Supplementary Table S1 One Hundred Twenty-Six Genes Composing Our Prognostic Index
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Primepcr™Assay Validation Report
PrimePCR™Assay Validation Report Gene Information Gene Name katanin p80 (WD repeat containing) subunit B 1 Gene Symbol KATNB1 Organism Human Gene Summary Microtubules polymers of alpha and beta tubulin subunits form the mitotic spindle of a dividing cell and help to organize membranous organelles during interphase. Katanin is a heterodimer that consists of a 60 kDa ATPase (p60 subunit A 1) and an 80 kDa accessory protein (p80 subunit B 1). The p60 subunit acts to sever and disassemble microtubules while the p80 subunit targets the enzyme to the centrosome. Katanin is a member of the AAA family of ATPases. Gene Aliases KAT RefSeq Accession No. NC_000016.9, NT_010498.15 UniGene ID Hs.275675 Ensembl Gene ID ENSG00000140854 Entrez Gene ID 10300 Assay Information Unique Assay ID qHsaCIP0026589 Assay Type Probe - Validation information is for the primer pair using SYBR® Green detection Detected Coding Transcript(s) ENST00000379661 Amplicon Context Sequence CACCAAGACAGCCTGGAAGTTGCAAGAGATCGTCGCGCATGCCAGCAACGTGT CCTCACTGGTGCTGGGCAAAGCCTCCGGGCGGCTGCTGGCTACAGGCGGGGAT GACTGCCGCGTCAACCTGTGGTCCATCAACAAGCCCAACTGCATCATGAGCCTG ACG Amplicon Length (bp) 132 Chromosome Location 16:57771173-57778314 Assay Design Intron-spanning Purification Desalted Validation Results Efficiency (%) 100 R2 0.9991 cDNA Cq 21.47 cDNA Tm (Celsius) 89 Page 1/5 PrimePCR™Assay Validation Report gDNA Cq 35.43 Specificity (%) 100 Information to assist with data interpretation is provided at the end of this report. Page 2/5 PrimePCR™Assay Validation Report KATNB1, Human Amplification -
KIAA0556 Is a Novel Ciliary Basal Body Component Mutated in Joubert Syndrome Anna A
Sanders et al. Genome Biology (2015) 16:293 DOI 10.1186/s13059-015-0858-z RESEARCH Open Access KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome Anna A. W. M. Sanders1†, Erik de Vrieze2,3†, Anas M. Alazami4†, Fatema Alzahrani4, Erik B. Malarkey5, Nasrin Sorusch6, Lars Tebbe6, Stefanie Kuhns1, Teunis J. P. van Dam7, Amal Alhashem8, Brahim Tabarki8, Qianhao Lu9,10, Nils J. Lambacher1, Julie E. Kennedy1, Rachel V. Bowie1, Lisette Hetterschijt2,3, Sylvia van Beersum3,11, Jeroen van Reeuwijk3,11, Karsten Boldt12, Hannie Kremer2,3,11, Robert A. Kesterson13, Dorota Monies4, Mohamed Abouelhoda4, Ronald Roepman3,11, Martijn H. Huynen7, Marius Ueffing12, Rob B. Russell9,10, Uwe Wolfrum6, Bradley K. Yoder5, Erwin van Wijk2,3*, Fowzan S. Alkuraya4,14* and Oliver E. Blacque1* Abstract Background: Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures. Results: Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome. Patient-derived fibroblasts displayed reduced ciliogenesis potential and abnormally elongated cilia. Investigation of disease pathophysiology revealed that Kiaa0556-/- null mice possess a Joubert syndrome-associated brain-restricted phenotype. Functional studies in Caenorhabditis elegans nematodes and cultured human cells support a conserved ciliary role for KIAA0556 linked to microtubule regulation. First, nematode KIAA0556 is expressed almost exclusively in ciliated cells, and the worm and human KIAA0556 proteins are enriched at the ciliary base. -
Environmental Influences on Endothelial Gene Expression
ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community. -
To Study Mutant P53 Gain of Function, Various Tumor-Derived P53 Mutants
Differential effects of mutant TAp63γ on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science By Shama K Khokhar M.Sc., Bilaspur University, 2004 B.Sc., Bhopal University, 2002 2007 1 COPYRIGHT SHAMA K KHOKHAR 2007 2 WRIGHT STATE UNIVERSITY SCHOOL OF GRADUATE STUDIES Date of Defense: 12-03-07 I HEREBY RECOMMEND THAT THE THESIS PREPARED UNDER MY SUPERVISION BY SHAMA KHAN KHOKHAR ENTITLED Differential effects of mutant TAp63γ on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression BE ACCEPTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Master of Science Madhavi P. Kadakia, Ph.D. Thesis Director Daniel Organisciak , Ph.D. Department Chair Committee on Final Examination Madhavi P. Kadakia, Ph.D. Steven