DOCSLIB.ORG

De Rol Van ECT2L in Normale En Maligne T-Cel Ontwikkeling Maaike

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
De Rol Van ECT2L in Normale En Maligne T-Cel Ontwikkeling Maaike De rol van ECT2L in normale en maligne T-cel ontwikkeling Maaike VAN TRIMPONT Verhandeling ingediend tot het verkrijgen van de graad van Master in de Biomedische Wetenschappen Promotor: Prof. Dr. Pieter Van Vlierberghe Begeleider: Dr. Filip Matthijssens Vakgroep Pediatrie en genetica Academiejaar 2015-2016 De rol van ECT2L in normale en maligne T-cel ontwikkeling Maaike VAN TRIMPONT Verhandeling ingediend tot het verkrijgen van de graad van Master in de Biomedische Wetenschappen Promotor: Prof. Dr. Pieter Van Vlierberghe Begeleider: Dr. Filip Matthijssens Vakgroep Pediatrie en genetica Academiejaar 2015-2016 “De auteur en de promotor geven de toelating deze masterproef voor consultatie beschikbaar te stellen en delen ervan te kopiëren voor persoonlijk gebruik. Elk ander gebruik valt onder de beperkingen van het auteursrecht, in het bijzonder met betrekking tot de verplichting uitdrukkelijk de bron te vermelden bij het aanhalen van resultaten uit deze masterproef.” 9 mei 2016 Maaike Van Trimpont Pieter Van Vlierberghe VOORWOORD “I have not failed. I’ve successfully discovered 10000 things that won’t work” zei Thomas Ed- ison ooit. Wetenschap gaat inderdaad niet alleen om het uitvinden van dingen, maar ook om het ontdekken waarom sommige dingen niet werken. Hoewel het uitvoeren van deze masterproef niet altijd van een leien dakje ging, kan ik toch zeggen dat ik oprecht trots ben op het eindre- sultaat. Zes jaar geleden had ik nooit verwacht om hier te staan met alle kennis die ik nu heb. Mijn ouders hebben hierin een grote rol gespeeld en ik zou hen dan ook graag bedanken voor de kans die ze mij gegeven hebben om te studeren. Ook mijn vriend mag ik niet vergeten te bedanken om mij steeds te steunen tijdens alle hectische dagen. In het bijzonder wens ik mijn promotor Prof. Dr. Pieter Van Vlierberghe te bedanken, die dank- zij zijn grote deskundigheid binnen het vakgebied een grote bijdrage leverde aan de kwaliteit van deze masterproef. Ik zou ook graag Filip Matthijssens bedanken voor de tijd en energie die hij in dit project heeft geïnvesteerd om mij een goede begeleiding te geven, steeds te antwoor- den op mijn vragen en praktische hulp te geven. Ik wil Pieter en Filip eveneens bedanken voor de goede adviezen en suggesties voor deze masterproef. Gedurende dit jaar heb ik zeer veel bijgeleerd. De persoon die hierin een grote rol heeft gespeeld is Bea, dus bij deze een hele dikke merci aan Bea! Dankzij jou heb ik nu heel wat technieken onder de knie. Ik zal je tips and tricks, uitmuntende zangkunsten en humor in het labo nooit vergeten en ik zal hier steeds met een lach aan terugdenken. Een andere persoon die ik hiervoor moet bedanken is Lindy. Ook bij jou kon ik steeds met vragen of bedenkingen terecht. Dan rest mij nog Renate te bedanken om mij een middagje te vergezellen naar de faculteit van de bio- ingenieurs. Ook mijn lieve medestudenten Nienke en Nathalie mag ik niet vergeten. Zonder Nienke was ik ongetwijfeld nog steeds bezig met de paginanummering in Word en grafieken in Excel. Natha- lie zorgde dan weer voor een komische noot met haar opmerkingen en we konden steeds met elkaar lachen, zelfs wanneer we onze masterproef weer wat minder zagen zitten. Ik zal de her- inneringen aan de lange dagen in het labo met ons drietjes zeker koesteren. Ook de leuke sfeer en andere studenten in ons veel te kleine studentenlokaaltje zal ik nooit vergeten! i INHOUDSOPGAVE Voorwoord ............................................................................................................................................... i Inhoudsopgave......................................................................................................................................... ii Afkortingenlijst ....................................................................................................................................... v Samenvatting ........................................................................................................................................... 1 Summary ................................................................................................................................................. 2 1. Inleiding........................................................................................................................................... 3 1.1 Leukemie ................................................................................................................................. 3 1.1.1 Definitie en enkele cijfers ................................................................................................ 