Seminar 26 Sept: Modelling rate of decline (slope) of a biomarker as a quantitative genetic trait using mixed effects models: application to loss of renal function (GFR) in type 1 diabetes
UCL Genetics Institute Newsletter December 2014
New members of UGI
During her time studying for a BSc in Biological Studies at UCL Claire became increasingly interested in computational biology and quickly decided that this was the route she wanted to follow. To this end Claire completed a Masters Degree at Imperial College London. This post was funded by a BBSRC studentship and under the guidance of Professor Sternberg and Professor Stumpf she undertook both collaborative work developing bioinformatics tools to aid the identification of SNPs as well as later continuing this research theme independently to focus on predicting the disease causing propensity of these polymorphisms.
Having completed her MSc Claire worked in the Shepherd Group at Birkbeck as an Associate Research Fellow examining the potential implications of observed antibody cross-reactivity to haemagglutinin subtypes. Having now returned to UCL as a member of both UGI and the Cancer Institute, she is a PhD student in Dr Plagnol’s group on a project utilising systems immunology approaches to evaluate the extent to which GvHD is driven by TCR repertoire-dependent or independent factors. This research, funded by a Gordon Pillar studentship, is taking place in collaboration with the Institute of Immunity and Transplantation at the Royal Free Hospital under the joint supervision of Dr Vincent Plagnol, Professor Ronjon Chakraverty and Dr Clare Bennett.
Saioa recently finished a PhD at the University of the Basque Country (Spain). Her research focused on the study of the mechanisms and selective forces that have driven human skin colour evolution. In October 2014, Saioa joined Garrett Hellenthal’s group to analyse genome-wide DNA from a cohort of individuals sampled from over 90 different ethnic groups in Ethiopia and the Sudans with the aim to describe the genetic structure of this part of Africa in relation to other world-wide samples, infer groups' ancestral histories and early migration events, and to determine the features (e.g. geography, shared language/religion) that shape genetic diversity and promote or temper intermixing among groups.
Stephen Price’s visit to Shanxi Normal University, China
Stephen Price just spent four weeks working at a lab at Shanxi Normal University, China, where he was collaborating on a project to study ranavirus outbreaks in farmed Chinese giant salamanders. The species is critically endangered,
endemic to China, and the biggest amphibian on earth, growing up to six feet. Despite being so vulnerable in the wild this salamander is intensively farmed for food and the farms have been experiencing severe disease and die-offs due to ranavirus. As well as training local collaborators in virus isolation, Stephen made a trip to the local aqua market to sample animals there (see pics) but spent more time craving bread and potatoes than acquiring a taste for herps!
Overview paper on the CANDELA project on Latin America for studying the diversity of physical appearance and their evolution by Kaustubh Adhikari
Having a highly heterogeneous genetic background due to a history of extensive mixing between Native Americans and people arriving from Europe and Africa, Latin America shows great variation in physical appearance and hence offers an excellent opportunity to examine the genetic basis of the differentiation in physical appearance between Africans, Europeans and Native Americans. The region is also an advantageous setting in which to examine the interplay of genetic, physical and social factors in relation to ethnic/racial self-perception. This project presents the most extensive analysis of genetic ancestry, physical diversity and self-perception of ancestry yet conducted in Latin America. Noticing significant geographic variation in ancestry across the region, this variation is consistent with demographic history and census information, influencing many aspects of physical appearance. It is also observed that self-perception is highly influenced by physical appearance, and that variation in physical appearance biases self-perceived relative to genetically estimated ancestry.
ASHG meeting in San Diego
Dr. Valentina Cipriani recently attended the ASHG meeting in San Diego (18-22 Oct 2014) where she presented results from a large-scale exome GWAS of age-related macular degeneration (AMD) on behalf of the International AMD Genomics Consortium (IAMDGC). IAMDGC (26 research groups from 10 countries) has carried out the largest genotyping ever conducted on AMD, pulling together 25,000 cases and 25,000 controls. This was carried out as a single centralised experiment, and notably, each study member agreed to share individual participant data, so that IAMDGC could perform a mega-analysis as opposed to a meta-analysis. The number of AMD loci was substantially expanded to a total of thirty-four, including sixteen novel loci. Ongoing pathway and gene expression analyses have already showed that genes in most of the novel loci nicely fit into known relevant AMD pathways, boosting the link between genetic association and biology of AMD. Further planned analyses include much-needed sequencing of all the associated loci to discover novel rare variation and obtain a more complete picture of the complex genetics of AMD.
