DOCSLIB.ORG

Large Scale Analysis of Olfactory Receptors with Highly Genetically Variations in Relation with Specific Anosmia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Large Scale Analysis of Olfactory Receptors with Highly Genetically Variations in Relation with Specific Anosmia Large scale analysis of olfactory receptors with highly genetically variations in relation with specific anosmia Dissertation to obtain the degree Doctor Philosophiae (Doctor of Philosophy, PhD) At the Faculty of Biology and Biotechnology Ruhr-University Bochum International Graduate School of Biosciences Ruhr-University Bochum (Department of Cell Physiology) Submitted by Kaveh Ashti Baghaei From (Tehran, Iran) Bochum, Germany (June, 2013) First supervisor: Prof. Dr. Dr. Dr. Hanns Hatt Second supervisor: Prof. Dr. Stefan Wiese Umfassende Analyse Olfaktorischer Rezeptoren in Bezug auf genetische Varianten im Zusammenhang mit spezifischer Anosmie Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften der Fakultät für Biologie und Biotechnologie an der Internationalen Graduiertenschule Biowissenschaften der Ruhr-Universität Bochum angefertigt im Lehrstuhl für Zellphysiologie vorgelegt von Kaveh Ashti Baghaei Aus Tehran, Iran Bochum Juni, 2013 Referent: Prof. Dr. Dr. Dr. Hanns Hatt Korreferent: Prof. Dr. Stefan Wiese To my parents, brother and wife whose love and support sustained me throughout. Erklärung Hiermit erkläre ich, dass ich die Arbeit selbständig verfasst und bei keiner anderen Fakultät eingereicht und dass ich keine anderen als die angegebenen Hilfsmittel verwendet habe. Es handelt sich bei der heute von mir eingereichten Dissertation um sechs in Wort und Bildvöllig übereinstimmende Exemplare. Weiterhin erkläre ich, dass digitale Abbildungen nur die originalen Daten enthalten und in keinem Fall inhaltsverändernde Bildverarbeitung vorgenommen wurde. Kaveh Ashti Baghaei Bochum Jun.2013 Contents 1. Introduction ............................................................................................................................ -1- 1.1 Olfactory system .................................................................................................................... -1- 1.2 Olfactory receptors (ORs) ...................................................................................................... -2- 1.2.1 Segregating pseudogenes (SPGs) ........................................................................................ -4- 1.2.2 Copy number variations (CNVs) ........................................................................................ -6- 1.3 Olfactory signal transduction pathways ............................................................................. -8- 1.4 Functional expression of olfactory receptors in recombinant systems ............................. -10- 1.5 Odourant perception ........................................................................................................... -12- 1.5.1 Chemical structure basis of odourant ............................................................................ -13- 1.5.2 Olfactory Dysfunction ................................................................................................... -16- 1.5.3 Specific anosmia ........................................................................................................... -18- Aim of study .............................................................................................................................. -21- 2. Materials and Methods ....................................................................................................... -23- 2.1 DNA constructs and plasmids .......................................................................................... -23- 2.2 Mutagenesis by Overlap Extension PCR .......................................................................... -26- 2.3 Odourant library ................................................................................................................ -27- 2.4 Cell culture and transient DNA transfection .................................................................... -30- 2.5 Ca-imaging ........................................................................................................................ -31- 2.6 Stimulation and screening with odourants ....................................................................... -33- 2.7 Strategy of screening ........................................................................................................ -34- 2.8 CRE-Luciferase ................................................................................................................ -35- 2.9 CRE-SEAP assay ............................................................................................................. -37- 2.10 Immunohistochemistry ................................................................................................... -39- 2.11 Data analysis ................................................................................................................... -40- 3. Results ................................................................................................................................... -41- 3.1 Identification of SPG and CNV OR candidates ................................................................. -41- 3.2 Large scale investigation of olfactory receptors ................................................................ -44- 3.3 Deorphanization of olfactory receptors ............................................................................. -49- 3.4 Ca-imaging and CRE-luciferase: similarities and differences ........................................... -55- 3.5 Cell surface expression of olfactory receptors .................................................................. -57- 3.6 Broadly-narrowly tune of olfactory receptors ................................................................... -58- 3.7 Distance between odourants and response variability in the olfactory system ................. -59- 3.8 Similar odourant structure, similar response? .................................................................... -62- 3.9 Relation between odour specificity and receptor sequence .............................................. -64- 3.10 Single nucleotide polymorphism and odourant responses: Functional analysis of OR1B and OR10Q1-mutants ................................................................. -66- 4. Discussion .............................................................................................................................. -73- 4.1 Large scale investigation of ORs including SPGs and CNVs .......................................... -73- 4.2 Broadly and narrowly tuned olfactory receptors .............................................................. -81- 4.3 Scent and Chemistry .......................................................................................................... -82- 4.4 5a-androst-16-en-3one (urinous) and ω-pentadecalactone (musky) molecules ................. -85- Summary ................................................................................................................................... -87- Zusammenfassung .................................................................................................................... -90- Publication bibliography ......................................................................................................... -93- List of Figures ......................................................................................................................... -108- List of Tables .......................................................................................................................... -110- Abbreviations ......................................................................................................................... -111- Publications ............................................................................................................................ -113- Curriculum Vitae ................................................................................................................. -115- Acknowledgements ................................................................................................................ -117- Introduction 1. Introduction: 1.1 Olfactory system The human olfactory system has the remarkable capacity to recognise and discriminate a large number of different chemical components and odour molecules. As a chemical sensor, the olfactory system is effective on social and sexual behaviour and quality of life since odourants can evoke memories and emotions or influence our mood. Odourant perception starts with the chemical interaction between an odourant molecule and an olfactory receptor expressed in an olfactory sensory neuron (OSN). These neurons are located in the olfactory epithelium (OE), which is covered with a mucous layer which supplies lipid/protein-rich secretions for the OE surface. Most parts of the human nasal cavity consist of ciliated columnar respiratory epithelial tissue. The upper section of the nasal cavity, lining the cribriform plate, consists of OSNs (Morrison & Costanzo 1990). OSNs are bipolar cells with a single unbranched dendrite with axons penetrating through the cribriform plate to the olfactory bulb of the brain (Fig. 1.1). Axons of mitral cell then leave the olfactory bulb (OB) to higher brain structures including the piriform cortex, hippocampus and amygdale. About 10–25 cilia, each ~5 μm long, extend from the knob of each OSN (Menco 1980; Morrison & Costanzo 1992). Each OSN expresses just one type of olfactory receptor (OR) protein which is the first level for the primary events of chemo-sensory transduction. - 1 - Introduction Figure 1.1: Different
Load more

Recommended publications
  • European Patent Office of Opposition to That Patent, in Accordance with the Implementing Regulations
    (19) TZZ Z_T (11) EP 2 884 280 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: G01N 33/566 (2006.01) 09.05.2018 Bulletin 2018/19 (21) Application number: 13197310.9 (22) Date of filing: 15.12.2013 (54) Method for evaluating the scent performance of perfumes and perfume mixtures Verfahren zur Bewertung des Duftverhaltens von Duftstoffen und Duftstoffmischungen Procédé d’evaluation de senteur performance du parfums et mixtures de parfums (84) Designated Contracting States: (56) References cited: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB WO-A2-03/091388 GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR • BAGHAEI KAVEH A: "Deorphanization of human olfactory receptors by luciferase and Ca-imaging (43) Date of publication of application: methods.",METHODS IN MOLECULAR BIOLOGY 17.06.2015 Bulletin 2015/25 (CLIFTON, N.J.) 2013, vol. 1003, 19 June 2013 (2013-06-19), pages229-238, XP008168583, ISSN: (73) Proprietor: Symrise AG 1940-6029 37603 Holzminden (DE) • KAVEH BAGHAEI ET AL: "Olfactory receptors coded by segregating pseudo genes and (72) Inventors: odorants with known specific anosmia.", 33RD • Hatt, Hanns ANNUAL MEETING OF THE ASSOCIATION FOR 44789 Bochum (DE) CHEMORECEPTION, 1 April 2011 (2011-04-01), • Gisselmann, Günter XP055111507, 58456 Witten (DE) • TOUHARA ET AL: "Deorphanizing vertebrate • Ashtibaghaei, Kaveh olfactory receptors: Recent advances in 44801 Bochum (DE) odorant-response assays", NEUROCHEMISTRY • Panten, Johannes INTERNATIONAL, PERGAMON PRESS, 37671 Höxter (DE) OXFORD, GB, vol.