3 1.1.2 Classificatie leukemie ...................................................................................................... 3 1.1.3 Normale en maligne hematopoëse ................................................................................... 4 1.1.4 Normale en maligne T-cel ontwikkeling ......................................................................... 5 1.1.5 Early T-cell precursor acute lymphoblastic leukemia ..................................................... 7 1.1.6 ECT2L mutaties en leukemie ........................................................................................... 7 1.2 Epithelial cell transforming 2 oncogene-like .......................................................................... 8 1.2.1 ECT2L gen ....................................................................................................................... 8 1.2.2 Domeinen ........................................................................................................................ 9 1.2.3 Functie ........................................................................................................................... 10 1.2.4 Orthologen en modelorganismen .................................................................................. 11 1.2.5 Expressie ....................................................................................................................... 12 1.3 ECT2L in andere kankers ...................................................................................................... 14 2. Materiaal en Methoden .................................................................................................................. 16 2.1 Conditioneel knockout muismodel ........................................................................................ 16 2.2 Collecteren muisweefsels ...................................................................................................... 18 2.3 RNA isolatie .......................................................................................................................... 18 2.4 cDNA synthese ...................................................................................................................... 18 2.5 qPCR ..................................................................................................................................... 18 2.6 Cellyse ................................................................................................................................... 19 2.7 Meten van eiwitconcentraties ................................................................................................ 19 2.8 Western blot analyse ............................................................................................................. 19 2.9 Transfectie van cellen ............................................................................................................ 19 3. Resultaten ...................................................................................................................................... 21 ii 3.1 Expressie in T-ALL cellijnen ................................................................................................ 21 3.1.1 Visualisatie van het ECT2L eiwit in T-ALL cellijnen met Western blot ...................... 21 3.1.2 ECT2L expressie analyse met qPCR in T-ALL cellijnen .............................................. 22 3.1.3 Visualisatie van het ECT2L eiwit in T-ALL cellijnen via Western blot analyse met het Aviva Biology Systems antilichaam ............................................................................................. 23 3.2 Expressie in humane weefsels ............................................................................................... 23 3.2.1 ECT2L expressie analyse met qPCR in humane weefsels ............................................. 23 3.3 Expressie in muisweefsels ..................................................................................................... 24 3.3.1 Visualisatie van het Ect2l eiwit in muisweefsels en MOLT-4 met Western blot .......... 24 3.3.2 Ect2l expressie analyse met qPCR op selectie van muisweefsels ................................. 26 3.3.3 Visualisatie van het ECT2L eiwit in muisweefsels via Western blot analyse met het Aviva Biology Systems antilichaam ............................................................................................. 26 3.4 ECT2L expressie in longkanker cellijnen .............................................................................. 27 3.4.1 ECT2L expressie analyse met qPCR in longkanker cellijnen ....................................... 27 3.4.2 ECT2L expressie analyse met qPCR in longkanker cellijnen met nieuwe primers ....... 29 3.5 Cellulaire lokalisatie van het ECT2L eiwit ........................................................................... 30 3.5.1 Visualisatie van ECT2L-GFP en ECT2L-3xFLAG getransfecteerde
