Genomics—from the lab to clinical practice - BMJ Editor's Choice 30 Nov 2013
Publication date: 5 December 2013
There are about 20 000 genes in the human genome. Until recently, clinicians seeking to diagnose a genetic condition have had to select single genes to be sequenced. The process is slow, expensive, and often unsuccessful. Now that the cost of DNA sequencing has fallen so dramatically, it’s cheaper and easier to sequence the entire genome, with huge potential benefit to our understanding of disease. But this bounty brings with it clinical and ethical questions, as Caroline Wright and colleagues explain (full article). Who should be tested? How much of the genome should be sequenced? What should patients be told? What do we do about incidental findings? And how should an individual’s genomic data be stored? Uppermost in clinicians’ minds may be the question of how best to interpret the information that is now so abundantly available. It may be easy enough to identify a gene that explains a patient’s clinical presentation, such as the genetic variant for Charcot- Marie-Tooth disease. But because of incomplete or age dependent penetrance, finding a genetic variant that is known to cause a disease doesn’t mean the person has or will develop that disease. Because we still have limited understanding of many genetic variants, we should beware of overinterpreting the data, say Wright and colleagues. “Our ability to generate data now far outstrips our ability to interpret them.” Sequencing the entire genome will inevitably reveal unexpected findings, some of which will cause confusion and distress. In a linked commentary, Alastair Kent discusses the impact on patients (full article). The new ease of genomic testing is mainly good news, he says. But the potential for unexpected findings makes it hard for patients to specify in advance how they would like these to be dealt with. “Do I want to know if my genome reveals that I am likely to develop a serious condition which may or may not be related to the one for which I had DNA analysis in the first place? Is there a difference between diseases that have treatments and those that do not?” He would like his doctor to discuss these things before proceeding. But what levels of consent need to be obtained ahead of time? Wright and colleagues warn that genomic sequencing too easily becomes screening by another name. As with all screening, we will need to avoid overstating the benefits and underestimating the harms. And each combination of genetic variant and associated disease will need to beevaluated separately in terms of whether the disease is treatable and at what risk and cost. To stop us straying into untargeted and unmanageable genomic screening, the authors suggest a clinically targeted approach. This would mean partitioning the data and only interrogating those parts that relate to the presenting clinical problem.
Research Associate - Parkinson's Biocurator position available
Publication date: 5 December 2013
We are seeking a full-time or part-time Biocurator for the Parkinson’s Gene Ontology Annotation Project.
For further details visit UCL vacancies page
UCL's Prof Hugh Gurling dies aged 63
Publication date: 11 November 2013
It is with great sadness that I want to inform you of the sudden death of Prof Hugh Gurling. Hugh has been a personal friend and colleague for many years, and has been an Associate Member of UGI and served on its Advisory Board since its inception. Prof Dave Curtis has written an obituary for Hugh which can be accessed here. He will be sorely missed.
Cellular resolution models for even skipped regulation in the entire Drosophila embryo - Nick Luscombe publishes in eLIFE
Publication date: 20 August 2013
Full Article: e-LIFE
Congratulations to Doug Speed for being named the best FMT-BIR Young Biometrician of the year!
Publication date: 29 July 2013
Photo L-R: Professor David Spiegelhalter, Professor Stephen Senn, Doug Speed and Professor Simon Thompson
Doug has been named the best young biometrician in the UK by the Fisher Memorial Trust and Biometric Society. Stephen Senn, the Secretary of the Fisher Memorial Trust, presented the award to Doug Speed on 3rd July 2013 before David Spiegelhalter gave the keynote talk.
Mapping the effects of nature and nurture, Oliver Davis features in Wellcome Trust blog
Publication date: 15 July 2013
Link to full article: Wellcome Trust blog
BHF Grant awarded to Dr Ruth Lovering
Publication date: 22 May 2013
Dr Ruth Lovering, Professor Philippa Talmud, Professor Steve Humphries, Professor Manuel Mayr (King's College) and Dr Rolf Apweiler (EBI) have been awarded over £500,000 funding from the British Heart Foundation to improve the annotation of genes associated with cardiovascular diseases and processes. The funding will support two post-doctoral research associates for 5 years in the Institute of Cardiovascular Science. The team will create protein and microRNA annotations using Gene Ontology as well as capture protein-protein interactions. The project is dependent on established and new collaborations with the European Bioinformatics Institute and the Sanger Institute (Hinxton).
Nick Luscombe elected to EMBO
Publication date: 21 May 2013
Nick Luscombe has been elected as a member of EMBO - congratulations to Nick!
Please find further details here:
Study questions effectiveness of genetic testing strategy for inherited high cholesterol, Steve Humphries publishes in The Lancet
Publication date: 25 February 2013
Blood screening that is preventing heart attacks–but not in England, Prof Humphries is mentioned in a Guardian article
Publication date: 29 January 2013
Suzanne Sheppard is painfully aware of the devastation heart disease can wreak. Her father, Christopher Rogers, died of a massive heart attack in 1988 when he was 41 and she was 15. His father had also died unusually young – at 54 – and, again, of what doctors call a myocardial infarction.
Nick Luscombe publishes in Cell
Publication date: 20 November 2012
Direct competition between hnRNP C and U2AF65 protects the transcriptome from the uncontrolled exonization of Alu elements.
Vacancy: Research Associate in Statistical Genetics
Publication date: 20 November 2012
Salary: £32,055 - £38,744 per annum
Closing Date: 5pm on 14 Dec 2012
Further information: main UCL vacancy page
UGI's Prof Francois Balloux co-authors paper on genetics and climate reconstructions to track the global spread of modern humans out of Africa
Publication date: 18 September 2012
Research indicates the out-of-Africa spread of humans was dictated by the appearance of favourable climatic windows. By integrating genetics with high resolution historical climate reconstructions, scientists have been able to predict the timing and routes taken by modern humans during their expansion out of Africa. Their research reveals that the spread of humans out of Africa was dictated by climate, with their entry into Europe possibly delayed by competition with Neanderthals.
