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    • July 2008 . ISSUE 59 GENETICS SOCIETY NEWS www.genetics.org.uk IN THIS ISSUE Genetics Society News is edited by Steve Russell. Items for future issues should be sent to Steve Russell, preferably by email to • Genetics Society Epigenetics Meeting s.russell@gen.cam.ac.uk, or hard copy to Department of Genetics, • Genetics Society Sponsored Meetings University of Cambridge, Downing Street, Cambridge CB2 3EH. The Newsletter is published twice a year, with copy dates of 1st June and • Travel, Fieldwork and Studentship Reports 26th November. • John Evans: an Appreciation Cocoons of the parasitoid wasp Cotesia vestalis on cabbage leaf in Taiwan. From the • Twelve Galton Lectures fieldwork report by Jetske G. de Boer on page 36. • My Favourite Paper
    • A WORD FROM THE EDITOR A word from the editor ow soon until the $1000 based on the results of tests we H genome is actually with us and individual sequencing is widespread? The barely understand! Here in the UK there is currently a moratorium, adhered to by publication of increasing most insurers, on the use of numbers of individual human genetic testing information for genome sequences suggests assessing life insurance that we should start to consider applications. It is important some of the implications that this remains in place and associated with the availability its effectiveness is reviewed of personal genetic well before the current information. In this issue we moratorium expires in 2011. present two articles reflecting The Human Genetics on his issue: a report from a Commission Genetics Society sponsored (http://www.hgc.gov.uk) meeting recently held in monitor issues relating to Cambridge organised by The genetic discrimination in the Triple Helix, an international UK and are a point of contact undergraduate organisation, as for those with any concerns in the Millennium Technology Prize. On a less well as our Taxi Driver column this area. happy note, the Society was sad to learn of the by Andrew Grierson. In recent death of John Evans, a much-respected relation to the societal The implications of using figure in international genetics. Our president implications of personal personal sequence data in Elect, Veronica van Heyningen, presents an genetic information, on May society has some echoes with appreciation of his life in science. 21st this year, the U.S. President the eugenics movement signed into law the Genetic prominent in the early 20th We have a report of the recent Genetics Society Information Non- Century and in this issue Mike meeting on epigenetics along with other society- discrimination Act (GINA). Majerus reviews the recent sponsored meetings and a selection of reports The new legislation will publication of a volume of from members who received travel or fieldwork prohibit employers and health lectures marking the Centenary grants. I hope you enjoy this issue and, as insurers from discriminating of the Galton Institute that always, anything you want to get off your chest, against individuals on the basis provides some historical scientifically speaking, can be published in our of their personal genetic context to this important Taxi Driver column. I also welcome any other information and was driven by current debate. material you feel would be of interest to the the joint efforts of the Society membership and you can contact me to American Society of Human We are happy to report a flurry sound out potential articles. Genetics, the Coalition for of awards for current and past Genetic Fairness, the Genetic presidents of the Genetics Alliance and other Society. Our current president, Steve Russell organizations in the genetics Brian Charlesworth, receives community. See the NHGRI the Weldon Memorial Prize, University of Cambridge website www.genome.gov/24519851 former president Michael for more details of this Ashburner receives the Thomas important step forward in Hunt Morgan Medal and Alex preventing discrimination Jeffries has been nominated for 2 . GENETICS SOCIETY NEWS . ISSUE 59
    • Issue 59 . July 2008 NEWS . FEATURES . REPORTS . LISTINGS For more details please contact: The Genetics Society . Roslin BioCentre CONTENTS Wallace Building . Roslin . Midlothian . EH25 9PP Tel: 0131 200 6391 . Fax: 0131 200 6394 email: mail@genetics.org.uk Website: www.genetics.org.uk The Genetics Society Journals Heredity (www.nature.com/hdy/) Managing Editor: Prof Richard A. Nichols, QMUL, UK Genes and Development (www.genesdev.org/) REGULARS European Editor: Prof Winship Herr, Lausanne, Switzerland Meeting Announcements 4 - 10 President Prof. Brian Charlesworth, University of Edinburgh Evolution of Sex and Asexual Reproduction Human Genetic Disease: President-elect From Model Organisms to the Clinic Prof. Veronica van Heyningen, MRC Human Genetics Unit, Edinburgh Mammalian Genetics and Development e versa? There are multiple contrasting approaches to these problems: theoretical versus empirical appr Vice-Presidents netical verses ecological explanations, field versus laboratory systems. This meeting will bring together ands in current research. Workshop Prof. J. Steve Jones, University College London External Meetings Diary Prof. John Brookfield, University of Nottingham Prof. Ian Jackson, MRC Human Genetics Unit, Edinburgh Sectional Interests Groups Honorary Secretary Genetics Society Business 11 - 18 Prof. Patricia E Kuwabara, University of Bristol AGM Honorary Treasurer Committee News Prof Josephine Pemberton, University of Edinburgh Genetics Society Awards Scientific Meetings Officer Postgraduate Rep Dr Andrew Ward, University of Bath Heredity News Biosciences Federation News Newsletter Editor Dr Steve Russell, University of Cambridge Promega Young Geneticist of the Year Postgraduate Representative Genetics Society Meeting Reports 19 - 21 Mr Tom Nowakowski, University of Edinburgh Frontiers in Epigenetics Ordinary Committee Members Dr Hilary Ashe, University of Manchester Genetics Society Sponsored Events 22 - 24 Dr Mark A. Beaumont, University of Reading Dr Ewan Birney, European Bioinformatics Institute Mammalian Genetics, Development & Disease Dr Tanita Casci, Nature Reviews Genetics Who Owns My Genome? Dr Liam Dolan, John Innes Centre, Norwich Dr Alison Dunn, University of Leeds Prof. Adam Eyre-Walker, University of Sussex Dr Anne Ferguson-Smith, University of Cambridge Dr DJ de Koning, Roslin Institute, Midlothian Prof. Graham Moore, John Innes Centre, Norwich FEATURES Dr Tom Weaver, Medical Solutions PLC Dr Tanya Whitfield, University of Sheffield A Taxi Driver Writes 25 - 28 Book Review: Twelve Galton Lectures 29 - 30 Design John Evans: an appreciation 31 - 32 Round & Red Creative . 15 Poole Road My Favourite Paper 33 - 34 Woking . Surrey . GU21 6BB Tel: 01483 596 226 . www.round&red.com Fieldwork and Studentship Reports 35 - 37 Fungal Pathogens Printing Parasitoid Wasps RPM Print & Design . Spur Road . Quarry Lane Chichester . West Sussex . PO19 8PR . UK Tel: 01243 787 077 . admin@rpm-repro.co.uk Student Travel Reports 38 - 44 DNA Replication & Recombination Advertising in Genetics Society News represents an RNAi, microRNA and ncRNA opportunity to reach a large community of professional Alternative Splicing & Disease geneticists. For rates please email mail@genetics.org.uk Atlantic Salmon Drosophila www.genetics.org.uk . 3
    • Evolution of Sex and Asexual Reproduction One day meeting. Friday 5 September 2008 at the University of Bath, UK While the maintenance of sex and recombination remains an intellectual challenge, the long term persistence of some asexuals is equally puzzling. What if anything can be learnt about the former issues by studying the latter and vice versa? There are multiple contrasting approaches to these problems: theoretical versus empirical approaches, genetical verses ecological explanations, field versus laboratory systems. This meeting will bring together all of these strands in current research. Speakers: Scientific organisers: Christina Burch (North Carolina, USA) Laurence Hurst (Bath) and Roger Butlin (Sheffield) Jukka Jokela (Zurich, Switzerland) Peter Keightley (Edinburgh, UK) Featuring: Ryszard Korona (Krakow, Poland) 2008 Mendel Medal winner, Dunja Lamatsch (Mondsee, Austria) Matthew Meselson (Harvard, USA) Thomas Lenormand (Montpellier, France) Mike Lynch (Indiana, USA) 2008 Balfour Lecture by Stefan Scheu (Darmstadt, Germany) Daven Presgraves (Rochester, New York) Registration Fees: Genetics Society members £30, non-members (academic) £80, non-members (non-academic) £135 Student members can apply for travel grants to offset the cost of attending this meeting (see website for details). Visit the Genetics Society website for further details and to register for the meeting: www.genetics.org.uk/home.
    • A Joint One Day Genetics Society and British Society for Human Genetics Meeting Human Genetic Disease: From model organism to the clinic Friday 28th November 2008, The Royal Society, London SCIENTIFIC ORGANISERS Genetics Society: Lizzy Fisher (UCL) and Andrew Ward (Bath) BSHG: Phil Beales (ICH, London), Eamonn Maher (Birmingham) and Andrew Wilkie (IMM, Oxford) SPEAKERS Robin Ali (University College London, UK) Kathryn Anderson (Sloan-Kettering Institute, New York) Han Brunner (Nijmegen, Netherlands) Juan Botas (Baylor College of Medicine, Texas, USA) Neal Copeland (Institute of Molecular and Cell Biology, Singapore) Wofgang Driever (Freiburg, Germany) Jill Helms (Stanford University, USA) Jenny Morton (University of Cambridge, UK) Nadia Rosenthal (EMBL, Monterotondo, Italy) The 2008 Genetics Society Medal will be awarded to Nick Hastie (MRC Human Genetics Unit, Edinburgh) Further details will be made available at www.genetics.org.uk
    • A meeting of The Genetics Society The Mammalian Genetics and Development Workshop 20th - 21st November 2008 . Institute of Child Health, UCL, 30 Guilford Street, London WC1N 1EH The Mammalian Genetics and Development Workshop is a small annual meeting that aims to cover any aspects of the genetics and development of mammals. Meetings are based on the submitted abstracts, and usually include diverse topics ranging from early mammalian development (not exclusively human or mouse), imprinting and positional cloning of disease genes to human population genetics and association studies. In recent years, presentations on other model systems (such as chick and zebrafish) have also been included where these relate to general developmental questions or disease models. The meeting is traditionally a venue for post-docs and PhD students to talk rather than laboratory heads and so is an excellent training ground and friendly, informal forum for discussing new results. In keeping with this objective, we offer TWO PRIZES of £150 to individual post- graduate/post-doctoral presenters who, in the opinion of a panel of judges, have given an outstanding presentation. A further prize is also offered, thanks to the generosity of the editors of Mammalian Genome (Springer). The prizewinner receives £150, a book of choice from the Springer range plus a year's subscription to Mammalian Genome. One additional prize of £200 will be awarded to the speaker judged to have given the best presentation of a genetics-based research project. Promega, who will also sponsor the wine reception at this meeting, generously contributes this prize. Registration A £10 registration fee is payable by all attendees on arrival at the meeting. The fee entitles registrants to attend all of the scientific sessions, to receive the abstract booklet and tea/coffee refreshments on both days. Speakers and chairpersons will be provided with lunch, free of charge, on the day of their presentation. Other participants will be expected to make their own arrangements for lunch. All participants are responsible for organising their own overnight accommodation, if required, although we can advise on places to stay. There will also be a wine/cheese reception (sponsored by Promega) on the first day of the meeting. Abstract Submission All Workshop presentations will be in lecture format (15 or 30 minutes), chosen from abstracts submitted prior to the meeting. If you would like to present a paper at the Workshop please send your abstract by e-mail to the following address: MGD.Workshop@ich.ucl.ac.uk. With the authors' permission, abstracts will be published in Genetical Research.
