End of Year Report 2009-2010 GENE PARK END OF YEAR REPORT 2009 - 2010

Foreword

The Wales Gene Park supports medical genetic research and its translation to advances in healthcare, delivers education and facilitates engagement in genetic issues in the NHS and with the public. Through its work it seeks to ensure that the many opportunities presented by new genetic knowledge and technologies are seized in Wales.

Genetics is integral to many areas of modern medicine and much of the research and translation and professional education undertaken by the Wales Gene Park occurs at the interface between medical genetics and mainstream medical specialities. It supports development of DNA analysis that forms a major strand of modern diagnosis for both inherited and acquired disease and that is often critical to the provision of appropriate treatment. It also supports the development of genetic approaches to identify those at risk of disease enabling earlier intervention and improved outcomes.

Our work with the wider public serves several purposes. It helps patients and families affected by genetic disorders to influence the development of health services, health policies and the research agenda. It brings young people at school face to face with the issues and opportunities raised by genetics. These young people are the future scientists and health care providers for Wales. Their enthusiasm and insightful engagement is hugely encouraging.

During the current year the Wales Assembly Government renewed its funding for the Wales Gene Park for a further 5 years. The Wales Gene Park will use its resources to ensure that Wales continues to punch far above its weight in this fast moving area of biomedical science.

Julian Sampson Chairman

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Contents Work Package 1: Work Package 2:

Work Package 1 Management & Genomics Facility Management & Governance 3 Governance Facilit

Work Package 2 The Wales Gene Park Executive Management The Facility provides Sanger Genomic Facility 3 Team (EMT) represents stakeholders from the sequencing and high NHS Wales, HEIs undertaking medical genetic resolution melt (HRM) research in Wales and Techniquest. The EMT analysis for mutation Work Package 3 meets three times per year to review progress, detection in research and Transgenics 4 address problems, consider feedback from the diagnostic applications. It Advisory Group, note the outcomes of quarterly also provides automated review meetings held with the Wales Office of liquid handling for PCR set- Work Package 4 Research and Development (WORD) Project up and DNA extraction for Education & Public Engagement 4 Management Team and to agree any changes the Wales Cancer Bank. to the work plan. Throughout the 2009-2010 Work Package 5 The Chairman, Secretary and Strategic Director reporting period J Colley Societal Issues & Public Voice 8 of the Wales Gene Park meet quarterly with the and the Facility team have WORD Wales Gene Park Project Management worked on the COINtrans Work Package 6 Team to review quarterly reports. Progress is project investigating the The Sir Peter Harper Clinical Research mapped against milestones set out in the genetic basis of response to and side effects Fellowship in Medical Genetics 9 annual work plan, any variations are discussed from chemotherapy for metastatic colorectal in and agreed and opportunities for future approximately 2000 cases and controls developments are considered. Cardiff University recruited from across the UK. At the time of Work Package 7 Finance Department provides quarterly budget writing this project is close to completion and Cardiovascular Genetics 10 returns to WORD and undertakes reconciliation further details are provided in the report for at the end of each financial year. Work Package 9, Cancer Genetics.

Work Package 8 The Wales Gene Park Advisory Group meets The Facility has been used for diagnostic Neuropsychiatric Genetics 10 twice a year to ensure the governance and analysis of the TSC1 and TSC2 genes by HRM appropriate reporting structures for Wales Gene and sequence analysis for UK NHS users and Park within Cardiff University. for health providers from abroad (99 contracts Work Package 9 completed in this reporting period). The data Cancer Genetics 11 generated have been utilised in a study of the pathogenic effects of TSC1 missense mutations that were heretofore incorrectly considered to Selected Publications 13 be non disease-causing (Mozaffari M et al. BMC Medical Genetics 2009 11;10:88).

Selected Presentations 18 The Facility has undertaken a study of somatic mutations associated with mTOR pathway activation in neuroendocrine tumours of the Media Coverage 20 pancreas (see Work Package 9, Cancer Genetics). Selected Grants funding Genetic A tender specification has been developed for Research in Wales 21 a next generation sequencing platform for implementation by the Facility during the year Financial Statement 22 2010-2011.