UGI's Prof Andres Ruiz-Linares reports in Nature Native Americans descend from three key migrations
Publication date: 16 July 2012
Scientists have found that Native American populations — from Canada to the southern tip of Chile — arose from at least three migrations, with the majority descended entirely from a single group of First American migrants that crossed over through Beringia, a land bridge between Asia and America that existed during the ice ages, more than 15,000 years ago.
4 Scholarships available for MSc in Genetics of Human Disease
Publication date: 19 June 2012
The UGI MSc in Genetics of Human Disease has been awarded a training grant from MRC. UGI is offering the Masters Excellence Scholarships (£4,200 towards fees and £15,740 stipend) for up to to 4 academically outstanding UK/EU students per year.
UGI Spring 2012 Newsletter
Publication date: 22 May 2012
The latest issue of UGI Newsletter is ready to view.
Direct observation of the interconversion of normal and pathogenic forms of α-synuclein, Prof Nick Wood publishes in Cell
Publication date: 15 May 2012
15 May 2012
Cremades N, Cohen SIA, Emma Deas, Abramov AY, Chen AY, Orte A, Sandal M, Clarke RW, Dunne P, Aprile FA, Bertoncini CW, Wood NW, Knowles TPJ, Dobson CM, Klenerman D. Direct observation of the interconversion of normal and pathogenic forms of α-synuclein. Cell 2012 (in press)
Research paper: X-linked megalocornea caused by mutations in CHRDL1 identifies an essential role for ventroptin in anterior segment development
Publication date: 30 April 2012
Webb, TR and Matarin, M and Gardner, JC and Kelberman, D and Hassan, H and Ang, W and Michaelides, M and Ruddle, JB and Pennell, CE and Yazar, S and Khor, CC and Aung, T and Yogarajah, M and Robson, AG and Holder, GE and Cheetham, ME and Traboulsi, EI and Moore, AT and Sowden, JC and Sisodiya, SM and Mackey, DA and Tuft, SJ and Hardcastle, AJ (2012) X-linked megalocornea caused by mutations in CHRDL1 identifies an essential role for ventroptin in anterior segment development. Am J Hum Genet , 90 (2) 247 - 259.
Full paper can be obtained from here.
Article: How a mother's genes can increase birth weight
Publication date: 26 April 2012
Researchers at the UCL Institute of Child Health have found a single genetic variant inherited from the mother significantly increases a baby’s birth weight.
On average, the RS1 variant of PHLDA2 increases birth weight by 93g (~3%) if inherited from the mother and 155g (~5%) if inherited from the maternal grandmother via the mother. This is a highly significant effect for a single gene, and the first known example of a genetic variant affecting birth weight through maternal inheritance of an imprinted gene.
Fetal growth is an important area of research which takes into account the future health of babies. As such, the gene (PHLDA2) is already known to have a profound effect on birth weight by acting as a growth suppressor. In this instance, the gene is only “switched on” from the copy inherited from its mother. The copy from the father is silent. Genes regulated in this way are termed ‘imprinted’.
Three separate cohorts of babies were checked in this study, including the Avon Longitudinal Study of Parents and Children (ALSPAC). Taking into consideration the average birth weight of a baby is 3000 grams, 155 grams is a very significant weight increase. This is a similar magnitude to the reduction in birth weight caused by maternal smoking, a well-established cause of concern to obstetricians.
This study also describes the more common RS2 variant, which is only found in humans. The authors have hypothesised that it has evolved to produce a smaller baby as a protective effect to enhance the mother’s survival during childbirth. The father’s lack of involvement in evolutionarily terms may stem from his own survival not being at stake and he can continue to reproduce with other females.
For one gene to have this magnitude of effect on a baby's birth weight is very significant
Dr Gudrun Moore, Great Ormond Street Hospital Children's Charity Professor of Clinical and Molecular Genetics at the UCL Institute of Child Health, comments:
“Most of us will think of both the mother’s and father’s genes as having an equal influence on birth weight. Scientists for some time have recognised the particular influence of the mother’s genes, but this is the first time we have seen to what extent.
“For one gene to have this magnitude of effect on a baby’s birth weight is very significant. We suspect it will be the first of many examples once further details of interactions of the genome with the epigenome are unravelled. ”
Research into the PHLDA2 gene is part of a programme of work that will continue beyond this study. Further insight into the function of PHLDA2 along with other imprinted genes will help to establish the genetic basis of fetal growth as well as the common and serious complications of pregnancy, such as when a fetus is unable to achieve its genetically determined potential size (Intrauterine Growth Restriction).
The full article, published in the American Journal of Human Genetics, can be accessed at here.
A matter of priorities: Bacteria evolved way to safeguard crucial genetic material, Prof Nick Luscombe publishes in Nature
Publication date: 26 April 2012
23 April 2012
Different genes mutate at different rates, in the bacterium E. coli.
Credit: EMBL / I. Martincorena.
UCL student Anna Rose has been awarded the Tony Jackson Memorial Prize for 2011
Publication date: 6 March 2012
UCL student Anna Rose (UCL Medical School), who also briefly studied at the Genetics Instute for MSc in Genetics of Human Disease, has been awarded the Tony Jackson Memorial Prize for 2011 for her work with HIV positive children in Zambia.
Article: Four Genetic Loci Influencing Electrocardiographic Indices of Left Ventricular Hypertrophy
Publication date: 17 January 2012
Below is an abstract of a paper recently published by Sonia Shah from UGI. The full article can be found here.