    • 7 EXTERNAL MEETINGS DIARY If you would like to announce a meeting that you think may be of interest to Genetics Society members, please contact the newsletter editor Steve Russel s.russell@gen.cam.ac.uk. XX International Congress of Genetics Mycological Society of America 2008 12th – 17th July 2008 9th – 13th August 2008 Berlin, Germany Pennsylvania, USA further info www.geneticsberlin2008.com/ further info www.outreach.psu.edu/programs/ mycology/ International Society for Animal Genetics 2008 20th – 24th July 2008 Molecular Biology of Archaea 2008 Amsterdam, The Netherlands 19th – 20th August 2008 further info www.isag2008.nl/ St Andrews, UK further info www.biochemistry.org/meetings/ DNA Topology and Topoisomerases (Topo2008) programme.cfm?Meeting_No=SA079 20th – 23rd July 2008 John Innes Centre, UK 9th International Conference on Systems further info www.liv.ac.uk/sbs/Topo2008/Register.html Biology 22nd – 28th August 2008 2008 Yeast Genetics and Molecular Biology Meeting Göteborg, Sweden 22nd – 27th July 2008 further info http://icsb-2008.org/ Toronto, Canada further info www.yeast-meet.org/ Agricultural Biotechnology International Conference 19th International Conference 24th – 27th August 2008 on Arabidopsis Research Cork, Ireland 23rd – 27th July 2008 further info www.abic.ca/abic2008/html/ Montreal, Canada program.html further info www.plantconferences.org/ Arabidopsis2008/ GARNet/SEB Plant Symposium 8th – 10th September 2008 International Symposium on Induced Nottingham. UK Mutations in Plants further info http://garnet.arabidopsis.info/ 12th – 15th August 2008 Vienna, Austria ESF-EMBO Symposium on Bacterial Networks further info www-pub.iaea.org/MTCD/Meetings/ 13th – 18th September 2008 Announcements.asp?ConfID=167 Sant Feliu de Guixols, Spain further info www.esf.org/index.php?id=4565 RNA 2008 28th July – 3rd August 2008 Berlin, Germany further info www.rna2008.mpg.de/ www.genetics.org.uk . 7
    • EXTERNAL MEETINGS DIARY 8 4th London Fly Meeting Annual Symposium: DNA damage: From 19th September 2008 Causes to Cures London, UK 15th – 17th December 2008 further info http://lfm2008.org.uk Robinson College, Cambridge, UK further info www.biochemistry.org/meetings/ Molecular Genetics of Aging programme.cfm?Meeting_No=SA084 24th – 28th September 2008 Cold Spring Harbor Laboratory, USA Epigenetics, Development and Human Disease further info http://meetings.cshl.edu/meetings/ 5th – 10th January 2009 aging08.shtml Breckenridge, USA further info HUGO 13th Human Genome Meeting www.keystonesymposia.org/Meetings/ 27th – 30th September 2008 ViewMeetings.cfm?MeetingID=978 Hyderabad, India further info http://hgm2008.hugo-international.org/ Fourth Biennial Conference of the International Biogeography Society 10th Human Genome Variation Meeting 8th – 12th January 2009 15th – 17th October 2008 Mérida, México Toronto, Canada Invited symposia will feature talks on the further info www.tcag.ca/hgv2008/ biogeography of disease, patterns and processes in biotic transition zones, disjunct distributions in Advances in Nucleic Acid Detection & Quantification Asia and America, and the biogeography of species 28th – 29th October 2008 extinction. Attendees are invited to submit Hinxton Hall, Cambridge, UK abstracts for oral and poster presentations. The further info www.biochemistry.org/meetings/ conference will also include workshops, field programme.cfm?Meeting_No=SA092 excursions, and social events. Registration, contact, and additional information may be found at: Mouse Genetics & Genomics: Development & Disease http://www.biogeography.org. 29th October – 2nd November 2008 further info http://www.biogeography.org Cold Spring Harbor Laboratory, USA further info http://meetings.cshl.edu/meetings/ Miami Winter Symposium 2009: Interpreting mouse08.shtml the Human Genome 24th – 28th January 2009 58th American Society for Human Genetics Meeting Miami, USA 11th – 15th November 2008 further info www.nature.com/ Philadelphia, USA natureconferences/MWS2009 further info www.ashg.org/2008meeting/ index.shtml Cancer Genetics and Epigenetics IV International Conference on Legume Genomics 25th – 30th January 2009 and Genetics Ventura, USA 7th – 12th December 2008 further info www.grc.org/programs.aspx?year= Puerto Vallarta, Mexico 2009&program=cancer further info www.ccg.unam.mx/iclgg4/ 8 . GENETICS SOCIETY NEWS . ISSUE 59
    • 9 SECTIONAL INTEREST GROUPS The Genetics Society helps support several sectional interest groups by providing meeting sponsorship. We currently have 8 groups who organise sectional interest meetings with the organizers and dates of any forthcoming meetings are listed below. We include short reports form two of our groups on their recent activities. If you are interested in any of these areas, please contact the relevant organiser. Groups who wish to be considered for sectional interest group status should contact the Treasurer, Josephine Pemberton, in the first instance. Arabidopsis London Fly Meetings: The London Fly Meetings Organiser: Ruth Bastow (ruth@arabidopsis.info) (LFMs) are monthly gatherings of Drosophila groups GARNet/SEB Plant Symposium 8th – 10th September in the London area held at the Cancer Research UK 2008, University of Nottingham. London Research Institute on the third Wednesday of http://garnet.arabidopsis.info/ each month, and are organised by the London Fly Group. Recent attendance at the monthly meetings Archaea group has been excellent, frequently topping 50 Organiser: Thorsten Allers participants. The meetings start with an informal (thorsten.allers@nottingham.ac.uk) mixer, during which fly stocks and stories are often Molecular Biology of Archaea 2008 exchanged, followed by one or two speakers. Usually, 19th – 20th August 2008, University of St Andrews. the speakers are from participating labs, but we also http://www.biochemistry.org/meetings/programme.cf occasionally host external speakers, such as Ulrike m?Meeting_No=SA079 Gaul from Rockefeller University on September 5th 2007 who presented her latest work on glial cell British Yeast Group development. Topics covered by our local speakers in Organiser: Alistair Goldman 2007 included Src signalling in imaginal discs (Paul (a.goldman@sheffield.ac.uk) Langton, Tapon lab, CRUK), DIAP2 in the control of cell death (Paulo Ribeiro, Meier lab, Breakthrough C. elegans Cancer Centre), the circadian clock and light (Nikolai Organiser: Stephen Nurrish (s.nurrish@ucl.ac.uk) Peschel Stanewsky lab, Queen Mary’s) and insulin signalling in the CNS (Irene Miguel-Aliaga Gould lab, Ecological Genetics Group NIMR). Finally, we enjoyed a fabulous Lebanese Organiser: Barbara Jones (b.jones@ccw.gov.uk) buffet for our festive December meeting, and even more fabulous science as Andrea Brand (Gurdon Genetics Society Pombe Club Institute, Cambridge) presented her lab’s exciting Organiser: Jacky Hayles (j.hayles@cancer.org.uk) new work on stem cell populations in the nervous system. In addition to the monthly meetings, the Mammalian Genetics & Development London Fly Group also organises the highly Organisers: Elizabeth M. Fisher and Nick Greene successful biannual international London Fly Contact: mgd.workshop@ich.ucl.ac.uk Meetings. The 4th London Fly Meeting will be on Fri 9th September 2008 at King’s POP group College(http://lfm2008.org.uk/). Organiser: Deborah Charlesworth (Deborah.Charlesworth@ed.ac.uk) The Zebrafish Forum Organiser: Rachel Ashworth (r.ashworth@ucl.ac.uk), Drosophila Caroline Brennan (C.H.Brennan@qmul.ac.uk), Organiser: David Ish-Horowicz Corinne Houart (corinne.houart@kcl.ac.uk). (david.horowicz@cancer.org.uk) There are meetings at 5:30pm-8.00pm on the first Monthly meetings are organised by: Thursday of every other month. Room G12, New Joe Bateman (joseph_matthew.bateman@kcl.ac.uk) Hunt's House, King's College - London SE1 1UL www.genetics.org.uk . 9
    • SECTIONAL INTEREST GROUPS 10 The Zebrafish Forum from two different perspectives Manuela Lahne and Rachel Ashworth, QMUL. progenitor cells become transferase and sulfatases both of which are specified to one of several involved in the regulation of heparan sulfatation distinct fates, using the and showed vascular phenotypes ranging from vertebrate neural crest as a vascular oedema to reduced branching. This model system. In February the presentation was followed by Tom Chipperfield, zebrafish forum was held at who identified targets of the transcription factor UCL, thanks to Masa Tada, and Sox10 in neural crest cells. He carried out his included three speakers. research using microarray techniques and in situ Manuel Batista, University of hybridisation. The final speaker, Rachel n this report we bring a Cambridge, described his work Ashworth, is investigating the role of neural I roundup of past meetings: December and February as examining Pax2 and its role in the specification of activity induced calcium signals on the development of slow muscle fibres. She used described by Rachel Ashworth, interneurons. Issac Bianco, calcium imaging techniques as well as along with an overview of the University College London immunocytochemistry to determine muscle March meeting from Manuela talked about his work on phenotypes in zebrafish mutants. The meeting Lahne, a new member of the analysis of lateralised circuitry gave me an opportunity to gain insight into the zebrafish community. We in the zebrafish brain, with versatility of research questions that are tackled would also like to draw your focus on the habenular nuclei. using zebrafish, as well as the techniques that attention to an upcoming Helen Bodmer, from the Home are used to carry out this research. Moreover, meeting on zebrafish welfare, Office, led a group discussion attending the meeting allowed me to acquire and husbandry, and maintenance, to regarding defining consolidate basic knowledge regarding zebrafish be held at UCL in October. developmental stages. anatomy and development. It was also helpful to meet with researchers in the field and discuss The December meeting, held at In March I had the pleasure of related subjects in a relaxed environment with a Queen Mary University of attending the fish forum at the glass wine. I am now looking forward to London, had a packed Weatherhall Institute of zebrafish forums in the future. programme including 3 Medicine in Oxford, organized speakers and posters. Tessa by Roger Patient and co-hosted Peterkin from University of with the monthly Forthcoming events: Oxford described her developmental biology club. October 2008 Zebrafish Forum at UCL investigation of the role of This was the first zebrafish (date to be confirmed). GATA transcription factors, forum I attended after only GATA 4, 5 and 6, in vertebrate recently moving into a research Zebrafish welfare, husbandry, and maintenance: heart development. Gavin area that uses this model this is a one-off meeting designed as a forum for Wright from The Sanger organism. The three speakers, both technical staff and researchers, involving Institute presented work on Sally Stringer, Tom subjects interesting and useful to all groups with large scale screening for novel Chipperfield and Rachel an interest in zebrafish. The meeting will involve low affinity transient Ashworth, are investigating aspects of zebrafish welfare, husbandry and extracellular-ligand pair very different topics and talked maintenance, alongside more research-based interactions. The group is about some of their most recent topics. The aim is to encourage discussion of using zebrafish to determine discoveries. Sally Stringer some of the more practical but often overlooked the functional significance of described vascular development aspects of this model organism. There will be a identified cell surface in zebrafish with the specific presentation of posters and people are interactions in vivo. Robert focus on heparan sulfates. She encouraged to bring along any appropriate work. Kelsh from University of Bath used morpholinos in order to Please contact the event organizers of this one gave an overview of their work knock down two groups of off event for more information: examining how pluripotent enzymes, the hexosulftate-6-O- Carly Nicholls c.nicholls@qmul.ac.uk 10 . GENETICS SOCIETY NEWS . ISSUE 59
    • 11 GENETICS SOCIETY BUSINESS Annual General Meeting he Annual General Meeting physical event, many members who took the time to register T of the Society, where new members are admitted and took advantage of the new electronic voting system, for their votes. committee members elected, which we are very grateful. The AGM admitted 218 new was formally held during the The AGM is an essential part of members and voted in favour of recent Epigenetics meeting in the running of the Society and the committee nominees for Norwich. In addition to the we thank all of the members new committee members. The new committee members are: President-Elect (to succeed Brain Charlesworth in 2009): Veronica van Heyningen Vice-President (Corporate Affairs): Ian Jackson Vice-President (External Relations): John Brookfield Honorary Secretary: Patty Kuwabara Postgraduate Representative: Tom Nowakowski Committee area “E” Adam Eyre-Walker (evolutionary, ecological & population genetics) Committee area “F” Tom Weaver (corporate genetics & biotechnology) Committee News his year, the time has owes a particular debt of grateful to Hazel Hutchison for her work in the T come to bid farewell to several long-serving officers gratitude to John and Helen, who unselfishly volunteered office during this period. Fortunately, we now have a new Executive Officer, Christine Fender, of the Society: the Honorary last year for an extra year’s and I am confident that the new officers that Secretary, John Armour, the service. This was done in have come onto the Committee can look Vice-President for External order to help us through the forward to a smoothly running operation. I am Relations, Bill Hill, and the difficult period when the delighted to welcome them aboard. I am sure Vice-President for Corporate Society’s office lacked an that John, Bill and Helen will enjoy their well- Affairs, Helen Sang. They Executive Officer, with the deserved leisure hours, if their other duties have all given outstanding, result that a considerable allow them to have any. and unremunerated, service burden of work fell upon their to the Society. The Society shoulders. We should also be Brian Charlesworth, President www.genetics.org.uk . 11
    • GENETICS SOCIETY BUSINESS 12 Genetics Society Awards Winner of the 2009 Balfour Lectureship The Sir Kenneth Mather Memorial he Balfour Lecture, named Matt became a group leader at T after the Earl of Balfour, the Society’s first President, is the Sanger Institute in 2003, where he quickly demonstrated Prize awarded annually to mark both flair and imagination for his is an annual prize of contributions to the field of genetics by an outstanding genomic analysis. He was the senior author on an influential T £150 to reward a BSc, MSc or PhD student of any UK young investigator. We are paper published in Nature (2006), University or Research delighted to announce that the which highlighted the importance of global Institution who has shown 2009 Balfour Lecturer will be variation in copy number on the human genome; outstanding performance in Dr. Matthew Hurles, Wellcome he was also a member of a team that published the areas of quantitative or Trust Sanger Institute, an analysis of the impact of copy number population genetics. Hinxton, Cambridge. Matt’s variation on gene expression and disease research career has been susceptibility in Science (2007). Matt’s study of Nominations should be made devoted to understanding the human evolution has also led him to assess how between July 1st and basis of human variation from genome dynamics mediated by mechanisms such November 1st inclusive of each both a genetic and as homologous recombination have affected year through the local Head of archaeological perspective. human evolution. Department or School of the nominee. Nominations should consist of no more than one page of A4, setting out the case for the nomination, including Winner of the 2009 Genetics Society Medal relevant comparison with other students where possible. Nominations should be sent to he GS medal is awarded played a leading role in T annually to recognise outstanding research generating high-resolution genetic and physical maps of the the Head of School, School of Biosciences, The University of Birmingham, Birmingham, B15 contributions in genetics and mouse genome, and he continues 2TT, clearly labelled as a the Genetics Society is to foster the development and nomination for "The Sir delighted to announce that the application of functional Kenneth Mather Memorial winner of the 2009 medal is genomic tools in the post- Prize". Professor Stephen Brown genomic era. Steve is perhaps most closely FMedSci, MRC Mammalian identified with the large-scale mouse ENU Nominations will be assessed Genetics Unit, Harwell. Steve mutagenesis programme at Harwell. This project by a panel of two people with is internationally recognised was designed to identify mutations in genes that experience in the area of for his seminal contributions to produced disease phenotypes, which could be quantitative/population mouse and mammalian exploited in order to learn about the basis of genetics, one from the genetics, and he has been one of human disease. To this end, Steve’s research University of Birmingham and the driving forces behind the group has successfully identified and studied the the other nominated by the UK development of the MRC developmental genetics of gene mutations Genetics Society. Decisions Harwell site, where he is underlying hearing loss in humans. will be announced in December currently director. Steve has each year. 12 . GENETICS SOCIETY NEWS . ISSUE 59
