Evaluation of Current Methods Used to Analyze the Expression Profiles of ATP-Binding Cassette Transporters Yields an Improved Drug-Discovery Database
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EXTENDED CARRIER SCREENING Peace of Mind for Planned Pregnancies
Focusing on Personalised Medicine EXTENDED CARRIER SCREENING Peace of Mind for Planned Pregnancies Extended carrier screening is an important tool for prospective parents to help them determine their risk of having a child affected with a heritable disease. In many cases, parents aren’t aware they are carriers and have no family history due to the rarity of some diseases in the general population. What is covered by the screening? Genomics For Life offers a comprehensive Extended Carrier Screening test, providing prospective parents with the information they require when planning their pregnancy. Extended Carrier Screening has been shown to detect carriers who would not have been considered candidates for traditional risk- based screening. With a simple mouth swab collection, we are able to test for over 419 genes associated with inherited diseases, including Fragile X Syndrome, Cystic Fibrosis and Spinal Muscular Atrophy. The assay has been developed in conjunction with clinical molecular geneticists, and includes genes listed in the NIH Genetic Test Registry. For a list of genes and disorders covered, please see the reverse of this brochure. If your gene of interest is not covered on our Extended Carrier Screening panel, please contact our friendly team to assist you in finding a gene test panel that suits your needs. Why have Extended Carrier Screening? Extended Carrier Screening prior to pregnancy enables couples to learn about their reproductive risk and consider a complete range of reproductive options, including whether or not to become pregnant, whether to use advanced reproductive technologies, such as preimplantation genetic diagnosis, or to use donor gametes. -
Molecular Characterization and Structural Implications of 25 New ABCB4 Mutations in Progressive Familial Intrahepatic Cholestasis Type 3 (PFIC3)
European Journal of Human Genetics (2007) 15, 1230–1238 & 2007 Nature Publishing Group All rights reserved 1018-4813/07 $30.00 www.nature.com/ejhg ARTICLE Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3) Dario Degiorgio1, Carla Colombo2, Manuela Seia1, Luigi Porcaro1, Lucy Costantino1, Laura Zazzeron2, Domenico Bordo3 and Domenico A Coviello*,1 1Laboratorio di Genetica Medica, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy; 2Centro Fibrosi Cistica, Universita` degli Studi di Milano, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy; 3Bioinformatica e Proteomica Strutturale, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal-recessive disorder due to mutations in the ATP-binding cassette, subfamily B, member 4 gene (ABCB4). ABCB4 is the liver-specific membrane transporter of phosphatidylcholine, a major and exclusive component of mammalian bile. The disease is characterized by early onset of cholestasis with high serum c-glutamyltranspeptidase activity, which progresses into cirrhosis and liver failure before adulthood. Presently, about 20 distinct ABCB4 mutations associated to PFIC3 have been described. We report the molecular characterization of 68 PFIC3 index cases enrolled in a multicenter study, which represents the largest cohort of PFIC3 patients screened for ABCB4 mutations to date. We observed 31 mutated ABCB4 alleles in 18 index cases with 29 distinct mutations, 25 of which are novel. Despite the lack of structural information on the ABCB4 protein, the elucidation of the three-dimensional structure of bacterial homolog allows the three-dimensional model of ABCB4 to be built by homology modeling and the position of the mutated amino-acids in the protein tertiary structure to be located. -
ABCB5 Recombinant Protein Cat
ABCB5 Recombinant Protein Cat. No.: 92-176 ABCB5 Recombinant Protein Specifications SPECIES: Human SOURCE SPECIES: E. coli SEQUENCE: Ile141-Val247 FUSION TAG: N-Trx tag TESTED APPLICATIONS: APPLICATIONS: This recombinant protein can be used for biological assays. For research use only. PREDICTED MOLECULAR 29.4 kD WEIGHT: Properties Greater than 95% as determined by reducing SDS-PAGE. PURITY: Endotoxin level less than 0.1 ng/ug (1 IEU/ug) as determined by LAL test. PHYSICAL STATE: Lyophilized Lyophilized from a 0.2 um filtered solution of 20mM PB,150mM NaCl,pH7.4. It is not BUFFER: recommended to reconstitute to a concentration less than 100 ug/ml. Dissolve the lyophilized protein in ddH2O. September 23, 2021 1 https://www.prosci-inc.com/abcb5-recombinant-protein-92-176.html Lyophilized protein should be stored at -20˚C, though stable at room temperature for 3 weeks. STORAGE CONDITIONS: Reconstituted protein solution can be stored at 4-7˚C for 2-7 days. Aliquots of reconstituted samples are stable at -20˚C for 3 months. Additional Info OFFICIAL SYMBOL: ABCB5 ALTERNATE NAMES: ATP-binding cassette sub-family B member 5, P-glycoprotein ABCB5, ABCB5 P-gp, ABCB5 ACCESSION NO.: Q2M3G0 GENE ID: 340273 Background and References ATP-binding cassette sub-family B member 5(ABCB5) is a plasma membrane-spanning protein. ABCB5 is principally expressed in physiological skin and human malignant melanoma. ABCB5 has been suggested to regulate skin progenitor cell fusion and mediate chemotherapeutic drug resistance in stem-like tumor cell subpopulations in BACKGROUND: human malignant melanoma. It is commonly over-expressed on circulating melanoma tumour cells. -