    [Show full text]
  • WO 2019/068007 Al Figure 2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/068007 Al 04 April 2019 (04.04.2019) W 1P O PCT (51) International Patent Classification: (72) Inventors; and C12N 15/10 (2006.01) C07K 16/28 (2006.01) (71) Applicants: GROSS, Gideon [EVIL]; IE-1-5 Address C12N 5/10 (2006.0 1) C12Q 1/6809 (20 18.0 1) M.P. Korazim, 1292200 Moshav Almagor (IL). GIBSON, C07K 14/705 (2006.01) A61P 35/00 (2006.01) Will [US/US]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., C07K 14/725 (2006.01) P.O. Box 4044, 7403635 Ness Ziona (TL). DAHARY, Dvir [EilL]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., P.O. (21) International Application Number: Box 4044, 7403635 Ness Ziona (IL). BEIMAN, Merav PCT/US2018/053583 [EilL]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., P.O. (22) International Filing Date: Box 4044, 7403635 Ness Ziona (E.). 28 September 2018 (28.09.2018) (74) Agent: MACDOUGALL, Christina, A. et al; Morgan, (25) Filing Language: English Lewis & Bockius LLP, One Market, Spear Tower, SanFran- cisco, CA 94105 (US). (26) Publication Language: English (81) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of national protection available): AE, AG, AL, AM, 62/564,454 28 September 2017 (28.09.2017) US AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/649,429 28 March 2018 (28.03.2018) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (71) Applicant: IMMP ACT-BIO LTD.
    [Show full text]
  • Functional and Structural Characterization of Olfactory Receptors in Human Heart and Eye
    DISSERTATION to obtain the degree Doctor Rerum Naturalium (Dr.rer.nat.) at the Faculty of Biology and Biotechnology International Graduate School Biosciences Ruhr-University Bochum Functional and structural characterization of olfactory receptors in human heart and eye Department of Cellphysiology submitted by Nikolina Jovancevic from Zadar, Croatia Bochum February 2016 First Referee: Prof. Dr. Dr. Dr. Hanns Hatt Second Referee: Prof. Dr. Stefan Wiese DISSERTATION zur Erlangung des Grades eines Doktors der Naturwissenschaften der Fakultät für Biologie und Biotechnologie an der Internationalen Graduiertenschule Biowissenschaften der Ruhr-Universität Bochum Funktionale und strukturelle Charakterisierung olfaktorischer Rezeptoren im humanen Herzen und Auge Lehrstuhl für Zellphysiologie vorgelegt von Nikolina Jovancevic aus Zadar, Kroatien Bochum Februar 2016 Referent: Prof. Dr. Dr. Dr. Hanns Hatt Korreferent: Prof. Dr. Stefan Wiese To my family TABLE OF CONTENTS TABEL OF CONTENT 1 INTRODUCTION 1 1.1 G protein-coupled receptors 1 1.1.1 General 1 1.1.2 Structure and classification 2 1.1.3 Olfactory Receptors 4 1.2 Function of olfactory receptors 9 1.2.1 The olfactory system 9 1.2.2 Ectopic expression of olfactory receptors 11 1.3 Excursus: Anatomy and physiology of the heart 13 1.3.1 Anatomy of the heart and blood circuit 14 1.3.2 The cardiac conduction system 15 1.3.3 Excitation-contraction coupling 16 1.3.4 Cardiac GPCRs: Modulation of cardiac contraction 17 1.4 Excursus: Anatomy and physiology of the eye 18 1.4.1 Anatomy of the retina 19
    [Show full text]
  • Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib
    Supplementary Online Content Chen G, McQuade JL, Panka DJ, et al. Clinical, molecular and immune analysis of dabrafenib-trametinib combination treatment for metastatic melanoma that progressed during BRAF inhibitor monotherapy: a phase 2 clinical trial. JAMA Oncology. Published online April 28, 2016. doi:10.1001/jamaoncol.2016.0509. eMethods. eReferences. eTable 1. Clinical efficacy eTable 2. Adverse events eTable 3. Correlation of baseline patient characteristics with treatment outcomes eTable 4. Patient responses and baseline IHC results eFigure 1. Kaplan-Meier analysis of overall survival eFigure 2. Correlation between IHC and RNAseq results eFigure 3. pPRAS40 