J. Berberich, Ph.D. Michael Leffak, Ph.D. Joseph F. Thomas, Jr., Ph.D. Dean, School of Graduate Studies 3 Abstract Khokhar, Shama K. M.S., Department of Biochemistry and Molecular Biology, Wright State University, 2007 Differential effect of TAp63γ mutants on transactivation of p53 and/or p63 responsive genes and their effects on global gene expression. p63, a member of the p53 gene family, known to play a role in development, has more recently also been implicated in cancer progression. Mice lacking p63 exhibit severe developmental defects such as limb truncations, abnormal skin, and absence of hair follicles, teeth, and mammary glands. Germline missense mutations of p63 have been shown to be responsible for several human developmental syndromes including SHFM, EEC and ADULT syndromes and are associated with anomalies in the development of organs of epithelial origin. -
Single-Cell Profiling Identifies Impaired Adaptive NK Cells Expanded After HCMV Reactivation in Haploidentical HSCT
Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT Elisa Zaghi, … , Enrico Lugli, Domenico Mavilio JCI Insight. 2021;6(12):e146973. https://doi.org/10.1172/jci.insight.146973. Research Article Hematology Immunology Graphical abstract Find the latest version: https://jci.me/146973/pdf RESEARCH ARTICLE Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT Elisa Zaghi,1 Michela Calvi,1,2 Simone Puccio,3 Gianmarco Spata,1 Sara Terzoli,1 Clelia Peano,4 Alessandra Roberto,3 Federica De Paoli,3 Jasper J.P. van Beek,3 Jacopo Mariotti,5 Chiara De Philippis,5 Barbara Sarina,5 Rossana Mineri,6 Stefania Bramanti,5 Armando Santoro,5 Vu Thuy Khanh Le-Trilling,7 Mirko Trilling,7 Emanuela Marcenaro,8 Luca Castagna,5 Clara Di Vito,1,2 Enrico Lugli,3,9 and Domenico Mavilio1,2 1Unit of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. 2BIOMETRA, Università degli Studi di Milano, Milan, Italy. 3Laboratory of Translational Immunology, 4Institute of Genetic and Biomedical Research, UoS Milan, National Research Council, and Genomic Unit, 5Bone Marrow Transplant Unit, and 6Molecular Biology Section, Clinical Investigation Laboratory, IRCCS Humanitas Research Hospital, Milan, Italy. 7Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 8Department of Experimental Medicine, University of Genoa, Genoa, Italy. 9Flow Cytometry Core, IRCCS Humanitas Research Hospital, Milan, Italy. Haploidentical hematopoietic stem cell transplantation (h-HSCT) represents an efficient curative approach for patients affected by hematologic malignancies in which the reduced intensity conditioning induces a state of immunologic tolerance between donor and recipient. -
Functional Characterization of the New 8Q21 Asthma Risk Locus
Functional characterization of the new 8q21 Asthma risk locus Cristina M T Vicente B.Sc, M.Sc A thesis submitted for the degree of Doctor of Philosophy at The University of Queensland in 2017 Faculty of Medicine Abstract Genome wide association studies (GWAS) provide a powerful tool to identify genetic variants associated with asthma risk. However, the target genes for many allergy risk variants discovered to date are unknown. In a recent GWAS, Ferreira et al. identified a new association between asthma risk and common variants located on chromosome 8q21. The overarching aim of this thesis was to elucidate the biological mechanisms underlying this association. Specifically, the goals of this study were to identify the gene(s) underlying the observed association and to study their contribution to asthma pathophysiology. Using genetic data from the 1000 Genomes Project, we first identified 118 variants in linkage disequilibrium (LD; r2>0.6) with the sentinel allergy risk SNP (rs7009110) on chromosome 8q21. Of these, 35 were found to overlap one of four Putative Regulatory Elements (PREs) identified in this region in a lymphoblastoid cell line (LCL), based on epigenetic marks measured by the ENCODE project. Results from analysis of gene expression data generated for LCLs (n=373) by the Geuvadis consortium indicated that rs7009110 is associated with the expression of only one nearby gene: PAG1 - located 732 kb away. PAG1 encodes a transmembrane adaptor protein localized to lipid rafts, which is highly expressed in immune cells. Results from chromosome conformation capture (3C) experiments showed that PREs in the region of association physically interacted with the promoter of PAG1. -