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Work Package 3: Work Package 4: Educational Programme for Schools and College Transgenic Production Education & Public Genetics Road-show for Schools 2009 Facility (TPF) Engagement The Genetics Road-show ran from September to December 2009. Thirty schools throughout all counties of Wales hosted programmes The Transgenic Production The Education and Public Engagement Work delivered by experts from the research, justice Facility (TPF) has undertaken Package is delivered across three areas: and health service communities. These were pronuclear microinjection, education for health and biomedical science attended by 3,348 students. blastocyst microinjection, professionals, schools and colleges and rederivation and the public. The programme addressed advances in DNA cryopreservation for technology, their potential benefits to society, researchers primarily from and ethical concerns. Both schools and Cardiff University, but also Attendance numbers, Wales Gene Park Education Genetic Road-show - Ysgol Tregib, Llandeilo and Engagement Programme, 2003-2009 speakers said that they would like to take part for clients in the Scotland, in a similar project in the future. Ireland and Germany. Public discussion: GM Food for Thought 5000 2003 A newspaper article on the road-show The work of the facility during the reporting 2004 27th April 2009 4500 appeared in the ‘Western Telegraph’ on period has comprised: 2005 A discussion on GM food was held with a public 2006 Wednesday 30th December 2009 4000 2007 audience at the Gartholwg Lifelong Learning Blastocyst microinjection - 9 projects 2008 Centre, Church Village, Pontypridd. The panel 3500 2009 Teachers’ Genetics Network comprised Prof Denis Murphy, University of An electronic newsletter is distributed to the Pronuclear microinjection - 5 projects 3000 Glamorgan, Jonathon Harrington - a farmer and a Network each term, to keep members informed of member of CropGen, Dr Michael Antoniou, King’s Rederivation - 19 projects 2500 forthcoming events and teaching resources. The College London and Haf Elgar, Friends of the newsletter is a useful tool to keep in touch with Earth Cymru. 47 attendees. 2000 Cryopreservation - Bio-Cool teachers across Wales and bordering counties. cryopreservation machine was purchased 1500 Public talk: The Real Gene-eration Game! and has been heavily used with 30 in 30th April 2009 1000 progress or completed Educational Programme for the Public “The Real Gene-eration Game!” explored how 500 genetics could be used to investigate the The transgenic mouse strains produced by the Community Group Events ancestral roots of people in Britain. The speakers 0 Facility model human genetic disorders Health Schools Public The Wales Gene Park has developed several were Dr Bruce Winney, University of Oxford, and including bowel cancer and dementia and have Professionals discussion games based on the Democs© Dr Turi King, University of Leicester. 42 attendees. enabled research into the genetic mechanisms system developed by the New Economics of these disorders and pre-clinical studies of Foundation. Wales Gene Park’s ‘Discuss DNA – Science Café Cardiff: Should Everyone Be novel therapy. Added to the DNA Database? Educational Programme for Health The National DNA Database’ and ‘The $1000 Genome’, have proved popular choices together 5th May 2009 and Biomedical Professionals with Democs topics such as ‘Over the counter Science Café Cardiff invited the The National genetic testing’ and ‘GM Crops ’ Approximately DNA Database on Trial project team to talk at The 2nd Cardiff Symposium on Clinical 100 people, from a variety of organisations, the May event. The National DNA Database on Cardiovascular Genetics attended various events throughout the year. Trial was a joint public engagement project from 23rd – 24th November 2009 the University of Glamorgan, The Wales Gene This 2 day international symposium held in 14th April 2009 Park, Techniquest and University with Cardiff was organised in conjunction with Dr D Women’s Institute, St Fagans funding from the Wellcome Trust. It encouraged Kumar, Institute of Medical Genetics. It focused 15th July 2009 young people to explore social and ethical on recent developments, current best practice Women’s Institute, Whitchurch & Llandaff issues surrounding the National DNA Database and the challenges of delivering the integrated via a mock trial. The talk was given by Dr services for inherited cardiovascular conditions. 22 February 2010 Rachel Iredale, (Universities of Glamorgan and 189 Delegates from as far afield as Australia University of the 3rd Age, Cardiff Cardiff), who led the project and chaired by and Canada joined National and International 9 March 2020 Claudine Anderson, Wales Gene Park. 37 speakers at the event. Rhiwbina Conservative Ladies’ Group public participants.

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DNA Database Digital Stories: From Cheek Fiction and fact in film: The imaginaries of Attendance Figures for Educational Events April 2009 - March 2010 to Court science and society 17th September 2009 14th & 29th March 2010 Health Professionals Schools Public The Human Genetics Commission approached The MRC Centre for Neuropsychiatric Genetics Month Event /Academics /Colleges the DNA Database on Trial team to produce a and Genomics with the Centre for the Economic short video for a public audience which would and Social Aspects of Genomics and the School 2009 explain how and why DNA is used in the criminal of Nursing and Midwifery Studies, justice system. A premiere screening of the film The Wales Gene Park and Chapter Arts Centre April Public Discussion, Cardiff 42 took place on 17 September 2009 at organised two “sciSCREEN” events at Chapter Public Discussion, Gartholwyg 47 Techniquest. 109 attendees. with support from the British Science Association. Democs 15

After the screening, a panel (Dr R Iredale – sciSCREEN promotes the engagement of society May Science Café 37 Universities of Glamorgan and Cardiff, Professor in biomedical science and genetics issues using Reach the Heights Launch 31 S Bain - Swansea University -, C Evans – film. 212 people attended the screenings. Due to StoryWorks - and C Anderson - The Wales Gene the popularity of the events, further sciSCREENs June Science & the Public Conference Park - answered questions from the audience via were planned for later in 2010. (Breakout session) 26 the Chair (Dr Rachel Iredale). The video was widely disseminated on Internet sites, including The work of the July Democs 20 Youtube and is available in DVD. National Genetics Education and August Facilitating young people’s exploration about Development Centre the $1000 genome: Beacons for Wales has been supported in Wales by the Wales September Schools' Roadshow 133 The Wales Gene Park was awarded £6615.84 Gene Park Genetics Interest Group Officer: Cheek to Court Premiere 109 from the Beacons for Wales to facilitate young peoples’ ideas about a $1000 genome. Expansion of the free educational web resource October Schools' Roadshow 1454 Telling Stories, Understanding Real Life Genetics The project ran over a six week period in www.tellingstories.nhs.uk has been developed November Cardiovascular Genetics 189 February and March 2010 and used drama, art, for education of health professionals. The site Schools' Roadshow 1469 film and hands-on experiments to encourage won ‘Best use of new technologies’ category at DNA Photocopying 65 young people from Butetown Youth Pavilion and the 2009 Association of Healthcare Parc Prison to explore the wider issues Communicators Communicating Health awards. December Schools' Roadshow 292 surrounding developments in gene technology. 35 new stories have been added to the site along After the final workshops the artwork produced with expert commentaries from health 2010 will be on public display. professionals including a cystic fibrosis specialist The project supported university staff and nurse, a GP and a consultant colorectal surgeon. January Training Workshops ($1000 Genome) 42 180 students in public engagement. The project was Ninety three stories have been mapped to the Discuss DNA 102 run in partnership with Cesagen and Techniquest. genetic component of Dabbling with DNA 117 the GP curriculum set DNA Photocopying A free training workshop on engagement out by the Royal College methods for Cardiff university staff and post- of General Practitioners. February Democs 18 graduate students took place at Techniquest on $1000 Genome Workshops 39 80 Thursday 21 January 2010. Due to its popularity, The Genetics and Merthyr Youth project (GAMY) School talks 58 a second workshop was also organised. 42 funded by the Wellcome Trust has been working people took part and feedback was very positive. with 16-19 year olds in the Merthyr Tydfil area to March Democs 44 find out more about their ideas and attitudes Sci Screen (1) 138 towards genetics, particularly in relation to health. Sci Screen (2) 74 The young people involved constructed family $1000 Genome Workshops 61 trees and produced digital stories. More Academic Medical Careers Event 61 information is available at www.gamyproject.org.uk Schools Talks 65 A ‘Genetics Rap’ from Oort Kuiper is available at Science Week Presentations 76 http://genomics.research.glam.ac.uk/media/files/d ocuments/2009-10-14/Genetics_rap.wmv and via YouTube.

