Next Steps in the Sequence

Total Page:16

File Type:pdf, Size:1020Kb

Next Steps in the Sequence Next steps in the sequence The implications of whole genome sequencing for health in the UK PHG Foundation project team and authors Dr Caroline Wright* Programme Associate Dr Hilary Burton Director Ms Alison Hall Project Manager (Law) Dr Sowmiya Moorthie Project Coordinator Dr Anna Pokorska-Bocci‡ Project Coordinator Dr Gurdeep Sagoo Epidemiologist Dr Simon Sanderson Associate Dr Rosalind Skinner Senior Fellow ‡ Corresponding author: [email protected] * Lead author Disclaimer This report is accurate as of September 2011, but readers should be aware that genome sequencing technology and applications will continue to develop rapidly from this point. This report is available from www.phgfoundation.org Published by PHG Foundation 2 Worts Causeway Cambridge CB1 8RN UK Tel: +44 (0)1223 740200 Fax: +44 (0)1223 740892 October 2011 © 2011 PHG Foundation ISBN 978-1-907198-08-3 Cover photo: http://www.sxc.hu/photo/914335 The PHG Foundation is the working name of the Foundation for Genomics and Population Health, a charitable organisation (registered in England and Wales, charity no. 1118664; company no. 5823194) which works with partners to achieve better health through the responsible and evidence-based application of biomedical science. Acknowledgements Dr Tom Dent contributed the section on risk prediction in the Other Applications chapter. Dr Richard Fordham contributed to the Health Economics chapter. Professor Anneke Lucassen, Dr Kathleen Liddell and Professor Jenny Hewison contributed to the Ethical, Legal and Social Implications chapter. Dr Ron Zimmern contributed to the Policy Analysis and Recommendations chapters. The PHG Foundation is grateful for the expert guidance and advice provided by the external Steering Group, in particular to Dr Jo Whittaker, Mr Chris Mattocks and Dr Paul Flicek for their extensive comments on the manuscript. The project team would also like to thank Dr Sarah Wordsworth for her initial advice on the health economics content, and all the participants of the two invited expert workshops (see Appendices), whose valuable contributions helped shape the recommendations within this report. Funding This project was funded by the PHG Foundation, with additional financial support from Illumina. The second expert workshop for the project was supported by the University of Cambridge Centre for Science and Policy (CSaP) and the Wellcome Trust. The contributions of these supporters are gratefully acknowledged. Contents Executive summary ....................................................................3 Glossary of acronyms ..................................................................7 Glossary of genetic terms ............................................................9 1 Introduction .................................................................... 11 2 The human genome .......................................................... 13 3 DNA sequencing technologies ............................................. 19 4 Informatics ..................................................................... 33 5 Applications in inherited and heritable diseases ....................... 45 6 Applications in cancer ....................................................... 59 7 Other potential applications ................................................ 75 8 Ethical, legal and social implications ..................................... 85 9 Health economics ............................................................109 10 Laboratory service delivery models ......................................123 11 Analysis and policy development ........................................141 12 Policy recommendations ....................................................153 13 References ....................................................................161 14 Appendices ....................................................................181 Next steps in the sequence 2 The implications of whole genome sequencing for health in the UK Executive summary Context and process The rapid development of new high-throughput and massively parallel DNA sequencing technologies has substantially reduced both the cost and the time required to sequence an entire human genome. It may soon be easier and cheaper to sequence an entire genome than to sequence a single gene or genotype a series of known mutations. Whole genome sequencing, together with our evolving knowledge of genes and disease, is likely to change the current practice of medicine and public health by facilitating more accurate, sophisticated and cost-effective genetic testing. The development of genomic medicine was considered in a House of Lords Report in 2009, which identified the need for a strategic vision for implementation of genomic technologies within the National Health Service (NHS) to maximise both their health and cost benefits.The PHG Foundation – an organisation dedicated to the evaluation of genome-based technologies for the benefit of health and healthcare – formulated a response to that report, and has subsequently undertaken a year-long project to evaluate the implications of whole genome sequencing for health services and develop recommendations that will facilitate its adoption into the NHS to improve patient care. During the preparation of this report, the authors were guided by the following key questions: a) What is the role of new DNA sequencing technologies in medicine and population health, in the short to medium term, and how will they alter or augment routine clinical practice? b) What new ethical, legal, social and economic issues are raised by whole genome sequencing? c) What are the implications of whole genome sequencing for diagnostic services within the UK and health services more generally? d) What operational barriers exist to adoption within health services