Supplementary Table 1: Adhesion Genes Data Set
Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like, -
WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT (51) International Patent Classification: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, C12Q 1/68 (2018.01) A61P 31/18 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, C12Q 1/70 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/US2018/056167 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (22) International Filing Date: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 16 October 2018 (16. 10.2018) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 62/573,025 16 October 2017 (16. 10.2017) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, ΓΕ , IS, IT, LT, LU, LV, (71) Applicant: MASSACHUSETTS INSTITUTE OF MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TECHNOLOGY [US/US]; 77 Massachusetts Avenue, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Cambridge, Massachusetts 02139 (US). -
Supp Material.Pdf
Simon et al. Supplementary information: Table of contents p.1 Supplementary material and methods p.2-4 • PoIy(I)-poly(C) Treatment • Flow Cytometry and Immunohistochemistry • Western Blotting • Quantitative RT-PCR • Fluorescence In Situ Hybridization • RNA-Seq • Exome capture • Sequencing Supplementary Figures and Tables Suppl. items Description pages Figure 1 Inactivation of Ezh2 affects normal thymocyte development 5 Figure 2 Ezh2 mouse leukemias express cell surface T cell receptor 6 Figure 3 Expression of EZH2 and Hox genes in T-ALL 7 Figure 4 Additional mutation et deletion of chromatin modifiers in T-ALL 8 Figure 5 PRC2 expression and activity in human lymphoproliferative disease 9 Figure 6 PRC2 regulatory network (String analysis) 10 Table 1 Primers and probes for detection of PRC2 genes 11 Table 2 Patient and T-ALL characteristics 12 Table 3 Statistics of RNA and DNA sequencing 13 Table 4 Mutations found in human T-ALLs (see Fig. 3D and Suppl. Fig. 4) 14 Table 5 SNP populations in analyzed human T-ALL samples 15 Table 6 List of altered genes in T-ALL for DAVID analysis 20 Table 7 List of David functional clusters 31 Table 8 List of acquired SNP tested in normal non leukemic DNA 32 1 Simon et al. Supplementary Material and Methods PoIy(I)-poly(C) Treatment. pIpC (GE Healthcare Lifesciences) was dissolved in endotoxin-free D-PBS (Gibco) at a concentration of 2 mg/ml. Mice received four consecutive injections of 150 μg pIpC every other day. The day of the last pIpC injection was designated as day 0 of experiment. -
Molecular Effects of Isoflavone Supplementation Human Intervention Studies and Quantitative Models for Risk Assessment
Molecular effects of isoflavone supplementation Human intervention studies and quantitative models for risk assessment Vera van der Velpen Thesis committee Promotors Prof. Dr Pieter van ‘t Veer Professor of Nutritional Epidemiology Wageningen University Prof. Dr Evert G. Schouten Emeritus Professor of Epidemiology and Prevention Wageningen University Co-promotors Dr Anouk Geelen Assistant professor, Division of Human Nutrition Wageningen University Dr Lydia A. Afman Assistant professor, Division of Human Nutrition Wageningen University Other members Prof. Dr Jaap Keijer, Wageningen University Dr Hubert P.J.M. Noteborn, Netherlands Food en Consumer Product Safety Authority Prof. Dr Yvonne T. van der Schouw, UMC Utrecht Dr Wendy L. Hall, King’s College London This research was conducted under the auspices of the Graduate School VLAG (Advanced studies in Food Technology, Agrobiotechnology, Nutrition and Health Sciences). Molecular effects of isoflavone supplementation Human intervention studies and quantitative models for risk assessment Vera van der Velpen Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. Dr M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Friday 20 June 2014 at 13.30 p.m. in the Aula. Vera van der Velpen Molecular effects of isoflavone supplementation: Human intervention studies and quantitative models for risk assessment 154 pages PhD thesis, Wageningen University, Wageningen, NL (2014) With references, with summaries in Dutch and English ISBN: 978-94-6173-952-0 ABSTRact Background: Risk assessment can potentially be improved by closely linked experiments in the disciplines of epidemiology and toxicology. -