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Work Package 5: Rare Disease UK Wales Neurological Alliance (WNA) Work Package 6: To mark Rare Disease Day 2010 in Wales, a The Genetic Interest Group Officer is an active Societal Issues reception was held in the Senedd, National Executive Committee member representing 27 The Sir Peter Harper Assembly, Cardiff Bay, hosted by Helen-Mary voluntary organisations and groups and the & Public Voice Jones AM. 100,000 plus people affected by neurological Clinical Research conditions in Wales.

Familial Hypercholesterolaemia (FH) project Fellowship in Medical The FH Family Forum is a group of Genetics approximately 250 affected families in Wales that has been established by the Wales Gene Park Genetic Interest Group Officer. It has been active Dr D Mark Davies, won the Welsh Livery Guild’s in raising awareness of the condition amongst Merit Award for 2009 for work undertaken during public, healthcare professionals and policy his Clinical Research Fellowship. makers in NHS Wales.

The British Heart Foundation and the Welsh Assembly Government have committed £645,000 p.a. to fund and deliver a Wales-wide family cascade screening programme for FH.

WNA members with Pippa Britton, Paralympian, at the The new NHS Wales service is the first of its kind launch of the cross-party group for neuroscience at the National Assembly in the UK - leading the way in this area of primary MRI scans showing shrinkage of kidney tumour in a patient prevention of coronary heart disease and with Tuberous Sclerosis following treatment with rapamycin implementing the guidelines published by NICE In 2009/10, the Alliance successfully launched in 2008. the National Assembly Cross Party Group for The Guild promotes education, science and fine Neurosciences. The Group is chaired by Mark arts in Wales and its Merit Award is made Isherwood AM and is well-attended by annually for excellence and innovation by an Assembly Members from all the political parties, individual working in one of these fields. health professionals and affected families and professionals. Dr Davies worked on tuberous sclerosis, an inherited disorder which leads to the A grant of £4,500 was awarded to WNA from development of tumours in many organs Over 80 families and colleagues and 19 AMs the Big Lottery Fund to build a bilingual website including the kidneys. He tested whether the attended. There were presentations from Prof for patients, families and healthcare drug rapamycin - originally isolated from bacteria Julian Sampson, Mrs Chris Humphreys (family professionals wanting information regarding in a soil sample from the Easter Islands - might member, pictured right together with Professor services for neurological conditions in Wales. be able to compensate for the TSC genes not Sampson and Alistair Kent, GIG) and Dr Tony functioning properly in people with tuberous Jewell (Chief Medical Officer for Wales, sclerosis. Over 2 years the experimental pictured left). Media coverage included BBC treatment led to a reduction in the size of kidney Radio Wales, BBC Newyddion and the tumours in all 16 patients in the trial. This Western Mail. success generated great interest from the commercial pharmaceutical sector and led to the start of a large scale international clinical trial.

The Livery Guild selected Dr Davies for his work in advancing the understanding of inherited disease. The Merit Award citation states: “His burgeoning national and international reputation brings considerable credit to Cardiff University and to Wales.” The results of the work have been presented at national and international scientific meetings and are currently being published.

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Wales Epilepsy Research Network Work Package 7: Work Package 8: (WERN) RRG Work Package 9: Cardiovascular Genetics Neurogenetics and Wales Gene Park is supporting DNA banking at Cancer Genetics the epilepsy Biobank (e-Biobank) at the Institute Psychiatric genetics of Life Sciences, Swansea in relation to projects The Familial Hypercholesterolemia (FH) on brain cortical malformation and early onset Cardiff University Cancer Genetics Building Cascade Testing Project epilepsy and has included technical support for Cardiff University have invested approximately This project is developing a co-ordinated Genomics, Psychiatry and Society e-Biobank in its plans from 2010 onwards. £5M in a state-of-the-art research building service for patients with FH, estimated to Dr Bartlett, jointly funded by CESAgen and dedicated to Cancer Genetics on the Heath number 6,000 in Wales. In August 2009, the Wales Gene Park, is undertaking an Park campus and immediately adjacent to the Health Minister, Mrs Edwina Hart, confirmed ethnographic study of psychiatric genetics. existing Institute of Medical Genetics. The that the Welsh Assembly Government would This has examined the presentation of building was completed early in 2010 and fund delivery of an FH cascade screening psychiatric genetic concepts and research by provides superb facilities for much of the programme for Wales in partnership with BHF the British press and by genetic testing cancer-related work of the Wales Gene Park. at £640K per annum based upon a pilot project companies. He presented findings at a The researchers have started to move into the supported by the Wales Gene Park. The pilot symposium in Washington DC. A small-scale building at the time of writing of this report and project trialled in Wales the Dutch Cascade quantitative study of UK Bioinformatics is being the official opening by the Fist Minister is Testing System for FH (Pass Clinical). The full undertaken in collaboration with Dr Jamie Lewis scheduled for December 2nd 2010. project work includes project management, of the MRC Neuropsychiatric Genetics and genetic counselling, genotyping, dedicated Genomics Centre. computer software and patient support. Psychology & Cancer Genetics A National Steering group has been established Dr Brain has won further funding from BUPA to advise on the implementation of the Wales FH Foundation to continue collecting data on the MRI scans showing a range of congenital brain malformations. Dr D Pilz (Medical Genetics) has established Cascade project with representation from Wales psychological impact of ovarian cancer one of the largest cohorts of affected patients from around Gene Park and the FH cascade service for Wales screening in a large UK cohort of women at high the world to enable genetic studies to take place in Wales. will be formally launched in November 2010. genetic risk – the PsyFOCS study. A linked PhD studentship has been funded by the Emma Sudden Cardiac Death and Long QT Jane Demery Bequest Fund to develop a Syndrome decision support tool for women considering This project links the Institute of Medical whether to remain on ovarian screening or opt Genetics and the Wales Heart Research for prophylactic surgery to remove their ovaries. Institute to identify and characterise the A psychosocial evaluation of lung cancer functional effects of mutations in genes screening (UK Lung Screening pilot trial) is associated with inherited cardiac arrhythmias. being led by the Cardiff group. It will establish technology for tests that enable patients to receive early treatment for inherited arrhythmias and avoid preventable deaths. The work forms an important aim of the Cardiovascular Research Group – Cymru RRG.

