DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2005/0112574 A1 Gamble Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2005/0112574 A1 Gamble Et Al US 2005O112574A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0112574 A1 Gamble et al. (43) Pub. Date: May 26, 2005 (54) DNA SEQUENCES FOR HUMAN (30) Foreign Application Priority Data ANGIOGENESIS GENES Sep. 27, 2001 (AU)............................................ PR 7973 (76) Inventors: Jennifer Ruth Gamble, Stirling (AU); Sep. 27, 2001 (AU)............................................ PR 7974 Christopher Norman Hahn, Modbury Oct. 11, 2001 (AU)............................................ PR 8210 (AU); Mathew Alexander Vadas, Oct. 29, 2001 (AU)............................................ PR 8532 Stirling (AU) Nov. 13, 2001 (AU)............................................ PR 8838 Aug. 28, 2002 (AU)...................................... 2002951O32 Correspondence Address: JENKINS, WILSON & TAYLOR, P. A. Publication Classification 3100 TOWER BLVD SUTE 1400 (51) Int. Cl." ............................ C12O 1/68; CO7H 21/04; DURHAM, NC 27707 (US) C12N 9/64 (52) U.S. Cl. ............................. 435/6; 435/69.1; 435/226; (21) Appl. No.: 10/489,740 435/320.1; 435/325; 536/23.2 (22) PCT Filed: Sep. 19, 2002 (57) ABSTRACT An isolated nucleic acid molecule comprising the Sequence (86) PCT No.: PCT/AUO2/O1282 Set forth in one of SEO ID Numbers: 1 to 20. Patent Application Publication May 26, 2005 Sheet 1 of 11 US 2005/0112574 A1 Figure 1 O 0.5 3 6 24 hr O OS 3 6 24 hr Class A (up at 0.5 hr) Class B (up at 3 hr) Class C (down at 0.5 hr) Class D (down at 3hr) Class E (other patterns) Class F (unregulated) Control s GAPDH1 Patent Application Publication May 26, 2005 Sheet 2 of 11 US 2005/0112574 A1 s A HUVEC T3 er HUVECTO HUSMC--P HUSMC-P Fibroblasts HEK293 DU145 N MB-231 M LM12-15 HepG2 HeLa Jurkat KG-la K562 f 5 Patent Application Publication May 26, 2005 Sheet 3 of 11 US 2005/0112574 A1 ac en > We er l? Ce Ces ur O C a HUVEC T3 (g: A.> We ef HUVECTO E.af N s HUSMC-HP en HUSMC-P s We z Fibroblasts s HEK293 c es , a Y. 9 DU145 i. 3. MDA-MB-231 LlM12-15 HeLa Jurkat KG-la K562 as a A-4p a se r is as ad aro A A at 8 p as aw at are a was a v are 5 Patent Application Publication May 26, 2005 Sheet 4 of 11 US 2005/0112574 A1 Figure 4 5.0 4.0 C9 V a 3.0 É 2.0 O s 1.0 0.0 EV ASBNO69R Patent Application Publication May 26, 2005 Sheet 5 of 11 US 2005/0112574 A1 Figure 5 1.25 1.00 O 0.75 2 as9 0.50 A O 0.25 0.00 EV ASBNO69A EV ASBNO69A Day0 Day3 Patent Application Publication May 26, 2005 Sheet 6 of 11 US 2005/0112574 A1 Figure 6 ASBNO69R Patent Application Publication May 26, 2005 Sheet 7 of 11 US 2005/0112574 A1 Figure 7 ASBNO96 1.00 5 0.75 s is 0.50 A. d 0.25 0.00 Day 0 Day 3 Patent Application Publication May 26, 2005 Sheet 8 of 11 US 2005/0112574 A1 Figure 8 40 23 OO 1. O NL FN NIL FN EV ASBNO96 Patent Application Publication May 26, 2005 Sheet 9 of 11 US 2005/0112574 A1 Figure 9 Patent Application Publication May 26, 2005 Sheet 10 of 11 US 2005/0112574 A1 Figure 10 EV ASBNO96 Patent Application Publication May 26, 2005 Sheet 11 of 11 US 2005/0112574 A1 Figure 11 Basal E-selectin 4-hr TNF induced (MFI) E-selectin (MFI) Normal HUVEC O.O3 26.5 ASGNG12 US 2005/0112574 A1 May 26, 2005 DNA SEQUENCES FOR HUMAN ANGIOGENESIS known about the changes in cell morphology leading to GENES lumen formation or the Signals required for ECS to construct this feature. TECHNICAL FIELD 0007 An in vitro model of angiogenesis has been created 0001. The present invention relates to novel nucleic acid from human umbilical vein ECs plated onto a 3 dimensional Sequences (“angiogenic genes”) involved in the process of collagen matrix (Gamble et al., 1993). In the presence of angiogenesis. Each of the angiogenic genes encode a phorbol myristate acetate (PMA) these cells form capillary polypeptide that has a