DOCSLIB.ORG

Blood Donor Genotyping

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Blood Donor Genotyping Blood Donor Genotyping Nicholas S. Gleadall Department of Haematology University of Cambridge This dissertation is submitted for the degree of Doctor of Philosophy Gonville & Caius College September 2020 I would like to dedicate this thesis to the 813,212 donors, patients and healthy individuals whose data this work has used. Their decision to share personal medical and genetic information so that it may be used for the benefit of others is laudable. I hope that thework presented here meets the expectations they had when making such a valuable donation. Declaration I hereby declare that except where specific reference is made to the work of others, the contents of this dissertation are original and have not been submitted in whole or in part for consideration for any other degree or qualification in this, or any other university. This dissertation is my own work and contains nothing which is the outcome of work done in collaboration with others, except as specified in the text and Acknowledgements. This dissertation contains fewer than 65,000 words including appendices, bibliography, footnotes, tables and equations and has fewer than 150 figures. Nicholas S. Gleadall September 2020 Blood Donor Genotyping Nicholas S. Gleadall Abstract Transfusion of blood is one of the oldest and most widely used clinical interventions. In 2020 the World Health Organisation reported that globally 118.5 million blood donations had been collected worldwide. This blood will be used to provide life-saving transfusion support for millions of individuals with a wide range of medical conditions. To ensure the safety of each blood transfusion it is common policy to identify and ensure compatibility between the ABO and RhD antigens of both donor and recipient. Although this policy prevents the majority of adverse haemolytic transfusion reaction’s (HTR), approximately 3% of recipients become sensitised following an immune reaction to a non-self blood group antigen after a single transfusion episode. This proportion can rise dramatically in patients requiring frequent transfusion support, with immunisation rates as high as 60% being reported for some haemoglobinopathy patients. Sensitisation to non-self red blood cell (RBC) antigens confers a lifetime risk of HTRs, which from 2013 through 2017 were responsible for 17% (32 of 185) and 6% (7 of 110) of transfusion-related deaths reported to the US Food and Drug Administration and Serious Hazards of Transfusion UK, respectively. Furthermore, sensitisation can render transfusion- dependent patients non-transfusable and cause haemolytic disease in pregnancy which is potentially life-threatening to the fetus. A more precise blood matching policy will reduce sensitisation rates, however, adoption of this is resisted because of perceived logistical challenges, donor typing costs, and the lack of evidence from large scale clinical trials that reducing sensitisation rates results in health gains. Antibody-based haemagglutination tests are the current gold standard for RBC antigen typing; however, reliable reagents and high-throughput techniques are not available for all clinically relevant antigens. DNA-based tests have been used to overcome these limitations, and a range of in-house and commercial assays have been developed for donor genotyping. However, due to the limited number of antigens typed for and the low throughput capacity of these assays, they have not been widely applied to blood donor typing. Advances in the technologies used for genome-wide genotyping and sequencing have substantially reduced the cost of generating genetic variation data at population scale. Mul- tiple studies have demonstrated that it is possible to extract antigen typing information from the data produced by these technologies, indicating that they could be used to deliver vii genomics-based precision transfusion medicine to the patient bedside. However, the same studies also highlight a series of challenges that would have to be overcome before these technologies could be safely integrated into the clinical laboratory. In this thesis, I will present the work that has been done to overcome some of the issues surrounding the interpretation of blood cell antigen typing from genomic data and the development of a universal donor genotyping platform which can be used by blood supply organisations worldwide to implement of a policy of precision transfusion medicine. Acknowledgements The work presented in this thesis has been made possible through the continued support of many individuals. Firstly, I would like to thank Karen, Stephen and Sam - my family - for supporting me throughout my studies. I would like to thank all friends, loungers, crewmates, and ghost house residents who have kept