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Colorectal Cancer Pancreatic Neuroendocrine Tumours Publications The Wales Gene Park has worked in Genetic and immunohistochemical analysis collaboration with the Institute of Human of a UK series of pancreatic neuroendocrine Genetics, Bonn, Germany and Leiden University tumours is underway, focusing on somatic Baer K, Waldvogel HJ, Faull RL, Rees MI. Clarke AJ. What is at stake in the predictive Medical Centre, the Netherlands, to establish the mutations that activate mTOR signalling in Localization of glycine receptors in the human genetic testing of children? Fam Cancer 9(1) world’s largest cohort of patients with MUTYH- tumours. The study will provide initial data on forebrain, brainstem, and cervical spinal cord: (Mar 2010) pp19-22. associated polyposis. The research project has whether drugs that the Wales Gene Park is an immunohistochemical review. Front Mol yielded a series of high profile papers defining investigating in relation to tuberous sclerosis Neurosci 2 (epub 4 Nov 2009). Clarke AJ. Musings on genome medicine: the the phenotype, genotype-phenotype may also hold promise for these rare tumours. value of family history. Genome Med. 2009 Aug correlations, and prognosis of the disorder. Barker N, Ridgway RA, van Es JH., van de 3;1(8):75 Preclinical Trials in Tuberous Sclerosis (TSC) Wetering M, Begthel H, van den Born M Clarke AJ, Cooper DN. GWAS: heritability The COINtrans project has completed studies Preclinical trials have been completed using Danenberg, Clarke AR, Sansom OJ and Clevers missing in action? Eur J Hum Genet. 2010 Mar to identify SNPs associated with response to genetically engineered in vivo models. These H (2009) Crypt Stem Cells as the Cells-of- 17. [Epub ahead of print] and side effects of chemotherapy for metastatic studies have tested a series of candidate Origin of Intestinal Cancer. Nature 457 colorectal cancer. The results are being therapeutic agents and a variety of therapeutic (7229):608-11. Chung SK, Skinner JR, Rees MI (2010). prepared for publication and include the strategies (Table 1). identification of a prognostic SNP. Baird FE, Bett KJ, MacLean C, Tee AR, Hundal Molecular Genetics of Arrhythmias. Clinical HS, Taylor PM. Tertiary active transport of Cardiovascular Genetics: Chapter 16; Principles amino acids reconstituted by coexpression of and Practice. Oxford University Press Table 1. Drugs and potential drugs currently under investigation System A and L transporters in Xenopus in pre-clinical trials in transgenic Tsc mouse models. oocytes. Am J Physiol Endocrinol Metab, Chung S-K, Vanbellingham J-F, Mullins JGL, Volume 297, 3 (September 2009) Robinson A, Hantke J, Hammond CL, Gilbert D, pp.E822-E829 Freilinger M, Ryan M, Kruer MC, Masri A, Drug/Compound Commercial Partner Target / Mechanism Gurses C, Ferrie C, Harvey K, Shiang R, Bird TG, Cole A, Hay T et al. A novel inducible Christoodoulou J, Andermann F, Andermann E, Metformin None (off patent) AMPK agonist genetic murine model of hepatocyte Thomas RH, Harvey RJ, Lynch JW, Rees MI senescence causes a massive hepatic oval cell (2010). Pathophysiological mechanisms of Sirolimus Wyeth mTOR inhibitor response and complete hepatocyte GLRA1 mutations in human hyperekplexia. Journal of Neuroscience RAD001/Everolimus Novartis mTOR inhibitor replacement from endogenous progenitor cells Journal of Hepatology Volume: 50 Pages: S3- Sorafenib Bayer Multiple tyrosine kinase inhibitor S3 (2009) Dallosso AR, Jones S, Azzopardi D, Moskvina V, Al-Tassan N, Williams GT, Idziaszczyk S, Davies Sunitinib Pfizer Multiple tyrosine kinase inhibitor Bonnet CS, Aldred M, von Ruhland C, Harris R, DR, Milewski P, Williams S, Beynon J, Sampson JR, Cheadle JP. The APC Variant p.Glu1317Gln Fluvastatin Novartis/Sandoz HMGcoA reductase inhibitor Sandford R, Cheadle JP. Defects in cell polarity underlie TSC and ADPKD-associated predisposes to colorectal adenomas by a novel Atorvastatin Pfizer HMGcoA reductase inhibitor cystogenesis. Hum Mol Genet, Volume 18, 12 mechanism of relaxing the target for tumorigenic (June 2009) pp.2166-2176 somatic APC mutations. Hum Mutat, Volume 30, Nelfinavir Pfizer Protease inhibitor 10 (October 2009) pp.1412-1418 G-493 Genentech Dual mTOR/PI3Kinase inhibitor Buchert, M; Athineos, D; ABbud, HE; et al. Genetic Dissection of Differential Signaling Davies DM, Sampson JR. Small-molecule signal- PI-103 Genentech Dual mTOR/PI3Kinase inhibitor Threshold Requirements for the Wnt/beta- transduction inhibitors: targeted therapeutic Catenin Pathway In Vivo Plos Genetics Volume: agents for single-gene disorders. J Med Genet, Akti-1/2 QualiSyn AKT1 and AKT2 inhibitor 6 Issue: 1 (2010) Volume 47, 3 (March 2010) pp.145-149