    • GENETICS SOCIETY BUSINESS 13 Presidents Recognised We are happy to report on the international recognition the current and past presidents of the Genetics Society have recently enjoyed: Brian Charlesworth Prof. Michael Ashburner Prof. Alex Jeffreys Current society president Prof. The Genetics Society of America Another past president, Prof Alex Jeffreys, Brian Charlesworth, Edinburgh has awarded the Thomas Hunt has been selected as one of the four final University, has received the Morgan Medal to past president, nominees for the Millennium Technology Weldon Memorial Prize, awarded Prof. Michael Ashburner, Prize, a very prestigious Finnish award that by the University of Oxford to University of Cambridge. The recognises innovators who contribute to recognise the most noteworthy medal recognises lifetime improvements in quality of life. The final contributions to the development contributions in the field of result should be available by the time you of mathematical or statistical genetics. get the newsletter and is available at: methods applied to biological www.millenniumprize.fi/ problems. Postgraduate Representative uring the 2008 spring BSDB and BSCB in Edinburgh as principal investigators or a postdocs. This D meeting of the Genetics Society I was elected to the in spring 2007, the Genetics Society wishes continue its kind of interaction is of vital importance for students who have to consider their future position of postgraduate engagement in organising careers. representative for the Genetics postgraduate symposia, Society. During my two-year workshops and social events; Furthermore, we hope that Promega will tenure I will be aiming to perhaps extending their scope continue to sponsor awards for young scientists strengthen the involvement of by organising meetings with to mark their excellence in postgraduate the Genetics Society in the academic staff at different research much in line with the 2008 Young issues of postgraduate students stages of their scientific Geneticist of the Year Award competition. The to help young scientists activelycareers. I believe providing Genetics Society would like to be involved in participate in scientific opportunities for students to selecting finalists for such competitions. meetings, symposia and meet junior postdocs, principal conferences. On this occasion I investigators setting up their We are also happy to consider applications for would like to outline the laboratories and senior support in organising student events at scientific strategies for the near future. members of academia in a meetings at conferences, not necessarily friendly environment will make organised by the Society. Such applications and Following the positive feedback students feel they can ask other suggestions for ways in which the Genetics from students after the questions about their specific Society could support students should be workshops and the social event project, future job opportunities directed to me, the postgraduate students’ organised during the joint in other labs, or simply how representative, in the first instance meeting of the Genetics Society, they feel about their positions (s0454833@sms.ed.ac.uk). Tom Nowakowski. www.genetics.org.uk . 13
    • GENETICS SOCIETY BUSINESS 14 Heredity News joint venture by NPG Engledow, RA Fisher, EB Ford, A The first article in the and The Genetics A Greenwood, JBS Haldane, J first issue of Heredity summarises the genetic Society has just Hammond, H Hunter, TJ research at UK completed scanning all of the Jenkin, DE Lea, K. Mather, LS institutions. back issues of the Societies’ Penrose, RR Race, W Robb, CH journal, Heredity. These are Waddington) and is well worth now all freely available from perusing to see the state-of-the- the Journal Web Site art at the time. There are many (http://www.nature.com/hdy/i fabulous papers in the archive, ndex.html) as fully searchable a few that caught my eye from PDF files. This is an excellent the early issues include: The resource for the community Genetic Component of and encompasses some of the Language by Cyril Darlington Hardey and EB Ford was most vibrant research in UK (1: p269), Problems in Microbial particularly entertaining). genetics. The very first Genetics by Joshua Lederberg Overall the quality of the article, Genetic Research in (2: p145), Morphism and scanning is very good, a few Britain 1939 – 1945. (1047) Evolution by Julian Huxley (9: pages I examined are at a slight Heredity 1: 1-17, provides an p1) and On the Change in angle, but as I mention above, overview of genetic research Population Fitness by Natural all the text is fully searchable. during the war years via a Selection by Motoo Kimura (12: Just search the journal site for series of abstracts from a 1945 p145). Along with these and your favorite genetic term or Genetical Society conference. many more fascinating papers author and revel in these The contributor list reads like there are some very interesting classic papers. the cast list of Giants in book reviews (a review by Peter Genetics – (DG Catcheside, MB Medewar of Evolution as a Crane, CD Darlington, F Process edited by J Huxley, AC This is an excellent resource for the community and encompasses some of the most vibrant research in UK genetics. 14 . GENETICS SOCIETY NEWS . ISSUE 59
    • GENETICS SOCIETY BUSINESS 16 News From The Biosciences Federation www.bsf.ac.uk Steve Russell . University of Cambridge n important new With the IoB currently representing individual A development for UK bioscience comes with the scientists and the BSF more focused on organisations, joint announcement by the Biosciences Federation and the the proposed new body will provide a broad platform Institute of Biology that they are working together with the for representing Biosciences on the political stage. aim of joining forces to form a single body representing environmental problems such Activities include reports on British biology. With the IoB as the consequences of climate open access publishing, currently representing change. Constructively systematics and taxonomy, individual scientists and the engaging with both the public genomic medicine, the research BSF more focused on and politicians. Assessing the excellence framework and organisations, the proposed provision of adequate biosecurity. new body will provide a broad resources for life sciences platform for representing research, especially in Nominations are being Biosciences on the political emerging areas where new accepted for the 2008 BSF stage. Both organisations are tools and skills are essential. Science Communication consulting their respective Exploring how biology Awards for research-active memberships to ensure broad education from the schoolroom scientists who make support for the proposed to the workplace can be outstanding and consistent merger and it is hoped that the effectively structured. Figures contributions in the area of new organisation will come from industry and biological public science communication. into being next year. Society science funding bodies are There are two categories: one Presidents Prof. Raymond supportive of the proposal and for young scientists, PhD or Dwek (IoB) and Prof Dame believe that biology will benefit masters students or graduates Nancy Rothwell (BSF) set out from a unified voice in policy with less than a year of some of the key challenges forums. postdoctoral experience and that face the biosciences in the one for established researchers. 21st Century at a meeting held The BSF continues its policy Nominations close of the 24th at the Royal Society in May. work in a variety of areas, August 2008, with the prizes These include: maximising the responding to a range of awarded in November this year. social and economic benefits of consultation exercises and The nomination form can be new discoveries and their input can be accessed at obtained at the BSF website. addressing challenging the BSF website (www.bsf.ac.uk). 16 . GENETICS SOCIETY NEWS . ISSUE 59
    • GENETICS SOCIETY BUSINESS 17 Promega Young Geneticist of the Year s we announced in the last Dr Paul Glands of Promega A Newsletter, the Promega Young Geneticist of the Year presented their awards. The winner, Carol Anne Edwards competition was judged at the gave a talk on her work at the 18th Mammalian Genetics and meeting and we present an Development Workshop last abstract of her fascinating November. The winner and investigations into the runners-up were invited to the evolution of Genomic Genetics Society Epigenetics imprinting here. meeting this May where Carol Anne Edwards delivers her talk at the Epigenetics meeting (right) The Evolution of Genomic Imprinting: A comparative analysis of the DLK1/DIO3 domain in extant vertebrates. Carol Anne Edwards . Department of Physiology, Development and Neuroscience, University of Cambridge Genomic imprinting is a mammals. This theory process by which certain predicts that oviparous mammalian genes are monotremes will not imprint expressed from only one but viviparous marsupials will. parentally inherited copy, with The DLK1/DIO3 cluster the other allele being (approximately 1 million base repressed. Imprinted genes pairs long) is ideal for therefore lose the advantages investigating the evolution of that diploidy provide against imprinting as all of the protein recessive mutations. This has coding genes within the cluster led to much speculation on are expressed in the placenta, how and why imprinting including a gene related to a Carol Anne Edwards delivers her talk at the Epigenetics meeting evolved. Functional data Ty3-gypsy retrotransposon, indicates that genomic RTL1. In addition, this region imprinting arose alongside contains many functionally placentation in therian significant genomic features www.genetics.org.uk . 17
    • GENETICS SOCIETY BUSINESS 18 such as differentially expression and epigenetic methylated regions (DMRs), analysis in platypus and long non-coding RNAs (GTL2), wallaby suggest the paternal small functional RNAs (C/D chromosome in eutherians is snoRNAs and microRNAs) and most similar to the ancestral antisense transcripts. DLK1/DIO3 region. The DLK1/DIO3 imprinted The snoRNA and microRNA domain was mapped and clusters in the domain were sequenced in a marsupial shown to be eutherian specific, (tammar wallaby) and causing a region of relative monotreme (platypus). DLK1 expansion in these species, and DIO3 genes were identified whereas one specific eutherian in both species and found to be region was resistant to biallelically expressed. expansion. A full length GTL2 Imprinted expression of genes gene was not identified in non- within this region is therefore eutherian species but a restricted to the eutherian number of expressed lineage. A seven way evolutionary conserved regions comparative sequence analysis show that this long ncRNA of the entire DLK1/DIO3 region gene is present in non- in chicken, platypus, wallaby, eutherians. A region opossum, dog, mouse and orthologous to the human was performed. retrotransposon like gene, Results indicate that genomic RTL1, was identified in both signatures previously marsupials, but not in platypus associated with imprinting or chicken. In marsupials the clusters i.e. SINE depletion and RTL1 gene lacks an open From top: Promega Representative Dr Paul increased GC content, were reading frame and is not Glands presents the winners with their awards: only associated with the expressed. This indicates that, imprinted eutherian in marsupials, RTL1 did not 1st prize Carol Ann Edwards DLK1/DIO3 region, suggesting gain a function (or lost it) and (The Department of Physiology, Development these features evolved in the the sequence diverged. Hence, and Neuroscience, University of Cambridge) region alongside the in eutherians RTL1 has evolved acquisition of imprinting. The into a new gene with a 2nd prize Christina Marques IG-DMR, the imprinting function in placentation, an (University of Porto, Portugal) control region for the domain, event that may have driven the is not present in non-eutherian evolution of imprinted 3rd prize Paris Veltsos species. Comparative expression within the region. (Queen Mary University, London) References Edwards, C.A. & Ferguson-Smith, A.C. (2007) Mechanisms regulating imprinted genes in clusters. Curr Opin Cell Biol, 19: 281-289. Edwards, C.A., Rens, W., Clark, O., Mungall, A.J., Hore, T., Marshall Graves, J.A., Dunham, I., Ferguson-Smith, A.C. & Ferguson-Smith, M.A. (2007) The evolution of imprinting: chromosomal mapping of orthologues of mammalian imprinted domains in monotreme and marsupial mammals. BMC Evol Biol, 7: 157. 18 . GENETICS SOCIETY NEWS . ISSUE 59
    • 19 GENETICS SOCIETY MEETING REPORTS The Genetics Society Spring Meeting Frontiers in Epigenetics Saturday 10 May 2008, John Innes Centre, Norwich. Mary Byrne . John Innes Centre and Irina Stancheva, University of Edinburgh he 2008 Spring Meeting of viruses and potentially harmful However, work on Tobacco T the Society was centred on epigenetics and served to highlight the multiple transposons is possibly an evolutionarily ancient role of gene silencing pathways. While rattle virus (TRV) provides a hint on resilience of the meristem to virus infection. and often interconnected plants have evolved silencing TRV invades the meristem but mechanisms involved in diverse mechanisms for defence, fails to propagate in these cells organisms. The term viruses correspondingly encode due to silencing by small RNAs. epigenetics refers to changes in proteins that inactivate key This silencing potentially gene expression that are stable components of plant silencing establishes an epigenetic state between cell divisions, and pathways. One of these virus in daughter cells, thereby sometimes between proteins is an F-box protein, limiting virus spread to organs generations, but do not involve which mediates degradation of initiating from the meristem. changes in the underlying DNA the key small RNA effector sequence of the organism. ARGONAUTE1 protein. The While small RNA pathways are Heritable non-sequence based precise protein degradation an important part of pathogen changes are most often thought mechanism remains to be and genome defence they also to involve modification of DNA elucidated, but clearly differs contribute to many or chromatin and, in recent from the typical proteosome developmental processes in years, there has been much pathway conferred by many F- plants and animals. Scott progress on how these box proteins. On the plant side, Poethig (University of modifications are established one mechanism of defence Pennsylvania) described work and maintained. Mechanisms against systemic virus infection on heterochronic development of epigenetic inheritance also is exclusion from the shoot or phase change in Arabidopsis. involve RNA either indirectly apex or meristem, which Many targets of microRNAs through chromatin harbours the stem cell encode developmental modification and have also been population essential for regulatory proteins so isolation proposed as heritable units continued generation of new of mutants affecting phase potentially directly imparting organs and for growth of the change has lead to the cellular memory. plant. The mechanism of this identification and functional exclusion has remained elusive. characterization of key The meeting started with a presentation by David Heritable non-sequence based changes are most often Baulcombe (University of Cambridge) on small RNA thought to involve modification of DNA or chromatin pathways in plants and the role these regulatory elements have and, in recent years, there has been much progress on in defence against virus infection. Suppression of how these modifications are established and maintained. www.genetics.org.uk . 19
    • GENETICS SOCIETY MEETING REPORTS 20 components of small RNA challenging problem. Vincent marsupial and monotreme mammals (see the pathways, including small RNA Colot (CNRS) discussed a previous article). We had two further talks on binding Argonaute proteins. system to address these genomic imprinting in mammals, focusing on Phase change involves questions. A well known gene basic mechanisms involved in the regulation of successive expression of two in Arabidopsis, DDM1, is imprinted loci, establishment and maintenance different microRNAs: down required to maintain of DNA methylation at differentially methylated regulation of the corresponding methylation states of control regions (DMRs) and the importance of target genes mediate the heterochromatin but is also these mechanisms in embryo development and transition from juvenile to known to influence methylation understanding human disease. Ann Ferguson- adult phases of growth. of some euchromatin. The Smith (University of Cambridge) highlighted the Targets of early expressed ddm1 mutant is being used to significance of differentially methylated miR156 are the SPL gene generate recombinant inbred imprinted regions and non-coding RNAs in family. Surprisingly, all 10 SPL lines that enable a test for regulating the monoallelic expression of genes in family members vary possible stable imprinted clusters. She focused on an exciting considerably in size but all have multigenerational inheritance new discovery indicating that a KRAB family retained miR156 target sites of chromatin changes. zinc-finger protein Zfp57 is involved in and individual genes from Phenotypic variation across maintenance of maternal and paternal DNA different clades still modulate these lines provides a means for methylation imprints in the early cleavage mouse phase change indicating an identifying epigenetic changes embryos. Although the precise mechanism of essential role for SPL genes in that impact on plant growth Zfp57 function is unknown (Zfp57 deficiency is his process. SPL genes through quantitative trait maternal effect lethal), a hypothesis was put positively regulate late analysis. Furthermore, forward that Zfp57 might recruit DNA expressed miR172 and down analysis of methylation states methyltransferases enzymes in order to actively regulation of AP2-like targets after multiple generations maintain DNA methylation at imprinted regions of miR172 are needed for following ddm1 induced during the embryonic stages when most of the transition to adult growth. demethylation is identifying genome undergoes a wave of global Components of this pathway regions of heterochromatin demethylation. act in phase transition in maize that are remethylated and indicating conservation across regions that are not readily Marisa Bartolomei (University of Pennsylvania) broad land plant lineages. By remethylated suggesting presented recent work from her lab dissecting the analogy, progressive distinct mechanisms act to function of the insulator protein CTCF in oocytes maturation of Caenorhabditis maintain genome-wide and early preimplantation embryos. CTCF has elegans through juvenile to integrity. an important role in regulating enhancer activity adult phases of growth is also and DNA methylation at the imprinted Igf2/H19 regulated by successive In animals, epigenetic locus and provides a platform for binding of the expression of microRNAs, so mechanisms are involved in a cohesin complex. Ablation of the maternal pool possibly this is a common variety of biological of CTCF in oocytes, by Zp3 promoter- driven theme in eukaryote life cycle phenomena such as regulation shRNA, led to early embryonic lethality possibly progression. gene expression, genomic caused by delay in zygotic gene activation, imprinting, X-chromosome biallelic expression of imprinted genes and While we now have a handle on inactivation in placental chromosome segregation defects. A more many genes involved in mammals and maintenance of general downregulation of gene expression was establishing epigenetic states genome architecture. After observed in CTCF depleted oocytes, indicating an important question is Carol Edwards (University of that CTCF may have an important role in whether epigenetic changes are Cambridge), the recipient of the regulation of gene expression by bringing the of adaptive significance. Promega Young Geneticist of enhancers and promoters in close proximity. Identifying epigenetic changes the Year Award, presented her in natural populations and work on the comparative The function of CTCF as well as insulator and understanding the significance analysis of the imprinted Dlk- silencer elements dominated the talk by Rob of these changes is a Dio3 gene cluster in eutherian, White (University of Cambridge). His lab, in 20 . GENETICS SOCIETY NEWS . ISSUE 59