role in angiogenesis. In View of the tubes within 24 hours. With the addition of anti-integrin realisation that these genes play a role in angiogenesis, the antibodies, the usually unicellular tubes (thought to reflect invention is also concerned with the therapy of pathologies an immature, poorly differentiated phenotype) are converted asSociated with angiogenesis, the Screening of drugs for pro to form a multicellular lumen through the inhibition of or anti-angiogenic activity, the diagnosis and prognosis of cell-matrix interactions and promotion of cell-cell interac pathologies associated with angiogenesis, and in Some cases tions. This model has Subsequently allowed the investigation the use of the nucleic acid Sequences to identify and obtain of the morphological events which occur in lumen forma full-length angiogenesis-related genes. tion. 0008 For the treatment of diseases associated with angio BACKGROUND ART genesis, understanding the molecular genetic mechanisms of 0002 The formation of new blood vessels from pre the proceSS is of paramount importance. The use of the in existing vessels, a process termed angiogenesis, is essential vitro model described above (Gamble et al., 1993), a model for normal growth. Important angiogenic processes include that reflects the critical events that occur during angiogen those taking place in embryogenesis, renewal of the esis in Vivo in a time dependent and broadly Synchronous endometrium, formation and growth of the corpus luteum of manner, has provided a tool for the identification of the key pregnancy, wound healing and in the restoration of tissue genes involved. Structure and function after injury. 0009. A number of genes have been identified from this 0003. The formation of new capillaries requires a coor model to be differentially expressed during the angiogenesis dinated Series of events mediated through the expression of process. Functional analysis of a Subset of these angiogenic multiple genes which may have either pro- or anti-angio genes and their effect on endothelial cell function and genic activities. The process begins with an angiogenic proliferation is described in detail below. Stimulus to existing vasculature, usually mediated by growth factorS Such as vascular endothelial growth factor or basic 0010. The isolation of these angiogenic genes has pro fibroblast growth factor. This is followed by degradation of Vided novel targets for the treatment of angiogenesis-related the extracellular matrix, cell adhesion changes (and disrup disorders. tion), an increase in cell permeability, proliferation of endot helial cells (ECs) and migration of ECs towards the site of DISCLOSURE OF THE INVENTION blood vessel formation. Subsequent processes include cap 0011. The present invention provides isolated nucleic illary tube or lumen formation, stabilisation and differentia acid molecules, which have been shown to be regulated in tion by the migrating ECs. their expression during angiogenesis (see Tables 1 and 2). 0004. In the (normal) healthy adult, angiogenesis is vir tually arrested and occurs only when needed. However, a 0012. In a first aspect of the present invention there is number of pathological situations are characterised by provided an isolated nucleic acid molecule as defined by enhanced, uncontrolled angiogenesis. These conditions SEO ID Numbers: 1 to 20 and laid out in Table 1. include cancer, rheumatoid arthritis, diabetic retinopathy, 0013 Following the realisation that these molecules, and pSoriasis and cardiovascular diseases Such as atherosclero those listed in Table 2, are regulated in their expression Sis. In other pathologies Such as ischaemic limb disease or during angiogenesis, the invention provides isolated nucleic in coronary artery disease, growing new vessels through the acid molecules as defined by SEQ ID Numbers: 1 to 114, promotion of an expanding vasculature would be of benefit. and laid out in Tables 1 and 2, or fragments thereof, that play 0005. A number of in vitro assays have been established a role in an angiogenic process. Such a proceSS may include, which are thought to mimic angiogenesis and these have but is not restricted to, embryogenesis, menstrual cycle, provided important tools to examine the mechanisms by wound repair, tumour angiogenesis and exercise induced which the angiogenic process takes place and the genes most muscle hypertrophy. likely to be involved. 