Clarke AJ. Genetic testing of children with a Davies JS, Chung SK, Thomas RH, Robinson A, family history of progressive neurologic disease. Hammond CL, Mullins JG, Carta E, Pearce BR, Child Care Hlth Dev, 36, Jan 2010. Harvey K, Harvey RJ, Rees MI. The glycinergic system in human startle disease: a genetic Clarke AJ. How is genetic profiling going to screening approach. Frontiers in Molecular impact the practice of paediatrics in the future? Neuroscience. 2010 Mar 23;3:8. Child Care Hlth Dev, 36, Jan 2010

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Dunlop EA, Dodd KM, Seymour LA, Tee AR. Jacobssen JC, Bawden SC, Rudiger SR, Kumar RA, Pilz D, Babatz TD, Cushion T, Paynter SJ, Andrews KJ, Vinh NN, Kelly CM, Mammalian target of rapamycin complex 1- McLaughlan CJ, Reid SJ, Waldvogel HJ, Harvey K, Topf M, Yates L, Robb S, Uyanik G, Rosser AE, Amso NN, Dunnett SB. Membrane mediated phosphorylation of eukaryotic MacDonald ME, Gusella JF, Walker SK, Kelly Mancini GM, Rees MI, Harvey RJ, Dobyns WB permeability coefficients of murine primary initiation factor 4E-binding protein 1 requires JM, Webb GC, Faull RLM, Rees MI, Snell RG (2010). TUBA1A mutations cause wide neural brain cells in the presence of multiple protein-protein interactions for (2010). An Ovine transgenic Huntington’s spectrum lissencephaly and suggest that cryoprotectant. Cryobiology, Volume 58, 3 (June substrate recognition. Cell Signal, Volume 21, 7 Disease model. Human Molecular Genetics; multiple neuronal migration pathways converge 2009) pp.308-314 (July 2009) pp.1073-1084 19(10): 1873-1882. on alpha tubulins. Human Molecular Genetics 19(14): 2817-2827. Phelps C, Bennett P, Jones H, Hood K, Brain K, Dunlop EA, Tee AR. Mammalian target of Johnston JA, Rees MI, Smith PE. Epilepsy Murray A. The development of a cancer rapamycin complex 1: signalling inputs, genetics: clinical beginnings and social Quinn L, Busse M, Khalil H, Richardson S, Rosser genetic-specific measure of coping: the substrates and feedback mechanisms. Cell consequences. Quarterly Journal of Medicine A, Morris H. Client and therapist views on GRACE. Psychooncology (October 2009) Signal, Volume 21, 6 (June 2009) pp.827-835 2009 102(7):497-499 exercise programmes for early-mid stage Parkinson's disease and Huntington's disease. Phesse, TJ; Clarke, AR Normal stem cells in Francis LW, Gonzalez D, Ryder T, Baer K, Rees Jones N, Vogt S, Nielsen M, Christian D, Wark Disabil Rehabil, Volume 32, 11 (2010) pp.917-928 cancer prone epithelial tissues British Journal MI, White JO, and Conlan RS, Wright CW PA, Eccles D, Edwards E, Evans DG, Maher ER, of Cancer Volume: 100 Issue: 2 Pages: 221-227 (2010). Development and validation of Vasen HF, Hes FJ, Aretz S, Sampson JR. MacCormick JM, McAlistair H, Crawford J, (2009) simultaneous multi-parameter, ultra-structural Increased colorectal cancer incidence in French J, Crozier I, Shelling AN, Nel C, Rees MI, characterisation of human mammalian cells. obligate carriers of heterozygous mutations in Skinner JR (2009). Misdiagnosis and delayed Rafi I, Qureshi N, Lucassen A, Modell M, Elmslie Journal of Microscopy MUTYH. Gastroenterology. 2009 recognition of long-QT syndrome frequency, F, Kai J, Kirk M, Starey N, Goff S, Brennan P, Aug;137(2):489-94 contributing factors and consequences. Annals Hodgson S. (2009) 'Over-the-counter' genetic Gladding P, Evans C-A, Crawford J, Chung SK, of Emergency Medicine; 54(1): 26-32. testing: what does it really mean for primary Vaughan A, Webster D, Neas K, Love DR, Rees Kelly CM, Handley OJ, Rosser AE. Human trials care? Br J Gen Pract. 59(561):283-7 MI, Shelling AN, Skinner JR (2010). for neurodegenerative disease. Methods Mol McDowell IFW, Hadfield G and Humphries SE Posthumous diagnosis of long QT syndrome Biol, Volume 549 (2009) pp.33-47 Chapter on Familial Hypercholesterolaemia in Sampson JR, Jones N. MUTYH-associated from neonatal screening cards. Heart Rhythm "Clinical Cardiovascular Genetics, Principles polyposis. Best Pract Res Cl Ga, Volume 23, 2 7(4): 481-486. (With editorial and front-cover) Kelly CM, Precious SV, Scherf C, Penketh R, and Practice" Oxford University Press Ed (April 2009) pp.209-218 Amso NN, Battersby A, Allen ND, Dunnett SB, Kumar and Elliot. March 2009 Grindedal EM, Renkonen-Sinisalo L, Vasen H, Rosser AE. Neonatal desensitization allows Shorning B, Zabkiewicz J, McCarthy A, Evans G, Sala P, Blanco I, Gronwald J, Apold J, long-term survival of neural xenotransplants Morgan R, Tonkin E, Kirk M (2009) A chance to Pearson H, Winton DJ, Sansom OJ, Ashworth Eccles DM, Sanchez AA, Sampson J, Jarvinen without immunosuppression. Nat Methods, be heard: what motivates people to tell their A and Clarke AR (2009) Lkb1 Deficiency Alters HJ, Bertario L, Crawford GC, Stormorken AT, Volume 6, 4 (April 2009) pp.271-273 healthcare stories? Interconnection Quarterly Goblet and Paneth Cell Differentiation in the Maehle L, Moller P. Survival in women with MMR Journal 2(5) Online journal available at Small Intestine. PloS One 4(1):e4264. (2009) mutations and ovarian cancer: a multicentre Grindedal EM, Renkonen-Sinisalo L Dr, Vasen www.icwhatsnew.com study in Lynch syndrome kindreds. J Med H, Evans G, Sala P, Blanco I, Gronwald J, Apold Song, F; Phesse, T; Jenkins, J; et al. Cited 1 is a Genet, Volume 47, 2 (February 2010) pp.99-102 J, Eccles DM, Sánchez AA, Sampson J, Mozaffari M, Hoogeveen-Westerveld M, novel colorectal cancer gene whose deficiency Järvinen HJ, Bertario L, Crawford GC, Kwiatkowski D, Sampson J, Ekong R, Povey S, inhibits the growth of colorectal cancer GUT Hay, T; Matthews, JR; Pietzka, L; et al. Stormorken AT, Maehle L, Møller P. J Survival in den Dunnen JT, van den Ouweland A, Halley D, Volume: 58 Pages: A3-A3 (2009) Poly(ADP-Ribose) Polymerase-1 Inhibitor Women with MMR mutations and Ovarian Nellist M. Identification of a region required for Treatment Regresses Autochthonous Cancer; A Multicentre Study in Lynch Syndrome TSC1 stability by functional analysis of TSC1 Thomas RH, Stephenson JBP, Harvey RJ, Rees Brca2/p53-Mutant Mammary Tumors In vivo J Med Genet; 2010;47:99-102 missense mutations found in individuals with MI (2010). Hyperekplexia: Stiffness, startle and and Delays Tumor Relapse in Combination with tuberous sclerosis complex. BMC Med Genet. syncope. Journal of Paediatric Neurology; 8(1): Carboplatin Cancer Research Volume: 69 Kirk M and Tonkin E (2009) Understanding the 2009 Sep 11;10:88. 11-14. Issue: 9 Pages: 3850-3855 (2009) role of genetics and genomics in health 1: background. Nursing Times 105: 45: 18-22. Pearson HB, Phesse TJ and Clarke AR (2009) Thomas RH, Hammond CL, Bodger OG, Rees Hilgart J, Phelps C, Bennett P, Hood K, Brain K, K-ras and Wnt signalling synergise to accelerate MI, Smith PEM, WERN and James Lind Alliance Murray A. "I have always believed I was at high Kirk M and Tonkin E (2009) Understanding the prostate tumourigenesis in the mouse. Cancer (2010). Identifying and Prioritising Epilepsy risk..." The role of expectation in emotional role of genetics and genomics in health 2: Research 69(1):94-101. Treatment Uncertainties. Journal of Neurology, responses to the receipt of an average, implications for nursing practice. Nursing Neurosurgery and Psychiatry (in press). moderate or high cancer genetic risk Times; 105: 46, 19-23. Pearson, HB; Phesse, TJ; Clarke, AR K-ras and assessment result: a thematic analysis of free- Wnt Signaling Synergize to Accelerate Prostate Thomas RH and Rees MI (2010). Genetic text questionnaire comments. Fam Cancer. Tumorigenesis in the Mouse Cancer Research Advances in Epilepsy. Epilepsy Professional 2010 Jan 30. [Epub ahead of print] Volume: 69 Issue: 1 Pages: 94-101 (2009) 14: 10-14