Functional Rescue of Misfolding ABCA3 Mutations by Small Molecular Correctors Susanna Kinting, Stefanie Ho¨ Ppner, Ulrike Schindlbeck, Maria E
Human Molecular Genetics, 2018, Vol. 27, No. 6 943–953 doi: 10.1093/hmg/ddy011 Advance Access Publication Date: 9 January 2018 Original Article ORIGINAL ARTICLE Functional rescue of misfolding ABCA3 mutations by small molecular correctors Susanna Kinting, Stefanie Ho¨ ppner, Ulrike Schindlbeck, Maria E. Forstner, Jacqueline Harfst, Thomas Wittmann and Matthias Griese* Department of Pediatric Pneumology, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians University, German Centre for Lung Research (DZL), 80337 Munich, Germany *To whom correspondence should be addressed at: Department of Pediatric Pneumology, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians University, German Centre for Lung Research (DZL), Lindwurmstraße 4, 80337 Munich, Germany. Tel: þ49 89 440057870; Fax: þ49 89 440057872; Email: [email protected] Abstract Adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3), a phospholipid transporter in lung lamellar bodies (LBs), is essential for the assembly of pulmonary surfactant and LB biogenesis. Mutations in the ABCA3 gene are an important genetic cause for respiratory distress syndrome in neonates and interstitial lung disease in children and adults, for which there is currently no cure. The aim of this study was to prove that disease causing misfolding ABCA3 mutations can be corrected in vitro and to investigate available options for correction. We stably expressed hemagglutinin (HA)-tagged wild-type ABCA3 or variants p.Q215K, p.M760R, p.A1046E, p.K1388N or p.G1421R in A549 cells and assessed correction by quantitation of ABCA3 processing products, their intracellular localization, resembling LB morphological integrity and analysis of functional transport activity. We showed that all mutant proteins except for M760R ABCA3 were rescued by the bithiazole correctors C13 and C17. -
Blueprint Genetics ABCC11 Single Gene Test
ABCC11 single gene test Test code: S02680 Phenotype information Apocrine gland secretion, variation in Alternative gene names MRP8 Test Strengths The strengths of this test include: CAP accredited laboratory CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance Careful construction of clinically effective and scientifically justified gene panels Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level Our publicly available analytic validation demonstrating complete details of test performance ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this test’) Our rigorous variant classification scheme Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data Our comprehensive clinical statements Test Limitations This test does not detect the following: Complex inversions Gene conversions Balanced translocations Mitochondrial DNA variants Repeat expansion disorders unless specifically mentioned Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above non-coding variants covered by the test). This test may not reliably detect the following: Low level mosaicism (variant with a minor allele fraction of 14.6% is detected with 90% probability) Stretches of mononucleotide repeats Indels larger than 50bp Single exon deletions or duplications Variants within pseudogene regions/duplicated segments The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics. For additional information, please refer to the Test performance section and see our Analytic Validation. -
Association Between the ABCC11 Gene Polymorphism and the Expression of Apolipoprotein D by the Apocrine Glands in Axillary Osmidrosis
MOLECULAR MEDICINE REPORTS 11: 4463-4467, 2015 Association between the ABCC11 gene polymorphism and the expression of apolipoprotein D by the apocrine glands in axillary osmidrosis ZHECHEN ZHU1, HONGWEI ZHANG1, GUANGHUA LUO2, NING XU3 and ZHONGLAN PAN1 1Department of Plastic and Burn Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210003; 2Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China; 3Section of Clinical Chemistry and Pharmacology, Institute of Laboratory Medicine, Lund University, Lund S-221 85, Sweden Received April 1, 2014; Accepted December 9, 2014 DOI: 10.3892/mmr.2015.3274 Abstract. It has been suggested that the adenosine triphos- gene in the mediation of osmidrosis by enhancing the transi- phate-binding cassette sub-family C member 11 (ABCC11) tion of odor precursors via the ApoD pathway. gene polymorphism and