DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 7,695,916 B2 Iakoubova Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 7,695,916 B2 Iakoubova Et Al US007695916B2 (12) United States Patent (10) Patent No.: US 7,695,916 B2 IakoubOVa et al. (45) Date of Patent: Apr. 13, 2010 (54) GENETIC POLYMORPHISMS ASSOCIATED NCBI Cluster Report: rs20455, Revised: May 25, 2006, Retrieved WITH CORONARY EVENTS AND DRUG from the Internet: <URL: htp://www.ncbi.nlm.nih.gov/SNP/ RESPONSE, METHODS OF DETECTION AND Snp refcgi?=rs20455>. USES THEREOF Wozniak, et al., “The Novel Protein KBP Regulates Mitochondria Localization by Interaction with a Kinsian-Like Protein', BMC Cell Biology, Oct. 14, 2005, vol. 6:35, pp. 1-15. (75) Inventors: Olga Iakoubova, San Ramon, CA (US); MutDB Gene: KIF6, Retrieved from the Internet:<URL: http://www. James Devlin, Lafayette, CA (US); mutdb.org/cgi-bin/muutdb.pl?id=KIF6&geneid=221458. Charles Rowland, San Leandro, CA KIF6 GeneCard, Retrieved from the Internet: <htp://genecards.ccbb. (US); Carmen Tong, Dublin, CA (US) re.kr/cgi-bin/carddisp.pl?gene=C6orf102&Snp show mode=1& Snp=666. (73) Assignee: Celera Corporation, Alameda, CA (US) Morrison, et al., “Prediction of Coronary Heart Disease Risk Using a Genetic Risk Score: The Atherosclerosis Risk in Communities (*) Notice: Subject to any disclaimer, the term of this Study”. American Journal of Epidemiology, Jul. 2007, vol. 166:1, pp. patent is extended or adjusted under 35 28-35, Epub Apr. 18, 2007. U.S.C. 154(b) by 0 days. Bare, et al., “Five Common Gene Variants Identify Elevated Genetic Risk for Coronary Heart Disease'. Genetics in Medicine, Oct. 2007. vol. 9, No. 10, pp. 682-689. (21) Appl. No.: 12/077,935 Iakoubova, et al., “Association of the Trp719Arg Polymorphism in Kinesin-Like Protein 6 with Myocardial Infarction and Coronary (22) Filed: Mar. 21, 2008 Heart Disease in 2 Prospective Trials: the CARE and WOSCOPS Trials”, Journal of American College of Cardiology, Jan. 29, 2008, (65) Prior Publication Data vol. 51: 4. pp. 435-443. US 2008/0241846A1 Oct. 2, 2008 Shiffman, et al., "A Kinesin Family Member 6 Variant is Associated with Coronary Heart Disease in the Women's Health Study”. Journal of American College of Cardiology, Jan. 29, 2008, vol. 51: 4, pp. Related U.S. Application Data 444-448. (60) Provisional application No. 60/919,885, filed on Mar. International Search Report and Written Opinion dated Sep. 15. 22, 2007. 2008. International Preliminary Report on Patentability for PCT/US2008/ (51) Int. Cl. 03857, dated Oct. 1, 2009. CI2O I/68 (2006.01) Primary Examiner Young J Kim CI2P 19/34 (2006.01) (74) Attorney, Agent, or Firm—Celera Corporation (52) U.S. Cl. .......................... 435/6: 435/91.1; 435/91.2 (58) Field of Classification Search ....................... None (57) ABSTRACT See application file for complete search history. The present invention provides compositions and methods (56) References Cited based on genetic polymorphisms that are associated with coronary heart disease (particularly myocardial infarction), U.S. PATENT DOCUMENTS aneurysm/dissection, and/or response to drug treatment, par 2007/005971.0 A1 3/2007 Luke et al. ticularly statin treatment. For example, the present invention 2007/OO72821 A1 3/2007 Iakoubova et al. relates to nucleic acid molecules containing the polymor phisms, variant proteins encoded by these nucleic acid mol OTHER PUBLICATIONS ecules, reagents for detecting the polymorphic nucleic acid Iakoubova, et al., “Association of the Trp719Arg Polymorphism in molecules and variant proteins, and methods of using the Kinesin-Like Protein 6 with Myocardial Infarction and Coronary nucleic acid molecules and proteins as well as methods of Heart Disease in 2 Prospective Trials: the CARE and WOSCOPS using reagents for their detection. Trials”, Journal of American College of Cardiology, Jan. 29, 2008, vol. 51: 4. pp. 435-443; with 7 page on-line appendix (pp. 1-7). 25 Claims, No Drawings US 7,695,916 B2 1. 