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Vogt S, Jones N, Christian D, Engel C, Nielsen Yang T, Chung SK, Zhang W, Mullins JG, M, Kaufmann A, Steinke V, Vasen HF, Propping McCulley CH, Crawford J, MacCormick J, Eddy Published Conference P, Sampson JR, Hes FJ, Aretz S. Expanded CA, Shelling AN, French JK, Yang P, Skinner JR, Extracolonic Tumor Spectrum in MUTYH- Roden DM, Rees MI . Biophysical properties of Proceedings Associated Polyposis. Gastroenterology, 9 KCNQ1 mutations associated with long-QT Volume 137, 6 (December 2009) pp.1976-1985 syndrome. Circ Arrhythmia Electrophysiology Borry P, Evers-Kiebooms G, Cornel MC, Clarke Johnston JA, Thomas RH, Hammond CL, 2(4):417-426 Aug 2009 A, Dierickx K, PPPC, ESHG. Genetic testing in Morris HR, Smith PEM, Rees MI. Bench-to- Waldvogel HJ, Baer K, Eady E, Allen KL, Gilbert asymptomatic minors Background bedside: first molecular epilepsy outcomes from RT, Mohler H, Rees MI, Nicholson LF, Faull RL. Zhao JT, Hill AP, Varghese A, Cooper AA, Swan considerations towards ESHG the Wales epilepsy research network: s novel Differential localization of gamma-aminobutyric H, Laitinen-Forsblom PJ, Rees MI, Skinner JR, Recommendations. Eur J Hum Genet. 2009 GABRG2 mutation in an epilepsy family. ABN acid type A and glycine receptor subunits and Campbell TJ, Vandenberg JI. Not all hERG pore Jun;17(6):711-9. Epub 2009 Mar 11. Joint Annual Meeting/Spanish-Society-of- gephyrin in the human pons, medulla oblongata domain mutations have a severe phenotype: Neurology, Liverpool, ENGLAND, 22 Jun 2009 - and uppermost cervical segment of the spinal G584S has an inactivation gating defect with Davies D, Rosser AE, Sarangi S. Carers' 26 Jun 2009. J Neurol Neurosurg Psychiatry cord: an immunohistochemical study. Journal mild phenotype compared to G572S, which has participation in decision making in a 2009;80:e3 of Comparative Neurology; 2010 Feb a dominant negative trafficking defect and a Huntington's disease management clinic. Univ 1;518(3):305-28. severe phenotype. J Cardiovascular Warwick, York, England (August 2009) Journal Johnston JA, Thomas RH, Hammond CL, Mor - Electrophysiology 2009 Aug;20(8):923-30. Epub Of Medical Genetics, Volume 46 (September ris HR, Smith PE, Rees MI. A novel GABRG2 Waldvogel HJ, Baer K, Gilbert RT, Gai W-P, 2009 Apr 10. 2009) pp.S107-S107 mutation in an epilepsy family. 63rd Annual Rees MI, Faull RLM (2009). The Cellular Meeting of the American-Epilepsy-Society, Localisation of GABAA and Glycine Receptors Henderson B, Kumar D, Nicol M, Brain K, Iredale Boston, MA, 04 Dec 2009 - 08 Dec 2009. in the Human Basal Ganglia. Advances in R, Clarke A. A focus group study of health care EPILEPSIA. 50. (Nov 2009) Behavioural Biology (Springer): IBAGS IX professionals involved in the care of families in Chapter (1); Part 3; 225-237. Wales affected by sudden arrhythmic death Maughan T, Adams RA, Smith CG, Seymour syndrome (SADS). British Human Genetics MT, Wilson R, Meade AM, Fisher D, Madi A, Conference, Univ Warwick, York, England, 31 Aug Cheadle J, Kaplan R. Addition of cetuximab to 2009 - 02 Sep 2009. Journal Of Medical Genetics , oxaliplatin-based combination chemotherapy Volume 46 (September 2009) pp.S47-S47 (CT) in patients with KRAS wild-type advanced colorectal cancer (ACRC): a randomised superi - Iredale R, Owens S. How, what and when to tell ority trial (MRC COIN). Berlin, Germany (Sep - the children? Factors that influence the tember 2009) Ejc Supplements, Volume 7, 3 communication between parent and child about (September 2009) pp.4-5 being a carrier of a balanced chromosome translocation. Univ Warwick, York, England Taverner NV, Madden K, Iredale R. Influences on (August 2009) Journal Of Medical Genetics, Young People's Attitudes to Genetics and Volume 46 (September 2009) pp.S102-S102 Health. Univ Warwick, York, England (August 2009) Journal Of Medical Genetics, Volume 46 Iredale R, Murray A. Patient Open Days at the (September 2009) pp.S105-S105 Cancer Genetics Service for Wales. Univ Warwick, York, England (August 2009) Journal Waldvogel HJ, Baer K, Eady E, Allen KL, Gilbert Of Medical Genetics, Volume 46 (September RT, Mohler H, Rees MI, Nicholson LF, Faull RL. 2009) pp.S108-S108 Differential localization of gamma-aminobutyric acid type A and glycine receptor subunits and Johnston JA, Hammond CL, Thomas RH, gephyrin in the human pons, medulla oblongata Morris HR, Smith PEM, Rees MI. Wales epilepsy and uppermost cervical segment of the spinal research network: research at the multifaceted cord: an immunohistochemical study. J J Comp coalface: a model for other research networks. Neurol. 2010 Feb 1;518(3):305-28. ABN Joint Annual Meeting/Spanish-Society-of- Neurology, Liverpool, ENGLAND, 22 Jun 2009 - 26 Jun 2009. J Neurol Neurosurg Psychiatry 2009 80: e3