and how should they be tackled? In this report, we have brought together a diverse range of relevant information and stakeholder opinions to produce a comprehensive overview of the clinical impact of sequencing whole human genomes in the short to medium term. Although the scope of this project is large, we believe that it is crucial to consider the numerous different aspects together in order to make informed recommendations about the possible implementation of such a wide-ranging and potentially disruptive technology. To the best of our knowledge, no other group has produced such a comprehensive overview of the status quo and subsequently developed realistic future scenarios for medical human genome sequencing. The first ten chapters of this report present background research undertaken throughout 2010-11 by the PHG Foundation and supervised by an expert steering group. The chapters cover a broad range of topics relevant to the implementation of whole genome sequencing: 1) Project methodology and terms of reference 2) Introduction to the human genome 3) DNA sequencing technologies 4) Informatics and analysis 5) Applications of whole genome sequencing in inherited and heritable diseases 6) Applications of whole genome sequencing in cancer 7) Other health applications (specifically risk prediction, pharmacogenetics and tissue typing) 8) Ethical, legal and social issues 9) Health economics 10) Laboratory service delivery models 3 Next steps in the sequence The final two chapters present an analysis of discussions at two invited stakeholder workshops, held in March and June 2011, in which we developed scenarios and recommendations for implementation of whole genome sequencing within the UK. Summary of key findings Whole genome sequencing (WGS) has novel implications beyond traditional genetic testing because of the sheer volume and complexity of data generated. Each individual genome contains around 3-4 million variants that are not present in the reference human genome sequence. Only a small number of these variants will have important clinical consequences, and although some may also have implications for family relatedness, the vast majority will be of uncertain or no clinical or personal significance. In addition, cancer genomes have numerous additional somatic alterations superimposed on the patient’s inherited genome. These acquired changes constitute the ‘genetic fingerprint’ of each cancer type in an individual patient, but again, only a small number will be clinically significant. Understanding the health impact of individual genomic variants presents a considerable challenge for analysis, interpretation and management of the data. Although most WGS to date has been carried out in a research setting (or through consumer genomics companies), here we focus specifically on service delivery within the NHS for the purpose of improving patient diagnosis, clinical outcomes or disease prevention. In this scenario, it is useful to make a distinction between an assay (sequencing an individual’s genome) and a test (analysing any portion of that genome sequence for a specific purpose).The former contains no medical information per se, but is essentially a translation of the genetic code from DNA into a string of data stored on a computer; next generation sequencing (NGS) technologies have radically reduced both the cost and time required to accomplish this process. In contrast, the latter is an interpretive step which requires purposeful analysis of the genome sequence, directed by clinical symptoms/phenotypes or disease risk and informed by prior knowledge of the likely pathogenicity of genomic variants. Although the cost and time to sequence a human genome has decreased dramatically,
Recommended publications
  • Analysis of Gene Expression Data for Gene Ontology
    ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins.
    [Show full text]
  • Trajectory and Uniqueness of Mutational Signatures in Yeast Mutators
    Trajectory and uniqueness of mutational signatures in yeast mutators Sophie Loeilleta,b, Mareike Herzogc, Fabio Pudduc, Patricia Legoixd, Sylvain Baulanded, Stephen P. Jacksonc, and Alain G. Nicolasa,b,1 aInstitut Curie, Paris Sciences et Lettres Research University, CNRS, UMR3244, 75248 Paris Cedex 05, France; bSorbonne Universités, Université Pierre et Marie Curie Paris 06, CNRS, UMR3244, 75248 Paris Cedex 05, France; cWellcome/Cancer Research UK Gurdon Institute and Department of Biochemistry, Cambridge CB2 1QN, United Kingdom; and dICGex NGS Platform, Institut Curie, 75248 Paris Cedex 05, France Edited by Richard D. Kolodner, Ludwig Institute for Cancer Research, La Jolla, CA, and approved August 24, 2020 (received for review June 2, 2020) The acquisition of mutations plays critical roles in adaptation, evolution, known (5, 15, 16). Here, we conducted a reciprocal functional ap- senescence, and tumorigenesis. Massive genome sequencing has proach to inactivate one or several genes involved in distinct ge- allowed extraction of specific features of many mutational landscapes nome maintenance processes (replication, repair, recombination, but it remains difficult to retrospectively determine the mechanistic oxidative stress response, or cell-cycle progression) in Saccharomy- origin(s), selective forces, and trajectories of transient or persistent ces cerevisiae diploids, establish the genome-wide mutational land- mutations and genome rearrangements. Here, we conducted a pro- scapes of mutation accumulation (MA) lines, explore the underlying spective reciprocal approach to inactivate 13 single or multiple evolu- mechanisms, and characterize the dynamics of mutation accumu- tionary conserved genes involved in distinct genome maintenance lation (and disappearance) along single-cell bottleneck passages. processes and characterize de novo mutations in 274 diploid Saccharo- myces cerevisiae mutation accumulation lines.