2 GENETIC POLYMORPHISMIS ASSOCATED interventions: coronary artery bypass graft, angioplasty and WITH CORONARY EVENTS AND DRUG stent placement, in addition to clinical records of MI, angina, RESPONSE, METHODS OF DETECTION AND or coronary death. USES THEREOF As used herein, CHD is defined in accordance with how this term is defined in the Framingham Heart Study (i.e., as CROSS-REFERENCE TO RELATED encompassing MI, angina pectoris, coronary insufficiency, APPLICATIONS and coronary heart disease death), and may also include revascularization, percutaneous transluminal coronary This application claims the benefit of U.S. provisional angioplasty (PTCA), and coronary artery bypass graft application Ser. No. 60/919,885, filed on Mar. 22, 2007, the 10 (CABG). Angina pectoris includes unstable angina in par contents of which are hereby incorporated by reference in its ticular. entirety into this application. The SNPs described herein may further be useful for such cardiovascular events as Vulnerable plaque and stroke. FIELD OF THE INVENTION Myocardial Infarction (MI) 15 Myocardial infarction (MI), also referred to as a “heart The present invention is in the field of coronary heart attack, is the most common cause of mortality in developed disease (CHD), particularly myocardial infarction (MI), as countries. The incidence of MI is still high despite currently well as aneurysm/dissection and drug response, particularly available preventive measures and therapeutic intervention. response to statin treatment. In particular, the present inven More than 1,500,000 people in the U.S. suffer acute MI each tion relates to specific single nucleotide polymorphisms year, many without seeking help due to unrecognized MI, and (SNPs) in the human genome, and their association with one third of these people die. The lifetime risk of coronary CHD, aneurysm/dissection, and/or variability in responsive artery disease events at age 40 is 42.4% for men, nearly one in ness to statin treatment (including preventive treatment) two, and 24.9% for women, or one in four. D. M. Lloyd-Jones, between different individuals. The SNPs disclosed hereincan Lancet 353:89-92 (1999). be used as targets for the design of diagnostic reagents and the 25 MI is a multifactorial disease that involves atherogenesis, development of therapeutic agents, as well as for disease thrombus formation and propagation. Thrombosis can result association and linkage analysis. In particular, the SNPs of in complete or partial occlusion of coronary arteries. The the present invention are useful for identifying an individual luminal narrowing or blockage of coronary arteries reduces who is at an increased or decreased risk of developing CHD oxygen and nutrient Supply to the cardiac muscle (cardiac (particularly MI) and aneurysm/dissection, for early detec 30 ischemia), leading to myocardial necrosis and/or stunning. tion of the disease, for providing clinically important infor MI, unstable angina, and sudden ischemic death are clinical mation for the prevention and/or treatment of CHD and aneu manifestations of cardiac muscle damage. All three endpoints rySm/dissection, for predicting the seriousness or are part of acute coronary syndrome since the underlying consequences of CHD and aneurysm/dissection in an indi mechanisms of acute complications of atherosclerosis are vidual, for determining the prognosis of an individuals 35 considered to be the same. recovery from CHD and aneurysm/dissection, for screening Atherogenesis, the first step of pathogenesis of MI, is a and selecting therapeutic agents, and for predictingapatients complex interaction between blood elements, mechanical response to therapeutic agents such as evaluating the likeli forces, disturbed blood flow, and vessel wall abnormality that hood of an individual responding positively to statins, par results in plaque accumulation. An unstable (Vulnerable) ticularly for the treatment or prevention of CHD (such as MI) 40 plaque was recognized as an underlying cause of arterial and aneurysm/dissection. The SNPs disclosed herein are also thrombotic events and MI. A Vulnerable plaque is a plaque, useful for human identification applications. Methods, often not stenotic, that has a high likelihood of becoming assays, kits, and reagents for detecting the presence of these disrupted or eroded, thus forming a thrombogenic focus. MI polymorphisms and their encoded products are provided. due to a Vulnerable plaque is a complex phenomenon that 45 includes: plaque vulnerability, blood vulnerability (hyperco BACKGROUND OF THE INVENTION agulation, hypothrombolysis), and