0014. In addition, the present invention provides isolated 0006 Lumen formation is a key step in angiogenesis. The nucleic acid molecules as defined by SEQ ID Numbers: 1 to presence of vacuoles within ECS undergoing angiogenesis 114, and laid out in Tables 1 and 2 (hereinafter referred to as have been reported and their involvement in lumen forma “angiogenic genes”, “angiogenic nucleic acid molecules' or tion has been postulated (Folkman and Haudenschild, 1980; “angiogenic polypeptides” for the sake of convenience), or Gamble et al., 1993). The general mechanism of lumen fragments thereof, that play a role in diseases associated formation suggested by Folkman and Haudenschild (1980), with the angiogenic process. Diseases may include, but are has been that vacuoles form within the cytoplasm of a not restricted to, cancer, rheumatoid arthritis, diabetic ret number of aligned ECs which are later converted to a tube. inopathy, psoriasis, cardiovascular diseaseS Such as athero The union of adjacent tubes results in the formation of a Sclerosis, ischaemic limb disease and coronary artery dis continuous unicellular capillary lumen. However, little is CSC. US 2005/0112574 A1 May 26, 2005 0.015 The invention also encompasses an isolated nucleic alter angiogenic gene-encoding Sequences for a variety of acid molecule that is at least 70% identical to any one of the purposes. These include, but are not limited to, modification angiogenic genes of the invention and which plays a role in of the cloning, processing, and/or expression of the gene the angiogenic process.
Load more

Recommended publications
  • Pirfenidone Is Renoprotective in Diabetic Kidney Disease
    BASIC RESEARCH www.jasn.org Pirfenidone Is Renoprotective in Diabetic Kidney Disease ʈ Satish P. RamachandraRao,*†‡ Yanqing Zhu,‡ Timothy Ravasi,§ Tracy A. McGowan,‡ Irene Toh,‡ Stephen R. Dunn,‡¶ Shinichi Okada,*† Michael A. Shaw,** and Kumar Sharma*†‡ *Center for Renal Translational Medicine, Division of Nephrology-Hypertension, Department of Medicine, and ʈ §Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, Scripps NeuroAIDS Preclinical Studies Centre, and †Veterans Administration San Diego Healthcare System, La Jolla, California, ‡Center for Novel Therapies in Kidney Disease, Department of Medicine, ¶Cancer Genomics Facility, Kimmel Cancer Center, and **Proteomics and Mass Spectrometry Core Facility, Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania ABSTRACT Although several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. Here, we evaluated the role of PFD in regulation of the extracellular matrix. In mouse mesangial cells, PFD decreased TGF-␤ promoter activity, reduced TGF-␤ protein secretion, and inhibited TGF-␤–induced Smad2-phosphor- ylation, 3TP-lux promoter activity, and generation of reactive oxygen species. To explore the therapeutic potential of PFD, we administered PFD to 17-wk-old db/db mice for 4 wk. PFD treatment significantly reduced mesangial matrix expansion and expression of renal matrix genes but did not affect albuminuria. Using liquid chromatography with subsequent electrospray ionization tandem mass spectrometry, we iden- tified 21 proteins unique to PFD-treated diabetic kidneys. Analysis of gene ontology and protein–protein interactions of these proteins suggested that PFD may regulate RNA processing.