    [Show full text]
  • Genome Analysis and Knowledge
    Dahary et al. BMC Medical Genomics (2019) 12:200 https://doi.org/10.1186/s12920-019-0647-8 SOFTWARE Open Access Genome analysis and knowledge-driven variant interpretation with TGex Dvir Dahary1*, Yaron Golan1, Yaron Mazor1, Ofer Zelig1, Ruth Barshir2, Michal Twik2, Tsippi Iny Stein2, Guy Rosner3,4, Revital Kariv3,4, Fei Chen5, Qiang Zhang5, Yiping Shen5,6,7, Marilyn Safran2, Doron Lancet2* and Simon Fishilevich2* Abstract Background: The clinical genetics revolution ushers in great opportunities, accompanied by significant challenges. The fundamental mission in clinical genetics is to analyze genomes, and to identify the most relevant genetic variations underlying a patient’s phenotypes and symptoms. The adoption of Whole Genome Sequencing requires novel capacities for interpretation of non-coding variants. Results: We present TGex, the Translational Genomics expert, a novel genome variation analysis and interpretation platform, with remarkable exome analysis capacities and a pioneering approach of non-coding variants interpretation. TGex’s main strength is combining state-of-the-art variant filtering with knowledge-driven analysis made possible by VarElect, our highly effective gene-phenotype interpretation tool. VarElect leverages the widely used GeneCards knowledgebase, which integrates information from > 150 automatically-mined data sources. Access to such a comprehensive data compendium also facilitates TGex’s broad variant annotation, supporting evidence exploration, and decision making. TGex has an interactive, user-friendly, and easy adaptive interface, ACMG compliance, and an automated reporting system. Beyond comprehensive whole exome sequence capabilities, TGex encompasses innovative non-coding variants interpretation, towards the goal of maximal exploitation of whole genome sequence analyses in the clinical genetics practice. This is enabled by GeneCards’ recently developed GeneHancer, a novel integrative and fully annotated database of human enhancers and promoters.
    [Show full text]
  • C. Elegans Whole Genome Sequencing Reveals Mutational Signatures Related to Carcinogens and DNA Repair Deficiency
    Downloaded from genome.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press C. elegans whole genome sequencing reveals mutational signatures related to carcinogens and DNA repair deficiency Authors: Bettina Meier * (1); Susanna L Cooke * (2); Joerg Weiss (1); Aymeric P Bailly (1,3); Ludmil B Alexandrov (2); John Marshall (2); Keiran Raine (2); Mark Maddison (2); Elizabeth Anderson (2); Michael R Stratton (2); Anton Gartner * (1); Peter J Campbell * (2,4,5). * These authors contributed equally to this project. Institutions: (1) Centre for Gene Regulation and Expression, University of Dundee, Dundee, UK. (2) Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK. (3) CRBM/CNRS UMR5237, University of Montpellier, Montpellier, France. (4) Department of Haematology, University of Cambridge, Cambridge, UK. (5) Department of Haematology, Addenbrooke’s Hospital, Cambridge, UK. Address for correspondence: Dr Peter J Campbell, Dr Anton Gartner, Cancer Genome Project, Centre for Gene Regulation and Expression, Wellcome Trust Sanger Institute, The University of Dundee, Hinxton CB10 1SA, Dow Street, Cambridgeshire, Dundee DD1 5EH UK. UK. Tel: +44 (0) 1223 494745 Phone: +44 (0) 1382 385809 Fax: +44 (0) 1223 494809 E-mail: [email protected] E-mail: [email protected] Running title: mutation profiling in C. elegans Keywords: mutation pattern, genetic and environmental factors, C. elegans, cisplatin, aflatoxin B1, whole-genome sequencing. Downloaded from genome.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT Mutation is associated with developmental and hereditary disorders, ageing and cancer. While we understand some mutational processes operative in human disease, most remain mysterious.
