2 in humans), Vps52, Vps53, and Vps54 (Con- and other tethering factors engage the SNARE fusion ibear and Stevens, 2000; Siniossoglou and Pelham, 2001, 2002; machinery are poorly understood.
    [Show full text]
  • 1 Phosphoproteomics Reveals That the Hvps34 Regulated SGK3 Kinase
    bioRxiv preprint doi: https://doi.org/10.1101/741652; this version posted August 20, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44 Nazma Malik1, 2, Raja S Nirujogi1, Julien Peltier1, 3, Thomas Macartney1, Melanie Wightman1, Alan R Prescott4 , RoBert Gourlay1, Matthias Trost1, 5, Dario R. Alessi1, * Athanasios Karapetsas1, * 1 Medical Research Council (MRC) Protein Phosphorylation and UBiquitylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK 2 Current address: Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 3 Current address: Department of Bioanalysis, Immunogenicity & Biomarkers, GlaxoSmithKline R&D, Park Road, Ware, SG12 0DP, UK 4 Dundee Imaging Facility, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK 5 Current address: Faculty of Medical Sciences, Institute for Cell and Molecular Biosciences, Newcastle upon Tyne NE2 4HH, UK *Correspondence to Athanasios Karapetsas ([email protected]) and Dario R Alessi ([email protected]) Abstract The serum- and glucocorticoid-regulated kinase (SGK) isoforms contriBute resistance to cancer therapies targeting the PI3K pathway. SGKs are homologous to Akt and these kinases display overlapping specificity and phosphorylate several suBstrates at the same residues, such as TSC2 to promote tumor growth By switching on the mTORC1 pathway.
    [Show full text]
  • Supplementary Figures and Table
    SUPPLEMENTARY DATA Supplementary Figure 1. ©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db141 -0066/-/DC1 SUPPLEMENTARY DATA Supplementary Figure 2. ©2014 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db142 -0066/-/DC1 SUPPLEMENTARY DATA -/- Supplementary Table 1. Fold increase of Ser/Thr/Tyr phosphorylation in livers of MKP-3 male mice versus wild type male mice fed on a high fat diet (n=5 for each group). Symbol Name Phosphorylation KO/WT ratio Q Value sites Apoptosis ACIN1 Acin1 protein S64 11.4 0.02 T66 8.3 0.02 API5 Apoptosis inhibitor 5 S461 2.2 0.03 S462 1.8 0.03 AIFM3 Apoptosis-inducing factor 3 S30 7.4 0.03 TP53BP2 Apoptosis-stimulating of p53 protein 2 S479 3.7 0.02 ACIN1 Apoptotic chromatin condensation inducer S64S70 5.7 0.02 1 S208 7.1 0.02 S210 7.0 0.02 S479S482S491 105.7 0.03 S729 2.8 0.02 PEA15 Astrocytic phosphoprotein PEA-15 S116 10.8 0.02 BAG3 BAG family molecular chaperone regulator S179 3.3 0.02 3 S353S357 2.3 0.03 S360 2.3 0.03 S390 8.4 0.02 BNIP2 BCL2/adenovirus E1B 19 kDa-interacting S114 3.9 0.02 protein 2 alpha BNIP3 BCL2/adenovirus E1B 19 kDa protein- S60 19.8 0.03 interacting protein 3 S85T86 14.5 0.02 S88 6.1 0.02 BCL2L13 Bcl-2-like protein 13 S387 4.0 0.02 T389 3.1 0.02 CAAP1 Caspase activity and apoptosis inhibitor S183 2.3 0.03 CARD6 Card6 caspase recruitment domain family, S809 3.6 0.03 member 6 CASP8 Caspase-8 S188 2.2 0.02 DAP Death-associated protein S51 5.4 0.02 DAPK2 Death-associated protein kinase 2 S299 3.8 0.02 S349 3.5 0.02 FAF1 FAS-associated factor 1 S269 17.1 0.04 GAS2 Growth arrest-specific protein 2 T282 5.3 0.02 S283 7.4 0.02 S287 5.3 0.02 S289 7.4 0.02 GCH1 GTP cyclohydrolase 1 S24 3.9 0.02 HTT Huntingtin S398S409S411 9.7 0.02 KRT18 Keratin, type I cytoskeletal 18 T9 2.7 0.02 S31S32S35 2.8 0.02 S43S45 3.1 0.02 PDCD5 MCG128907 S119 10.7 0.02 Y126 4.0 0.02 BNIP3I MCG2480, isoform CRA_b S61S62 12.9 0.03 S63S64 8.1 0.02 ©2014 American Diabetes Association.