Load more

Recommended publications
  • Clinical Validation of the Tempus Xt Next-Generation Targeted Oncology Sequencing Assay
    www.oncotarget.com Oncotarget, 2019, Vol. 10, (No. 24), pp: 2384-2396 Research Paper Clinical validation of the tempus xT next-generation targeted oncology sequencing assay Nike Beaubier1, Robert Tell1, Denise Lau1, Jerod R. Parsons1, Stephen Bush1, Jason Perera1, Shelly Sorrells1, Timothy Baker1, Alan Chang1, Jackson Michuda1, Catherine Iguartua1, Shelley MacNeil1, Kaanan Shah1, Philip Ellis1, Kimberly Yeatts1, Brett Mahon1, Timothy Taxter1, Martin Bontrager1, Aly Khan1, Robert Huether1, Eric Lefkofsky1 and Kevin P. White1 1Tempus Labs Inc., Chicago, IL 60654, USA Correspondence to: Nike Beaubier, email: [email protected] Kevin P. White, email: [email protected] Keywords: tumor profiling, next-generation sequencing assay validation Received: August 03, 2018 Accepted: February 03, 2019 Published: March 22, 2019 Copyright: Beaubier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT We developed and clinically validated a hybrid capture next generation sequencing assay to detect somatic alterations and microsatellite instability in solid tumors and hematologic malignancies. This targeted oncology assay utilizes tumor- normal matched samples for highly accurate somatic alteration calling and whole transcriptome RNA sequencing for unbiased identification of gene fusion events. The assay was validated with a combination of clinical specimens and cell lines, and recorded a sensitivity of 99.1% for single nucleotide variants, 98.1% for indels, 99.9% for gene rearrangements, 98.4% for copy number variations, and 99.9% for microsatellite instability detection. This assay presents a wide array of data for clinical management and clinical trial enrollment while conserving limited tissue.
    [Show full text]
  • University of Groningen Development of Bioinformatic Tools And
    University of Groningen Development of bioinformatic tools and application of novel statistical methods in genome- wide analysis van der Most, Peter Johannes IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2017 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): van der Most, P. J. (2017). Development of bioinformatic tools and application of novel statistical methods in genome-wide analysis. University of Groningen. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 07-10-2021 Chapter 8 Genome-wide survival meta-analysis of age at first cannabis use Camelia C.
    [Show full text]
  • Whole Exome Sequencing in Families at High Risk for Hodgkin Lymphoma: Identification of a Predisposing Mutation in the KDR Gene
    Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 2Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 3Ad - vanced Biomedical Computing Center, Leidos Biomedical Research Inc.; Frederick National Laboratory for Cancer Research, Frederick, MD; 4Westat, Inc., Rockville MD; 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; and 6Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA ©2016 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2015.135475 Received: August 19, 2015. Accepted: January 7, 2016. Pre-published: June 13, 2016. Correspondence: [email protected] Supplemental Author Information: NCI DCEG Cancer Sequencing Working Group: Mark H. Greene, Allan Hildesheim, Nan Hu, Maria Theresa Landi, Jennifer Loud, Phuong Mai, Lisa Mirabello, Lindsay Morton, Dilys Parry, Anand Pathak, Douglas R. Stewart, Philip R. Taylor, Geoffrey S. Tobias, Xiaohong R. Yang, Guoqin Yu NCI DCEG Cancer Genomics Research Laboratory: Salma Chowdhury, Michael Cullen, Casey Dagnall, Herbert Higson, Amy A.
    [Show full text]
  • WO 2015/048577 A2 April 2015 (02.04.2015) W P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/048577 A2 April 2015 (02.04.2015) W P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 48/00 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/US20 14/057905 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 26 September 2014 (26.09.2014) KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (25) Filing Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (26) Publication Language: English SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/883,925 27 September 2013 (27.09.2013) US (84) Designated States (unless otherwise indicated, for every 61/898,043 31 October 2013 (3 1. 10.2013) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: EDITAS MEDICINE, INC.