Cytogenetic Analysis of a Pseudoangiomatous Pleomorphic/Spindle Cell Lipoma
ANTICANCER RESEARCH 37 : 2219-2223 (2017) doi:10.21873/anticanres.11557 Cytogenetic Analysis of a Pseudoangiomatous Pleomorphic/Spindle Cell Lipoma IOANNIS PANAGOPOULOS 1, LUDMILA GORUNOVA 1, INGVILD LOBMAIER 2, HEGE KILEN ANDERSEN 1, BODIL BJERKEHAGEN 2 and SVERRE HEIM 1,3 1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; 2Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; 3Faculty of Medicine, University of Oslo, Oslo, Norway Abstract. Background: Pseudoangiomatous pleomorphic/ appearance’ (1). To date, only 20 patients have been described spindle cell lipoma is a rare subtype of pleomorphic/spindle in the literature with this diagnosis, 15 of whom were males cell lipoma. Only approximately 20 such tumors have been (1-10). The pseudoangiomatous pleomorphic/spindle cell described. Genetic information on pseudoangiomatous lipomas were mostly found in the neck (seven patients) and pleomorphic/spindle cell lipoma is restricted to a single case shoulders (four patients), but have also been seen in the in which deletion of the forkhead box O1 (FOXO1) gene was cheek, chest, chin, elbow, finger, subscapular region, and found, using fluorescence in situ hybridization (FISH). thumb. Genetic information on pseudoangiomatous Materials and Methods: G-banding and FISH analyses were pleomorphic/ spindle cell lipoma is restricted to one case only performed on a pseudoangiomatous pleomorphic/spindle cell (8) in which fluorescence in situ hybridization (FISH) with a lipoma. Results: G-banding of tumor cells showed complex probe for the forkhead box O1 ( FOXO1 ) gene, which maps karyotypic changes including loss of chromosome 13. FISH to chromosome sub-band 13q14.11, showed a signal pattern analysis revealed that the deleted region contained the RB1 indicating monoallelic loss of the gene in 57% of the gene (13q14.2) and the part of chromosome arm 13q (q14.2- examined cells. -
The Interaction of DNA Repair Factors ASCC2 and ASCC3 Is Affected by Somatic Cancer Mutations
ARTICLE https://doi.org/10.1038/s41467-020-19221-x OPEN The interaction of DNA repair factors ASCC2 and ASCC3 is affected by somatic cancer mutations Junqiao Jia 1, Eva Absmeier1,5, Nicole Holton1, Agnieszka J. Pietrzyk-Brzezinska1,6, Philipp Hackert2, ✉ Katherine E. Bohnsack 2, Markus T. Bohnsack2,3 & Markus C. Wahl 1,4 The ASCC3 subunit of the activating signal co-integrator complex is a dual-cassette Ski2-like nucleic acid helicase that provides single-stranded DNA for alkylation damage repair by the 1234567890():,; α-ketoglutarate-dependent dioxygenase AlkBH3. Other ASCC components integrate ASCC3/ AlkBH3 into a complex DNA repair pathway. We mapped and structurally analyzed inter- acting ASCC2 and ASCC3 regions. The ASCC3 fragment comprises a central helical domain and terminal, extended arms that clasp the compact ASCC2 unit. ASCC2–ASCC3 interfaces are evolutionarily highly conserved and comprise a large number of residues affected by somatic cancer mutations. We quantified contributions of protein regions to the ASCC2–ASCC3 interaction, observing that changes found in cancers lead to reduced ASCC2–ASCC3 affinity. Functional dissection of ASCC3 revealed similar organization and regulation as in the spliceosomal RNA helicase Brr2. Our results delineate functional regions in an important DNA repair complex and suggest possible molecular disease principles. 1 Laboratory of Structural Biochemistry, Freie Universität Berlin, D-14195 Berlin, Germany. 2 Department of Molecular Biology, University Medical Centre Göttingen, Göttingen, Germany. 3 Göttingen Center for Molecular Biosciences, Georg-August-Universität, Göttingen, Germany. 4 Helmholtz-Zentrum Berlin für Materialien und Energie, Macromolecular Crystallography, D-12489 Berlin, Germany. 5Present address: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.