American Society of Human Genetics 64th meeting update by Warren Emmett & Cian Murphy
The 64th meeting of the American Society of Human Genetics (ASHG) took place a fortnight ago in San Diego. Formal proceedings kicked off with a few luke warm talks, one by IBM selling the supercomputer Mr Watson as potential cancer drug discovery tool and a talk from the new google biology group who produced an ethnicity divided PCA plot based on 1000 genome data. Consequently, Daniel Macarthur trumped this
plot with a 3d version in his talk containing nearly 60x the data. Then started the mania of hundreds of concurrent talks and thousands of posters, we both enjoyed the high energy, carefully prepared presentations and free coffee. One of our favourite talks was by the Broad’s Daniel MacArthur. He discussed the Exome Aggregation Consortium, which has just realised its data from over 61,000 exomes. By dwarfing projects such as 1000g, this promises to revolutionise the study of rare disease. Building on this was a talk by Kaitlin Samocha, who leveraged these data to generate a genome-wide model of genes that displayed a Loss of Function (LOF) constraint: such genes are more constrained than expected and are therefore thought to be evolutionarily important. Furthermore, one can drill down to the exon level. It was shown that the first 7 exons of KCNQ4 are significantly constrained; while interesting in of itself, mapping this to a specific protein domain would be more informative.
Some great talks were focused on the creative use of next gen sequencing technologies. A structural variation (SV) talk showed that more than 50% of balanced SVs are undetected due to their complex nature. Complex SVs often consist of multiple combinations of inversions, deletions and duplications. It was interesting to see effective genome coverage can be increased by leveraging insert size give them 64X coverage. Another talk used Hi-C data (an approach designed to comprehensively detect chromatin interactions) to identify enchancer-promoter interactions as the dna-protein-dna interaction was picked up in this data, very exciting to see thousands of novel experimentally validated promoter-enhancer pairs. Another presentation boasted a highly optimised whole genome sequence analysis pipeline going from 50X genome data to annotated variants in 13 hours compared to standard pipelines taking more than 10x that.
On the second last day our very own Dr. Valentina Cipriani gave a great talk on the genetics of age-related macular degeneration.
ASHG 2014 was a very enjoyable experience, least of all as it took place at the San Diego convention centre on the waterfront, which meant starting and ending the day with beautiful views of the bay.
Abstracts mentioned above:
Title: Integrated analysis of protein-coding variation in over 90,000 individuals from exome sequencing data.(94) (10:30AM-10:45AM on Mon) (Platform) Author(s): D. G. MacArthur, M. Lek, E. Banks, R. Poplin, T. Fennell, K. Samocha, B. Thomas, K. Karczewski, S. Purcell, P. Sullivan, S. Kathiresan, M. I. McCarthy, M. Boehnke, S. Gabriel, D. M. Altshuler, G. Getz, M. J. Daly, Exome Aggregation Consortium
Title: Leveraging genetic variation from over 55,000 exomes to explore patterns of functional constraint on human protein-coding genes.(198) (04:30PM-04:45PM on Mon) (Platform) Author(s): K. Samocha, M. Lek, D. MacArthur, M. Daly, Exome Aggregation Consortium Keywords: Statistical Genetics and Genetic Epidemiology, KW008 - bioinformatics, KW031 - computational tools, KW080 - genome sequencing, KW087 - identification of disease genes
Title: The landscape and clinical impact of cryptic structural variation in autism and related neuropsychiatric disorders.(16) (02:15PM-02:30PM on Sun) (Platform) Author(s): H. Brand, V. Pillalamarri, R. Collins, S. Eggert, M. Stone, I. Blumenthal, C. O'Doushlaine, E. Braaten, J. Rosenfeld, S. Mccarroll, J. Smoller, A. Doyle, M. Talkowski
Title: Identification and characterization of enhancer and target gene pairs in mammalian genomes.(164) (12:00NOON-12:15PM on Mon) (Platform) Author(s): Y.-C. Hwang, C.-F. Lin, O. Valladares, J. Malamon, Q. Zheng, B. Gregory, L.-S. Wang
Title: SpeedSeq: A 24-hour alignment, variant calling, and genome interpretation pipeline.(44) (03:15PM-03:30PM on Sun) (Platform) Author(s): C. Chiang, R. M. Layer, G. G. Faust, M. R. Lindberg, A. R. Quinlan, I. M. Hall
Title: Unravelling the complex genetics of age-related macular degeneration — The International AMD Genomics Consortium (IAMDGC).(384) (04:45PM-05:00PM on Tue) (Platform) Author(s): V. Cipriani on behalf of the International AMD Genomics Consortium (IAMDGC)
World’s End case
In October, 1977 two teenage girls; Christine Eadie, 17, and Helen Scott, 17, were murdered in Edinburgh.
The case is so named because both victims were last seen alive leaving the World's End Pub in Edinburgh's Old Town. The only living person to stand trial accused of the murders, Angus Sinclair, was acquitted in 2007 in controversial circumstances.
A change in the double jeopardy laws meant that Sinclair was retried. David Balding, Chris Steele and Adrian analysed about 15 DNA samples for this case (far more than in any other case) and none of them was straightforward as the DNA was old and degraded. David attended the court in Edinburgh on four different occasions to give evidence and to hold meetings whilst Adrian and Chris did a lot of work getting the program in shape for these complex analyses.This infamous case has recently finally came to an end. The jury took only 2 hours to find Angus Sinclair guilty.
Angus Sinclair was already in jail for life for other similar murders however this case has set a precedent of a successful double jeopardy conviction as well as providing satisfaction for the families of the victims.