me entertained throughout my PhD, I have been incredibly fortunate to meet you all. Secondly, from the NIHR BioResource, INTERVAL, COMPARE and DIS-III study teams I would like to thank Emanuele Di Angelantonio, John Bradley, Sarah Fahle, John M Jongerius, Nathalie Kingston, Jyoti Khadake, Amy McMahon, Susan Mehenny, Carmel Moore, Jennifer Sambrook, Olga Shamardina, Kathy Stirrups, Tiffany C. Timmer, Katja van den Hurk, Matt Walker, and Neil Walker for the genotyping and patient data they provided that was so crucial to this study. Thirdly, from the ISBT, NHS Blood and Transplant, and Sanquin I would like to thank Christoph Gassner, Alan Grey, Shane Grimsley, Peter Ligthart, and Nicole Thornton for taking the time to give me an education in Immunoheamtology and Judith Chapman, Gail Miflin, Dave Roberts, and Jill Storry who have publicly supported this work and helpedto bring it to the attention of the wider transfusion medicine community. A special thanks must go to William Astle, Kim Brugger, Karyn Megy, and Christopher Penkett who have done me hundreds of favours and put up with continual questions for four years. I would also like to give special thanks to Debra Fletcher and Lindsay Walker who have without fail managed to keep me organised, on-time, and generally alive throughout. From the Blood transfusion Genomics Consortium and my extensive panel of co- supervisors, I would like to thank Adam Butterworth, Jeremy Gollub, William Lane, John Ord, Ellen van der Schoot, Barbera Veldhuisen, Nicholas Watkins, and Connie Westhoff who have committed countless hours of their time to this project and to my professional development. Last but certainly not least, I would like to thank Willem H Ouwehand who has been consistently supportive, generous with his time and ideas, and an inspiration throughout. Being his student has been a privilege and a joy, I could not have asked for a better supervisor. x Because of him, I have had the opportunity to complete 1 PhD, visit 9 countries, give 32 presentations, win 6 prizes, receive 1 Lancet rejection, receive 1 Blood Advances acceptance, meet 1 billionaire, climb in the Rocky Mountains, sail on Lake Ontario, save William Lane from drowning in the Rhine, and make no less than 25 Circos plots. I will never be able to thank him enough for his decision to give me an opportunity to study for my PhD at the University of Cambridge. Table of contents List of figures xv List of tables xvii Nomenclature xix 1 Introduction1 1.1 A brief history of blood transfusion . .1 1.2 Blood group antigens . .3 1.3 Pre-transfusion testing and donor screening . .4 1.4 The molecular basis of blood group antigens . .7 1.4.1 The ABO blood group system . .7 1.4.2 The Kell blood group system . 11 1.5 Donor Genotyping . 11 1.6 Population Scale Genotyping . 13 1.7 Aims . 17 2 Materials and Methods 19 2.1 Overview . 19 2.2 An overview of Axiom array genotyping . 22 2.3 Next Generation Sequencing . 26 2.4 Bioinformatics . 30 2.4.1 bloodTyper . 30 2.4.2 HLA impute . 32 2.4.3 BWA, SAMtools, and BCFtools . 34 2.4.4 Genome Analysis Toolkit, Manta and Canvas . 34 2.4.5 Axiom Analysis Suite . 34 2.5 Summary of external data sources . 35 2.6 Blood Donor DNA samples . 35 xii Table of contents 2.6.1 INTERVAL panel (n=1,257) . 35 2.6.2 NIHR BioResource panel (n=507) . 36 2.6.3 COMPARE and DIS3 panel (n=7,477) . 36 2.7 Clinical RBC and PLT antigen typing data . 37 2.8 RBC and HPA Antigen typing concordance analysis . 39 2.9 HLA antigen typing concordance analysis . 39 2.10 Data availability . 40 2.11 My contribution to each chapter . 40 3 Mapping blood group antigens to the human genome 43 3.1 Abstract . 43 3.2 Introduction . 44 3.3 Chapter Workflow . 46 3.4 The Blood transfusion Genomics Consortium . 48 3.5 Data driven review of ISBT reference transcripts . 49 3.6 Exploring whole-genome sequencing data . 53 3.6.1 Further validation of the bloodTyper WGS algorithm . 53 3.6.2 Antigen typing 13,037 whole genomes . 54 3.6.3 Variation in the Kell blood group system . 60 3.7 Discussion . 65 4 A universal donor genotyping platform 69 4.1 Abstract . 69 4.2 Introduction . 70 4.3 Chapter workflow . 72 4.4 Stage 1 - Proof of principle . 74 4.5 Stage 2 - Designing an array for donor genotyping . 77 4.6 Stage 3: Large scale blinded trial of the UKBBv2 array . 83 4.6.1 Selection of trial set samples and initial genotyping quality control . 86 4.6.2 Allele frequency validation of the UKBBv2 array . 90 4.6.3 Overall antigen typing performance . 92 4.6.4 RBC antigen typing performance . 93 4.6.5 HPA antigen typing . 93 4.6.6 HLA antigen typing . 93 4.7 Impact of an extensively genotyped donor panel . 94 4.7.1 Identification of individuals with rare phenotypes . 96 4.7.2 Immediate clinical benefit of extended typing data . 96 Table of contents xiii 4.7.3 Donor and patient health information . 98 4.8 Discussion .