apolipoprotein D (ApoD), an odor precursor carrier, may be important in the formation of axil- Introduction lary odor. To date, few studies have examined the potential correlation between these two factors. The present study Osmidrosis is one of the most common complaints in the aimed to investigate the association between a 538 G>A departments of plastic surgery at the First Affiliated Hospital single-nucleotide polymorphism (SNP) of the ABCC11 gene of Nanjing Medical University (Nanjing, China). The apocrine and the mRNA expression levels of ApoD in the apocrine glands, which are located in the axilla, are the predominant gland of patients with osmidrosis. The 538 G>A polymor- cause of axillary odor (1). This is due to the fat-like secretion phism genotypes of 33 patients with a clinical diagnosis of produced by the apocrine glands, which is broken down into osmidrosis were analyzed by polymerase chain reaction (PCR) volatile odorous substances by bacteria (2). -
Transcriptional and Post-Transcriptional Regulation of ATP-Binding Cassette Transporter Expression
Transcriptional and Post-transcriptional Regulation of ATP-binding Cassette Transporter Expression by Aparna Chhibber DISSERTATION Submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Pharmaceutical Sciences and Pbarmacogenomies in the Copyright 2014 by Aparna Chhibber ii Acknowledgements First and foremost, I would like to thank my advisor, Dr. Deanna Kroetz. More than just a research advisor, Deanna has clearly made it a priority to guide her students to become better scientists, and I am grateful for the countless hours she has spent editing papers, developing presentations, discussing research, and so much more. I would not have made it this far without her support and guidance. My thesis committee has provided valuable advice through the years. Dr. Nadav Ahituv in particular has been a source of support from my first year in the graduate program as my academic advisor, qualifying exam committee chair, and finally thesis committee member. Dr. Kathy Giacomini graciously stepped in as a member of my thesis committee in my 3rd year, and Dr. Steven Brenner provided valuable input as thesis committee member in my 2nd year. My labmates over the past five years have been incredible colleagues and friends. Dr. Svetlana Markova first welcomed me into the lab and taught me numerous laboratory techniques, and has always been willing to act as a sounding board. Michael Martin has been my partner-in-crime in the lab from the beginning, and has made my days in lab fly by. Dr. Yingmei Lui has made the lab run smoothly, and has always been willing to jump in to help me at a moment’s notice. -
P-Glycoprotein Drug Transporters in the Parasitic Nematodes Toxocara Canis and Parascaris
Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2019 P-glycoprotein drug transporters in the parasitic nematodes Toxocara canis and Parascaris Jeba Rose Jennifer Jesudoss Chelladurai Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Parasitology Commons, and the Veterinary Medicine Commons Recommended Citation Jesudoss Chelladurai, Jeba Rose Jennifer, "P-glycoprotein drug transporters in the parasitic nematodes Toxocara canis and Parascaris" (2019). Graduate Theses and Dissertations. 17707. https://lib.dr.iastate.edu/etd/17707 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. P-glycoprotein drug transporters in the parasitic nematodes Toxocara canis and Parascaris by Jeba Rose Jennifer Jesudoss Chelladurai A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Veterinary Pathology (Veterinary Parasitology) Program of Study Committee: Matthew T. Brewer, Major Professor Douglas E. Jones Richard J. Martin Jodi D. Smith Tomislav Jelesijevic The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2019 Copyright © Jeba Rose Jennifer Jesudoss Chelladurai, 2019. -
A Functional ABCC11 Allele Is Essential in the Biochemical
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector See related commentary on pg 344 ORIGINAL ARTICLE A Functional ABCC11 Allele Is Essential in the Biochemical Formation of Human Axillary Odor Annette Martin1,3, Matthias Saathoff1,3, Fabian Kuhn2, Heiner Max1, Lara Terstegen1 and Andreas Natsch2 The characteristic human axillary odor is formed by bacterial action on odor precursors that originate from apocrine sweat glands. Caucasians and Africans possess a strong axillary odor ,whereas many Asians have only a faint acidic odor. In this study, we provide evidence that the gene ABCC11 (MRP8), which encodes an apical efflux pump, is crucial for the formation of the characteristic axillary odor and that a single-nucleotide polymorphism (SNP) 538G-A, which is prominent among Asian people, leads to a nearly complete loss of the typical odor components in axillary sweat. The secretion of amino-acid conjugates of human-specific odorants is abolished in homozygotic carriers of the SNP, and steroidal odorants and their putative precursors are significantly reduced. Moreover, we show that ABCC11 is expressed and localized in apocrine sweat glands. These data point to a key function of ABCC11 in the secretion of odorants and their precursors from apocrine sweat glands. SNP 538G-A, which also determines human earwax type, is present on an extended haplotype, which has reached 495% frequency in certain populations in recent human evolution. A strong positive selection in mate choice for low-odorant partners with a dysfunctional ABCC11 gene seems a plausible explanation for this striking frequency of a loss-of-function allele. -