    • GENETICS SOCIETY MEETING REPORTS 21 collaboration with Steve that Xist RNA and Polycomb Russell and co-workers, has group proteins are dispensable recently published a high- for initiation but are essential resolution map of CTCF for maintenance of imprinted binding over several large X-inactivation in the mouse regions of Drosophila genome, embryo. This raises the including the Hox loci. Rob question of what is the highlighted the importance of mechanism and factors CTCF enhancer blocking involved in the initiation of activity and CTCF-mediated imprinted X-inactivation. establishment of chromatin boundaries at the Abdominal B These chromosome studies locus for body patterning were complemented by during Drosophila development. impressive genome-wide An interesting interplay analyses of chromatin-nuclear Genetics Society President Brian Charlesworth introduces the 2007 between Polycomb group lamina interactions in Balfour Lecture delivered by Miltos Tsiantis, Department of Plant Sciences, University of Oxford proteins and CTCF was also Drosophila and human cells observed at these loci presented by Bas van Steensel suggesting that in some (Netherlands Cancer Institute). instances Polycomb binding His lab is using the Dam-ID may be irrelevant for the technique to map protein conversion of this energy into growth through activity of a nearby gene but interaction sites on DNA. photosynthesis. A remarkable feature of these could have an impact on a more When applied to human lamin specialized organs is the variety and variation in distal one by inactivating an B and Emerin proteins, the form. Tsiantis described research aimed at enhancer element. Thus long- mapping revealed that large, understanding how this variation may arise and range enhancer-promoter several megabase in length, this is being addressed through comparisons of interactions in Drosophila, and regions of the genome depleted genetic regulation of leaf form in the simple leaf probably other systems, are of genes and active species Arabidopsis and the close relative likely to be regulated in a transcription associate with the Cardamine hirsuta, which has a compound leaf. complex manner by insulator nuclear periphery. An The lobes in the compound leaf of Cardamine proteins and Polycomb interesting feature of these appear to originate from the marginal of the leaf, complexes. lamina-associated domains in a region long thought of as comprising a (LADs) is that their sharp marginal meristem. One component that is Terry Magnuson (University of boundaries are often marked required for Cardamine compound leaf formation North Carolina) gave perhaps with either CTCF binding sites involves a KNOX homeodomain protein, which is the most surprising talk of the or active gene promoters and confined to the meristem in the Arabidopsis meeting. He focused on the role CpG islands. It will be simple leaf but expressed in the Cardamine of non-coding RNA Xist and important to gain further compound leaf. Since functional studies can be Polycomb complexes in X- understanding of how these carried out in both species it has been possible to chromosome inactivation. He domains are established, demonstrate the likely importance of cis- presented data indicating that maintained and modified to regulatory regions in species-specific expression imprinted inactivation of allow transcription of LAD- pattern differences of one KNOX gene. Further paternal X chromosome (Xp) resident genes. work implicates a role for the hormone auxin initiates and proceeds normally together with KNOX genes in sculpting leaf in mouse embryos inheriting The final talk of the meeting shape. Tractable genetic and genomic resources Xp devoid of Xp Xist RNA as was the Balfour Lecture in Cardamine, such as the isolation of novel well as in the absence of PRC2 presented by Miltos Tsiantis compound leaf mutants, are providing a wealth complex and accumulation of (University of Oxford). The of opportunity to further understand the histone H3K27 methylation on plant leaf is an organ molecular basis for species variation in leaf the inactive Xp. He proposed specialized for light capture and development. www.genetics.org.uk . 21
    • GENETICS SOCIETY SPONSORED EVENTS 22 1st Mammalian Genetics, Development and Disease Meeting 29th June 2007, School of Biosciences, Cardiff University Rosalind John . School of Biosciences, Cardiff University his purpose of this meeting embryonic stem cells, which conservation programs have T was to promote the exchange of ideas and have created new routes to experimental mammalian been successful and where DNA profiling has produced more information between genetics and functional accurate estimates of giant researchers working primarily, genomics. He also discussed panda population numbers. His but not exclusively, on the impact that genome unique contribution to this mammalian genetics, sequencing projects have had meeting was greatly development and disease. We on fields as diverse as cancer, appreciated by all attendees aimed to attract early-career neurobiology and human with many individuals researchers working on genetic disorders. He finished commenting on how his talk mammals from all over the UK by saying that, despite huge emphasised the global but with a particular focus on advances in research, we still consequences of advances in those located in the South West have a long way to go before modern genetics techniques. of England and Wales, where unravelling the complexity of no such opportunity currently The first talk of the day was the genome and the epigenetic existed. The format was based events that regulate its from Vicki Marsh, a third year on the Mammalian Genetics function. PhD student with Alan Clarke and Development Workshop at Cardiff, who spoke about her with presentations from early The Keynote Speaker of the day work on the role of Pten in the researchers, postdoctoral was Mike Bruford whose intestine. She eloquently fellows and PhD students. We interests encompass molecular outlined the complex strategy advertised this meeting ecology, conservation genetics that allowed her to study the through the Cardiff university and evolutionary biology. He consequences of conditional website, by sending flyers to spoke passionately about the loss of expression of Pten in the University head of departments alarming depletion of genetic mouse intestine in the context and by direct emailing of resources throughout the world of Apc deficiency. This leads to colleagues. and the research being carried the rapid development of out orientated towards applying adenocarcinoma and she The meeting was opened by Sir molecular genetics to preserve proposed that Akt might be a Martin Evans, Director of the endangered species. He gave potential therapeutic target in School of Biosciences, Professor one compelling example of the this process. The next talk was of Mammalian Genetics of dramatic collapse of the orang- from Ben Colleypriest, a first Cardiff University and recipient utan population in Borneo that MPhil/PhD research student of the Nobel Prize in has been linked to human with Vasanta Subramanian Physiology or Medicine in 2007. activity and outlined the from the Department of In his introduction, Martin genetic strategies that are Biology and Biochemistry at outlined the some of the being undertaken to ensure Bath University who presented fundamental developments, that these unique animals his work on an in vitro model of including the discovery and survive and prosper. He also Barrett’s oesophagus and the modification of mouse gave an example of characterisation of Cdx2 22 . GENETICS SOCIETY NEWS . ISSUE 59
    • GENETIC SOCIETY SPONSORED EVENTS 23 expression. Staying with the Daniela Riccardi’s group in spoke about a novel splice cancer theme, we heard a talk Cardiff. She presented variant of VEGF which from Anthony Dallosso, a preliminary results from the intriguingly acts as an anti- postdoctoral fellow at Bristol CaR knock out mouse and angiogenic isoform in contrast University with Keith Brown, elegantly illustrated the use of to the more commonly known who discussed the use of ex-plant material in the variant of VEGF which is methylated DNA analysis of this key angiogenic. immunoprecipitation to developmental process. identify targets of DNA The final talk of the day was methylation in paediatric We had a number of talks from from Anthony Isles, a recent cancer. After an unexpected Cardiff-based groups using recruit to the Department of interruption by a fire alarm, we mammalian systems to Psychological Medicine at then heard two talks in the investigate and model Cardiff, who discussed the stem cell theme. Susan Hunter, neurological disorders evolutionary role of genomic a long time associate of Martin including Alzheimer’s (Mariah imprinting. Although Evans, presented her recent Lelos and Amy Reichelt from commonly thought to be work describing the microarray Mark Good’s group), involved predominantly in analysis of the transcriptome of Huntington’s disease (Mia regulating embryonic growth, embryonic stem cell lines in Deschepper from Lesley Jones’ recent work suggest that many comparison with material group), Schizophrenia (Anne imprinted genes also play a role isolated from the inner cell Kirtley from Kerrie Thomas’s in post natal development mass of the developing embryo group), Frontotemporal including influencing risk at different time points. E4.5 is Dementia (Trevor Humby) and taking behaviour. a traditional time point at also Amyotrophic Lateral which stem cells are derived Sclerosis (Ben Crabtree, Bath) Prizes of £75 were awarded to but she found that ES cells reflecting the relative Brenda Meinhardt and Anthony most resemble the E5.5 concentration of expertise in Dallaso before the meeting embryonic ectoderm. Alysia behavioural and basic ended in a wine reception Battersby, a postdoctoral fellow neuroscience at the meeting kindly funded by GRI. with Nick Allen in Cardiff, then both at the whole organism described the potential of using level and the molecular level. This first meeting in Cardiff human ES cells in replacement covered the full breadth of therapy, with a specific focus on At the beginning of the research in Genetics from the directed differentiation into meeting Martin Evans spoke molecular analysis of a single forebrain precursors using a about the complexity of the mRNA molecule to number of techniques mammalian genome. Although investigation of the genetic including engineering we may now know the DNA profile of planet Earth. We had transgenic hESCs to carry sequence, we still need to presentations from students in fluorescent reporter genes for unravel the complexities of the the first year of their PhD to FACs sorting. We then had a genome. This was nicely one from the Nobel Prize presentation from Simon illustrated by two talks on RNA winner, Martin Evans. We Tunster, a second year PhD splicing. Shane Wainwright hope, in future years, to student in my group describing (Cardiff) spoke about his work maintain the calibre of these our mouse model of placental on an alternative splice variant meeting with continued insufficiency in which foetal of ADAMTS4 present in human support from The Genetics programming may be studied. patients with osteoarthritis Society, The Company of The role of the extracellular while Dawid Nowak, a Biologists, Cardiff School of calcium sensing receptor in postdoctoral fellow with David Bioscience, Wales Gene Park lung branching was discussed Bates, University of West and GRI. by Brenda Reinhardt from England and Bristol University, www.genetics.org.uk . 23
    • GENETIC SOCIETY SPONSORED EVENTS 24 A Triple Helix Meeting: Who Owns My Genome? 20th February 2008, University of Cambridge Harsh Bhatt . The Triple Helix, Cambridge ith the ever-increasing PHG Foundation. Technology W advances in gene technology and a society with journalist and author, Glyn Moody, discussed how perhaps more individualism in translating the genetic its manner than ever before, the information from an analogue prospect of personal genome version (within our cells) to a sequencing is one that is digital one (via sequencing) David Summers of the Genetics Department neither too remote, nor the could enable us to ‘google’ our in Cambridge (standing) chairs the Triple Helix Meeting easiest to ignore. Who then own genome. Furthermore, should have access to this with the seemingly exponential information, how may it be rise in information storage used and what are the ethical efficiency, a suggested view of implications? Thanks to the the future included people support of The Genetics sporting wristbands with Society, The Triple Helix microchips containing their Cambridge were able to debate personal genetic information, these questions and more in - making it possible to do a quick “Hands Off My Genes: The check for any abnormal ethics and implications of genotype in a potential partner. personal genome sequencing”, But what, as was asked, would The audience were keen to explore issues relating to genetic confidentiality. where a panel of experts we say is the ‘right time’ for attempted to address a few of such information to be these issues surrounding the exchanged – before deciding to our genetic data to assess our subject. have children, prior to marriage candidacy. Moreover, with or indeed on the first date? genomics now being sold as not The Triple Helix is an just a medical tool but also a international undergraduate- Finally, Harald Schmidt, lifestyle choice in itself, some run organisation that aims at Assistant Director at the healthy scepticism about its promoting an open forum for Nuffield Council on Bioethics, scope and applicability is all students as well as the wider brought into focus the ethical but natural. However, the public to explore the issues surrounding personal panel were unanimous in interdisciplinary issues genome sequencing, amongst concluding that when it comes surrounding science and these being the idea of ‘the to our own personality and society. right to not know’ when it came identity, no genome alone could to incurable diseases, and map out one’s sense of humour Setting the scene by proposed how varied our own or indeed their love for science introducing what information responses to such a concept and following a query can be obtained through these might be. regarding the implications of genetic tests in the first place, tracing geographical genetic and how it may be applied, were With the discussion then open origins to explicate one’s own Andrew Read, Professor of to the floor, a highly volatile cultural background, the Human Genetics at the topic emerged in the idea of evening ended with a reminder University of Manchester and insurance companies and of there being “no definite test Dr. Caroline Wright from the potential employers requesting for Welshness”…! 24 . GENETICS SOCIETY NEWS . ISSUE 59
    • 25 FEATURES A Taxi Driver Writes... The personal genome: whose DNA is it anyway? Andrew Grierson . Academic Neurology Unit, School of Medicine and Biomedical Sciences, University of Sheffield populations for attributing What is the genetic risk factors in personal polygenic diseases such as diabetes and heart disease. In genome? these cases it is suggested that this balance of science and The landmark publication of society is for the general good: the first draft of the human there is genetic solidarity genome sequence in 2001 amongst the study population, heralded a new beginning in and by working together they human genetics: the post might eventually help genome era. Three complete themselves by developing genome sequences later, in 2008 preventative measures or we are on the verge of the 1000 treatments for the diseases genome project and the $1000 prevalent in their societies. genome. These developments offer the most exciting The rest of the world generally opportunities for human lives in genetically admixed genetics: to identify and populations, so can we learn investigate genetic variation in more about human diseases, all of us, with the power to our evolution and origins from correlate genome-wide studying their genetics? The genotype data with human answer from a number of disease phenotypes. perspectives would seem to be Personalised genome data is yes. George Church, of Personalised already available from a Harvard University, was an number of commercial early adopter of DIY Genetics. healthcare or laboratories, for around $1000, He predicted that a personal modern day but does this raise more genome project would be questions than it is likely to beneficial to society, and snake oil? answer? advocated a policy of openness when sharing individuals’ A number of companies The power of studying human genome sequence data. In the including Decodeme, 23andme genetics in disease risk past 12 months a number of and Navigenics offer genome- association studies is well commercial genomics wide SNP-chip analysis for understood. It is exemplified by companies have emerged, but about $1000. In addition, a host the work conducted in Iceland will they help realise the of other companies offer and other genetically isolated predicted benefits? specific genetic risk tests, www.genetics.org.uk . 25
    • FEATURES 26 distinct from those diagnostic General practitioners may be increasingly confronted by tests used by hospitals and clinics for diagnostic purposes. patients arriving with the results of a whole genome Genome-wide analysis is currently offered without any scan in their hand, asking what clinical intervention is legislative regulation, on the grounds that the service is on offer since they have a 10 fold increased risk of educational not medical. However on the websites of two developing Alzheimer’s Disease. of these companies there are tools for ascribing an individual’s genetic risk of this issue, both 23andme and reliable, as they are not subject developing a range of common Decodeme were clear in saying to the same rigorous quality diseases such as Rheumatoid that the SNP data could best be control as diagnostic tests. Arthritis and Diabetes. These used as an indication of risk, Second, the clinical validity of tools carry specific disclaimers and thus the early uptake of an genetic associations is largely such as: “While the Odds established clinical diagnostic in a constant state of flux, they Calculator is neither a medical test. In many diseases the best are active areas of research diagnostic nor a substitute for clinical outcomes are rather than diagnostic aids. medical advice, it can help you associated with early diagnosis. Third, the use of genetic data confront the bewildering array It should be noted that we in clinical practice, in terms of of health news reported in the needn’t understand the the risk or benefit to the mass media and help you decide mechanistic basis for a genetic individual, is questionable. where you may want to focus association for it to be a valid Although there is often data your attention” on the 23andme indicator of increased risk of supporting beneficial effects of webpage. Given that these may disease. diet or lifestyle change for be polygenic disorders it seems disease prevention, these unlikely that SNPs are If uptake of such personal studies are not usually currently sufficient to genetics services increases, as it conducted in a genetically accurately predict risk in more surely will, there is likely to be defined ‘at risk’ population. than a subset of people. Of greater need for genetic course a human geneticist counselling. General Ethical issues are also raised- might be able to understand the practitioners may be does the recipient of an nature of an odds ratio, but increasingly confronted by increased or decreased risk without expert guidance on patients arriving with the have a duty to warn his family hand, it is clear that risk results of a whole genome scan members of the result? How information obtained in this in their hand, asking what should this be approached? way could be misleading. While clinical intervention is on offer Will it have any effect on some may see this as little more since they have a 10 fold reproductive decision making? than a genetic horoscope, increased risk of developing These questions are the domain others have promoted these Alzheimer’s Disease. This of the genetic counsellor - but is services as an empowering highlights one problem of there a safety net in place? lifestyle choice, where marketing personalised Furthermore some people physician, scientist and genetics directly to the identified as having a decreased participant form a virtuous consumer, rather than via a genetic risk of disease might circle. The novelty of this medical practitioner. The New interpret this as a justification relationship is that the patient England Journal of Medicine to overindulge in a known gains a personal stake in the outlined three more problems environmental risk, such as ongoing scientific research with these tests in a recent drinking or smoking. effort. When approached on editorial: first the tests are not 26 . GENETICS SOCIETY NEWS . ISSUE 59