Load more

Recommended publications
  • A Multiscale Tool to Explore Genomic Conservation
    SynVisio: A Multiscale Tool to Explore Genomic Conservation A Thesis Submitted to the College of Graduate and Postdoctoral Studies in Partial Fulfillment of the Requirements for the degree of Master of Science in the Department of Computer Science University of Saskatchewan Saskatoon By Venkat Kiran Bandi ©Venkat Kiran Bandi, May/2020. All rights reserved. Permission to Use In presenting this thesis in partial fulfilment of the requirements for a Postgraduate degree from the University of Saskatchewan, I agree that the Libraries of this University may make it freely available for inspection. I further agree that permission for copying of this thesis in any manner, in whole or in part, for scholarly purposes may be granted by the professor or professors who supervised my thesis work or, in their absence, by the Head of the Department or the Dean of the College in which my thesis work was done. It is understood that any copying or publication or use of this thesis or parts thereof for financial gain shall not be allowed without my written permission. It is also understood that due recognition shall be given to me and to the University of Saskatchewan in any scholarly use which may be made of any material in my thesis. Requests for permission to copy or to make other use of material in this thesis in whole or part should be addressed to: Head of the Department of Computer Science 176 Thorvaldson Building 110 Science Place University of Saskatchewan Saskatoon, Saskatchewan Canada S7N 5C9 Or Dean College of Graduate and Postdoctoral Studies University of Saskatchewan 116 Thorvaldson Building, 110 Science Place Saskatoon, Saskatchewan S7N 5C9 Canada i Abstract Comparative analysis of genomes is an important area in biological research that can shed light on an organism's internal functions and evolutionary history.
    [Show full text]
  • A Zebrafish Reporter Line Reveals Immune and Neuronal Expression of Endogenous Retrovirus
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.21.427598; this version posted January 21, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. A zebrafish reporter line reveals immune and neuronal expression of endogenous retrovirus. Noémie Hamilton1,2*, Amy Clarke1, Hannah Isles1, Euan Carson1, Jean-Pierre Levraud3, Stephen A Renshaw1 1. The Bateson Centre, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK 2. The Institute of Neuroscience, University of Sheffield, Sheffield, UK 3. Macrophages et Développement de l’Immunité, Institut Pasteur, CNRS UMR3738, 25 rue du docteur Roux, 75015 Paris *Corresponding author: [email protected] Abstract Endogenous retroviruses (ERVs) are fossils left in our genome from retrovirus infections of the past. Their sequences are part of every vertebrate genome and their random integrations are thought to have contributed to evolution. Although ERVs are mainly kept silenced by the host genome, they are found activated in multiple disease states such as auto-inflammatory disorders and neurological diseases. What makes defining their role in health and diseases challenging is the numerous copies in mammalian genomes and the lack of tools to study them. In this study, we identified 8 copies of the zebrafish endogenous retrovirus (zferv). We created and characterised the first in vivo ERV reporter line in any species. Using a combination of live imaging, flow cytometry and single cell RNA sequencing, we mapped zferv expression to early T cells and neurons.