heart Vulnerability (sensi tivity of the heart to ischemia or propensity for arrhythmia). Coronary Heart Disease (CHD), Recurrent myocardial infarction (RMI) can generally be Aneurysm/Dissection, and Response to Statin 50 viewed as a severe form of MI progression caused by multiple Treatment Vulnerable plaques that are able to undergo pre-rupture or a pre-erosive state, coupled with extreme blood coagulability. The present invention relates to SNPs that are associated The current diagnosis of MI is based on the levels of with the occurrence of coronary heart disease (CHD), par troponin I or T that indicate the cardiac muscle progressive ticularly myocardial infarction (MI), as well as aortic aneu 55 necrosis, impaired electrocardiogram (ECG), and detection rysm and dissection. The present invention also relates to of abnormal ventricular wall motion orangiographic data (the SNPs that are associated with variability between different presence of acute thrombi). However, due to the asymptom individuals in their response to treatment (including preven atic nature of 25% of acute MIs (absence of atypical chest tive treatments)
Load more

Recommended publications
  • ERK Phosphorylation of MED14 in Promoter Complexes During Mitogen-Induced Gene Activation by Elk-1 Matthew D
    Published online 17 September 2013 Nucleic Acids Research, 2013, Vol. 41, No. 22 10241–10253 doi:10.1093/nar/gkt837 ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 Matthew D. Galbraith1,2, Janice Saxton1,LiLi1, Samuel J. Shelton1,3, Hongmei Zhang1,4, Joaquin M. Espinosa2 and Peter E. Shaw1,* 1School of Biomedical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, NG7 2UH, UK, 2Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, CO 80309, USA, 3Department of Neurology, Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 90089, USA and 4Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China Received March 22, 2013; Revised August 21, 2013; Accepted August 28, 2013 ABSTRACT INTRODUCTION The ETS domain transcription factor Elk-1 stimu- The specific and temporal co-ordination of gene expres- lates expression of immediate early genes (IEGs) in sion is a fundamental process of cell-based life with response to mitogens. These events require phos- patterns of gene expression controlling proliferation, dif- phorylation of Elk-1 by extracellular signal-regulated ferentiation and cell death. Immediate early gene (IEG) expression has revealed how crucial regulatory events kinase (ERK) and phosphorylation-dependent inter- revolve around the interface between pathway-specific action of Elk-1 with co-activators, including histone transcription factors and components of the transcription acetyltransferases and the Mediator complex. Elk-1 machinery, involving a plethora of protein interactions also recruits ERK to the promoters of its target and modifications (1,2).
    [Show full text]
  • UC Riverside UC Riverside Previously Published Works
    UC Riverside UC Riverside Previously Published Works Title Analysis of the Candida albicans Phosphoproteome. Permalink https://escholarship.org/uc/item/0663w2hr Journal Eukaryotic cell, 14(5) ISSN 1535-9778 Authors Willger, SD Liu, Z Olarte, RA et al. Publication Date 2015-05-01 DOI 10.1128/ec.00011-15 License https://creativecommons.org/licenses/by-nc-sa/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Analysis of the Candida albicans Phosphoproteome S. D. Willger,a Z. Liu,b R. A. Olarte,c M. E. Adamo,d J. E. Stajich,c L. C. Myers,b A. N. Kettenbach,b,d D. A. Hogana Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USAa; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USAb; Department of Plant Pathology and Microbiology, University of California, Riverside, California, USAc; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USAd Candida albicans is an important human fungal pathogen in both immunocompetent and immunocompromised individuals. C. albicans regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm forma- tion, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that pro- tein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in C. albicans regulation, we performed a deep analysis of the phosphoproteome in C. albicans. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins.