    • FEATURES 27 Academic founder mutations in colonial Genetic immigrant families, to the use approaches to of surnames for historical genealogists –- personal genetics population ascertainment from synergy at work the current inhabitants of Viking settlements. One group of amateur Genetic association studies are geneticists for whom numerous in the scientific These academic investigations personalised genomics has been literature, but in recent years a have implications for forensic particularly welcome are new type of experiment has science and human genealogists who have turned been made possible, the whole evolutionary genetics. In the to their own DNA in the quest genome association study. UK we are in the unique, and of identifying their ancestors. Although these studies provide questionable, position of having This field has been driven unbiased estimates of genome- a police DNA database forward by Brian Sykes and wide genetic association across including approximately 25% of Stephen Oppenheimer, amongst populations, their large size the male population and 7% of others, who have written also increases the likelihood of the female population. A cost popular science books type II error, that is failing to benefit analysis of this describing their own surveys of detect a weakly significant situation is beyond the scope of the genetic ancestry of the association after correcting for this article, but it seems likely Britain and Ireland. These a large sample size. Interest in that an increasing number of authors are affiliated with the the predictive power of genetic convictions will continue to be companies Oxford Ancestors variation in human disease has made on the basis of DNA and Ethnoancestry, which prompted various genome re- evidence. Therefore a better together with the US-based sequencing projects, the most understanding of human Family Tree DNA share the ambitious of which was genetic variation will support majority of the genetic announced last year. The 1000 such police investigations. genealogy market. The impact genomes project is an Human evolutionary genetics of these companies is international collaboration that embraces studies of the earliest highlighted by the fact that aims to generate a fossilised remains, through pre- Oxford Ancestors turned over comprehensive catalogue of and early historical periods, up £1 million last year, and Family sequence variation in multiple to the present day. Tree DNA maintain databases human populations. Pilot Determining the genetic containing Y chromosome studies are currently underway, mutation events that underlie haplotypes from over 124,000 to determine the best technical, human evolutionary progress is customers and mitochondrial computational and analytical essential to understand the DNA records from over 65,000 approaches. Some academic present make-up of our customers. The general idea is studies are already of a genomes, and can perhaps be that these companies market personal nature, from the used to predict future SNP and microsatellite DNA identification of genetic evolutionary events. tests, the results of which can be shared amongst all customers via public databases. In the UK we are in the unique, and questionable, This aids genealogists in finding relatives when position of having a police DNA database including conventional paper-based genealogical research reaches a approximately 25% of the male population and 7% dead end. Y chromosome data alone has led to the creation of of the female population. over 4,500 surname projects, www.genetics.org.uk . 27
    • FEATURES 28 This community of amateur geneticists are proof of the power of genetic solidarity, and via online forums and email newsgroups, news of informative SNP markers and new branches in phylogenetic trees spreads rapidly. which enables particularly established academic markers represent the best enthusiastic genealogists to investigators. predictive tests for a disease, carry out phylogenetic analysis their uptake amongst the and predict shared ancestry in population is likely to be very the distant past. The future of low where there is no effective clinical treatment available. A This community of amateur personal genetics possible benefit may be certain geneticists are proof of the types of cancer where early power of genetic solidarity, and Subject to government detection is known to be a via online forums and email intervention, personal genetic strong predictor of survival. newsgroups, news of testing is here to stay. Indeed a informative SNP markers and number of media Positive aspects include new branches in phylogenetic commentators have drawn unbiased and large-scale trees spreads rapidly. Recently analogies to the rapid and correlation of for example a group of dramatic rise in the purchase of genotype/phenotype in humans, Decodeme customers interested personal computers since the which may bring about in genealogy collaborated by mid 1970s. Although this scale advances in forensic and sharing their data. They looked of uptake seems unlikely, as the clinical practice. Clinical for novel SNPs that might cost of personal genetic testing advances may or may not be define new branches of the Y drops, many more people are facilitated by a change in the chromosome R haplogroup, likely to sign up. Problems relationship between scientists, which is the most common exist in the area of regulation physicians and patients. group in Europe. They of genetic testing, particularly Identification and classification identified rs34276300 as a SNP those that are directly of SNPS in the 1000 genomes that might indicate an early marketed to consumers as project will enable academic branch in the R haplogroup, ‘medical lifestyle tests’. researchers to more fully and approached the DNA Identified SNPs will only annotate the human testing companies in order to account for a faction of the phylogenetic tree. Increased screen themselves, and a large total inherited risk, and there participation and data sharing network of fellow enthusiasts. may be differences between by amateur genetic Within 8 weeks of the original population groups. We can also genealogists may challenge posting on the genealogy-DNA predict an increase in demand academic groups in the quest to newsgroup hundreds of for genetic counselling services, define the phylogeny of human customers have been tested, that will rise in proportion to Y chromosome markers, at and many reported their the number of people taking least those that are common in rs34276300 genotype data and personal genetic tests. people of European ancestry. existing R haplogroup back to Furthermore it is likely that the forum, enabling these many reported genetic amateur geneticists to identify associations will not translate a new branch in the into disease mechanisms or phylogenetic tree in a timescale new targets for treatment in the that lays down the gauntlet to long term. Even if these 28 . GENETICS SOCIETY NEWS . ISSUE 59
    • FEATURES 29 Book Review Twelve Galton Lectures: A Centenary Selection with Commentaries Edited by Steve Jones and Milo Keynes: The Galton Institute ISBN 978-0-9546570-1-7 Michael M Majerus . Department of Genetics, University of Cambridge. On the improvement commentaries, you will be able on humans, and in particular how it might of our genetic future not only to judge the lectures interact with the human mind. This generated a independently of the long-term interest in human hereditary, Twelve Galton Lectures: A commentaries, but also to psychology and intelligence. His work in the field Centenary Selection with appraise the validity of the of eugenics began in the late 1870s, continued Commentaries is exactly what it latter. until the turn of the century, and became his says on the cover. The volume main preoccupation until his death in 1911. commemorates the centenary of All the lectures are concerned The Galton Institute, which with the issue of eugenics, Given the negative associations now surrounding started life as the Eugenics defined in 1883 by Francis eugenics, it is pertinent to note here that Galton Education Society in 1907, and Galton as “the scientific study of himself was a proponent of positive eugenics: operated under the name of the the biological and social factors that is “the augmentation of favoured stock”. Eugenics Society from 1926-1989. which improve or impair the Negative eugenics – preventing reproduction in There are two main elements to inborn qualities of human the genetically inferior – interested him little. the content; the texts of 12 of beings and of future That said, several of the lectures contained in this the Galton Lectures, which have generations”. In part, of course, volume speak in favour of negative eugenics, been delivered almost annually the book is a commemoration of particularly in respect of the “mentally unfit”. since 1914, and learned Francis Galton himself. Indeed, Over time, as a result of the 1935 negative eugenic introductions to these. Galton was the subject of the legislation, which led to the sterilisation of first lecture, given in 1914 by Sir 400,000 Germans, and to a lesser extent, the 60,000 I would suggest that the most Francis Darwin. Although most court ordered sterilisations in the United States instructive way to read this remembered for his work in and Sweden, the word eugenics has become book is to read it twice. First, eugenics, Galton was a anathema. Yet, we now regularly practice read each of the lectures alone, polymath. He defined negative eugenics in our hospitals, through ignoring the introductions: meteorological anticyclones, screening for a variety of genetic disorders and a simply note the lecturer and the discovered the uniqueness of range of consequential practices. Indeed, through year of delivery. Then read it fingerprints and their these lectures, although one can see how Galton’s again, in correct order, reading application to forensic science, original aims were to a large extent distorted and the introductions before and was a pioneer of genetic eugenics became discredited, it is interesting to revisiting each lecture. This pedigree analysis and note how many of the practices proposed in the way readers will consider the quantitative methods. He was early lectures are now considered more lectures uninfluenced by the in the forefront of the objectively and accepted by society. contemporary commentaries on controversy between the lectures, which, although Mendelians and biometricians In my course on evolutionary genetics in instructive and interesting in over continuously varying traits Cambridge, I have often said that many of the their own right, I found pre- that was eventually resolved by developments and statements in the field, and emptive, somewhat distracting Fisher (1918). Following the more particularly those that made them, should and occasionally overly publication of The Origin of be viewed in the context of their age; judged in judgmental. If you read the Species in 1859, he considered the light of what was known at that time and the lectures first and only then the the action of natural selection prevailing academic climate. Thus, for example, www.genetics.org.uk . 29
    • FEATURES 30 Fisher’s erroneous view that the rejection of racism and the need alleles of a gene would rarely, if for genetic improvement are ever, be selectively equivalent to elegantly argued and one another, should be seen synthesised into a holistic view against the limited knowledge of the multilayered interactions of protein chemistry and the between evolutionary processes ignorance of the chemistry of and genetic change. DNA of the late 1920s. Each of the lectures here should That said, however, all the similarly be read and lectures selected have considered in the temporal something too offer. To pick Sir Francis Galton, the father of the Eugenics Movement, and the logo context of its delivery. Together just one extract, I found a from the 1921 International Eugenics Conference. they give rich insights into passage from The Right Rev. E. changing social mores, views of W. Barnes’ lecture Some the way that humanity is Reflections on Eugenics and affected by selection and how Religion, delivered in 1926, insights into the changing views on birth control artificial selection might be, and arresting. It almost perfectly (from the negative to the positive) eugenics (from is being used to alter the describes a thesis that we would the positive to the apparently negative), abortion, natural processes that influence today call Intelligent Design. sex and artificial insemination. They deal with human evolution. Here, he recognises that both fit changes in morality, acceptability of social mores, and unfit variations arise, and the raise of the welfare state, and in passing, I will not give a critique of each proposes that it is as a result of comment of the problems associated both of the lectures here. Rather, I the environment that God has prejudice and political correctness. Although the will say that any reader is likely created, that the fit survive and book is not packaged appealingly (presumably in to find fascinating, insightful the unfit perish. He then part to keep its price to a minimum: £5.00 for a and sometimes surprising advocates that God has given hardback book of over 350 pages), I would opinions in many of the humanity the spiritual strongly recommend it to scholars and students of lectures. The lectures provide understanding to ensure that the natural and social sciences, as well as commentaries on eugenics from we do “not create an philosophers and politicians. the perspectives of religion, environment in which the feeble- social welfare, economics, minded, the criminal, and the Our potential to “improve future generations” is intelligence, sexuality, evolution insane can multiply rapidly”. increasing and will continue to increase as our and particularly pertinent to He concludes “When religious understanding of the human genome and recent discussions in the people realise that, in thus developmental genetics advances. The way that Commons, in vitro fertilisation. preventing the survival of the we use, or do not use, this power must be based on socially unfit, they are working cogent and objective appraisal of the complex With such a wide variety of in accordance with the plan by issues that touch on this sensitive subject. These subjects, not all lectures are which God has brought Twelve Galton Lectures provide a cogent, likely to appeal to or interest all humanity so far on its road, historical context in which to consider the readers equally. Thus, as an their objections to repressive manipulation of our genetic future. evolutionary geneticist, I found action will vanish”. Sir Julian Huxley’s 1962 lecture Eugenics in Evolutionary To conclude, I found both the References Perspective particularly lectures chosen and their Fisher, R.A. 1918 The correlation between stimulating. His insightful commentaries instructive, relatives on the supposition of Mendelian discussions of the evolutionary rewarding and thoroughly inheritance. Transactions of the Royal Society of consequences of Homo sapiens’ thought provoking. The volume Edinburgh, 52, 399-433. entry into the “psychosocial is a history of the evolution of phase”, the distribution of both eugenics and views on Galton, F. 1883 Inquiries into Human Faculty and variance in intelligence, the eugenics. The lectures give Its Development. Macmillan: London. 30 . GENETICS SOCIETY NEWS . ISSUE 59
    • FEATURES 31 Professor Henry John Evans CBE PhD DSc (Hon) FRSE 24th December 1930 – 1st July 2007 Veronica van Heyningen . MRC Human Genetics Unit, Western General Hospital, Edinburgh on chromosome structure and cloning human genes. Back in function in plants and fungi. the 1970s, naturally occurring He quickly made a number of chromosomal anomalies were significant advances – five of one of the few reliable sources his first six publications were in of information about the Nature – and was promoted to human genome and under Head of Cell Biology. John’s directorship the Unit became a centre of excellence Following this early success, for the use of cytogenetic John was appointed at the approaches to human genetics. young age of 34 to the Chair of Chromosome analysis of more Genetics at the University of than 10,000 consecutive Aberdeen where his research newborns led to several long- began to reflect a growing term follow-up studies. One key interest in human genetics. In family with a translocation 1969 he became Director of the segregating with severe MRC Clinical Population and psychiatric illness was followed ast year the Genetics Cytogenetics Unit, Edinburgh, with his continuing L Society lost a most distinguished member, which had opened two years earlier with the remit of encouragement, even after his retirement, eventually leading Professor (Henry) John Evans, monitoring chromosomal to the identification of the now who died aged 76. During his variation on a large scale in well-established gene DISC1 long and highly productive different subpopulations. (Disrupted in schizophrenia 1). career he contributed hugely to Arriving after the untimely With colleagues he contributed the field of genetics through his death of the inaugural director, to the development of early work on mutagens and Michael Court-Brown, John banding techniques, allowing chromosomes and as an MRC continued to support many of the unambiguous identification Unit director. the large projects in progress. of each human chromosome Work led by Patricia Jacobs, a and thus helping to open up the Born in Llanelli, South Wales, life-long friend, continued for era of gene mapping. These John attended Llanelli years after her departure. banding methods were used Grammar School and went on Longitudinal surveys of boys with radioactive in situ to the University College of with sex chromosome hybridisation to map satellite Wales at Aberystwyth, where anomalies revealed the detailed DNAs and with isoenzyme he received his BSc and PhD effects of an extra X or Y studies to make some of the degrees. In 1955 he joined the chromosome on physical health earliest chromosomal gene MRC Radiobiological Research and behaviour. It is easy to assignments. Unit at Harwell and set to work forget that there was a time analysing the effects of when there were no systematic John worked tirelessly to radiation and other mutagens methods for mapping and support and encourage the staff www.genetics.org.uk . 31