expression and PFS eFigure 4. Baseline and treatment-induced changes in immune infiltrates eFigure 5. PD-L1 expression eTable 5. Nonsynonymous mutations detected by WES in baseline tumors This supplementary material has been provided by the authors to give readers additional information about their work. © 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 eMethods Whole exome sequencing Whole exome capture libraries for both tumor and normal samples were constructed using 100ng genomic DNA input and following the protocol as described by Fisher et al.,3 with the following adapter modification: Illumina paired end adapters were replaced with palindromic forked adapters with unique 8 base index sequences embedded within the adapter. In-solution hybrid selection was performed using the Illumina Rapid Capture Exome enrichment kit with 38Mb target territory (29Mb baited). The targeted region includes 98.3% of the intervals in the Refseq exome database. Dual-indexed libraries were pooled into groups of up to 96 samples prior to hybridization.
    [Show full text]
  • OR4K2 (C-Term) Rabbit Polyclonal Antibody – AP53060PU-N
    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 AP53060PU-N OR4K2 (C-term) Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: IHC, WB Recommended Dilution: ELISA: 1/1000. Western Blot: 1/100-1/500. Immunohistochemistry on Paraffin Sections: 1/10-1/50. Reactivity: Human Host: Rabbit Isotype: Ig Clonality: Polyclonal Immunogen: KLH conjugated synthetic peptide between 283-312 amino acids from the C-terminal region of human Olfactory receptor 4K2 Specificity: This antibody recognizes Human Olfactory receptor 4K2 (C-term). Formulation: PBS containing 0.09% (W/V) Sodium Azide as preservative State: Aff - Purified State: Liquid purified Ig fraction Concentration: lot specific Purification: Protein A column, followed by peptide affinity purification Conjugation: Unconjugated Storage: Store undiluted at 2-8°C for one month or (in aliquots) at -20°C for longer. Avoid repeated freezing and thawing. Stability: Shelf life: one year from despatch. Gene Name: Homo sapiens olfactory receptor family 4 subfamily K member 2 (OR4K2) Database Link: Entrez Gene 390431 Human Q8NGD2 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 OR4K2 (C-term) Rabbit Polyclonal Antibody – AP53060PU-N Background: Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding- exon genes.
    [Show full text]
  • The Hypothalamus As a Hub for SARS-Cov-2 Brain Infection and Pathogenesis
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.08.139329; this version posted June 19, 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. The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis Sreekala Nampoothiri1,2#, Florent Sauve1,2#, Gaëtan Ternier1,2ƒ, Daniela Fernandois1,2 ƒ, Caio Coelho1,2, Monica ImBernon1,2, Eleonora Deligia1,2, Romain PerBet1, Vincent Florent1,2,3, Marc Baroncini1,2, Florence Pasquier1,4, François Trottein5, Claude-Alain Maurage1,2, Virginie Mattot1,2‡, Paolo GiacoBini1,2‡, S. Rasika1,2‡*, Vincent Prevot1,2‡* 1 Univ. Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition, DistAlz, UMR-S 1172, Lille, France 2 LaBoratorY of Development and PlasticitY of the Neuroendocrine Brain, FHU 1000 daYs for health, EGID, School of Medicine, Lille, France 3 Nutrition, Arras General Hospital, Arras, France 4 Centre mémoire ressources et recherche, CHU Lille, LiCEND, Lille, France 5 Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and ImmunitY of Lille (CIIL), Lille, France. # and ƒ These authors contriButed equallY to this work. ‡ These authors directed this work *Correspondence to: [email protected] and [email protected] Short title: Covid-19: the hypothalamic hypothesis 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.08.139329; this version posted June 19, 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.