    [Show full text]
  • Evolution and Function of Drososphila Melanogaster Cis-Regulatory Sequences
    Evolution and Function of Drososphila melanogaster cis-regulatory Sequences By Aaron Hardin A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Molecular and Cell Biology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Michael Eisen, Chair Professor Doris Bachtrog Professor Gary Karpen Professor Lior Pachter Fall 2013 Evolution and Function of Drososphila melanogaster cis-regulatory Sequences This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License 2013 by Aaron Hardin 1 Abstract Evolution and Function of Drososphila melanogaster cis-regulatory Sequences by Aaron Hardin Doctor of Philosophy in Molecular and Cell Biology University of California, Berkeley Professor Michael Eisen, Chair In this work, I describe my doctoral work studying the regulation of transcription with both computational and experimental methods on the natural genetic variation in a population. This works integrates an investigation of the consequences of polymorphisms at three stages of gene regulation in the developing fly embryo: the diversity at cis-regulatory modules, the integration of transcription factor binding into changes in chromatin state and the effects of these inputs on the final phenotype of embryonic gene expression. i I dedicate this dissertation to Mela Hardin who has been here for me at all times, even when we were apart. ii Contents List of Figures iv List of Tables vi Acknowledgments vii 1 Introduction1 2 Within Species Diversity in cis-Regulatory Modules6 2.1 Introduction....................................6 2.2 Results.......................................8 2.2.1 Genome wide diversity in transcription factor binding sites......8 2.2.2 Genome wide purifying selection on cis-regulatory modules......9 2.3 Discussion.....................................9 2.4 Methods for finding polymorphisms......................
    [Show full text]
  • A Burst of Protein Sequence Evolution and a Prolonged Period of Asymmetric Evolution Follow Gene Duplication in Yeast
    Downloaded from genome.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Letter A burst of protein sequence evolution and a prolonged period of asymmetric evolution follow gene duplication in yeast Devin R. Scannell1,2 and Kenneth H. Wolfe Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland It is widely accepted that newly arisen duplicate gene pairs experience an altered selective regime that is often manifested as an increase in the rate of protein sequence evolution. Many details about the nature of the rate acceleration remain unknown, however, including its typical magnitude and duration, and whether it applies to both gene copies or just one. We provide initial answers to these questions by comparing the rate of protein sequence evolution among eight yeast species, between a large set of duplicate gene pairs that were created by a whole-genome duplication (WGD) and a set of genes that were returned to single-copy after this event. Importantly, we use a new method that takes into account the tendency for slowly evolving genes to be retained preferentially in duplicate. We show that, on average, proteins encoded by duplicate gene pairs evolved at least three times faster immediately after the WGD than single-copy genes to which they behave identically in non-WGD lineages. Although the high rate in duplicated genes subsequently declined rapidly, it has not yet returned to the typical rate for single-copy genes. In addition, we show that although duplicate gene pairs often have highly asymmetric rates of evolution, even the slower members of pairs show evidence of a burst of protein sequence evolution immediately after duplication.
    [Show full text]
  • A Phd Position Is Available in the Research Group of Aoife Mclysaght
    A PhD position is available in the research group of Aoife McLysaght in Trinity College Dublin to work on comparative genomics of vertebrates with a focus on understanding dosage sensitive genes in terms of evolution and disease. The execution of the project will involve bioinformatics and computer programming as well as statistical analysis of data. For examples of the kinds of things we work on, look up our papers on PubMed: https://www.ncbi.nlm.nih.gov/pubmed?cmd=search&term=mclysaght+a[au]&dispmax=50 Applicants should be in the final year of, or hold, a bachelor's degree in molecular biology with an interest and aptitude for programming and bioinformatics; or vice versa (computer science bachelor's with an interest in molecular biology). Interest and enthusiasm for molecular evolution is essential. Students will be expected to be self-motivated and creative and to work closely with other members of the team. This is a four-year position and comes with a tax-free stipend of 18000euro and covers fees up to EU level (non-EU students may apply, but fees are only covered up to EU rates). TCD is Ireland’s top ranked University and a member of the League of European Research Universities (LERU). The McLysaght lab is funded by a European Research Council (ERC) Starting Grant. Lab: http://www.gen.tcd.ie/molevol/ Applications including a cover letter, CV, summary of scientific interests and reasons for being interested in our research group, and contact details for two referees should be made to [email protected].