    • FEATURES 32 at CAPCU: technicians were During his career John was awarded numerous trained in-house and through day-release to gain fellowships and prizes, culminating in a CBE in qualifications, while PhD students and postdocs were 1997 in recognition of his outstanding recruited worldwide. He was an enthusiastic and practical contribution to science. supporter of women scientists, making part time work possible on the effects of occupational During his career John was even in the 1970s. He also and environmental exposure to awarded numerous fellowships nurtured emerging early-day mutagens. He served on and prizes, culminating in a technologies: prototype numerous national and CBE in 1997 in recognition of automatic karyotyping was international bodies assessing his outstanding contribution to developed under Denis the effects of radiation and science. Despite these many Rutovitz, and homemade setting acceptable standards for accolades he was always fluorescence-activated cell occupational exposure. He was friendly and approachable, sorting equipment was also on the scientific advisory with a fine sense of humour. available before commercial boards of a number of Social occasions, such as machines appeared. In 1979 the prestigious research parties with ceilidhs, became Unit hosted the Fifth organisations, several dealing regular fixtures on the Unit International Human Gene with aspects of cancer calendar. Mapping Workshop and soon diagnosis and therapy. In afterwards John recruited some addition, he was founding Despite sad times, John always excellent scientists to take the governor and chair of the coped well, devotedly bringing Unit into the molecular epoch Caledonian Research up four teenage sons after the of genome mapping and Foundation, a charity untimely death of his first wife genomics, particularly Nick established to support research from cancer. His second wife, Hastie who eventually in Scotland through fellowships Ros, was herself a talented succeeded him as Director. I and studentships. cytogeneticist. Together they well recall the day we gathered hosted many parties for senior to discuss the next big Unit By the time he retired in 1994, and junior colleagues alike at project (9 June 1983 - a fateful the Unit housed around 250 their house with its lovely election day) and decided to staff and its work was garden and fine pictures by map the Wilms tumour and internationally renowned. Scottish artists collected over aniridia region on chromosome Chromosome biology is still a the years. Partly through the 11 using locally available major field of research and study of chromosomes in deletion cases. In 1988, at cytogenetics-based methods isolated populations, John John’s instigation, the Unit continue to be used routinely to came to love the island of underwent a symbolic name identify disease genes. Barra and spent many happy change, becoming the MRC Towards the end of his holidays there. Even quite Human Genetics Unit. The Directorship, John supported recently he worked on the employment and scientific the establishment of the restoration of a traditional training of clinicians was University of Edinburgh “blackhouse”. always encouraged and Centre for Molecular Medicine interactions in this fertile and the Edinburgh Cancer John will always be overlap area were set up Research Centre, both of which remembered by friends and worldwide. joined with the Human colleagues and his many Genetics Unit last year to form achievements will stand as Throughout his time at the the new Institute of Genetics testament to a fruitful and Unit, John continued to work and Molecular Medicine. successful life. 32 . GENETICS SOCIETY NEWS . ISSUE 59
    • FEATURES 33 My Favourite Paper (at least one of them) DJ De Koning . The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin BioCentre, Midlothian Genetical genomics: the added value from segregation Ritsert C. Jansen and Jan-Peter Nap. (2001) Trends Genet 17: 388-3911 hen this article mapped in an experimental W appeared, gene expression microarrays or GeneChips cross between divergent lines, while gene expression contrasts were obtained for the were becoming commonplace founder lines. The positions of in molecular biology. The QTL would be overlaid with majority of these studies the positions of differentially were, and still are, fairly expressed genes, suggesting straightforward comparisons positional candidate genes for of ‘treatments’ (healthy vs. the QTL2,3. diseased, high vs. low, etc.) and/or studying effects over Jansen and Nap proposed to a time-course. While this treat gene expression data like was all extremely useful, it any complex trait and search was of little help to the the genome for QTL affecting masses of researchers who these traits. A graphical were successfully hunting outline of Genetical Genomics for Quantitative Trait Loci is provided in the figure below. (QTL) in humans, mice, The principal of QTL detection drosophila and many and Genetical Genomics is to A graphical outline of Genetical agricultural species, but far exploit the genetic variation in Genomics. The figure was less successful at identifying a population that is genetically reproduced from De Koning et al 14 functional mutations variable for a functional trait underlying these QTL. of interest. Such a population can be created by crossing Alternatively, a population Research groups were already extreme lines or breeds, that shows variation for the supplementing their QTL followed by inter-mating of the trait of interest, like a herd of studies with gene expression resulting F1 generation to livestock or a population data in an attempt to speed up obtain an F2 or by cohort in humans, can be used the process from QTL to gene. backcrossing to one or both of directly to study the genetic For example, QTL would be the founder lines. variation within the www.genetics.org.uk . 33
    • FEATURES 34 population. For QTL mapping, networks underlying the context of functional trait the segregating population is functional variation can be variation. While several typed for molecular markers reverse-engineered4. It must be reviews of the methods are spanning the entire genome acknowledged that the available7,8, a very good and phenotypic records for the publication of the first actual example of dissecting a traits of interest are collected. Genetical Genomics type complex trait via Genetical For Genetical Genomics, studies follows closely from the Genomics is provided by appropriate tissue samples are Jansen and Nap paper, Mehrabian et al9. collected from the population indicating that the ideas were for gene expression analyses. already established and Ritsert Jansen is a statistician By combining pedigree data, experiments underway at the by training and initially he genomic marker data and time of publication5,6. focussed on methodology for functional trait data, QTL Nonetheless, the paper is the QTL detection; an area where affecting the trait of interest first to formalise the concept of he made quite some impact10-13. can be mapped to the genome. Genetical Genomics and, in my He has really made his mark in Likewise, by combining view, has inspired many Genetical Genomics, co- pedigree data, genotype data researchers to embrace this authoring no fewer than 14 and gene expression data, QTL approach as a powerful, albeit articles on the subject since for gene expression (so called quite costly, tool for complex the 2001 paper, addressing both eQTL) can be mapped to the trait dissection. methodological and design genome, and compared to the issues, as well as actual QTL for the functional traits1. Over the last 5 years, we have experimental studies. The By combining the location of seen a large number of strength of this article is in its functional QTL, eQTL, and Genetical Genomics studies, simplicity and how it conveys with the locations of genes starting from model organisms the potential of Genetical affected by the eQTL, as well and proof-of-principle type Genomics in a very accessible as the correlation structures studies, moving to general manner. It certainly provided between the affected genes and populations and doing me with the direction in which genes in the QTL areas, Genetical Genomics in the I wanted to take my research. References 1 Jansen,R.C. and Nap,J.P. (2001) Genetical genomics: the added value from segregation. Trends Genet. 17, 388-391 2 Wayne,M.L. and McIntyre,L.M. (2002) Combining mapping and arraying: An approach to candidate gene identification. Proc. Natl. Acad. Sci. U. S. A 99, 14903-14906 3 Liu,H.C. et al. (2001) A strategy to identify positional candidate genes conferring Marek's disease resistance by integrating DNA microarrays and genetic mapping. Anim Genet. 32, 351-359 4 Bing,N. and Hoeschele,I. (2005) Genetical Genomics Analysis of a Yeast Segregant Population for Transcription Network Inference. Genetics 5 Brem,R.B. et al. (2002) Genetic dissection of transcriptional regulation in budding yeast. Science 296, 752-755 6 Klose,J. et al. (2002) Genetic analysis of the mouse brain proteome. Nat. Genet. 30, 385-393 7 Rockman,M.V. and Kruglyak,L. (2006) Genetics of global gene expression. Nat. Rev. Genet. 7, 862-872 8 Gibson,G. and Weir,B. (2005) The quantitative genetics of transcription. Trends Genet. 21, 616-623 9 Mehrabian,M. et al. (2005) Integrating genotypic and expression data in a segregating mouse population to identify 5-lipoxygenase as a susceptibility gene for obesity and bone traits. Nat. Genet. 37, 1224-1233 10 Jansen,R.C. (1993) Interval mapping of multiple quantitative trait loci. Genetics 135, 205-211 11 Jansen,R.C. (1994) Controlling the type I and type II errors in mapping quantitative trait loci. Genetics 138, 871-881 12 Jansen,R.C. and Stam,P. (1994) High resolution of quantitative traits into multiple loci via interval mapping. Genetics 136, 1447-1455 13 Jansen,R.C. (1996) A general Monte Carlo method for mapping multiple quantitative trait loci. Genetics 142, 305-311 14 de Koning,D.J. et al. (2007) Livestock genomics: bridging the gap between mice and men. Trends in Biotechnology 25, 483-489 34 . GENETICS SOCIETY NEWS . ISSUE 59
    • REPORTS FROM HEREDITY FIELDWORK 35 AND JUNIOR SCIENTIST AWARDS Genotyping a fungal pathogen, Cryptococcus gattii Visit to the Centraal Bureau voor Schimmelculture, Institute of the Royal Netherlands Academy of Arts and Sciences. Hansong Ma . School of Biosciences, University of Birmingham fact that they are genetically visit, I learned how to conduct very similar to each other. We assays for all of these virulence are therefore very keen to carry traits, allowing us to quantify out experiments to establish each trait across all of the whether the variability in cryptococcal isolates. All the intracellular proliferation measurements were done at correlates with genotype both 25oC and 37oC in (MLST and AFLP grouping), triplicate. Interestingly, this different virulence factors and analysis revealed substantial isolation history (e.g. human, inter-strain variation for each veterinary, environmental). virulence factor measured. Cryptococcus gattii Such experiments will help to Intriguingly, intracellular reveal many complex parasitism does not seem to be Cryptococcus gattii, the relationships between determined by any single causative agent of recent intracellular proliferation and known virulence factor, cryptococcosis outbreak on the factors of interest that may although there was a Vancouver Islands in Canada, is not be immediately obvious, significant correlation between a fatal human fungal pathogen, and thus provide an insight into melanin production at 37oC and and unlike many other fungal the possible causes of intracellular proliferation rate. pathogens, it infects intracellular parasitism. It is possible that the rate is immunocompetent individuals. also determined by other Cryptococcus has long been Before the visit, the (unknown) virulence factors or known to survive and intracellular proliferation rate by a combination of these proliferate inside professional of 65 cryptococcal strains was analysed factors: we are phagocytes to achieve latency determined and from these currently undertaking and long term persistent. data, 40 C. gattii strains were statistical analysis to test for Previous work by our group has selected (20 are Vancouver complex correlations. found that strains that are good isolates) for phenotypic at proliferating inside (virulence trait quantification) For genotypic analysis, macrophages seem to kill mice and genotypic (AFLP) analyses Amplified Fragment Length faster, suggesting that such in order to reveal any factors Polymorphism (AFLP) was intracellular parasitism is a that contribute to fast carried out. AFLP is a PCR- major determinant of virulence intracellular proliferation. based genetic fingerprinting in Cryptococcus. Interestingly, Phenotypic analysis focused on technique with the capability of many of the Vancouver isolates three major virulence factors, detecting various proliferate better capsule size, melanin polymorphisms in different intracellularly than other C. production and enzyme activity genomic regions gattii strains isolated from the (especially proteinase and simultaneously. Due to its rest of the world, despite the phospholipase). During the sensitivity and reproducibility, www.genetics.org.uk . 35
    • HEREDITY FIELDWORK AND JUNIOR SCIENTIST AWARDS 36 AFLP has become widely used likely to be the case that strengthen our collaboration for the identification of genetic melanin production contributes with Teun Boekhout’s group, variation in strains. Based on significantly towards who are international experts the AFLP data obtained, an intracellular parasitism. in Cryptococcus systematics intra-species phylogeny tree of and molecular genetics. The chosen 40 strains was CBS, as a world fungal data obtained has made a generated. The construction of collection centre, holds a very significant contribution to our the tree revealed inter-genotype large number of C. gattii understanding of the molecular variation for different traits. isolates covering a wide range basis of macrophage For example, genotype 6 of genotypes and isolation intracellular parasitism by isolates were found to show histories. This visit was an Cryptococcus. It will form an increased melanin production excellent opportunity not only essential part of my PhD thesis at 37oC compared to genotype 4, to obtain valuable data and and will be submitted as a 5 and 7 isolates. Since genotype learn essential techniques (e.g. manuscript along with recently 6 isolates are associated with AFLP) that are not available in generated microarray data the Vancouver outbreak, it is our institute, but also to within the next few months. Diploid males in Taiwanese Cotesia vestalis parasitoids Jetske G. de Boer . Centre for Ecological and Evolutionary Studies, Groningen University. Heredity Field Grant awarded to Prof. L.W. Beukeboom abbage is an important developing from unfertilized and ecologically important C vegetable crop worldwide and from personal experience and fertilized eggs respectively. However, diploid males develop groups such as parasitoid wasps and pollinating bees, I can now conclude that no from fertilized eggs that are many of which have declined meal is complete without homozygous at a highly significantly in the some sort of cabbage in polymorphic sex locus under a Netherlands and Britain, along Taiwan. Cabbage also hosts mechanism called with insect-pollinated plants. plenty of insect pests, which complementary sex Yet, surprisingly little is in turn provide food to a wide determination (CSD; Whiting known about the frequency of range of natural enemies. In 1943). Diploid males represent diploid males in natural Taiwan, the hymenopteran a severe inbreeding depression populations of parasitoids, parasitoid Cotesia vestalis is because they are commonly with the exception of one of the most important unviable or sterile. Theoretical Habrobracon hebetor. natural enemies of models predict that CSD can diamondback moth larvae negatively affect population In February 2008, I visited the (Plutella xylostella), a common growth rate and sex ratio, and World Vegetable Center cabbage pest. All sexually increase extinction risk. CSD AVRDC in Taiwan to collect reproducing Hymenoptera are may therefore play a crucial naturally occurring C. vestalis haplo-diploid, with haploid role in conservation wasps with the goal of males and diploid females management of economically determining the frequency of 36 . GENETICS SOCIETY NEWS . ISSUE 59
    • HEREDITY FIELDWORK AND JUNIOR SCIENTIST AWARDS 37 diploid males under field use the collected wasps to A field owner in Taiwan anxiously inspects her conditions and assessing assess general genetic crops for pest damage. genetic variation. variation with microsatellite Diamondback moth larvae and markers. Very little is known parasitoid cocoons were about the mating structure of collected from eight different parasitoid wasps under field fields in four locations in the conditions and our data set lowlands of Western Taiwan. could provide more insight. In Host larvae were reared out in the future, I plan to collect C. the laboratory to allow vestalis from different parts of development of parasitoid the world to compare diploid The parasitoid wasp cocoons. Cocoons were then male frequencies and general C. vestalis transported back to our genetic variation in native and laboratory at Groningen introduced populations. C. University, the Netherlands, vestalis is native to Eurasia and where they emerged. More Africa and has been than 6,000 parasitoid cocoons successfully introduced in yielded over 4,000 adult wasps many countries for biological with a sex ratio between 41 and control of the diamondback 56 % males. Flow cytometry moth. This offers an ideal was used to analyze male opportunity to gain insight The Asian Vegetable ploidy. Thus far, diploid males into the potential effects of Research and have been found in 5 of the 8 bottlenecks or founder events Development Center field sites and their frequency on the sex determination load ranges from 0 to 3 %. The low in parasitoid wasps. I expect frequency of diploid males in genetic variation to be lower the native populations in and sex determination load to Taiwan may reflect very high be higher in introduced than in diversity of sex alleles and low native populations. inbreeding levels. In addition, we recently showed that CSD I am grateful to the Genetics in C. vestalis is likely based on Society for their help in multiple complementary sex funding this field trip and I loci and this would reduce the would like to thank Dr. expected frequency of diploid Ramasamy and Mrs. Lin and males dramatically (de Boer et Mrs. Yang and the other ladies al. 2008). of the insectary at AVRDC for their help during the fieldwork In addition to determining in Taiwan. diploid male frequencies, I will References 1 de Boer JG, PJ Ode, AK Rendahl, LEM Vet, J Whitfield and GE Heimpel (2008) Multiple locus complementary sex determination in the parasitoids Cotesia vestalis. Genetics accepted 2 Whiting PW (1943) Multiple alleles in complementary sex determination of Habrobracon. Genetics 28: 365-382 www.genetics.org.uk . 37