    [Show full text]
  • Lupus Nephritis Supp Table 5
    Supplementary Table 5 : Transcripts and DAVID pathways correlating with the expression of CD4 in lupus kidney biopsies Positive correlation Negative correlation Transcripts Pathways Transcripts Pathways Identifier Gene Symbol Correlation coefficient with CD4 Annotation Cluster 1 Enrichment Score: 26.47 Count P_Value Benjamini Identifier Gene Symbol Correlation coefficient with CD4 Annotation Cluster 1 Enrichment Score: 3.16 Count P_Value Benjamini ILMN_1727284 CD4 1 GOTERM_BP_FAT translational elongation 74 2.50E-42 1.00E-38 ILMN_1681389 C2H2 zinc finger protein-0.40001984 INTERPRO Ubiquitin-conjugating enzyme/RWD-like 17 2.00E-05 4.20E-02 ILMN_1772218 HLA-DPA1 0.934229063 SP_PIR_KEYWORDS ribosome 60 2.00E-41 4.60E-39 ILMN_1768954 RIBC1 -0.400186083 SMART UBCc 14 1.00E-04 3.50E-02 ILMN_1778977 TYROBP 0.933302249 KEGG_PATHWAY Ribosome 65 3.80E-35 6.60E-33 ILMN_1699190 SORCS1 -0.400223681 SP_PIR_KEYWORDS ubl conjugation pathway 81 1.30E-04 2.30E-02 ILMN_1689655 HLA-DRA 0.915891173 SP_PIR_KEYWORDS protein biosynthesis 91 4.10E-34 7.20E-32 ILMN_3249088 LOC93432 -0.400285215 GOTERM_MF_FAT small conjugating protein ligase activity 35 1.40E-04 4.40E-02 ILMN_3228688 HLA-DRB1 0.906190291 SP_PIR_KEYWORDS ribonucleoprotein 114 4.80E-34 6.70E-32 ILMN_1680436 CSH2 -0.400299744 SP_PIR_KEYWORDS ligase 54 1.50E-04 2.00E-02 ILMN_2157441 HLA-DRA 0.902996561 GOTERM_CC_FAT cytosolic ribosome 59 3.20E-33 2.30E-30 ILMN_1722755 KRTAP6-2 -0.400334007 GOTERM_MF_FAT acid-amino acid ligase activity 40 1.60E-04 4.00E-02 ILMN_2066066 HLA-DRB6 0.901531942 SP_PIR_KEYWORDS
    [Show full text]
  • Us 2018 / 0305689 A1
    US 20180305689A1 ( 19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0305689 A1 Sætrom et al. ( 43 ) Pub . Date: Oct. 25 , 2018 ( 54 ) SARNA COMPOSITIONS AND METHODS OF plication No . 62 /150 , 895 , filed on Apr. 22 , 2015 , USE provisional application No . 62/ 150 ,904 , filed on Apr. 22 , 2015 , provisional application No. 62 / 150 , 908 , (71 ) Applicant: MINA THERAPEUTICS LIMITED , filed on Apr. 22 , 2015 , provisional application No. LONDON (GB ) 62 / 150 , 900 , filed on Apr. 22 , 2015 . (72 ) Inventors : Pål Sætrom , Trondheim (NO ) ; Endre Publication Classification Bakken Stovner , Trondheim (NO ) (51 ) Int . CI. C12N 15 / 113 (2006 .01 ) (21 ) Appl. No. : 15 /568 , 046 (52 ) U . S . CI. (22 ) PCT Filed : Apr. 21 , 2016 CPC .. .. .. C12N 15 / 113 ( 2013 .01 ) ; C12N 2310 / 34 ( 2013. 01 ) ; C12N 2310 /14 (2013 . 01 ) ; C12N ( 86 ) PCT No .: PCT/ GB2016 /051116 2310 / 11 (2013 .01 ) $ 371 ( c ) ( 1 ) , ( 2 ) Date : Oct . 20 , 2017 (57 ) ABSTRACT The invention relates to oligonucleotides , e . g . , saRNAS Related U . S . Application Data useful in upregulating the expression of a target gene and (60 ) Provisional application No . 62 / 150 ,892 , filed on Apr. therapeutic compositions comprising such oligonucleotides . 22 , 2015 , provisional application No . 62 / 150 ,893 , Methods of using the oligonucleotides and the therapeutic filed on Apr. 22 , 2015 , provisional application No . compositions are also provided . 62 / 150 ,897 , filed on Apr. 22 , 2015 , provisional ap Specification includes a Sequence Listing . SARNA sense strand (Fessenger 3 ' SARNA antisense strand (Guide ) Mathew, Si Target antisense RNA transcript, e . g . NAT Target Coding strand Gene Transcription start site ( T55 ) TY{ { ? ? Targeted Target transcript , e .