    [Show full text]
  • Review 2015–16 Review
    Review 2015–16 Review 2015–16 AR cover 1.indd 1 3/2/2017 3:00:03 PM TO PRINT.indd 82 3/2/2017 1:56:30 PM Inside A year in view 4 A note from the President 11 A note from the Executive Secretary 13 We explore 17 We award 27 We engage 31 We advise 49 We support 55 New members 61 Donations 73 Bereavements 78 Accounts 80 This report covers the period from March 2015 to December 2016 TO PRINT.indd 1 3/2/2017 1:53:07 PM 156 new entries added to the Dictionary of Irish Biography 61 maps from Irish Historic Towns Atlas now available online 10 volumes of Documents on Irish Foreign Policy to date 6 US-Ireland Research Innovation Award winners 1 prehistoric bear bone excavated with RIA grants TO PRINT.indd 2 3/2/2017 1:53:08 PM 19 1,400 visits on 1,500 events and meetings Culture Night 2016 13,300 followers on Twitter 20,100 books sold 100,000,000 stamps inspired by A History of Ireland in 100 Objects 38,500 visitors 70,000 441,900 in research grants awarded downloads € of 1916 Portraits and Lives TO PRINT.indd 3 3/2/2017 1:53:09 PM US-Ireland Research Innovation Awards 2016: L–R Eddie Cullen, Ulster Bank; Minister for Jobs, Enterprise and Innovation, Mary Mitchell O’Connor, TD; Shaun Murphy, KPMG and James O’Connor, American Chamber of Commerce. Participant at Inspiring Ireland London Collection Day, organised by the Digital Repository of Ireland in March 2016.
    [Show full text]
  • SG Stories004-President-Of-Ireland
    COMMUNITY SYNTHETIC BIOLOGY EVENT LAUNCHES PRESIDENT OF IRELAND ETHICS INITIATIVE WHO? ▶ Science Gallery Dublin ▶ President of Ireland Ethics Initiative ▶ Drew Endy, Associate Professor of Stanford University Professor of Bioengineering, Stanford University Bioengineering Drew Endy came Hugh Whittall, Director of Nuffield to Science Gallery Dublin in Council on Bioethics, UK 2014 as the inaugural event of the ▶ Aoife McLysaght, Professor of Genetics, President of Ireland Ethics Initiative, Trinity College Dublin leading to awareness and ▶ Celsius Research Cluster, Dublin City discussion of critical ethical issues University around synthetic biology. ▶ President of Ireland Ethics Initiative WHAT? The President of Ireland Ethics Initiative is a series of discussions on prominent ethical issues headed by Irish President Michael D Higgins, and the inaugural event was held in Science Gallery Dublin in January 2014. Synthetic Biology pioneer Drew Endy, from Stanford University, spoke about synthetic biology and engaged in a discussion with audience members, geneticist Aoife McLysaght and Nuffield Council on Bioethics Director Hugh Whittall, exploring the nature and ethics of synthetic biology. The event tied in with Science Gallery Dublin’s synthetic biology themed GROW YOUR OWN... exhibition. Evaluation of the event was carried out by the Celsius Research Cluster in Dublin City University. Event attendees were asked questions about synthetic biology before and after the event, and the results showed an increase in awareness of synthetic biology
    [Show full text]
  • Evidence from Human, Yeast, and Plant Positionally Biased Gene Loss