    [Show full text]
  • Abstracts In
    ECCB 2014 Accepted Posters with Abstracts G: Bioinformatics of health and disease G01: Emile Rugamika Chimusa, Jacquiline Wangui Mugo and Nicola Mulder. Leveraging ancestry along the genome of admixed individuals to resolve missing heritability in disease scoring statistics Abstract: Human genetics has been haunted by the mystery of “missing heritability” of common traits. Although studies have discovered several variants associated with common diseases and traits, these variants typically appear to explain only a minority of the heritability. Resolving missing heritability, the difference between phenotypic variance explained by associated SNPs and estimates of narrow-sense heritability (h2), will inform strategies for disease mapping and prediction of complex traits. Among biased estimates of h2 due to epistatic interactions and rare variants not captured by genotyping arrays have been cited to be the most can be the most explanations for missing heritability. Here, we present an approach for estimating heritability of traits based on sharing local ancestry segments between pairs of unrelated individuals in an admixed population. From simulation data and real data, we demonstrated that our approach outperformed current approaches for estimating heritability of traits and holds values in admixture mapping for deconvoluting genes underlying ethnic differences in complex diseases risk. G02: Sylvain Mareschal, Pierre-Julien Viailly, Philippe Bertrand, Fabienne Desmots-Loyer, Elodie Bohers, Catherine Maingonnat, Karen Leroy, Thierry Fest and Fabrice Jardin. Next- Generation Sequencing applied to tailor targeted therapies in lymphoma: the RELYSE project Abstract: Non-Hodgkin Lymphomas (NHL) are lymphoid cell malignancies accounting for about 4% of all cancers, with an incidence rate of 12 cases per 100,000 and per year in Europe.
    [Show full text]
  • Advances in Understanding Cancer Genomes Through Second-Generation Sequencing
    Advances in understanding cancer genomes through second-generation sequencing Matthew Meyerson, Stacey Gabriel and Gad Getz Second-generation A major near-term medical impact of the genome comprehensive genome-based diagnosis of cancer is sequencing technology revolution will be the elucidation of mecha- becoming increasingly crucial for therapeutic decisions. Used in this Review to refer to nisms of cancer pathogenesis, leading to improvements During the past decades, there have been major sequencing methods that have in the diagnosis of cancer and the selection of cancer advances in experimental and informatic methods emerged since 2005 that second-generation sequencing parallelize the sequencing treatment. Thanks to for genome characterization based on DNA and RNA 1–5 process and produce millions technologies , recently it has become feasible to microarrays and on capillary-based DNA sequenc- of typically short sequence sequence the expressed genes (‘transcriptomes’)6,7, ing (‘first-generation sequencing’, also known as Sanger reads (50–400 bases) from known exons (‘exomes’)8,9, and complete genomes10–15 sequencing). These technologies provided the ability amplified DNA clones. of cancer samples. to analyse exonic mutations and copy number altera- It is also often known as next-generation sequencing. These technological advances are important for tions and have led to the discovery of many important advancing our understanding of malignant neoplasms alterations in the cancer genome20. because cancer is fundamentally a disease of the genome. However, there are particular challenges for the A wide range of genomic alterations — including point detection and diagnosis of cancer genome alterations. mutations, copy number changes and rearrangements For example, some genomic alterations in cancer are — can lead to the development of cancer.