    [Show full text]
  • Of Small Intestine Harboring Driver Gene Mutations: a Case Report and a Literature Review
    1161 Case Report A rare multiple primary sarcomatoid carcinoma (SCA) of small intestine harboring driver gene mutations: a case report and a literature review Zhu Zhu1#, Xinyi Liu2#, Wenliang Li1, Zhengqi Wen1, Xiang Ji1, Ruize Zhou1, Xiaoyu Tuo3, Yaru Chen2, Xian Gong2, Guifeng Liu2, Yanqing Zhou2, Shifu Chen2, Lele Song2#^, Jian Huang1 1Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, China; 2HaploX Biotechnology, Shenzhen, China; 3Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China #These authors contributed equally to this work. Correspondence to: Jian Huang. Department of Oncology, First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Kunming 560032, Yunnan Province, China. Email: [email protected]; Lele Song. HaploX Biotechnology, 8th floor, Auto Electric Power Building, Songpingshan Road, Nanshan District, Shenzhen 518057, Guangdong Province, China. Email: [email protected]. Abstract: Primary sarcomatoid carcinoma (SCA) is a type of rare tumor consisting of both malignant epithelial and mesenchymal components. Only 32 cases of SCA of the small bowel have been reported in the literature to date. Due to its rarity and complexity, this cancer has not been genetically studied and its diagnosis and treatment remain difficult. Here we report a 54-year-old male underwent emergency surgical resection in the small intestine due to severe obstruction and was diagnosed with multiple SCA based on postoperative pathological examination. Over 100 polypoid tumors scattered along his whole jejunum and proximal ileum. Chemotherapy (IFO+Epirubicin) was performed after surgery while the patient died two months after the surgery due to severe malnutrition. Whole-exome sequencing was performed for the tumor tissue with normal tissue as the control.
    [Show full text]
  • Identification and Characterisation of Murine Metastable Epialleles Conferred by Endogenous Retroviruses
    Identification and characterisation of murine metastable epialleles conferred by endogenous retroviruses Anastasiya Kazachenka Department of Genetics Darwin College University of Cambridge September 2017 This dissertation is submitted for the degree of Doctor of Philosophy The research in this dissertation was carried out in the Department of Genetics, University of Cambridge, under the supervision of Professor Anne Ferguson-Smith. This dissertation is the result of my own work and includes nothing which is the outcome of work done in collaboration except specified in the text. It is not substantially the same as any that I have submitted, or, is being concurrently submitted for a degree or diploma or other qualification at the University of Cambridge or any other University or similar institution except specified in the text. I further state that no substantial part of my dissertation has already been submitted, or, is being concurrently submitted for any such degree, diploma or other qualification at the University of Cambridge or any other University or similar institution except specified in the text It does not exceed the prescribed word limit of 60,000 words. 1 Summary Anastasiya Kazachenka Identification and characterisation of murine metastable epialleles conferred by endogenous retroviruses Repetitive sequences, including transposable elements, represent approximately half of the mammalian genome. Epigenetic mechanisms evolved to repress these potentially deleterious mobile elements. However, such elements can be variably silenced between individuals – so called ‘metastable epialleles’. The best known example is the A​vy locus where an endogenous retrovirus (ERV) of the intracisternal A-particle (IAP) class was spontaneously inserted upstream of the agouti coat colour gene, resulting in variable IAP promoter DNA methylation, variable expressivity of coat phenotype, and environmentally modulated transgenerational epigenetic inheritance within genetically identical individuals.