    Downloaded from genome.cshlp.org on December 3, 2012 - Published by Cold Spring Harbor Laboratory Press Positionally biased gene loss after whole genome duplication: Evidence from human, yeast, and plant Takashi Makino and Aoife McLysaght Genome Res. 2012 22: 2427-2435 originally published online July 26, 2012 Access the most recent version at doi:10.1101/gr.131953.111 Supplemental http://genome.cshlp.org/content/suppl/2012/09/17/gr.131953.111.DC1.html Material References This article cites 39 articles, 19 of which can be accessed free at: http://genome.cshlp.org/content/22/12/2427.full.html#ref-list-1 Creative This article is distributed exclusively by Cold Spring Harbor Laboratory Press Commons for the first six months after the full-issue publication date (see License http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/. Email alerting Receive free email alerts when new articles cite this article - sign up in the box at the service top right corner of the article or click here To subscribe to Genome Research go to: http://genome.cshlp.org/subscriptions © 2012, Published by Cold Spring Harbor Laboratory Press Downloaded from genome.cshlp.org on December 3, 2012 - Published by Cold Spring Harbor Laboratory Press Research Positionally biased gene loss after whole genome duplication: Evidence from human, yeast, and plant Takashi Makino1,2 and Aoife McLysaght1,3 1Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland; 2Department of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan Whole genome duplication (WGD) has made a significant contribution to many eukaryotic genomes including yeast, plants, and vertebrates.
    [Show full text]
  • Synteny-Based Analyses Indicate That Sequence Divergence Is Not the Main Source of Orphan Genes Nikolaos Vakirlis1, Anne-Ruxandra Carvunis2*, Aoife Mclysaght1*
    RESEARCH ARTICLE Synteny-based analyses indicate that sequence divergence is not the main source of orphan genes Nikolaos Vakirlis1, Anne-Ruxandra Carvunis2*, Aoife McLysaght1* 1Smurfit Institute of Genetics, Trinity College Dublin, University of Dublin, Dublin, Ireland; 2Department of Computational and Systems Biology, Pittsburgh Center for Evolutionary Biology and Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, United States Abstract The origin of ‘orphan’ genes, species-specific sequences that lack detectable homologues, has remained mysterious since the dawn of the genomic era. There are two dominant explanations for orphan genes: complete sequence divergence from ancestral genes, such that homologues are not readily detectable; and de novo emergence from ancestral non-genic sequences, such that homologues genuinely do not exist. The relative contribution of the two processes remains unknown. Here, we harness the special circumstance of conserved synteny to estimate the contribution of complete divergence to the pool of orphan genes. By separately comparing yeast, fly and human genes to related taxa using conservative criteria, we find that complete divergence accounts, on average, for at most a third of eukaryotic orphan and taxonomically restricted genes. We observe that complete divergence occurs at a stable rate within a phylum but at different rates between phyla, and is frequently associated with gene shortening akin to pseudogenization. *For correspondence: [email protected] (A-RC); Introduction [email protected] (AMcL) Extant genomes contain a large repertoire of protein-coding genes which can be grouped into fami- lies based on sequence similarity. Comparative genomics has heavily relied on grouping genes and Competing interests: The proteins in this manner since the dawn of the genomic era (Rubin, 2000).