    [Show full text]
  • Evolutionary Fate of Retroposed Gene Copies in the Human Genome
    Evolutionary fate of retroposed gene copies in the human genome Nicolas Vinckenbosch*, Isabelle Dupanloup*†, and Henrik Kaessmann*‡ *Center for Integrative Genomics, University of Lausanne, Ge´nopode, 1015 Lausanne, Switzerland; and †Computational and Molecular Population Genetics Laboratory, Zoological Institute, University of Bern, 3012 Bern, Switzerland Communicated by Wen-Hsiung Li, University of Chicago, Chicago, IL, December 30, 2005 (received for review December 14, 2005) Given that retroposed copies of genes are presumed to lack the and rodent genomes (7–12). In addition, three recent studies regulatory elements required for their expression, retroposition using EST data (13, 14) and tiling-microarray data from chro- has long been considered a mechanism without functional rele- mosome 22 (15) indicated that retrocopy transcription may be vance. However, through an in silico assay for transcriptional widespread, although these surveys were limited, and potential activity, we identify here >1,000 transcribed retrocopies in the functional implications were not addressed. human genome, of which at least Ϸ120 have evolved into bona To further explore the functional significance of retroposition fide genes. Among these, Ϸ50 retrogenes have evolved functions in the human genome, we systematically screened for signatures in testes, more than half of which were recruited as functional of selection related to retrocopy transcription. Our results autosomal counterparts of X-linked genes during spermatogene- suggest that retrocopy transcription is not rare and that the sis. Generally, retrogenes emerge ‘‘out of the testis,’’ because they pattern of transcription of human retrocopies has been pro- are often initially transcribed in testis and later evolve stronger and foundly shaped by natural selection, acting both for and against sometimes more diverse spatial expression patterns.
    [Show full text]
  • View of All NF-Κb Post-Translational Modifications See Review by Perkins [179]
    UNIVERSITY OF CINCINNATI Date: 8-May-2010 I, Michael Wilhide , hereby submit this original work as part of the requirements for the degree of: Master of Science in Molecular, Cellular & Biochemical Pharmacology It is entitled: Student Signature: Michael Wilhide This work and its defense approved by: Committee Chair: Walter Jones, PhD Walter Jones, PhD Mohammed Matlib, PhD Mohammed Matlib, PhD Basilia Zingarelli, MD, PhD Basilia Zingarelli, MD, PhD Jo El Schultz, PhD Jo El Schultz, PhD Muhammad Ashraf, PhD Muhammad Ashraf, PhD 5/8/2010 646 Hsp70.1 contributes to the NF-κΒ paradox after myocardial ischemic insults A thesis submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirement for the degree of Master of Science (M.S.) in the Department of Pharmacology and Biophysics of the College of Medicine by Michael E. Wilhide B.S. College of Mount St. Joseph 2002 Committee Chair: W. Keith Jones, Ph.D. Abstract One of the leading causes of death globally is cardiovascular disease, with most of these deaths related to myocardial ischemia. Myocardial ischemia and reperfusion causes several biochemical and metabolic changes that result in the activation of transcription factors that are involved in cell survival and cell death. The transcription factor Nuclear Factor-Kappa B (NF-κB) is associated with cardioprotection (e.g. after permanent coronary occlusion, PO) and cell injury (e.g. after ischemia/reperfusion, I/R). However, there is a lack of knowledge regarding how NF- κB mediates cell survival vs. cell death after ischemic insults, preventing the identification of novel therapeutic targets for enhanced cardioprotection and decreased injurious effects.