    [Show full text]
  • Systematic Evaluation of Genes and Genetic Variants Associated with Type 1 Diabetes Susceptibility
    Systematic Evaluation of Genes and Genetic Variants Associated with Type 1 Diabetes Susceptibility This information is current as Ramesh Ram, Munish Mehta, Quang T. Nguyen, Irma of September 24, 2021. Larma, Bernhard O. Boehm, Flemming Pociot, Patrick Concannon and Grant Morahan J Immunol published online 24 February 2016 http://www.jimmunol.org/content/early/2016/02/19/jimmun ol.1502056 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2016/02/19/jimmunol.150205 Material 6.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published February 24, 2016, doi:10.4049/jimmunol.1502056 The Journal of Immunology Systematic Evaluation of Genes and Genetic Variants Associated with Type 1 Diabetes Susceptibility Ramesh Ram,*,† Munish Mehta,*,† Quang T. Nguyen,*,† Irma Larma,*,† Bernhard O. Boehm,‡,x Flemming Pociot,{ Patrick Concannon,‖,# and Grant Morahan*,† Genome-wide association studies have found >60 loci that confer genetic susceptibility to type 1 diabetes (T1D).
    [Show full text]
  • Patterns of Sequence Conservation in Presynaptic Neural Genes
    University of Pennsylvania ScholarlyCommons Departmental Papers (CIS) Department of Computer & Information Science November 2006 Patterns of Sequence Conservation in Presynaptic Neural Genes Dexter Hadley University of Pennsylvania Tara Murphy University of Pennsylvania Otto Valladares University of Pennsylvania Sridhar Hannenhalli University of Pennsylvania Lyle H. Ungar University of Pennsylvania, [email protected] See next page for additional authors Follow this and additional works at: https://repository.upenn.edu/cis_papers Recommended Citation Dexter Hadley, Tara Murphy, Otto Valladares, Sridhar Hannenhalli, Lyle H. Ungar, Junhyong Kim, and Maja Bucan, "Patterns of Sequence Conservation in Presynaptic Neural Genes", . November 2006. Reprinted from Genome Biology, Volume 7, Issue 11, November 2006, pages R105.1-R105.19. Publisher URL: http://genomebiology.com/2006/7/11/R105 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/cis_papers/282 For more information, please contact [email protected]. Patterns of Sequence Conservation in Presynaptic Neural Genes Abstract Background: The neuronal synapse is a fundamental functional unit in the central nervous system of animals. Because synaptic function is evolutionarily conserved, we reasoned that functional sequences of genes and related genomic elements known to play important roles in neurotransmitter release would also be conserved. Results: Evolutionary rate analysis revealed that presynaptic proteins evolve slowly, although some members of large gene families exhibit accelerated evolutionary rates relative to other family members. Comparative sequence analysis of 46 megabases spanning 150 presynaptic genes identified more than 26,000 elements that are highly conserved in eight vertebrate species, as well as a small subset of sequences (6%) that are shared among unrelated presynaptic genes.
    [Show full text]
  • Identification and Characterization of a Novel Botulinum Neurotoxin
    ARTICLE Received 13 Jul 2016 | Accepted 2 Dec 2016 | Published 3 Aug 2017 DOI: 10.1038/ncomms14130 OPEN Identification and characterization of a novel botulinum neurotoxin Sicai Zhang1, Geoffrey Masuyer2, Jie Zhang1, Yi Shen1, Daniel Lundin2, Linda Henriksson2, Shin-Ichiro Miyashita1, Markel Martı´nez-Carranza2, Min Dong1 & Pål Stenmark2 Botulinum neurotoxins are known to have seven serotypes (BoNT/A–G). Here we report a new BoNT serotype, tentatively named BoNT/X, which has the lowest sequence identity with other BoNTs and is not recognized by antisera against known BoNTs. Similar to BoNT/B/D/F/G, BoNT/X cleaves vesicle-associated membrane proteins (VAMP) 1, 2 and 3, but at a novel site (Arg66-Ala67 in VAMP2). Remarkably, BoNT/X is the only toxin that also cleaves non-canonical substrates VAMP4, VAMP5 and Ykt6. To validate its activity, a small amount of full-length BoNT/X was assembled by linking two non-toxic fragments using a transpeptidase (sortase). Assembled BoNT/X cleaves VAMP2 and VAMP4 in cultured neurons and causes flaccid paralysis in mice. Thus, BoNT/X is a novel BoNT with a unique substrate profile. Its discovery posts a challenge to develop effective countermeasures, provides a novel tool for studying intracellular membrane trafficking, and presents a new potential therapeutic toxin for modulating secretions in cells. 1 Department of Urology, Boston Children’s Hospital, Department of Microbiology and Immunobiology and Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA. 2 Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden. Correspondence and requests for materials should be addressed to M.D.