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Selected Presentations

Cardiovascular Genetics Second Cardiff Symposium on Clinical Social Sciences & Public The British Science Association Science Cardiovascular Genetics Communication Conference, London 23rd – 24th November 2009 Engagement 23rd June 2009 Association of Genetic Nurses • Poster presentation: Evaluation of cascade Oral Presentation in conjunction with Dr Anita and Counsellors, Cardiff testing software for Familial British Sociological Association (BSA) Shaw (Techniquest) and Dr Rachel Iredale 31st March 2009 to 1st April 2009 Hypercholesterolaemia – the Wales pilot conference, Cardiff (University of Glamorgan) on the National DNA (Kate Haralambos) project. K. Haralambos, D. Townsend, B. 16th to 18th April Database on Trial project. Williams, A. Rees, J Williams, J. van Vliet, H. The paper, “Sequencing and Sentiment” was Progenika, Amsterdam Medical Centre, ten Hage, G.-J. Gerrits, I. Kindt, P. Lansberg, presented by A. Bartlett. British Science Association Science Holland C Gowing, A. Procter, J. Sampson, I. Communication Conference, London 27th April 2009 McDowell Economics of Genetic Technologies Seminar, 23rd & 24th June 2009 Ian McDowell gave a presentation about University of East Anglia Oral Presentation: Iredale R, Madden K. (2009) the FH Project. • Poster presentation: The Wales Familial 20th – 21st May 2009 Engaging Young People With Genetics. Hypercholesterolaemia (FH) Cascade Testing Pithara C, Cohen D, Shaw C, Brain K. Which are The Association for Clinical Biochemistry Initiative. Steering Group for Wales: Armon the most important attributes of clinical genetic Annual Conference Daniels, Linda Edmunds, Elizabeth Gould, services influencing user utility? Presentation of 18th to 21st May 2009 Professional Education Andar Gunneberg, Julian Halcox, Catrin preliminary results from a pilot user event. Ian McDowell conducted an FH workshop at Hanks, Jon Heron, Helen Husband, Martin Focus 2009 and also gave a poster presentation. AGNC Spring Meeting, April 2009, Cardiff Lane, Ian McDowell (Chair), Liam Penny, Association of Healthcare Communicators Prof. Maggie Kirk and Dr Rachel Iredale both Annie Procter, Alan Rees, Julian Sampson, Conference, Cardiff HEART UK North West Strategic health presented at the Association of Genetics Nurses Graham Shortland, Mike Spencer, Yee Ping 3rd & 4th June 2009 authority meeting & Counsellors annual conference. Emma Tonkin Teoh, Phillip Thomas, Phil Webb, Buddug Maggie Kirk, Rhian Morgan & Emma Tonkin 13th October 2009 and Rhian Morgan provided NGEDC and Telling Williams, Sue Wilshere accepted the Best New Media Award on behalf of Yee Ping Teoh (Lipid Consultant in North Wales) Stories information for delegates. Kathleen The National Genetics Education and and Kate Haralambos gave a Calzone (Senior Research Nurse, Genetics • Poster presentation: Constructing a Development Centre for the Telling Stories project presentation/demonstration of the FH cascade Division, National Cancer Institute, USA) also framework to evaluate cardiac genetics http://www.assochealth.org.uk/awards/award.ph testing IT system – Pass Clinical. presented a keynote paper as International services. Kirk M, Tonkin E, Llewellyn M, p?id=53 Visiting Senior Fellow, University of Glamorgan. Longley M, Cohen D, Edwards A, Simpson A. HEART UK, Liverpool British Society for Human Genetics, Warwick 24th – 26th June 2009 International Council of Nurses Conference, • Poster presentation: Confirmation of 31st August-2nd September 2009 Kate Haralambos gave a demonstration of the Durban South Africa Intragenic deletions in KCNQ1 – LQT type-1 Poster Presentation: Taverner N, Madden K, FH database to the Simon Broome Committee 30th June-4th July 2009 and determination of deletion breakpoints. Iredale R. (2009). Influences on Young People’s during a steering group meeting. Ian McDowell Maggie Kirk was an invited speaker at the Coleman SL, OCallaghan P, Nicol M, Butler R, Attitudes to Genetics and Health: The Genetics gave a presentation about the FH cascade conference. The NGEDC hosted an exhibition Stephens M, Kumar D, Rees MI and Merthyr Youth (GAMY) Project. testing in Wales and the database. stand. Washington DC, 4S conference British Human Genetics Conference 28th-31st October August 2009 Health Services Research Henderson B, Kumar D, Nicol M, Brain K, Iredale Cardiff University, KES seminar R, Clarke A. A focus group study of health care 6th November British Society for Human Genetics, Warwick professionals involved in the care of families in Andrew Bartlett presented ‘Big Science, Hidden 31st August-2nd September 2009 Wales affected by sudden arrhythmic death and Overt: Psychiatric Genetics after the Human Poster Presentation: Owens S, Iredale R. (2009) syndrome (SADS). Genome Project How, what and when to tell the children: Factors The Fourth Annual Science and the Public that influence parental disclosure of a child’s Conference, University of Brighton genetic test result 13th -14th June 2009 Oral Presentation: Claudine Anderson on The National DNA Database on Trial project