    [Show full text]
  • Variation in Protein Coding Genes Identifies Information
    bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 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-ND 4.0 International license. Animal complexity and information flow 1 1 2 3 4 5 Variation in protein coding genes identifies information flow as a contributor to 6 animal complexity 7 8 Jack Dean, Daniela Lopes Cardoso and Colin Sharpe* 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Institute of Biological and Biomedical Sciences 25 School of Biological Science 26 University of Portsmouth, 27 Portsmouth, UK 28 PO16 7YH 29 30 * Author for correspondence 31 [email protected] 32 33 Orcid numbers: 34 DLC: 0000-0003-2683-1745 35 CS: 0000-0002-5022-0840 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Abstract bioRxiv preprint doi: https://doi.org/10.1101/679456; this version posted June 21, 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-ND 4.0 International license. Animal complexity and information flow 2 1 Across the metazoans there is a trend towards greater organismal complexity. How 2 complexity is generated, however, is uncertain. Since C.elegans and humans have 3 approximately the same number of genes, the explanation will depend on how genes are 4 used, rather than their absolute number.
    [Show full text]
  • Med9 (N-17): Sc-243449
    SAN TA C RUZ BI OTEC HNOL OG Y, INC . Med9 (N-17): sc-243449 BACKGROUND APPLICATIONS In mammalian cells, transcription is regulated in part by high molecular weight Med9 (N-17) is recommended for detection of Med9 of human origin by co-activating complexes that mediate signals between transcriptional activa - Western Blotting (starting dilution 1:200, dilution range 1:100-1:1000), tors and RNA polymerase II (Pol II). The mediator complex is one such multi- immunoprecipitation [1-2 µg per 100-500 µg of total protein (1 ml of cell protein structure that functions as a bridge between regulatory proteins and lysate)], immunofluorescence (starting dilution 1:50, dilution range 1:50- Pol II, thereby regulating Pol II-dependent transcription. Med9 (mediator com - 1:500) and solid phase ELISA (starting dilution 1:30, dilution range 1:30- plex subunit 9), also known as MED25, is a 146 amino acid nuclear protein 1:3000); non cross-reactive with other Med family members. and component of the mediator complex. Med9 directly interacts with Med4 Suitable for use as control antibody for Med9 siRNA (h): sc-94034, Med9 and is encoded by a gene that maps to human chromosome 17p11.2. Chromo- shRNA Plasmid (h): sc-94034-SH and Med9 shRNA (h) Lentiviral Particles: some 17 comprises over 2.5% of the human genome, encodes over 1,200 sc-94034-V. genes and is associated with two key tumor suppressor genes, namely, p53 and BRCA1. Molecular Weight of Med9: 16 kDa. Positive Controls: HeLa whole cell lysate: sc-2200, K-562 whole cell lysate: REFERENCES sc-2203 or Hep G2 cell lysate: sc-2227.
    [Show full text]
  • 2014-Platform-Abstracts.Pdf
    American Society of Human Genetics 64th Annual Meeting October 18–22, 2014 San Diego, CA PLATFORM ABSTRACTS Abstract Abstract Numbers Numbers Saturday 41 Statistical Methods for Population 5:30pm–6:50pm: Session 2: Plenary Abstracts Based Studies Room 20A #198–#205 Featured Presentation I (4 abstracts) Hall B1 #1–#4 42 Genome Variation and its Impact on Autism and Brain Development Room 20BC #206–#213 Sunday 43 ELSI Issues in Genetics Room 20D #214–#221 1:30pm–3:30pm: Concurrent Platform Session A (12–21): 44 Prenatal, Perinatal, and Reproductive 12 Patterns and Determinants of Genetic Genetics Room 28 #222–#229 Variation: Recombination, Mutation, 45 Advances in Defining the Molecular and Selection Hall B1 Mechanisms of Mendelian Disorders Room 29 #230–#237 #5-#12 13 Genomic Studies of Autism Room 6AB #13–#20 46 Epigenomics of Normal Populations 14 Statistical Methods for Pedigree- and Disease States Room 30 #238–#245 Based Studies Room 6CF #21–#28 15 Prostate Cancer: Expression Tuesday Informing Risk Room 6DE #29–#36 8:00pm–8:25am: 16 Variant Calling: What Makes the 47 Plenary Abstracts Featured Difference? Room 20A #37–#44 Presentation III Hall BI #246 17 New Genes, Incidental Findings and 10:30am–12:30pm:Concurrent Platform Session D (49 – 58): Unexpected Observations Revealed 49 Detailing the Parts List Using by Exome Sequencing Room 20BC #45–#52 Genomic Studies Hall B1 #247–#254 18 Type 2 Diabetes Genetics Room 20D #53–#60 50 Statistical Methods for Multigene, 19 Genomic Methods in Clinical Practice Room 28 #61–#68 Gene Interaction