    [Show full text]
  • Supplementary Table 1 Double Treatment Vs Single Treatment
    Supplementary table 1 Double treatment vs single treatment Probe ID Symbol Gene name P value Fold change TC0500007292.hg.1 NIM1K NIM1 serine/threonine protein kinase 1.05E-04 5.02 HTA2-neg-47424007_st NA NA 3.44E-03 4.11 HTA2-pos-3475282_st NA NA 3.30E-03 3.24 TC0X00007013.hg.1 MPC1L mitochondrial pyruvate carrier 1-like 5.22E-03 3.21 TC0200010447.hg.1 CASP8 caspase 8, apoptosis-related cysteine peptidase 3.54E-03 2.46 TC0400008390.hg.1 LRIT3 leucine-rich repeat, immunoglobulin-like and transmembrane domains 3 1.86E-03 2.41 TC1700011905.hg.1 DNAH17 dynein, axonemal, heavy chain 17 1.81E-04 2.40 TC0600012064.hg.1 GCM1 glial cells missing homolog 1 (Drosophila) 2.81E-03 2.39 TC0100015789.hg.1 POGZ Transcript Identified by AceView, Entrez Gene ID(s) 23126 3.64E-04 2.38 TC1300010039.hg.1 NEK5 NIMA-related kinase 5 3.39E-03 2.36 TC0900008222.hg.1 STX17 syntaxin 17 1.08E-03 2.29 TC1700012355.hg.1 KRBA2 KRAB-A domain containing 2 5.98E-03 2.28 HTA2-neg-47424044_st NA NA 5.94E-03 2.24 HTA2-neg-47424360_st NA NA 2.12E-03 2.22 TC0800010802.hg.1 C8orf89 chromosome 8 open reading frame 89 6.51E-04 2.20 TC1500010745.hg.1 POLR2M polymerase (RNA) II (DNA directed) polypeptide M 5.19E-03 2.20 TC1500007409.hg.1 GCNT3 glucosaminyl (N-acetyl) transferase 3, mucin type 6.48E-03 2.17 TC2200007132.hg.1 RFPL3 ret finger protein-like 3 5.91E-05 2.17 HTA2-neg-47424024_st NA NA 2.45E-03 2.16 TC0200010474.hg.1 KIAA2012 KIAA2012 5.20E-03 2.16 TC1100007216.hg.1 PRRG4 proline rich Gla (G-carboxyglutamic acid) 4 (transmembrane) 7.43E-03 2.15 TC0400012977.hg.1 SH3D19
    [Show full text]
  • Dissecting Aberrant Proteolytic Ubiquitin Networks in Cancer
    TECHNISCHE UNIVERSITÄT MÜNCHEN Fakultät für Medizin III. Medizinische Klinik und Poliklinik Klinikum rechts der Isar Dissecting aberrant proteolytic ubiquitin networks in cancer Carmen Gloria Richter (M.Sc.) Vollständiger Abdruck der von der Fakultät für Medizin der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) genehmigten Dissertation. Vorsitzender: Prof. Dr. Dr. Andreas Pichlmair Prüfer der Dissertation: 1. Prof. Dr. Florian Bassermann 2. Prof. Dr. Bernhard Küster 3. Prof. Dr. Sebastian Theurich Die Dissertation wurde am 01.08.2019 bei der Technischen Universität München eingereicht und durch die Fakultät für Medizin am 07.04.2020 angenommen. Content 1 Summary ................................................................................................................... 1 2 Introduction .............................................................................................................. 3 2.1 Multiple myeloma ............................................................................................................3 2.1.1 Pathophysiology .........................................................................................................3 2.1.2 Clinical manifestation and diagnosis ...........................................................................5 2.1.3 Treatment ...................................................................................................................6 2.1.4 The role of MYC in multiple myeloma .........................................................................7
    [Show full text]
  • KRAB Zinc Finger Protein Diversification Drives Mammalian Interindividual Methylation Variability