    [Show full text]
  • Rabbit Anti-Human OR1B1 Polyclonal Antibody (CABT-B9128) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use
    Rabbit Anti-Human OR1B1 Polyclonal Antibody (CABT-B9128) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Product Overview Rabbit Polyclonal to Olfactory receptor 1B1. Specificity This antibody detects endogenous levels of Olfactory receptor 1B1 protein. Target Olfactory receptor 1B1 Immunogen Synthesized peptide derived from human Olfactory receptor 1B1 (Internal) Isotype IgG Source/Host Rabbit Species Reactivity Human Purification This antibody was affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogen. Conjugate Unconjugated Applications WB, IF, ELISA Molecular Weight 33 kDa Format Liquid Concentration Lot specific Buffer PBS containing 50% glycerol and 0.5% BSA Preservative 0.02% Sodium Azide Storage Store at -20°C, and avoid repeat freeze-thaw cycles. Warnings For research use only. BACKGROUND Introduction OR1B1 and other olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7- 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. A stop codon in the gene coding for this protein is responsible for functional diversity. The stop codon is more frequent in non- Africans than in African-Americans. Keywords OR1B1;olfactory receptor, family 1, subfamily B, member 1;olfactory receptor 1B1;OR9 B;olfactory receptor 9-B;olfactory receptor OR9-26;OR9-B;OR9-26; GENE INFORMATION Entrez Gene ID 347169 UniProt ID Q8NGR6 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 2 © Creative Diagnostics All Rights Reserved.
    [Show full text]
  • ARTICLE Extensive Copy-Number Variation of the Human Olfactory Receptor Gene Family
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector ARTICLE Extensive Copy-Number Variation of the Human Olfactory Receptor Gene Family Janet M. Young,1 RaeLynn M. Endicott,1 Sean S. Parghi,1 Megan Walker,1 Jeffrey M. Kidd,1,2 and Barbara J. Trask1,* As much as a quarter of the human genome has been reported to vary in copy number between individuals, including regions containing about half of the members of the olfactory receptor (OR) gene family. We have undertaken a detailed study of copy-number variation of ORs to elucidate the selective and mechanistic forces acting on this gene family and the true impact of copy-number variation on human OR repertoires. We argue that the properties of copy-number variants (CNVs) and other sets of large genomic regions violate the assump- tions of statistical methods that are commonly used in the assessment of gene enrichment. Using more appropriate methods, we provide evidence that OR enrichment in CNVs is not due to positive selection but is because of OR preponderance in segmentally duplicated regions, which are known to be frequently copy-number variable, and because purifying selection against CNVs is lower in OR-contain- ing regions than in regions containing essential genes. We also combine multiplex ligation-dependent probe amplification (MLPA) and PCR to assay the copy numbers of 37 candidate CNV ORs in a panel of ~50 human individuals. We confirm copy-number variation of 18 ORs but find no variation in this human-diversity panel for 16 other ORs, highlighting the caveat that reported intervals often overre- present true CNVs.