    [Show full text]
  • Evolution and Diversity of Copy Number Variation in the Great Ape Lineage
    Downloaded from genome.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Evolution and diversity of copy number variation in the great ape lineage Peter H. Sudmant1, John Huddleston1,7, Claudia R. Catacchio2, Maika Malig1, LaDeana W. Hillier3, Carl Baker1, Kiana Mohajeri1, Ivanela Kondova4, Ronald E. Bontrop4, Stephan Persengiev4, Francesca Antonacci2, Mario Ventura2, Javier Prado-Martinez5, Tomas 5,6 1,7 Marques-Bonet , and Evan E. Eichler 1. Department of Genome Sciences, University of Washington, Seattle, WA, USA 2. University of Bari, Bari, Italy 3. The Genome Institute, Washington University School of Medicine, St. Louis, MO, USA 4. Department of Comparative Genetics, Biomedical Primate Research Centre, Rijswijk, The Netherlands 5. Institut de Biologia Evolutiva, (UPF-CSIC) Barcelona, Spain 6. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain 7. Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA Correspondence to: Evan Eichler Department of Genome Sciences University of Washington School of Medicine Foege S-413A, Box 355065 3720 15th Ave NE Seattle, WA 98195 E-mail: [email protected] 1 Downloaded from genome.cshlp.org on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT Copy number variation (CNV) contributes to the genetic basis of disease and has significantly restructured the genomes of humans and great apes. The diversity and rate of this process, however, has not been extensively explored among the great ape lineages. We analyzed 97 deeply sequenced great ape and human genomes and estimate that 16% (469 Mbp) of the hominid genome has been affected by recent copy number changes.
    [Show full text]
  • A Novel Locus for Congenital Simple Microphthalmia Family Mapping to 17P12-Q12
    Genetics A Novel Locus for Congenital Simple Microphthalmia Family Mapping to 17p12-q12 Zhengmao Hu,1,2,3 Changhong Yu,3,4,5 Jingzhi Li,1 Yiqiang Wang,4 Deyuan Liu,1 Xinying Xiang,1,2 Wei Su,1 Qian Pan,1 Lixin Xie,*,4 and Kun Xia*,1,2 PURPOSE. To investigate the etiology in a family with autosomal- opia (ϩ7.00 to ϩ13.00 D), a high lens-to-eye volume ratio, and dominant congenital simple microphthalmia of Chinese origin. a high incidence of angle-closure glaucoma after middle age. ETHODS Some normal adnexal elements and eyelids are usually pres- M . A whole-genome scan was performed by using 382 1 microsatellite DNA markers after the exclusion of reported ent. It is also a common symptom in some other ocular candidates linked to microphthalmia. Additional fluorescent abnormalities. Approximately 80% of microphthalmia cases markers were genotyped for fine mapping. To find out the occur as part of syndromes that include other systemic malfor- mations, especially cardiac defects, facial clefts, microcephaly, novel predisposing gene, 14 candidate genes including 2,3 CRYBA1 and NCOR1 were selected to screen for the mutation and hydrocephaly. The reported prevalence of anophthal- mia or microphthalmia at birth is 0.66 of 10,000 around the by the PCR direct-sequencing method. Genome-wide single- 4 nucleotide polymorphism (SNP) genotyping was performed to world and 0.3 of 10,000 in China. find out the pathogenetic copy number variation, as well. Epidemiologic studies have indicated that both heritable and environmental factors cause microphthalmia. Although the RESULTS.