    [Show full text]
  • Human Genetics: International Projects and Personalized Medicine
    Drug Metabol Pers Ther 2016; 31(1): 3–8 Mini Review Maria Apellaniz-Ruiza, Cristina Gallegoa, Sara Ruiz-Pintoa, Angel Carracedo and Cristina Rodríguez-Antona* Human genetics: international projects and personalized medicine DOI 10.1515/dmpt-2015-0032 Received August 31, 2015; accepted October 19, 2015; previously Introduction published online November 18, 2015 Genetic variation databases describe naturally occur- Abstract: In this article, we present the progress driven ring genetic differences among individuals of the same by the recent technological advances and new revolu- species. This variation, accounting for 0.1% of our DNA tionary massive sequencing technologies in the field of [1], permits the flexibility and survival of a population human genetics. We discuss this knowledge in relation in the face of changing environmental circumstances, with drug response prediction, from the germline genetic but it also influences how people differ in their risk of variation compiled in the 1000 Genomes Project or in the disease or their response to drugs. It is well known that Genotype-Tissue Expression project, to the phenome- variability in response to drug therapy is the rule rather genome archives, the international cancer projects, such than the exception for most drugs, and these differences as The Cancer Genome Atlas or the International Cancer are among the major challenges in current clinical prac- Genome Consortium, and the epigenetic variation and its tice, drug development, and drug regulation [2, 3]. Thus, influence in gene expression, including the regulation of rather than accepting the “one drug fits all” approach, drug metabolism. This review is based on the lectures pre- researchers envision that drugs need to be tailored to fit sented by the speakers of the Symposium “Human Genet- the profile of each individual patient.
    [Show full text]
  • The Bio Revolution: Innovations Transforming and Our Societies, Economies, Lives
    The Bio Revolution: Innovations transforming economies, societies, and our lives economies, societies, our and transforming Innovations Revolution: Bio The The Bio Revolution Innovations transforming economies, societies, and our lives May 2020 McKinsey Global Institute Since its founding in 1990, the McKinsey Global Institute (MGI) has sought to develop a deeper understanding of the evolving global economy. As the business and economics research arm of McKinsey & Company, MGI aims to help leaders in the commercial, public, and social sectors understand trends and forces shaping the global economy. MGI research combines the disciplines of economics and management, employing the analytical tools of economics with the insights of business leaders. Our “micro-to-macro” methodology examines microeconomic industry trends to better understand the broad macroeconomic forces affecting business strategy and public policy. MGI’s in-depth reports have covered more than 20 countries and 30 industries. Current research focuses on six themes: productivity and growth, natural resources, labor markets, the evolution of global financial markets, the economic impact of technology and innovation, and urbanization. Recent reports have assessed the digital economy, the impact of AI and automation on employment, physical climate risk, income inequal ity, the productivity puzzle, the economic benefits of tackling gender inequality, a new era of global competition, Chinese innovation, and digital and financial globalization. MGI is led by three McKinsey & Company senior partners: co-chairs James Manyika and Sven Smit, and director Jonathan Woetzel. Michael Chui, Susan Lund, Anu Madgavkar, Jan Mischke, Sree Ramaswamy, Jaana Remes, Jeongmin Seong, and Tilman Tacke are MGI partners, and Mekala Krishnan is an MGI senior fellow.
    [Show full text]
  • Strategic Plan 2011-2016
    Strategic Plan 2011-2016 Wellcome Trust Sanger Institute Strategic Plan 2011-2016 Mission The Wellcome Trust Sanger Institute uses genome sequences to advance understanding of the biology of humans and pathogens in order to improve human health. -i- Wellcome Trust Sanger Institute Strategic Plan 2011-2016 - ii - Wellcome Trust Sanger Institute Strategic Plan 2011-2016 CONTENTS Foreword ....................................................................................................................................1 Overview .....................................................................................................................................2 1. History and philosophy ............................................................................................................ 5 2. Organisation of the science ..................................................................................................... 5 3. Developments in the scientific portfolio ................................................................................... 7 4. Summary of the Scientific Programmes 2011 – 2016 .............................................................. 8 4.1 Cancer Genetics and Genomics ................................................................................ 8 4.2 Human Genetics ...................................................................................................... 10 4.3 Pathogen Variation .................................................................................................. 13 4.4 Malaria
    [Show full text]
  • Whole-Genome Cancer Analysis As an Approach to Deeper Understanding of Tumour Biology
    British Journal of Cancer (2010) 102, 243 – 248 & 2010 Cancer Research UK All rights reserved 0007 – 0920/10 $32.00 www.bjcancer.com Minireview Whole-genome cancer analysis as an approach to deeper understanding of tumour biology ,1 2 RL Strausberg* and AJG Simpson 1J Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA; 2Ludwig Institute for Cancer Research, 605 Third Avenue, New York, NY 10158, USA Recent advances in DNA sequencing technology are providing unprecedented opportunities for comprehensive analysis of cancer genomes, exomes, transcriptomes, as well as epigenomic components. The integration of these data sets with well-annotated phenotypic and clinical data will expedite improved interventions based on the individual genomics of the patient and the specific disease. British Journal of Cancer (2010) 102, 243–248. doi:10.1038/sj.bjc.6605497 www.bjcancer.com Published online 22 December 2009 & 2010 Cancer Research UK Keywords: genome; transcriptome; exome; chromosome; sequencing The family of diseases that we refer to as cancer represents a field of tumourigenesis, on the basis of knowledge of gene families and of application for genomics of truly special importance and signal transduction networks. More recently, technological changes opportunity. It is perhaps the first area in which not only will in DNA sequencing, including the recently introduced ‘NextGen’ genomics continue to make major contributions to the under- instruments and associated molecular technologies, have enabled standing of the disease through holistic discovery of causal both higher-throughput and more sensitive assays that provide genome-wide perturbations but will also be the first field in which important new opportunities for basic discovery and clinical whole-genome analysis is used in clinical applications such as application (Mardis, 2009).