    [Show full text]
  • UNIVERSITY of CALIFORNIA, SAN DIEGO the Proteome of Mouse
    UNIVERSITY OF CALIFORNIA, SAN DIEGO The Proteome of Mouse Brain Microvessel Membranes and Basal Lamina A thesis submitted in partial satisfaction of the requirements for the degree Master of Science in Biology by Hyun Bae Chun Committee in charge: Professor Brian P. Eliceiri, Chair Professor Andrew D. Chisholm, Co-chair Professor Steven P. Briggs 2011 The Thesis of Hyun Bae Chun is approved and it is accepted in quality and form for publication on microfilm and electronically: ___________________________________________________________________ ___________________________________________________________________ Co-Chair ___________________________________________________________________ Chair University of California, San Diego 2011 iii TABLE OF CONTENTS Signature Page ………………………………….………………………………..….. iii Table of Contents …............................................................................................. iv List of Abbreviations …………………………….…………………………………… v List of Figures ………………………………………………………………………... vi List of Tables …………………………………………………………………………. vii List of Supplementary Tables ………………………………………………………. viii Acknowledgements ………………………………………………………………….. ix Abstract ……………………………………………………………………………….. x Introduction ……………………………………………………………………………. 1 Materials and Methods ……………………………………………………………….. 6 Results …………………………………………………………………………...…….. 10 Discussion ……………………………………………………………………………… 18 Figures ……………………………………………………………………………...….. 26 Tables…………………………………………………………………………………... 30 Supplementary Tables………………………………………………………………… 39 References……………………………………………………………….…………….
    [Show full text]
  • Dual Transgene Expression by Foamy Virus Vectors Carrying an Endogenous Bidirectional Promoter
    Gene Therapy (2010) 17, 380–388 & 2010 Macmillan Publishers Limited All rights reserved 0969-7128/10 $32.00 www.nature.com/gt ORIGINAL ARTICLE Dual transgene expression by foamy virus vectors carrying an endogenous bidirectional promoter A Andrianaki1,4, EK Siapati1,4, RK Hirata2, DW Russell2 and G Vassilopoulos1,3 1Cell and Gene Therapy Laboratory, Center for Basic Research II, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; 2Division of Haematology, Department of Medicine, University of Washington, Seattle, WA, USA and 3Division of Haematology, University of Thessaly Medical School, Larissa, Greece Several gene therapy applications require the transfer and (range from 76 to 18%). Comparison of EGFP and DNGFR simultaneous expression of multiple genes in the same cell. levels revealed that the side of the promoter that drives the In this study, we analyzed the potential for coordinated expression of the HNRNPH2 gene in the genome was expression of an endogenous bidirectional promoter located stronger and in accordance to its in situ activity. When tested on chromosome X, which controls the expression of the with CD34+ cells, transgene coexpression reached 35.3% heterogeneous nuclear ribonucleoprotein H2 (HNRNPH2) of all positive cells in progenitor assays and 16.8% of all and alpha-galactosidase (GLA) genes. The promoter was positive cells after transplantation in NOD/severe combined cloned in both transcriptional orientations in a foamy virus immunodeficient mice. In summary, we show that the (FV) vector backbone, whereas the enhanced green fluor- endogenous promoter used in this study holds bidirectional escent protein (EGFP) and low-affinity nerve growth factor activity in the context of FV vectors and can be used in gene receptor (DLNGFR) reporter genes were cloned in the 50–30 therapy applications requiring synchronized expression of two and 30–50 transcriptional orientations, respectively.