    [Show full text]
  • Explorations in Olfactory Receptor Structure and Function by Jianghai
    Explorations in Olfactory Receptor Structure and Function by Jianghai Ho Department of Neurobiology Duke University Date:_______________________ Approved: ___________________________ Hiroaki Matsunami, Supervisor ___________________________ Jorg Grandl, Chair ___________________________ Marc Caron ___________________________ Sid Simon ___________________________ [Committee Member Name] Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Neurobiology in the Graduate School of Duke University 2014 ABSTRACT Explorations in Olfactory Receptor Structure and Function by Jianghai Ho Department of Neurobiology Duke University Date:_______________________ Approved: ___________________________ Hiroaki Matsunami, Supervisor ___________________________ Jorg Grandl, Chair ___________________________ Marc Caron ___________________________ Sid Simon ___________________________ [Committee Member Name] An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Neurobiology in the Graduate School of Duke University 2014 Copyright by Jianghai Ho 2014 Abstract Olfaction is one of the most primitive of our senses, and the olfactory receptors that mediate this very important chemical sense comprise the largest family of genes in the mammalian genome. It is therefore surprising that we understand so little of how olfactory receptors work. In particular we have a poor idea of what chemicals are detected by most of the olfactory receptors in the genome, and for those receptors which we have paired with ligands, we know relatively little about how the structure of these ligands can either activate or inhibit the activation of these receptors. Furthermore the large repertoire of olfactory receptors, which belong to the G protein coupled receptor (GPCR) superfamily, can serve as a model to contribute to our broader understanding of GPCR-ligand binding, especially since GPCRs are important pharmaceutical targets.
    [Show full text]
  • Whole-Exome Sequencing Validates a Preclinical Mouse Model for the Prevention and Treatment of Cutaneous Squamous Cell Carcinoma Elena V
    Published OnlineFirst December 6, 2016; DOI: 10.1158/1940-6207.CAPR-16-0218 Research Article Cancer Prevention Research Whole-Exome Sequencing Validates a Preclinical Mouse Model for the Prevention and Treatment of Cutaneous Squamous Cell Carcinoma Elena V. Knatko1, Brandon Praslicka2, Maureen Higgins1, Alan Evans3, Karin J. Purdie4, Catherine A. Harwood4, Charlotte M. Proby1, Aikseng Ooi2, and Albena T. Dinkova-Kostova1,5,6 Abstract Cutaneous squamous cell carcinomas (cSCC) are among the detected in 15 of 18 (83%) cases, with 20 of 21 SNP mutations most common and highly mutated human malignancies. Solar located in the protein DNA-binding domain. Strikingly, multiple UV radiation is the major factor in the etiology of cSCC. Whole- nonsynonymous SNP mutations in genes encoding Notch family exome sequencing of 18 microdissected tumor samples (cases) members (Notch1-4) were present in 10 of 18 (55%) cases. The derived from SKH-1 hairless mice that had been chronically histopathologic spectrum of the mouse cSCC that develops in this exposed to solar-simulated UV (SSUV) radiation showed a medi- model resembles very closely the spectrum of human cSCC. We an point mutation (SNP) rate of 155 per Mb. The majority conclude that the mouse SSUV cSCCs accurately represent the (78.6%) of the SNPs are C.G>T.A transitions, a characteristic histopathologic and mutational spectra of the most prevalent UVR-induced mutational signature. Direct comparison with tumor suppressors of human cSCC, validating the use of this human cSCC cases showed high overlap in terms of both fre- preclinical model for the prevention and treatment of human quency and type of SNP mutations.
    [Show full text]