UGI MSc courses
In September we said goodbye to our students from last year. We are pleased to announce that 2013-14 the MSc Genetic of Human Disease (GHD) students passed the course with 10 distinctions and 1 Merit awarded. For our MSc Pharmacogenetics and Stratified Medicine (PGX) students, 1 Distinction and 3 merits were awarded with the rest passing successfully! Congratulations to Nada Essawy and Alison Kennedy who were both awarded a cash prize of £100 and a certificate for the Best Project and Ariadna Navarro Aragall and Constantinos Lipsos who were awarded a cash prize of £100 and a Certificate for being the best students from GHD and PGX respectively. We wish them all success in their future endeavours.
It is always very exciting for us to meet our next intake of students at the start of the academic year. This year Induction Day was held on 19th September. We were pleased to welcome 23 students from 15 different countries who joined the MSc GHD programme and 9 students, all from countries, who enrolled to the MSc PGX programme. Along with the welcoming talks from the teaching staff and course directors, each student gave a short presentation about themselves. It was interesting to hear what inspired our students to come to UCL to study our courses. The Induction day was followed by drinks at the Student Union bar that gave a chance for students to get know each other more and speak directly to programme directors, administrators and module organisers.
Here at UCL Genetics Institute we ensure our students are fully aware of the wide range of networking and learning opportunities available to the students in the form of lectures, seminars and other activities, both around campus and external to UCL. Students were invited to attend various events including non-UCL events such as the Progress Educational Trust event 'Genetic Conditions: How should your DNA be used in the 100,000 Genomes Project?’, social events such as dining out in Central London, organised by Dr Sayeda Abu-Amero, who brought together the MSc students and the teaching staff in relaxed informal environment.
Over the past month our MSc students were not only busy with their studies but also had to select a research project which they will embark on from Term 2. Each year we offer a wide range of lab-based and computer-based projects supervised by world-class researchers across UCL. The MSc Christmas party will take place on 11th December from 4pm in Rayne building.
The Admission for academic year 2015-16 will start in January 2015. For further information and how to apply for the MSc Genetics of Human disease, please visit our websites:
- you can watch a video about the MSc here
For the MSc Pharmacogenetics and Stratified Medicine go to:
- watch a video about the MSc here
Please contact Dr Elvira Mambetisaeva (firstname.lastname@example.org) if you have any question related to our MSc courses.
Bloomsbury Centre for Genetics Epidemiology and Statistics (BCGES)
The Centre held its Annual Scientific Meeting in July "Integrating the Genome with the Phenome". The event was held in conjunction with SEGEG and was well attended by colleagues from UCL / LSHTM and other UK research centres. The next Annual Meeting will be held on Tuesday 30th June 2015.
In September this year, the Centre also run its very popular short courses on Introduction to Genetic Epidemiology and High throughput sequencing. Information about next years' courses will be available from early 2015 on the Centre's website.
Thursday 15th January 2015, 1-2pm, Rose Room (Lower ground), LSHTM
Dr Jess Buxton, Centre for Cardiovascular Genetics, UCL
Title: Short telomeres and cardiometabolic disease risk: a causal link?
Monday 9 February2015, 1-2pm, Manson LT, LSHTM
Dr Damer Blake, Senior Lecturer in Molecular Parasitology, The Royal Veterinary College
Title: Parasite genetics for poultry: one less reason for the chicken to cross the road?
Monday 9 March 2015, 1-2pm, Manson LT, LSHTM
Dr Jordana Bell, Senior Lecturer / Head of Epigenomics Research Group, King’s College London Title: TBC
DNA Confirms: Here Lieth Richard III, Under Yon Parking Lot - Ancient bones discovered under a parking lot have been confirmed as those of the medieval king Richard III, through a DNA test that also raises questions about the legitimacy of Henry VIII and other famous English royals.
A statistical analysis led by David Balding and Mark Thomas calculated the chances that a man of Richard III's age with battle wounds and a curved spine could turn up at Greyfriars and not be the slain king. They conservatively estimated that chance at 6.7 million to 1.
Multiple Quantitative Trait Analysis Using Bayesian Networks. Marco Scutari, Phil Howell, David J. Balding, Ian Mackay
Evolution of extensively drug-resistant Mycobacterium tuberculosis from a susceptible ancestor in a single patient. Vegard Eldholm, Gunnstein Norheim, Bent von der Lippe, Wibeke Kinander, Ulf R Dahle, Dominique A Caugant, Turid Mannsåker, Anne Torunn Mengshoel, Anne Ma Dyrhol-Riise and Francois Balloux
A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans. Nicholas J. Timpson, Philippa J. Talmud, Steve E. Humphries, Eleftheria Zeggini, Nicole Soranzo et.al. & UK10K Consortium
Common variation near ROBO2 is associated with expressive vocabulary in infancy. Beate St Pourcain, Rolieke A.M. Cents, Andrew J.O. Whitehouse, Claire M.A. Haworth, Oliver S.P. Davis, et al.
Collapse of Amphibian Communities Due to an Introduced Ranavirus. Stephen J. Price, Trenton W.J. Garner, Richard A. Nichols, François Balloux, et al.
Statins and type 2 diabetes: genetic studies on target. Timothy M Frayling
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