    [Show full text]
  • Global Patterns of Changes in the Gene Expression Associated with Genesis of Cancer a Dissertation Submitted in Partial Fulfillm
    Global Patterns Of Changes In The Gene Expression Associated With Genesis Of Cancer A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at George Mason University By Ganiraju Manyam Master of Science IIIT-Hyderabad, 2004 Bachelor of Engineering Bharatiar University, 2002 Director: Dr. Ancha Baranova, Associate Professor Department of Molecular & Microbiology Fall Semester 2009 George Mason University Fairfax, VA Copyright: 2009 Ganiraju Manyam All Rights Reserved ii DEDICATION To my parents Pattabhi Ramanna and Veera Venkata Satyavathi who introduced me to the joy of learning. To friends, family and colleagues who have contributed in work, thought, and support to this project. iii ACKNOWLEDGEMENTS I would like to thank my advisor, Dr. Ancha Baranova, whose tolerance, patience, guidance and encouragement helped me throughout the study. This dissertation would not have been possible without her ever ending support. She is very sincere and generous with her knowledge, availability, compassion, wisdom and feedback. I would also like to thank Dr. Vikas Chandhoke for funding my research generously during my doctoral study at George Mason University. Special thanks go to Dr. Patrick Gillevet, Dr. Alessandro Giuliani, Dr. Maria Stepanova who devoted their time to provide me with their valuable contributions and guidance to formulate this project. Thanks to the faculty of Molecular and Micro Biology (MMB) department, Dr. Jim Willett and Dr. Monique Vanhoek in embedding valuable thoughts to this dissertation by being in my dissertation committee. I would also like to thank the present and previous doctoral program directors, Dr. Daniel Cox and Dr. Geraldine Grant, for facilitating, allowing, and encouraging me to work in this project.
    [Show full text]
  • Tissue-Specific Disallowance of Housekeeping Genes
    Downloaded from genome.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation Lieven Thorrez1,2,4, Ilaria Laudadio3, Katrijn Van Deun4, Roel Quintens1,4, Nico Hendrickx1,4, Mikaela Granvik1,4, Katleen Lemaire1,4, Anica Schraenen1,4, Leentje Van Lommel1,4, Stefan Lehnert1,4, Cristina Aguayo-Mazzucato5, Rui Cheng-Xue6, Patrick Gilon6, Iven Van Mechelen4, Susan Bonner-Weir5, Frédéric Lemaigre3, and Frans Schuit1,4,$ 1 Gene Expression Unit, Dept. Molecular Cell Biology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium 2 ESAT-SCD, Department of Electrical Engineering, Katholieke Universiteit Leuven, 3000 Leuven, Belgium 3 Université Catholique de Louvain, de Duve Institute, 1200 Brussels, Belgium 4 Center for Computational Systems Biology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium 5 Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard University, Boston, MA 02215, US 6 Unité d’Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, 1200 Brussels, Belgium $ To whom correspondence should be addressed: Frans Schuit O&N1 Herestraat 49 - bus 901 3000 Leuven, Belgium Email: [email protected] Phone: +32 16 347227 , Fax: +32 16 345995 Running title: Disallowed genes Keywords: disallowance, tissue-specific, tissue maturation, gene expression, intersection-union test Abbreviations: UTR UnTranslated Region H3K27me3 Histone H3 trimethylation at lysine 27 H3K4me3 Histone H3 trimethylation at lysine 4 H3K9ac Histone H3 acetylation at lysine 9 BMEL Bipotential Mouse Embryonic Liver Downloaded from genome.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Abstract We report on a hitherto poorly characterized class of genes which are expressed in all tissues, except in one.
    [Show full text]
  • Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress
    University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations Fall 2010 Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Renuka Nayak University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Computational Biology Commons, and the Genomics Commons Recommended Citation Nayak, Renuka, "Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress" (2010). Publicly Accessible Penn Dissertations. 1559. https://repository.upenn.edu/edissertations/1559 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1559 For more information, please contact [email protected]. Coexpression Networks Based on Natural Variation in Human Gene Expression at Baseline and Under Stress Abstract Genes interact in networks to orchestrate cellular processes. Here, we used coexpression networks based on natural variation in gene expression to study the functions and interactions of human genes. We asked how these networks change in response to stress. First, we studied human coexpression networks at baseline. We constructed networks by identifying correlations in expression levels of 8.9 million gene pairs in immortalized B cells from 295 individuals comprising three independent samples. The resulting networks allowed us to infer interactions between biological processes. We used the network to predict the functions of poorly-characterized human genes, and provided some experimental support. Examining genes implicated in disease, we found that IFIH1, a diabetes susceptibility gene, interacts with YES1, which affects glucose transport. Genes predisposing to the same diseases are clustered non-randomly in the network, suggesting that the network may be used to identify candidate genes that influence disease susceptibility.