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Cancer Genetics 2009-2012: Tenovus the Cancer Charity Media Coverage Selected New External £90,000 Professor Alan Clarke: Investigating the International Tuberous Sclerosis Symposium, Western Mail: Awards for Genetics immediate and therapeutic effects of MEK Chicago www.walesonline.co.uk/news/wales- inhibition and P13K inhibition in a genetically 23-26th September 2009 news/2009/08/13/teen-in-coma-after-holiday-att Health Research in relevant autchthonous model of human Platform presentations by Julian Sampson and ack-is-flown-home-91466-24396423/ colorectal cancer Cleo Bonnet: 1) Cell polarity and renal Wales, 2009 cystogenesis. 2) Current and future clinical trials. South Wales Argus: 2009-2012: The Wellcome Trust Poster: mTOR signalling in tsc. www.southwalesargus.co.uk/news/4555675.print 2009-2010: Partnership for Cures £43,220 /+familial+hypercholesterolaemia+south+wales+ Professor Alan Clarke: Epigenetics and cancer International Women’s Health Conference, £15,008 argus&cd=2&hl=en&ct=clnk&gl=uk University College London Dr Andrew Tee: Targeting glucose metabolism for 2009-2012: Cancer Research UK November 2009 the treatment of Birt Hogg Dube Syndrome University of Glamorgan Website: £268,265 Brain K & Lifford K. Factors influencing distress http://inform.glam.ac.uk/news/2009/06/05/glamo Professor Alan Clarke: Investigating the PI3 before familial ovarian cancer screening in 1000 2009: Rett Syndrome Association UK rgan-scoops-genetics-prize kinase and Ki-Ras pathway interactions in women. £20,000 Professor A Clarke: Cardiff Molecular Genetics colorectal cancer: new models and drug Wellcome News covered the award received validation Cancer Genetics Group, London Research Application in June 2009 by the Telling Stories project November 2009 (Best Use of New Media) from the 2009-2012: Wales Industry Group Lifford K & Brain K. Women’s decisions to 2009-2011: The Wellcome Trust Association of Healthcare Communicators. £25,000 withdraw from a familial ovarian cancer £118,364 Telling Stories was originally funded through Professor Mark Rees: Formation of the Clinical screening programme. Professor M O’Donovan: Characterising the a Wellcome Trust People Award. function of the schizophrenia susceptibility gene Network in epilepsy http://www.wellcome.ac.uk/stellent/groups/corp Centre for Life Newcastle upon Tyne ZNF804A oratesite/@msh_publishing_group/documents/w 2009-2012: Industrial Partner: UCB-Pharma 13th October eb_document/WTX057063.pdf £36,500 J Sampson invited speaker: Targeted treatment 2009-2012: Economic and Social Professor Mark Rees: A Clinical Fellow for the for tuberous sclerosis with mTOR inhibitors Research Council Media coverage of RDUK reception on 24th £118,364 Wales Epilepsy Research Network February 2010 Dr MC Bagley, Dr T Davis, Dr JE Latimer, http://www.walesonline.co.uk/news/health- Professor DG Kipling: A combined genetic and 2009-2013: Waterloo Foundation news/2010/02/22/as-wales-marks-rare-disease- small molecule approach to studying the role of £126,000 week-we-meet-one-sufferer-91466-25882994/ the p38/MK2 stress signalling pathway in a Professor Mark Rees: Wales Epilepsy Research human premature ageing syndrome Network e-Biobank Manager

2009-2012: Tenovus the Cancer Charity 2009-2014: Medical Research Council £90,000 £196,140 Professor J Cheadle: Identifying novel alleles that Professor M Owen: The Centre for predispose to colorectal cancer Neuropsychiatric Genetics and Genomics

2009-2012: Tenovus the Cancer Charity 2009-2014: Medical Research Council £88,270 £1,958,496 Prof FA Lai , Dr P J Rizkallah , Dr A Tee : Professor M Owen: The Centre for Structural analysis of the mTOR kinase domain Neuropsychiatric Genetics and Genomics by X-ray crystallography 2010-2011: NARSAD Research 2009-2012: Cancer Research UK £39,613 £197,602 Dr J Walters (MEDIC), Prof M Owen (MEDIC): Prof Alan Clarke, Prof Stephen Denyer, Prof Ketamine and cognition: The influence of a new Timothy Maughan: Cardiff Cancer Research susceptibility gene of schizophrenia. UK Centre

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