    • STUDENT TRAVEL REPORTS 38 Keystone Symposia DNA Replication and Recombination 10th - 14th February 2008 Santa Fe, New Mexico, USA Zhenhong (Belinda) Duan . Institute of Genetics, University of Nottingham his year Santa Fe begins containing three DNA polIII break repair, respectively, T a three-year commemoration of the 400 th cores can be assembled and is functional at a replication indicating that Aprataxin may be important for the repair of anniversary of its founding. fork. Three DNA polymerases DNA breaks. In fact, As soon as I arrived in the city, Aprataxin acts as a within one replisome appear to I found the stylish local enhance functionality on the proofreader for abortive buildings along the main lagging strand. The third ligation events in Base streets and countless polymerase probably also Excision Repair, in that it can museums, galleries and gift helps the replisome bypass selectively bind and remove 5’- shops displaying amazing art blocks on the leading and DNA adenylates from DNA pieces made by native Indian lagging blocks on either break sites. Their research artists. At the far-east end of strand. suggests that oxidative the city, mountains with snow damage within neuronal on a background of generous The program of the conference tissues of individuals with sunshine and blue sky brought was well organized. Each day AOA1, a progressive up a deeply pleasant feeling of there were plenary sessions neurological disorder caused excitement. Suddenly I with four speakers in the by mutation of the APTX gene, thought that scientific morning and three speakers in leads to the progressive research is also a kind of art. the evening, two workshops accumulation of persistent This might be the reason that focused on two different topics DNA nicks, and that the conference DNA with eight speakers each in the unrepaired 5’-adenylates are Replication and afternoon and poster session the causative lesion of this Recombination was held in at lunchtime or later evening. neurological disease. In post- Santa Fe, a unique city in Every day was busy but still mitotic neuronal cells, which richness of history, heritage, there was plenty of free time lack alternative replication- arts and culture. to talk with other researchers. dependent mechanisms that remove 5’-adenylates, these The conference opened on the Stephen C. West from London transcription-blocking lesions evening of the 10th February Research Institute is a great accumulate over a period of with Jack D. Griffith giving a speaker. His honest-style years leading to disease brief introduction to the slides and smooth talking progression. meeting. He told us stories attracted me to follow his about the research and family story of Aprataxin, which is a Stephen P. Bell from Howard life of Arthur Kornberg and product of APTX gene. Hughes Medical Institute is Nancy Nosssal, two great Aprataxin interacts with the another one of my favourite scientists we lost recently from DNA repair proteins XRCC1 speakers. His group is the field of DNA replication. and XRCC4, that in turn form interested in the strict E O’Donnell then gave the complexes with DNA ligase III regulation of the formation of keynote address “Dynamic and DNA ligase IV. The pre-replicative complex (pre- Mechanisms at the E.coli XRCC1/DNA ligase III and RC). Their work shows clearly Replication fork”. His group’s XRCC4/DNA ligase IV that the pre-RC kinase targets work shows that E.coli DNA complexes are involved in and modifies the MCMs, which polymerase III holoenzyme single- and double-strand bind to double strand DNA 38 . GENETICS SOCIETY NEWS . ISSUE 59
    • STUDENT TRAVEL REPORTS 39 near replication origins. Then strand of fork initially pauses Sculpture from the Museum of the the phosphorylated MCMs at -20 nucleotides from the Institute of American recruit DDK to pre-RC. In lesion and the leading strand Indian Arts, Santa Fe. consequence, the modification advances to the site of the of DDK stimulates pre-RC to crosslink with a nucleotide open the double strand DNA inserted across from the DNA near the replication origin and adduct. Lesion bypass is DNA replication is initiated. accompanied by dual incisions surrounding the ICL on one Johnannes Walter from parental strand. Ultimately, a Harvard medical School significant portion of the brought up their latest study input DNA is fully repaired. on the biochemical mechanism They suggested a new model of of replication-coupled DNA ICL repair, which avoids the interstrand cross-link (ICL) problem of replication fork repair, a field in which I am reconstruction in the old very interested because part of nice memories of the few days model. However, the new my current project is also ICL in the Santa Fe. I would like to model of ICL repair depends repair (but using genetic thank the Genetics Society for on two adjacent replication methods). They use plasmids providing me with a travel forks, which might not always containing a single site- grant for this conference. It be the case in vivo. specific ICL and a completely was a fantastic trip and I soluble replication extract The conference closed very return to my thesis writing from Xenopus Laevis eggs to specially with a piano concert with excitement and study the ICL repair in vivo. by Dr Karen Allred, a stimulation. Their beautiful denaturing successful solo recitalist. gels reveal that the lagging Beautiful music brought back Keystone Symposium on RNAi, MicroRNA and Non-Coding RNA, 25th – 30th March 2008, Whistler Resort, Canada Rachael Nimmo . Department of Biological Sciences, Lancaster University his was my first time at the remainder of the meeting as he likely that some will be organism and even cell T Keystone Symposia meeting on RNAi, MicroRNA, discussed his groups work on two new classes of short RNAs type specific. The 22G and 21U RNAs each seem to be associated with a different type of AGO and Non-Coding RNA and I recently identified in C. elegans, protein: the WAGOS (worm-specific Argonautes) have to say I was very the 21U and 22G RNAs, as well are required for 22G RNAs and PRG-1 for the impressed with the standard of as the many worm AGOs. It piRNA-like 21U RNAs. These latter RNAs may be the talks although it also made seems that there are many functionally analogous to piRNAs in that they me a little apprehensive at the different types of non-coding interact with a Piwi family AGO, have preference prospect of joining such a RNAs being identified by the for U at 5’ end as well as 3’ O-methylation and are competitive, rapidly expanding multitude of profiling projects localized to the germline. However they are field! The opening Keynote that are ongoing. It will be shorter than piRNAs, 21 versus 24-30 nucleotides speech was given, quite some time yet before we have a in length, and, rather than being transposon or appropriately, by Craig Mello. clear picture of all the RNAs repeat associated are produced from many His talk set the scene for the that are produced but it seems clusters in two regions of chromosome IV. Craig www.genetics.org.uk . 39
    • STUDENT TRAVEL REPORTS 40 proposed that the temperature Eric Olson presented an elegant way in which sensitive sterility associated miRNAs are integrated into gene regulatory with the prg-1 mutant when networks in cardiac muscle. There are a network cultured at 25oC, and the of miRNAs embedded within the myosin heavy finding that mouse Piwi chain genes, the Myo-miR network, which control proteins are expressed in testes the cardiac stress response and myocyte identity and are required for male through positive and negative feedback loops. fertility may imply a This was a good example of the way in which homologous heat-sensitive profiling miRNAs from specific tissues in normal process involved in germline and diseased states using both human samples maintenance that may explain Snowball fights at the Keystone RNAi and mouse disease models can be fertile ground why mammalian testes are Symposium in British Columbia for yielding information on the role of miRNAs located outside of the body. in disease, in normal development and under Another AGO, CSR-1, one of the conditions of stress. WAGOs, also has a striking developmental role: csr-1 be sites of piRNA biogenesis There were two talks describing the recently mutants are sterile and early and RNA processing. Indeed identified role for LIN-28 proteins in regulating embryos produced from csr-1 Haifan Lin presented data that the processing of the let-7 family miRNAs. The (RNAi) hermaphrodites have indicates that Piwi-piRNA let-7 primary transcript is present throughout defects in kinetochore polarity complexes bind to chromatin at development in embryos, ES cells and some resulting in failure to correctly telomeric associated sites (TAS) tumour cells but the mature miRNA is only undergo chromosome via interaction with the expressed late, in differentiated cells. Both Scott segregation. It is not yet clear chromosomal protein HP1 and Hammond and Narry Kim used a biochemical what (if any) role RNAi may be activate the formation of the approach to show that the LIN-28 protein playing in this process. piRNAs encoded in the TAS. inhibits processing of let-7; however their results differed quite considerably as to which step of Greg Hannon gave the second Carlo Croce gave a very wide- the processing pathway was affected. Hammond Keynote, describing his ranging talk on the diverse found that LIN-28 binds to the loop region of the pioneering work on the role of roles of miRNAs in cancer. One pri-miRNA and inhibits Drosha processing piRNAs in germline genome nice example is the miR-29 whereas Kim’s group found that the Dicer step defence against transposons, as family’s role in lung cancer. was repressed by LIN-28 via the polyuridylation well as more recent work on miR-29 miRNAs are often down- of the let-7 pre-miRNA. It is not clear how these identifying endogenously regulated in lung cancer two models can be reconciled but it is possible generated siRNAs in the whereas conversely, the DNMT- that, despite Kim’s findings that Drosha pri- mammalian female germline. 3A and B methyl transferases miRNA processing was apparently unaffected, These endo-siRNAs are often are upregulated and are both steps may be negatively regulated by LIN- generated from pseudogenes associated with poor prognosis 28. As a worm biologist I am intrigued by this and appear to regulate gene and so the finding that there new role for LIN-28, as of course this protein was expression. In addition, he are regions of miR-29 first discovered as being involved in the proposed that Piwi family complementarity in the 3’ UTRs heterochronic pathway in worms and is thought AGOs and piRNAs may have a of these genes suggested a role to be regulated by let-7 as well as lin-4 miRNAs. role in TGS, as well as PTGS, as for this family of miRNAs in I wonder if this role of LIN-28 in mammals may the founding member of the carcinogenesis. Indeed these also be conserved in worms where it would family, Piwi is localized to the miRNAs were found to directly presumably act in a positive feedback loop to nucleus in Drosophila nurse target DNMT-3A and -3B and prevent its repression by let-7 until the cells whereas other Piwi family restore normal patterns of DNA appropriate time. This kind of mechanism may AGOs, Ago3 and Aub are methylation when expressed in also be at play in higher organisms as the lin-4 localized in the cytoplasmic lung cancer cell lines and to and let-7 binding sites in the lin-28 3’ UTR are perinuclear nuage in the inhibit tumorigenicity in vitro conserved in mammals. germline, which are thought to and in vivo. 40 . GENETICS SOCIETY NEWS . ISSUE 59
    • STUDENT TRAVEL REPORTS 41 Another much talked about sites need not be located in the no doubt we will soon see these products coming topic was that of target 3’UTR since some apparently to market. However in the particularly prediction. It is a stumbling functional sites are found memorable final talk of the meeting on the use block in our analysis of miRNA within ORFs. This confirmed of LNAs to silence miRNA in primates, Morten function that we find it difficult my suspicions that by only Lindow urged us to stay single and naked – at to accurately predict looking for target sites in the 3’ least with regard to therapeutic short biologically relevant targets of UTR of genes and considering oligionucleotides! It seems that a single miRNAs. Although target only those that are conserved stranded molecule is better than a double prediction algorithms have as worthy of functional testing stranded molecule at entering cells, possibly as a been developed and many we are then creating a self- result of the greater exposure of hydrophobic hundreds of targets have been reinforcing (but possibly groups. predicted for each miRNA, misleading) cycle which means there are still relatively few that only conserved 3’UTR sites Finally, there were an abundance of miRNA and validated miRNA-target are validated! This then short RNA profiling projects presented in the interactions. The current apparently reassures us that poster sessions: the technologies for this have methods depend on our models are correct and so advanced rapidly, especially with the advent of conservation and the presence on and so forth. It had been deep sequencing. So I am sure that in the next of a seed sequence and some shown already by Joan Steitz’s few years we will see an explosion in the recent work carried out group that miRNA binding discovery of non-coding RNA-mediated independently by both David sites in 5’UTRs of genes are regulation in a wide variety of processes and the Bartel and Nikolaus Rajewsky, able to cause silencing but over-subscribed Keystone symposia on RNAi, using SILAC to measure until we start looking for miRNA and Non-coding RNA will no longer be changes in the proteome in endogenous sites in all regions viable. Instead we will see a splintering of the response to alterations in of the mRNA then we will not field as it expands. I just hope the quality of the miRNA levels, appears to go know how relevant this is. research does not suffer because this was one of some to way to confirming that the best meetings I have been lucky enough to this is important in many There were many talks on the attend – and we had chance to do some skiing! cases. However, it also seems use of RNAi and also miRNAs So I guess the take home message from the there are many non-conserved in therapy and with advances meeting is that we are only just discovering the target sites and, in addition, in cellular delivery techniques tip of the RNA iceberg. Watch this space! EURASNET Symposium and Workshop on Alternative Splicing and Disease 18th – 23rd February 2008, University of Montpellier, France Prabhakar Rajan . Institute of Human Genetics, Newcastle University, UK lternative pre-mRNA many aberrant splicing events splicing research groups from different A splicing increases the coding capacity of the are associated with human disease. In 2006, a European countries. Part of the EURASNET mission is to “promote understanding of the complex genome and proteomic Alternative Splicing Network regulation of alternative splicing in different diversity of eukaryotes. (EURASNET) was established systems” and to “establish an active and Global studies suggest that with funding from the vibrant network to share and exchange at least three quarters of European Commission Sixth information, methods and material among the human genes are Framework Programme (FP6), network partners” through a series of alternatively spliced, and bringing together several workshops and conferences. www.genetics.org.uk . 41
    • STUDENT TRAVEL REPORTS 42 This EURASNET workshop packages (Affymetrix the most up-to-date molecular and cellular was held in the university Expression Console and techniques in alternative splicing. This was an town of Montpellier on the Biotique XRAY) for analysis of excellent introductory workshop, which I would south coast of France. A a publically available colon strongly recommend to researchers in the field plenary symposium on cancer dataset. Pierre de la of alternative splicing and disease. I would like Alternative Splicing and Grange (INSERM, Paris) to thank the organisers for hosting the event, Disease was held on the first hosted an excellent seminar and the Genetics Society for sponsorship day, and included invited demystifying alternative towards this worthwhile and extremely speakers from several splicing bioinformatics for enjoyable trip. European EURASNET groups. non-specialists and explored a The Speakers introduced number of public splicing concepts and presented databases. He also findings from their own demonstrated his own research into alternative database (www.fast-db.com), splicing and disease, and also which very easy to use and can discussed the potential clinical also visualise Affymetrix Exon application of aberrant Array data. splicing detection and modulation. Of particular Other techniques covered relevance to my research in during the workshop included cancer biology were two talks the design, generation, and delivered in a session entitled transfection of reporter Splicing and Cancer: minigenes for study of Professor Guiseppe Biamonti alternative splicing, RNA Hands on experience at the Montpellier alternative splicing workshop discussed the effect of purification and RT-PCR, (courtesy Julia Kiosz) aberrant splicing events on localisation of GFP fusion cancer phenotypes and splicing factors by microscopy, epithelial to mesenchymal and siRNA. Of particular transition; and Professor interest were practical Elmar Stickeler detailed his sessions using two different own translational research technologies to correct mis- programme in gynaecological splicing in disease models. In oncology. the first, we used morpholino oligonucleotides to modulate The rest of the week was splicing of the Ron proto- dedicated to a practical “hands oncogene in cancer cells and in on” workshop covering a the second, we used antisense variety of techniques for study U7 snRNA to mask a splice site of alternative splicing and mutation in the β-globin gene disease. I was fortunate and correct aberrant splicing. enough to be part of a small group of 26 students selected Despite intensive 12-hour days to take part. The workshop in the lab, we had sufficient commenced with a series of time to explore Montpellier’s short talks from Affymetrix on historic town centre, vibrant the use of their GeneChip nightlife and even make a trip Exon Array system for the to the Mediterranean Sea! The detection of alternative workshop was a great splicing. Participants were opportunity to meet the able to try two software experts, and try out some of 42 . GENETICS SOCIETY NEWS . ISSUE 59