    [Show full text]
  • Supplementary Data
    SUPPLEMENTARY METHODS 1) Characterisation of OCCC cell line gene expression profiles using Prediction Analysis for Microarrays (PAM) The ovarian cancer dataset from Hendrix et al (25) was used to predict the phenotypes of the cell lines used in this study. Hendrix et al (25) analysed a series of 103 ovarian samples using the Affymetrix U133A array platform (GEO: GSE6008). This dataset comprises clear cell (n=8), endometrioid (n=37), mucinous (n=13) and serous epithelial (n=41) primary ovarian carcinomas and samples from 4 normal ovaries. To build the predictor, the Prediction Analysis of Microarrays (PAM) package in R environment was employed (http://rss.acs.unt.edu/Rdoc/library/pamr/html/00Index.html). When more than one probe described the expression of a given gene, we used the probe with the highest median absolute deviation across the samples. The dataset from Hendrix et al. (25) and the dataset of OCCC cell lines described in this manuscript were then overlaid on the basis of 11536 common unique HGNC gene symbols. Only the 99 primary ovarian cancers samples and the four normal ovary samples were used to build the predictor. Following leave one out cross-validation, a predictor based upon 126 genes was able to identify correctly the four distinct phenotypes of primary ovarian tumour samples with a misclassification rate of 18.3%. This predictor was subsequently applied to the expression data from the 12 OCCC cell lines to determine the likeliest phenotype of the OCCC cell lines compared to primary ovarian cancers. Posterior probabilities were estimated for each cell line in comparison to the following phenotypes: clear cell, endometrioid, mucinous and serous epithelial.
    [Show full text]
  • Supplemental Table 3 Two-Class Paired Significance Analysis of Microarrays Comparing Gene Expression Between Paired
    Supplemental Table 3 Two‐class paired Significance Analysis of Microarrays comparing gene expression between paired pre‐ and post‐transplant kidneys biopsies (N=8). Entrez Fold q‐value Probe Set ID Gene Symbol Unigene Name Score Gene ID Difference (%) Probe sets higher expressed in post‐transplant biopsies in paired analysis (N=1871) 218870_at 55843 ARHGAP15 Rho GTPase activating protein 15 7,01 3,99 0,00 205304_s_at 3764 KCNJ8 potassium inwardly‐rectifying channel, subfamily J, member 8 6,30 4,50 0,00 1563649_at ‐‐ ‐‐ ‐‐ 6,24 3,51 0,00 1567913_at 541466 CT45‐1 cancer/testis antigen CT45‐1 5,90 4,21 0,00 203932_at 3109 HLA‐DMB major histocompatibility complex, class II, DM beta 5,83 3,20 0,00 204606_at 6366 CCL21 chemokine (C‐C motif) ligand 21 5,82 10,42 0,00 205898_at 1524 CX3CR1 chemokine (C‐X3‐C motif) receptor 1 5,74 8,50 0,00 205303_at 3764 KCNJ8 potassium inwardly‐rectifying channel, subfamily J, member 8 5,68 6,87 0,00 226841_at 219972 MPEG1 macrophage expressed gene 1 5,59 3,76 0,00 203923_s_at 1536 CYBB cytochrome b‐245, beta polypeptide (chronic granulomatous disease) 5,58 4,70 0,00 210135_s_at 6474 SHOX2 short stature homeobox 2 5,53 5,58 0,00 1562642_at ‐‐ ‐‐ ‐‐ 5,42 5,03 0,00 242605_at 1634 DCN decorin 5,23 3,92 0,00 228750_at ‐‐ ‐‐ ‐‐ 5,21 7,22 0,00 collagen, type III, alpha 1 (Ehlers‐Danlos syndrome type IV, autosomal 201852_x_at 1281 COL3A1 dominant) 5,10 8,46 0,00 3493///3 IGHA1///IGHA immunoglobulin heavy constant alpha 1///immunoglobulin heavy 217022_s_at 494 2 constant alpha 2 (A2m marker) 5,07 9,53 0,00 1 202311_s_at