    KRAB zinc finger protein diversification drives mammalian interindividual methylation variability Tessa M. Bertozzia, Jessica L. Elmera, Todd S. Macfarlanb, and Anne C. Ferguson-Smitha,1 aDepartment of Genetics, University of Cambridge, CB2 3EH Cambridge, United Kingdom; and bThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, MD 20892 Edited by Peter A. Jones, Van Andel Institute, Grand Rapids, MI, and approved October 28, 2020 (received for review August 19, 2020) Most transposable elements (TEs) in the mouse genome are DNA methylation of the Avy IAP is established early in devel- heavily modified by DNA methylation and repressive histone opment across genetically identical mice and is correlated with a modifications. However, a subset of TEs exhibit variable methyl- spectrum of coat color phenotypes, which in turn display trans- ation levels in genetically identical individuals, and this is associated generational inheritance and environmental sensitivity (11–13). with epigenetically conferred phenotypic differences, environ- Both the distribution and heritability of Avy phenotypes are mental adaptability, and transgenerational epigenetic inheritance. influenced by genetic background (14–16). Therefore, the iden- The evolutionary origins and molecular mechanisms underlying tification and characterization of the responsible modifier genes interindividual epigenetic variability remain unknown. Using a can provide insight into the mechanisms governing the early repertoire of murine variably methylated intracisternal A-particle establishment of stochastic methylation states at mammalian (VM-IAP) epialleles as a model, we demonstrate that variable DNA transposable elements. methylation states at TEs are highly susceptible to genetic back- We recently conducted a genome-wide screen for individual ground effects.
    [Show full text]
  • Clinical, Immunological and Genetic Characteristic of Patients With
    ORIGINAL ARTICLE Clinical, immunological and genetic characteristic of patients with clinical phenotype associated to LRBA-deficiency in Colombia Características clínicas, inmunológicas y genéticas de pacientes con fenotipo clínico asociado a la deficiencia de LRBA en Colombia Catalina Martínez-Jaramillo1 , Sebastian Gutierrez-Hincapie1 , Julio César Orrego Arango2 , Gloria María Vásquez-Duque3 , Ruth María Erazo-Garnica3 , Jose Luis Franco1 and Claudia Milena Trujillo-Vargas1 1 Universidad de Antioquia, Facultad de Medicina, Grupo de Inmunodeficiencias Primarias, Medellin, Colombia, 2 Universidad de Antioquia, Grupo de Inmunología Celular e Inmunogenética, Medellin, Colombia, 3 Universidad de Antioquia, Programa de Posgrado, Reumatología Pediátrica, Medellin, Colombia *[email protected] Abstract Background: LPS-responsive beige -like anchor protein (LRBA) deficiency is a primary immunodeficiency OPEN ACCESS disease caused by loss of LRBA protein expression, due to biallelic mutations in LRBA Citation: Martínez-Jaramillo C, gene. LRBA deficiency patients exhibit a clinically heterogeneous syndrome. The Gutierrez-Hincapie S, Orrego main clinical complication of LRBA deficiency is immune dysregulation. Furthermore, AJC, Vásquez-Duque GM, Erazo- hypogammaglobulinemia is found in more than half of patients with LRBA-deficiency. To Garnica RM, Franco JL et al. date, no patients with this condition have been reported in Colombia Clinical, immunological and genetic characteristic of patients with clinical Objective: phenotype associated to LRBA- deficiency in Colombia.Colomb Med To evaluate the expression of the LRBA protein in patients from Colombia with clinical (Cali). 2019; 50(3): 176-91 http:// dx.org/1025100/cm.v50i3.3969 phenotype associated to LRBA-deficiency. Received: 25 Feb 2019 Methods: Revised: 28 Aug 2019 In the present study the LRBA-expression in patients from Colombia with clinical Accepted: 16 Sep 2019 phenotype associated to LRBA-deficiency was evaluated.