    [Show full text]
  • RBH-CHD Network Annual Report.Pdf
    The Royal Brompton & Harefield Hospital NHS Foundation Trust Royal Brompton Hospital Congenital Heart Disease Network 2018/19 Annual Report Authors: Dr Nitha Naqvi Dr Leonie Wong Lawrence Mack Simon Boote Approved by: Congenital Heart Disease Working Group Ratification Committee: Congenital Heart Disease Network Board Date Ratified: 29/04/2019 Chairman: Dr Angela Tillett Implemented by: For reference only Issue Date: April 2019 Version: 001 Review Date: March 2020 Review interval: 12 Months Issued: April 2019 Version: 001 Page | 1 Link - Contents 1 Contents Page 1 Contents Page .......................................................................................................................................... 2 2 A message from our Clinical Director ................................................................................................... 4 3 RBH-CHD Network Strategic Vision Statement .................................................................................. 5 4 Summary of Achievements Against our Work Plan – 2018/19 ......................................................... 5 5 Research ................................................................................................................................................... 6 5.1 Grants Awarded ................................................................................................................................ 7 5.2 Research Programmes Peer Reviewed Publications ................................................................. 7 5.3 Research Strategy
    [Show full text]
  • Ndidi Dike Nnadiekwe (Nigeria) 27
    n.paradoxa online, issue 4 August 1997 Editor: Katy Deepwell n.paradoxa online issue no.4 August 1997 ISSN: 1462-0426 1 Published in English as an online edition by KT press, www.ktpress.co.uk, as issue 4, n.paradoxa: international feminist art journal http://www.ktpress.co.uk/pdf/nparadoxaissue4.pdf August 1997, republished in this form: January 2010 ISSN: 1462-0426 All articles are copyright to the author All reproduction & distribution rights reserved to n.paradoxa and KT press. No part of this publication may be reprinted or reproduced or utilized in any form or by any electronic, mechanical or other means, including photocopying and recording, information storage or retrieval, without permission in writing from the editor of n.paradoxa. Views expressed in the online journal are those of the contributors and not necessarily those of the editor or publishers. Editor: [email protected] International Editorial Board: Hilary Robinson, Renee Baert, Janis Jefferies, Joanna Frueh, Hagiwara Hiroko, Olabisi Silva. www.ktpress.co.uk The following article was republished in Volume 1, n.paradoxa (print version) January 1998: N.Paradoxa Interview with Gisela Breitling, Berlin artist and art historian n.paradoxa online issue no.4 August 1997 ISSN: 1462-0426 2 List of Contents Editorial 4 VNS Matrix Bitch Mutant Manifesto 6 Katy Deepwell Documenta X : A Critique 9 Janis Jefferies Autobiographical Patterns 14 Ann Newdigate From Plants to Politics : The Particular History of A Saskatchewan Tapestry 22 Katy Deepwell Reading in Detail: Ndidi Dike Nnadiekwe (Nigeria) 27 N.Paradoxa Interview with Gisela Breitling, Berlin artist and art historian 35 Diary of an Ageing Art Slut 44 n.paradoxa online issue no.4 August 1997 ISSN: 1462-0426 3 Reading in Detail : An Analysis of the work of Ndidi Dike Nnadiekwe Katy Deepwell Ndidi Dike Nnadiekwe was born in London.
    [Show full text]