    [Show full text]
  • Algorithms to Integrate Omics Data for Personalized Medicine
    ALGORITHMS TO INTEGRATE OMICS DATA FOR PERSONALIZED MEDICINE by MARZIEH AYATI Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Thesis Adviser: Mehmet Koyut¨urk Department of Electrical Engineering and Computer Science CASE WESTERN RESERVE UNIVERSITY August, 2018 Algorithms to Integrate Omics Data for Personalized Medicine Case Western Reserve University Case School of Graduate Studies We hereby approve the thesis1 of MARZIEH AYATI for the degree of Doctor of Philosophy Mehmet Koyut¨urk 03/27/2018 Committee Chair, Adviser Date Department of Electrical Engineering and Computer Science Mark R. Chance 03/27/2018 Committee Member Date Center of Proteomics Soumya Ray 03/27/2018 Committee Member Date Department of Electrical Engineering and Computer Science Vincenzo Liberatore 03/27/2018 Committee Member Date Department of Electrical Engineering and Computer Science 1We certify that written approval has been obtained for any proprietary material contained therein. To the greatest family who I owe my life to Table of Contents List of Tables vi List of Figures viii Acknowledgements xxi Abstract xxiii Abstract xxiii Chapter 1. Introduction1 Chapter 2. Preliminaries6 Complex Diseases6 Protein-Protein Interaction Network6 Genome-Wide Association Studies7 Phosphorylation 10 Biweight midcorrelation 10 Chapter 3. Identification of Disease-Associated Protein Subnetworks 12 Introduction and Background 12 Methods 15 Results and Discussion 27 Conclusion 40 Chapter 4. Population Covering Locus Sets for Risk Assessment in Complex Diseases 43 Introduction and Background 43 iv Methods 47 Results and Discussion 59 Conclusion 75 Chapter 5. Application of Phosphorylation in Precision Medicine 80 Introduction and Background 80 Methods 83 Results 89 Conclusion 107 Chapter 6.
    [Show full text]
  • The Schizosaccharomyces Pombe Mediator
    FACULTY OF SCIENCE UNIVERSITY OF COPENHAGEN PhD thesis Michela Venturi The Schizosaccharomyces pombe Mediator. Roles in heterochromatinization and analysis of additional subunits Med9/Med11 This thesis has been submitted to the PhD School of The Faculty of Science, University of Copenhagen Academic advisor: Dr. Steen Holmberg Submitted: 28/03/13 Preface This PhD thesis represents the results of my PhD project carried out at the Transcription, Chromatin and DNA Repair Laboratory at University of Copenhagen, Department of Biology under the supervision of Dr. Steen Holmberg and as result of a collaboration with Dr. Claes M. Gustafsson’s Laboratory in Stockholm and Gothenburg, Sweden. This PhD project has been partly funded by “Regione Autonoma della Sardegna”, which provided funding for my living expenses and tuition fees. A paper written in collaboration with Michael Thorsen, Heidi Hansen, Steen Holmberg and Genevieve Thon is also included. 1 Table of Contents List of abbreviations....................................................................................................................................... 4 English abstract .............................................................................................................................................. 7 Danish abstract .............................................................................................................................................. 9 INTRODUCTION ........................................................................................................................................
    [Show full text]
  • MED9 Mouse Monoclonal Antibody [Clone ID: OTI6E3] 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 TA811890 MED9 Mouse Monoclonal Antibody [Clone ID: OTI6E3] Product data: Product Type: Primary Antibodies Clone Name: OTI6E3 Applications: WB Recommended Dilution: WB 1:2000 Reactivity: Human Host: Mouse Isotype: IgG1 Clonality: Monoclonal Immunogen: Full length human recombinant protein of human MED9 (NP_060489) produced in E.coli. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 16.2 kDa Gene Name: mediator complex subunit 9 Database Link: NP_060489 Entrez Gene 55090 Human Q9NWA0 Background: The multiprotein Mediator complex is a coactivator required for activation of RNA polymerase II transcription by DNA bound transcription factors. The protein encoded by this gene is thought to be a subunit of the Mediator complex. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008] Synonyms: MED25 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 MED9 Mouse Monoclonal Antibody [Clone ID: OTI6E3] – TA811890 Product images: HEK293T cells were transfected with the pCMV6- ENTRY control (Left lane) or pCMV6-ENTRY MED9 ([RC211226], Right lane) cDNA for 48 hrs and lysed.