    [Show full text]
  • Evolution of Dosage Compensation in Humans and Other Questions on Sex Chromosome Evolution in Eukaryotes Eugénie Pessia
    The Y rescued by the X ? : evolution of dosage compensation in humans and other questions on sex chromosome evolution in eukaryotes Eugénie Pessia To cite this version: Eugénie Pessia. The Y rescued by the X ? : evolution of dosage compensation in humans and other questions on sex chromosome evolution in eukaryotes. Biochemistry, Molecular Biology. Université Claude Bernard - Lyon I, 2013. English. NNT : 2013LYO10261. tel-01067259 HAL Id: tel-01067259 https://tel.archives-ouvertes.fr/tel-01067259 Submitted on 23 Sep 2014 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. No 261-2013 Année 2013 These` de l’universitedelyon´ Présentée devant L’UNIVERSITÉ CLAUDE BERNARD LYON 1 pour l’obtention du Diplomeˆ de doctorat (arrêté du 7 août 2006) soutenue publiquement le 12 décembre 2013 par Eugénie Pessia Comment le X vient-il à la rescousse du Y ? Évolution de la compensation de dosage des XY humains et autres questions sur l’évolution des chromosomes sexuels eucaryotes Directeur de thèse : Gabriel Marais Jury : Tatiana Giraud Rapporteur Judith Mank Rapporteur Gabriel Marais Directeur de thèse Marie S´emon Examinateur Frédéric Veyrunes Examinateur Cristina Vieira Examinateur 2 UNIVERSITE CLAUDE BERNARD - LYON 1 Président de l’Université M.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,841,436 B2 Gorodeski Et Al
    USOO8841436B2 (12) United States Patent (10) Patent No.: US 8,841,436 B2 Gorodeski et al. (45) Date of Patent: Sep. 23, 2014 (54) SCREENING, DIAGNOSING, TREATING AND 5,139,941 A 8/1992 Muzyczka et al. ............ 435/456 PROGNOSIS OF PATHOPHYSIOLOGIC 5,252.479 A 10/1993 Srivastava .......... 435/235.1 5,427,916 A 6/1995 Gewirtz et al. ................... 435/5 STATUS BY RNA REGULATION 5,849,902 A 12/1998 Arrow et al. ... 536,245 2002fO086356 A1 7, 2002 TuSchlet al. ... ... 435/69.1 (75) Inventors: George Gorodeski, Beachwood, OH 2002/0173478 A1 11/2002 Gewirtz. ......... 514.f44 A (US); Judith Potashkin, Gurnee, IL 2004/0014113 A1 1/2004 Yang et al. ..... ... 435/6.11 (US); Bentley Cheatham, Durham, NC 2004/001817.6 A1 1/2004 Tolentino et al. .. 424.93.21 (US s s 2005/0022725 A1 2/2005 Jurgensen et al. ............ 117/104 2005. O153918 A1 7, 2005 Chabot et al. ...... 514.f44 A 2006/0105360 A1 5/2006 Croceet al. .... ... 435.6.18 (73) Assignees: University Hospitals Cleveland 2006/0292616 A1 12/2006 Neely et al. .................. 435/6.12 Medical Center, Cleveland, OH (US); 2007/00264.03 A1 2/2007 Hatzigeorgiou et al. ... 435/6.11 Rosalind Franklin University of 2008/0171715 A1 7/2008 Brown et al. ................... 514,44 Medicine and Science, an Illinois Corporation, North Chicago, IL (US) FOREIGN PATENT DOCUMENTS WO WO93/24641 12/1993 (*) Notice: Subject to any disclaimer, the term of this WO WO94f13788 6, 1994 patent is extended or adjusted under 35 WO WO 2005078139 A2 8, 2005 U.S.C.
    [Show full text]