    [Show full text]
  • Searching for New Genes Involved in Familial Colorectal Cancer Type X by Whole-Exome Sequencing
    UNIVERSIDAD COMPLUTENSE DE MADRID FACULTAD DE CIENCIAS QUÍMICAS TESIS DOCTORAL Searching for new genes involved in familial colorectal cancer type X by whole-exome sequencing Búsqueda de nuevos genes implicados en el cáncer colorrectal familiar tipo X por secuenciación de exoma completo MEMORIA PARA OPTAR AL GRADO DE DOCTORA PRESENTADA POR Lorena Martín Morales Directoras Trinidad Caldés Llopis Pilar Garre Rubio Madrid © Lorena Martín Morales, 2019 UNIVERSIDAD COMPLUTENSE DE MADRID Facultad de Ciencias Químicas Departamento de Bioquímica y Biología Molecular TESIS DOCTORAL Searching for new genes involved in Familial Colorectal Cancer Type X by whole-exome sequencing Búsqueda de nuevos genes implicados en el Cáncer Colorrectal Familiar Tipo X por secuenciación de exoma completo MEMORIA PARA OPTAR AL GRADO DE DOCTOR PRESENTADA POR Lorena Martín Morales DIRECTORAS Trinidad Caldés Llopis Pilar Garre Rubio Madrid, 2019 DECLARACIÓN DE AUTORÍA Y ORIGINALIDAD DE LA TESIS PRESENTADA PARA OBTENER EL TÍTULO DE DOCTOR D./Dña.________________________________________________________________,Lorena Martín Morales estudiante en el Programa de Doctorado _____________________________________,de Bioquímica, Biología Molecular y Biomedicina de la Facultad de _____________________________Ciencias Químicas de la Universidad Complutense de Madrid, como autor/a de la tesis presentada para la obtención del título de Doctor y titulada: Searching for new genes involved in Familial Colorectal Cancer Type X by Whole -Exome Sequencing Búsqueda de nuevos genes implicados en el Cáncer Colorrectal Familiar Tipo X por secuenciación de exoma completo y dirigida por: Trinidad Caldés Llopis y Pilar Garre Rubio DECLARO QUE: La tesis es una obra original que no infringe los derechos de propiedad intelectual ni los derechos de propiedad industrial u otros, de acuerdo con el ordenamiento jurídico vigente, en particular, la Ley de Propiedad Intelectual (R.D.
    [Show full text]
  • KRAB Zinc Finger Protein Diversification Drives Mammalian Interindividual Methylation Variability
    KRAB zinc finger protein diversification drives mammalian interindividual methylation variability Tessa M. Bertozzia, Jessica L. Elmera, Todd S. Macfarlanb, and Anne C. Ferguson-Smitha,1 aDepartment of Genetics, University of Cambridge, CB2 3EH Cambridge, United Kingdom; and bThe Eunice Kennedy Shriver National Institute of Child Health and Human Development, The National Institutes of Health, Bethesda, MD 20892 Edited by Peter A. Jones, Van Andel Institute, Grand Rapids, MI, and approved October 28, 2020 (received for review August 19, 2020) Most transposable elements (TEs) in the mouse genome are DNA methylation of the Avy IAP is established early in devel- heavily modified by DNA methylation and repressive histone opment across genetically identical mice and is correlated with a modifications. However, a subset of TEs exhibit variable methyl- spectrum of coat color phenotypes, which in turn display trans- ation levels in genetically identical individuals, and this is associated generational inheritance and environmental sensitivity (11–13). with epigenetically conferred phenotypic differences, environ- Both the distribution and heritability of Avy phenotypes are mental adaptability, and transgenerational epigenetic inheritance. influenced by genetic background (14–16). Therefore, the iden- The evolutionary origins and molecular mechanisms underlying tification and characterization of the responsible modifier genes interindividual epigenetic variability remain unknown. Using a can provide insight into the mechanisms governing the early repertoire of murine variably methylated intracisternal A-particle establishment of stochastic methylation states at mammalian (VM-IAP) epialleles as a model, we demonstrate that variable DNA transposable elements. methylation states at TEs are highly susceptible to genetic back- We recently conducted a genome-wide screen for individual ground effects.
    [Show full text]