ABCB1 and ABCC11 Confer Resistance to Eribulin in Breast Cancer Cell Lines
www.impactjournals.com/oncotarget/ Oncotarget, Vol. 7, No. 43 Research Paper ABCB1 and ABCC11 confer resistance to eribulin in breast cancer cell lines Takaaki Oba1, Hiroto Izumi2, Ken-ichi Ito1 1Division of Breast, Endocrine and Respiratory Surgery, Department of Surgery (II), Shinshu University School of Medicine, Matsumoto, Japan 2Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan Correspondence to: Ken-ichi Ito, email: [email protected] Keywords: eribulin, drug resistance, breast cancer, ABCB1, ABCC11 Received: May 13, 2016 Accepted: August 09, 2016 Published: August 31, 2016 ABSTRACT This study aimed to elucidate the mechanisms underlying the resistance of breast cancer to eribulin. Seven eribulin-resistant breast cancer cell lines (MCF7/E, BT474/E, ZR75-1/E, SKBR3/E, MDA-MB-231/E, Hs578T/E, and MDA-MB-157/E) were established. mRNA and protein expression of ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 11 (ABCC11) increased in all eribulin-resistant cell lines compared to the parental cell lines. When ABCB1 or ABCC11 expression was inhibited by small interfering RNA in MCF7/E, BT474/E, and MDA-MB-231/E cells, eribulin sensitivity was partially restored. Moreover, eribulin resistance was attenuated additively by inhibiting ABCB1 and ABCC11 in MCF7/E cells. Additionally, overexpression of exogenous ABCB1 or ABCC11 in HEK293T cells conferred resistance to eribulin. MCF7/E and MDA- MB-231/E cells showed cross-resistance to paclitaxel, doxorubicin, and fluorouracil. Inhibition of ABCB1 partially restored paclitaxel and doxorubicin sensitivity. Partial restoration of fluorouracil sensitivity was induced by inhibiting ABCC11 in MCF7/E and MDA-MB-231/E cells. -
Potentiation of ABCA3 Lipid Transport Function by Ivacaftor and Genistein
Received: 21 February 2019 | Revised: 15 April 2019 | Accepted: 3 May 2019 DOI: 10.1111/jcmm.14397 ORIGINAL ARTICLE Potentiation of ABCA3 lipid transport function by ivacaftor and genistein Susanna Kinting1,2 | Yang Li1 | Maria Forstner1,2 | Florent Delhommel3,4 | Michael Sattler3,4 | Matthias Griese1,2 1Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Abstract LMU Munich, Munich, Germany ABCA3 is a phospholipid transporter implicated in pulmonary surfactant homoeosta‐ 2 Member of the German Center for Lung sis and localized at the limiting membrane of lamellar bodies, the storage compart‐ Research (DZL), Munich, Germany 3Institute of Structural Biology, Helmholtz ment for surfactant in alveolar type II cells. Mutations in ABCA3 display a common Zentrum München, Neuherberg, Germany genetic cause for diseases caused by surfactant deficiency like respiratory distress 4 Center for Integrated Protein Science in neonates and interstitial lung disease in children and adults, for which currently no Munich at Department Chemie, Technical University of Munich, Garching, Germany causal therapy exists. In this study, we investigated the effects of ivacaftor and gen‐ istein, two potentiators of the cystic fibrosis transmembrane conductance regulator Correspondence Matthias Griese, Department of Pediatrics, (CFTR), on ABCA3‐specific lipid transport function. Wild‐type (WT) and functional Dr. von Hauner Children's Hospital, ABCA3 mutations N568D, F629L, G667R, T1114M and L1580P were stably ex‐ University Hospital, LMU Munich, Munich, Germany. pressed in A549 cells. Three‐dimensional modelling predicted functional impairment Email: [email protected]‐muenchen. for all five mutants that was confirmed by in vitro experiments (all <14% of WT func‐ de tional activity). -
The Putative Mitochondrial Protein ABCB6
Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes Katalin Kiss, Anna Brozik, Nora Kucsma, Alexandra Toth, Melinda Gera, Laurence Berry, Alice Vallentin, Henri Vial, Michel Vidal, Gergely Szakacs To cite this version: Katalin Kiss, Anna Brozik, Nora Kucsma, Alexandra Toth, Melinda Gera, et al.. Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes. PLoS ONE, Public Library of Science, 2012, 7 (5), pp.e37378. 10.1371/journal.pone.0037378. hal-02309092 HAL Id: hal-02309092 https://hal.archives-ouvertes.fr/hal-02309092 Submitted on 25 May 2021 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. Distributed under a Creative Commons Attribution| 4.0 International License Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes Katalin Kiss1, Anna Brozik1, Nora Kucsma1, Alexandra Toth1, Melinda Gera1,