    [Show full text]
  • Sheet1 Page 1 Gene Symbol Gene Description Entrez Gene ID
    Sheet1 RefSeq ID ProbeSets Gene Symbol Gene Description Entrez Gene ID Sequence annotation Seed matches location(s) Ago-2 binding specific enrichment (replicate 1) Ago-2 binding specific enrichment (replicate 2) OE lysate log2 fold change (replicate 1) OE lysate log2 fold change (replicate 2) Probability NM_022823 218843_at FNDC4 Homo sapiens fibronectin type III domain containing 4 (FNDC4), mRNA. 64838 TR(1..1649)CDS(367..1071) 1523..1530 3.73 1.77 -1.91 -0.39 1 NM_003919 204688_at SGCE Homo sapiens sarcoglycan, epsilon (SGCE), transcript variant 2, mRNA. 8910 TR(1..1709)CDS(112..1425) 1495..1501 3.09 1.56 -1.02 -0.27 1 NM_006982 206837_at ALX1 Homo sapiens ALX homeobox 1 (ALX1), mRNA. 8092 TR(1..1320)CDS(5..985) 916..923 2.99 1.93 -0.19 -0.33 1 NM_019024 233642_s_at HEATR5B Homo sapiens HEAT repeat containing 5B (HEATR5B), mRNA. 54497 TR(1..6792)CDS(97..6312) 5827..5834,4309..4315 3.28 1.51 -0.92 -0.23 1 NM_018366 223431_at CNO Homo sapiens cappuccino homolog (mouse) (CNO), mRNA. 55330 TR(1..1546)CDS(96..749) 1062..1069,925..932 2.89 1.51 -1.2 -0.41 1 NM_032436 226194_at C13orf8 Homo sapiens chromosome 13 open reading frame 8 (C13orf8), mRNA. 283489 TR(1..3782)CDS(283..2721) 1756..1762,3587..3594,1725..1731,3395..3402 2.75 1.72 -1.38 -0.34 1 NM_031450 221534_at C11orf68 Homo sapiens chromosome 11 open reading frame 68 (C11orf68), mRNA. 83638 TR(1..1568)CDS(153..908) 967..973 3.07 1.35 -0.72 -0.06 1 NM_033318 225795_at,225794_s_at C22orf32 Homo sapiens chromosome 22 open reading frame 32 (C22orf32), mRNA.
    [Show full text]
  • Anti-MED9 Antibody (ARG59444)
    Product datasheet [email protected] ARG59444 Package: 50 μg anti-MED9 antibody Store at: -20°C Summary Product Description Rabbit Polyclonal antibody recognizes MED9 Tested Reactivity Hu, Ms, Rat Tested Application FACS, ICC/IF, IHC-P, WB Host Rabbit Clonality Polyclonal Isotype IgG Target Name MED9 Species Human Immunogen Recombinant protein corresponding to A55-E146 of Human MED9. Conjugation Un-conjugated Alternate Names Mediator of RNA polymerase II transcription subunit 9; Mediator complex subunit 9; MED25 Application Instructions Application table Application Dilution FACS 1:150 - 1:500 ICC/IF 1:200 - 1:1000 IHC-P 0.5 - 1 µg/ml WB 0.1 - 0.5 µg/ml Application Note IHC-P: Antigen Retrieval: Heat mediation was performed in Citrate buffer (pH 6.0) for 20 min. * The dilutions indicate recommended starting dilutions and the optimal dilutions or concentrations should be determined by the scientist. Properties Form Liquid Purification Affinity purification with immunogen. Buffer 0.9% NaCl, 0.2% Na2HPO4, 0.05% Sodium azide and 5% BSA. Preservative 0.05% Sodium azide Stabilizer 5% BSA Concentration 0.5 mg/ml Storage instruction For continuous use, store undiluted antibody at 2-8°C for up to a week. For long-term storage, aliquot and store at -20°C or below. Storage in frost free freezers is not recommended. Avoid repeated freeze/thaw cycles. Suggest spin the vial prior to opening. The antibody solution should be gently mixed before use. www.arigobio.com 1/4 Note For laboratory research only, not for drug, diagnostic or other use. Bioinformation Gene Symbol MED9 Gene Full Name mediator complex subunit 9 Background The multiprotein Mediator complex is a coactivator required for activation of RNA polymerase II transcription by DNA bound transcription factors.
    [Show full text]