    [Show full text]
  • Neuroretinal-Derived Caveolin-1 Promotes Endotoxin-Induced Inflammation in the Murine Retina
    bioRxiv preprint doi: https://doi.org/10.1101/2020.01.08.899377; this version posted January 10, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Neuroretinal‐Cav1 promotes retinal inflammation Neuroretinal-derived caveolin-1 promotes endotoxin-induced inflammation in the murine retina Jami M. Gurley1, Grzegorz Gmyrek1, Mark E. McClellan1, Stefanie M. Hauck2, Mikhail G. Dozmorov3, Jonathan D. Wren4, Daniel J. J. Carr1,5, and Michael H. Elliott1* 1 Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center (OUHSC) 2 Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) 3 Department of Biostatistics, Virginia Commonwealth University (VCU) 4 Arthritis and Clinical Immunology Research Program, Division of Genomics and Data Sciences, Oklahoma Medical Research Foundation (OMRF) 5 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC) Running title: Neuroretinal-Cav1 promotes retinal inflammation *To whom correspondence should be addressed: Michael H. Elliott: Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City OK 73104; [email protected] ; Tel.(405) 271-8001, ext.30024; Fax.(405) 271-8128. Keywords: caveolin-1; caveolin; caveolae; inflammation; neural retina; retina; retinal degeneration; immune response ABSTRACT model to deplete Cav1 specifically in the neural Chronic ocular inflammation is associated retinal (NR) compartment in order to clarify the with many retinal degenerative diseases that result role of neural retinal-specific Cav1 (NR-Cav1) in in vision loss.
    [Show full text]
  • Exome Sequencing for Bipolar Disorder Points to Roles of De Novo Loss-Of-Function and Protein-Altering Mutations
    OPEN Molecular Psychiatry (2016) 21, 885–893 © 2016 Macmillan Publishers Limited All rights reserved 1359-4184/16 www.nature.com/mp IMMEDIATE COMMUNICATION Exome sequencing for bipolar disorder points to roles of de novo loss-of-function and protein-altering mutations M Kataoka1,2,6, N Matoba1,3,6, T Sawada1, A-A Kazuno1, M Ishiwata1, K Fujii1,4, K Matsuo5, A Takata1 and T Kato1 Although numerous genetic studies have been conducted for bipolar disorder (BD), its genetic architecture remains elusive. Here we perform, to the best of our knowledge, the first trio-based exome sequencing study for BD to investigate potential roles of de novo mutations in the disease etiology. We identified 71 de novo point mutations and one de novo copy-number mutation in 79 BD probands. Among the genes hit by de novo loss-of-function (LOF; nonsense, splice site or frameshift) or protein-altering (LOF, missense and inframe indel) mutations, we found significant enrichment of genes highly intolerant (first percentile of intolerant genes assessed by Residual Variation Intolerance Score) to protein-altering variants in general population, an observation that is also reported in autism and schizophrenia. When we performed a joint analysis using the data of schizoaffective disorder in published studies, we found global enrichment of de novo LOF and protein-altering mutations in the combined group of bipolar I and schizoaffective disorders. Considering relationship between de novo mutations and clinical phenotypes, we observed significantly earlier disease onset among the BD probands with de novo protein-altering mutations when compared with non-carriers. Gene ontology enrichment analysis of genes hit by de novo protein-altering mutations in bipolar I and schizoaffective disorders did not identify any significant enrichment.
    [Show full text]
  • Gwas Meta-Analysis of Intelligence 1
    bioRxiv preprint doi: https://doi.org/10.1101/184853; this version posted September 6, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. GWAS META-ANALYSIS OF INTELLIGENCE 1 GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence Jeanne E Savage1#, Philip R Jansen1,2#, Sven Stringer1, Kyoko Watanabe1, Julien Bryois3, Christiaan A de Leeuw1, Mats Nagel1, Swapnil Awasthi4, Peter B Barr5, Jonathan R I Coleman6,7, Katrina L Grasby8, Anke R Hammerschlag1, Jakob Kaminski4,9, Robert Karlsson3, Eva Krapohl6, Max Lam10, Marianne Nygaard11,12, Chandra A Reynolds13, Joey W Trampush14, Hannah Young15, Delilah Zabaneh6, Sara Hägg3, Narelle K Hansell16, Ida K Karlsson3, Sten Linnarsson17, Grant W Montgomery8,18, Ana B Muñoz-Manchado17, Erin B Quinlan6, Gunter Schumann6, Nathan Skene17, Bradley T Webb19,20,21, Tonya White2, Dan E Arking22, Deborah K Attix23,24, Dimitrios Avramopoulos22,25, Robert M Bilder26, Panos Bitsios27, Katherine E Burdick28,29,30, Tyrone D Cannon31, Ornit Chiba-Falek32, Andrea Christoforou23, Elizabeth T Cirulli33, Eliza Congdon26, Aiden Corvin34, Gail Davies35, 36, Ian J Deary35,36, Pamela DeRosse37, Dwight Dickinson38, Srdjan Djurovic39,40, Gary Donohoe41, Emily Drabant Conley42, Johan G Eriksson43,44, Thomas Espeseth45,46, Nelson A Freimer26, Stella Giakoumaki47, Ina Giegling48, Michael Gill34, David
    [Show full text]