    • STUDENT TRAVEL REPORTS 43 SALSEA - SALMAN II (Salmon at Sea - Atlantic salmon Analysis Network) Symposium and Workshop on Population structuring of Atlantic salmon: from within rivers to between continents & Developing a scientific framework for trans-range stock identification of Atlantic salmon. 20th – 22nd February 2008, Paris, France Anna Finnegan . School of Biosciences, University of Exeter ALMAN is an informal markers and the Atlantic S network of researchers from North America and Europe undertaking Salmon Genome Project. It was incredible to attend such a focused meeting led by such microsatellite analysis of prominent researchers at the Atlantic salmon to address cutting edge of Atlantic a wide range of population salmon population genetics! genetics subjects. Initially Over the next two days, these set up to begin to themes were thrashed out in standardise a suite of lively debates during the The Atlantic salmon, Salmo salar. microsatellite markers used workshop. The various merits range-wide, this was the of new markers, sampling second SALMAN meeting strategies, analytical methods arranged to coincide with a and much more were explored major new international and discussed, and it was prog ramme to identify the certainly a great opportunity origins of Atlantic salmon for me, now in my third year of caught at sea, SALSEA my PhD, to discuss my thesis (Salmon at Sea). plans with the great The first day was dedicated to authorities in this area of a symposium, at which leading research. researchers presented an Despite all this lively banter, overview of the most up to there was still a little time to date literature on major see some Parisian sites. The themes encountered in this sponsors of the symposium, field. This ranged from the Total Foundation, assessing the genetic diversity arranged a private visit to the between continents, through excellent "Abysses" exhibition all scales, right down to at the Musée d’Histoire assessing the diversity Naturelle, and there was even between tributaries within sufficient time one evening to river catchments. Also visit the Louvre! I would like included were sessions on to thank the Genetics Society temporal stability of for awarding me a Junior populations, mixed stock Scientist grant, which helped analysis, optimum sampling to make this trip possible. strategies, new emerging www.genetics.org.uk . 43
    • STUDENT TRAVEL REPORTS 44 49th Annual Drosophila Research Conference 2nd – 6th April 2008, San Diego, USA Robin Harris . University of Manchester he 49th Annual Drosophila acquaintances could meet, me as an example of how, T Research Conference this year was held at the impressive aided somewhat by the ample supply of food and drink. simultaneously, we are able to both explore and understand 40-acre Town and Country the enormous complexities of a The next morning the main Resort in sunny San Diego, single gene performing fantastic conference began with the first California, and attracted well feats of splicing, and yet still be plenary session, which included over 1000 scientists from around in relatively ignorant of a number of fascinating talks, the world to present the most fundamental mechanisms notably a look into anti-viral cutting edge research regarding underpinning basic processes immunity by Sara Cherry of the the model organism Drosophila. such as transcription. University of Pennsylvania, and The five day meeting sponsored On each day of the conference a a brilliant insight into the by The Genetics Society of number of poster sessions were connection between cellular America brought together not trafficking, polarity and growth, run, which provided an only internationally renowned excellent chance to meet with given by David Bilder of the scientists from the USA, Europe other members of the University of California, and further a field, but also PIs, Drosophila research Berkeley, to mention just a postdocs and postgraduates community, and discuss their couple of the outstanding such as myself, to present and research face to face. I had an presentations. Following this discuss our work. The assembly opportunity to present a poster session, the concurrent covered an impressive number of my work, and was delighted platform presentations and of Drosophila research topics, workshops began, which gave a to find the field of stem cell and was organised into over 150 differentiation, the focus of my (sometimes difficult!) choice platform presentations, 14 PhD thesis, was a particularly between talks on four or five subject-specific workshops and well-represented area this year. different areas of research. Of more than 1000 posters that particular note for me were the I found that my poster was very were available 24 hours a day. well received, and the feedback I presentations given by Mike Needless to say there was gathered and connections I Levine of UC Berkeley, hardly an aspect of Drosophila made with fellow stem cell California who described the research that was not on show researchers was invaluable. phenomenon of paused at this years meeting. polymerase and the extent to Overall the conference was an The conference began with which this mechanism occurs in exciting experience and a great introductory talks from the the developing embryo, and the success, and has allowed me to meeting organisers, along with talk given by Brenton Graveley make important decisions historical lectures and a (University of Connecticut), in regarding my present and touching memoriam to collaboration with Don Rio, future work, as well as giving Seymour Benzer, the celebrated concerning the mechanism of me a broader understanding in father of fly neurogenetics. alternative splicing in the general of Drosophila research. Following a brief orientation, Dscam gene, which is known to I would like to thank the the first evening began with a encode over 38,000 distinct Genetics Society for awarding reception held in the resorts isoforms from 95 alternative me a Junior Scientist Grant that enormous Golden Ballroom, exons in this single gene alone. allowed me to attend the where old colleagues and new Each presentation stood out to conference. 44 . GENETICS SOCIETY NEWS . ISSUE 59
    • 45 GRANTS raduate students may apply for travel costs to attend these meetings. The cheapest Genetics Society one-day meetings G form of travel should be used if possible and student railcards used if travel is by train. Airfares will only be refunded in exceptional circumstances. Grants for overnight accommodation are not available. Applications for travel grants should be made using the registration form, before the final deadline for the meeting. hese include the annual Arabidopsis, C. elegans, S. pombe and Pop Group Meetings with Genetics Society T meetings. Graduate Students may apply for travel grants to attend these meetings. Applications should be sent to the Genetics Society, at least one month Sponsorship before the meeting. The cheapest form of travel should be used if possible and student railcards used if travel is by train. Airfares will only be refunded in exceptional circumstances. Genetics Society hD students and postdocs (within two years of viva) who have been members of Travel Grants for P the Genetics Society for at least one year may apply for grants of up to £300 to attend conferences in the area of Genetics that are not sponsored by the Genetics Junior Scientists Society (Please note a maximum of one grant every three years will be awarded to any junior scientist). Applications should be submitted by email at least one month before the meeting, to the GenSoc Office (mail@genetics.org.uk) using message subject “TGJS application“ and your surname. Applications should include a brief outline of the value of the meeting to the applicant, an outline of any presentation to be made at the meeting and estimated costs. Please ask your supervisor to send a very brief email in support. Recipients of travel grants will be asked to write a short report that may be included in the newsletter. Heredity Fieldwork and Training Grants supporting field-based genetic research and training urpose: To provide grants of up to £1,000 to cover the costs of travel and accommodation associated with pursuing P a field-based genetic research project or a visit to another laboratory for training (i.e. to learn a new technique). The scheme is not intended to cover the costs of salaries for those engaged in the fieldwork or the training, nor to fund attendance at conferences. The work should include a strong genetical component. Eligibility: The scheme is open to any member of the Genetics Society who has been member for at least one year engaged in field based genetic research involving plants, animals, fungi or microbes. The research field should be one in which results would typically be suitable for publication in the Society’s journal Heredity. Only one application from any research group will be admissible in any one year. Applications should be made on the form available from the Genetics Society’s web page. The application form requests a short summary of the research project for which funds are sought. This should explain the role of the proposed field research in the overall project, and indicate how the grant will be used to facilitate the field research. A detailed budget for the fieldwork will be required, as well as an outline of other possible sources of funding. Applications from PhD students or post-docs should be accompanied by a letter or e-mail of support from your supervisor. ?? Closing date: There will be one closing date of 31st January each year. Awards will be announced within one month of the closing date to allow ample time for fieldwork preparation. At the end of the grant a short report will be requested from the grant holder. This should be in a format that is suitable for publication in the Genetics Society newsletter. A maximum of one grant every three years will be awarded. www.genetics.org.uk . 45
    • GRANTS 46 Genes and Development summer studentships supporting field-based genetic research and training urpose: To provide financial support for undergraduate students in any area of genetics, to gain research P experience by carrying out a research project in the long vacation, usually prior to their final year. Studentships will only be awarded for students who have yet to complete their first degree i.e. who will still be undergraduates during the long vacation when they do the studentship. There are no restrictions concerning the nationality or membership status of the student, nor do they have to be a student at a UK university. A maximum of 40 studentships will be awarded. They will consist of an award of £150 per week for up to 10 weeks to the student plus an expenses grant of £500 to the host laboratory. The award will be made to the host institution. Applications are invited from members of the Genetics Society who have been members on or before the deadline of March 31st, and who run a research group within a University or Research Institute or a commercial research facility. Applications must be for a named student and must include the student's CV together with a reference from their tutor (or equivalent). Undergraduate students are encouraged to seek a sponsor and develop a project application with the sponsor. A panel of members of the Genetics Society committee will review applications. Feedback on unsuccessful applications will not be provided. The successful applicants will be required to submit a short report from the students within two months of completion of the project. Full details and on-line application form are available at the Genetics Society website Sir Kenneth Mather Memorial Prize his is an annual prize of £150 to reward a BSc, MSc or PhD student of any UK University or Research Institution T who has shown outstanding performance in the areas of quantitative/population genetics. Nominations should be made between July 1st and November 1st inclusive of each year through the local Head of Department or School of the nominee. Nominations should consist of no more than one page of A4, setting out the case for the nomination, including relevant comparison with other students where possible. Nominations should be sent to the Head of School, School of Biosciences, The University of Birmingham, Birmingham, B15 2TT, clearly labelled as a nomination for "The Sir Kenneth Mather Memorial Prize". Nominations will be assessed by a panel of two people with experience in the area of quantitative/population genetics, one from the University of Birmingham and the other nominated by the UK Genetics Society. Decisions will be announced in December each year. 46 . GENETICS SOCIETY NEWS . ISSUE 59
    • Personal Subscription Order Form 2008 Please return this from to: The Genetics Society, Wallace Building, Roslin BioCentre, Roslin, Midlothian, EH25 9PP The new personal subscription rate for Genes and Development for 2008 is £128, inclusive of airmail delivery. The subscription runs on a yearly basis from January 1st. The full subscription will be charged and back issues supplied when applications are made after January of each year. Name (BLOCK CAPITALS): ........................................................................................................................................................ Address: .......................................................................................................................................................................................... .......................................................................................................................................................................................................... Tel: ........................................................................... Fax: .......................................................................................................... Email: ............................................................................................................................................................................................ Payment Payment can be made by cheque (payable to “Genetics Society”), credit card (add 3.6%) or direct debit. If you already pay by direct debit you do not need to complete a new mandate. If you wish to set up a direct debit for your Genes and Development subscription, a mandate will be sent to you on receipt of this form. 1. I enclose a cheque or Sterling Eurocheque for £128. 2. I instruct you to use my existing direct debit agreement to debit my account in January each year for my subscription to Genes and Development. Signed .............................................................................................................................................................................. 3. I instruct you to set up a new direct debit agreement to debit my account in January each year for my subscription to Genes and Development and enclose the completed mandate Signed .............................................................................................................................................................................. 4. Please debit my Visa/Mastercard Credit Card Number ............................................................................................................ Expiry ............. / ............. Address where bill sent .................................................................................................................................................. ........................................................................................................................................................................................ Signed ..............................................................................................................................................................................
    • GENERAL INFORMATION 48 the Genetics Society AIMS postdocs. Promega UK is The Genetics Society was The Genetics Society was sponsoring travel to these founded in 1919 and is one of meetings and prizes for the best founded in 1919 and is one of the world’s first societies contributions, plus costs for the devoted to the study of the three winners to attend the the world’s first societies mechanisms of inheritance. following Spring Meeting and Famous founder members national finals. devoted to the study of the included William Bateson, JBS Haldane and AW Sutton. INVITED LECTURES mechanisms of inheritance. Membership is open to anyone The Mendel Lecture, in honour with an interest in genetical of the founder of modern research or teaching, or in the genetics, is given usually on with cytogenetics, with ecological, evolutionary practical breeding of plants and alternate years at a London and bio-metrical genetics and also with plant and animals. Meeting by an internationally animal breeding; and Genes and Development, distin-guished geneticist. which is jointly owned with Cold Spring Harbor MEETINGS Laboratories and which is concerned with The main annual event of the To encourage younger molecular and developmental aspects of genetics. Society is the Spring Meeting. geneticists, the Balfour This has at least one major Lectureship (Named after our Full and student members are entitled to reduced symposium theme with invited Founder President) recognises subscriptions both to these journals and also to speakers, and a number of the contribution to genetics of Genetical Research, published by Cambridge contributed papers and/or an outstanding young University Press, to Trends in Genetics, a poster sessions. investigator, who must monthly journal published by Elsevier with normally have less than ten review articles of topical interest aimed at the One day mini-symposia are held years postdoctoral research general reader, Nature Genetics, published by during the year in different experience at the time of the Nature Publishing company (MacMillan regions so that members from lecture. The winner gives the Magazines Limited), Current Biology journals, different catchment areas and lecture at the Spring Meeting. BioEssays and Chromosome Research. specialist groups within the society can be informed about INTERNATIONAL LINKS A newsletter is sent out twice a year to inform subjects of topical, local and The Society has many overseas members about meetings, symposia and other specialist interest. Like the members and maintains links items of interest. spring symposia these include with genetics societies in other papers both from local countries through the Inter- SPECIALIST INTERESTS members and from invited national Genetics Federation, Six specialist interest areas are covered by speakers. One of these meetings the Federation of European elected Committee Members: Gene Structure, always takes place in London in Genetics Societies and through Function and Regulation; Genomics; Cell & November. the International Union of Developmental Genetics; Applied and Microbiological Societies. Quantitative Genetics; Evolutionary, Ecological YOUNG GENETICISTS’ and Population Genetics; Corporate Genetics and MEETINGS PUBLICATIONS Biotechnology. The Committee Members are Currently there are three The Society publishes two responsible for ensuring that the various local meetings devoted to talks and major international scientific and national meetings cover all organisms within posters by students and junior journals: Heredity, concerned the broad spectrum of our members’ interests. 48 . GENETICS SOCIETY NEWS . ISSUE 59
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