    [Show full text]
  • Science at Trinity Faculty of Engineering, Mathematics and Science TR060 Biological & Biomedical Sciences Senior Freshman Programme 2019 - 2020
    Cover template_Layout 1 04/04/2018 09:53 Page 1 Science at Trinity Faculty of Engineering, Mathematics and Science TR060 Biological & Biomedical Sciences Senior Freshman Programme 2019 - 2020 tcd.ie/science This handbook applies to all students taking TR060: Biological and Biomedical Science. It provides a guide to what is expected of you on this programme, and the academic and personal support available to you. Please retain for future reference. The information provided in this handbook is accurate at time of preparation. Any necessary revisions will be notified to students via email and the Science Course Office website (http://www.tcd.ie/Science). Please note that, in the event of any conflict or inconsistency between the General Regulations published in the University Calendar and information contained in the course handbooks, the provisions of the General Regulations will apply. The Science Course Office Trinity College Produced by: The University of Dublin Dublin 2 Tel: +353 1 896 1970 Web address: http://www.tcd.ie/Science Edited by: Ms Anne O’Reilly and Ms Ann Marie Brady www.tcd.ie/science Contents Senior Freshman TR060: Biological and Biomedical Sciences Introduction 1 TR060: Biological and Biomedical Sciences overview and module selection 2 TR060: Biological and Biomedical Sciences Semester Structure 3 TR060: Biological and Biomedical Sciences Senior Freshman Module Choice Form 4 Change of Approved Module information 5 College Registration Information 5 The European Credit Transfer Accumulation System (ECTS) 6 TR060: Biological
    [Show full text]
  • Identification of Multiple Independent Horizontal Gene Transfers Into Poxviruses Using a Comparative Genomics Approach Kirsten a Bratke and Aoife Mclysaght*
    BMC Evolutionary Biology BioMed Central Research article Open Access Identification of multiple independent horizontal gene transfers into poxviruses using a comparative genomics approach Kirsten A Bratke and Aoife McLysaght* Address: Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland Email: Kirsten A Bratke - [email protected]; Aoife McLysaght* - [email protected] * Corresponding author Published: 27 February 2008 Received: 10 October 2007 Accepted: 27 February 2008 BMC Evolutionary Biology 2008, 8:67 doi:10.1186/1471-2148-8-67 This article is available from: http://www.biomedcentral.com/1471-2148/8/67 © 2008 Bratke and McLysaght; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Poxviruses are important pathogens of humans, livestock and wild animals. These large dsDNA viruses have a set of core orthologs whose gene order is extremely well conserved throughout poxvirus genera. They also contain many genes with sequence and functional similarity to host genes which were probably acquired by horizontal gene transfer. Although phylogenetic trees can indicate the occurrence of horizontal gene transfer and even uncover multiple events, their use may be hampered by uncertainties in both the topology and the rooting of the tree. We propose to use synteny conservation around the horizontally transferred gene (HTgene) to distinguish between single and multiple events. Results: Here we devise a method that incorporates comparative genomic information into the investigation of horizontal gene transfer, and we apply this method to poxvirus genomes.
    [Show full text]
  • Public Engagement
    08 Public Engagement Trinity achieves its mission Festivals and broadcasts to ‘engage wider society’ Trinity partners with national and international organisations to host events and festivals on campus. As in previous years, through festivals, lectures, the college took part in the annual fixtures Culture Night and events, exhibitions, Open House Dublin, and this year Front façade lighting up was showcasing research extended beyond Christmas and St Patrick’s Day with Front online, and through media façade turning rainbow for the Dublin Pride festival. Over 3,000 visitors attended PROBE: Research and social media activity. Uncovered in September, a free pop-up festival showcasing academic research, with over 50 live experiments, exclusive demonstrations, laboratory and observatory tours and inter- active workshops. PROBE, a collaboration between Trinity and Science Gallery Dublin in partnership with the British Council, was part of European Researchers’ Night, taking place in cities across the continent. RIGHT – PERFECTION exhibition at Science Gallery Dublin Trinity College Dublin – The University of Dublin ≥ The science programme Growing Up Live was broadcast live from Trinity’s Anatomy Museum as part of Science Week 2018. Annual Review 2018–2019 58 | 59 08.0 Public Engagement 08 The science programme Growing Up Live was broadcast discussion series have become annual events. The 5th annual live from Trinity’s Anatomy Museum as part of Science Week Edmund Burke lecture in October was delivered by Pulitzer 2018. Supported by Science Foundation Ireland and includ- Prize-winning poet Paul Muldoon who explored the rights of ing leading Trinity researchers, the three-part series tracked the artist in society.
    [Show full text]