Medical genome sequencing: understanding the genomes of disease
28-29 Oct, 2010
Barcelona, Spain

Organisers:

Draft Report

Summary

The meeting was aimed at establishing the European Forum for capturing the latest advances in genomic sequencing technologies and at implementing personalised genomic medicine. The two-day meeting “MEDICAL GENOME SEQUENCING: UNDERSTANDING THE GENOMES OF DISEASE” featured talks by international keynote speakers outlining the current status of medical sequencing, and exhibiting the technological challenges ahead. It provided an exceptional opportunity to bring together scientific leaders in genomic medicine and biotech companies. The meeting was attended by over 300 registrants, was webcasted at the Barcelona Biomedical Research Park and was followed by many investigators through the CRG website and twitter. In its first day, the symposium analysed the potential of new technologies in genome sequencing. Over the course of the day, various international experts spoke about their work in the field of sequencing the genome of complex human diseases. All over the world new initiatives and databases have emerged to catalogue structural changes, insertions, mutations and anomalies in DNA that are allowing for diseases as complex as cancer to be catalogued. The second day of the symposium revolved around the analysis of genome expression and regulation. Advances in the knowledge of the epigenetics and genetics of cellular populations are permitting a better understanding of the genetic basis for certain diseases. We are seeing that in some cases not only is the presence or absence of a mutation in a single gene important, but that the pattern of genome activation in the cells, its chromosomal compression and even the process of splicing is also relevant. Together, all of these advances are placing increasing downward pressure on the costs of DNA sequencing, allowing us to quickly and cheaply make available all of the information contained in our genome. Thanks to this, we will be able to know our individual predispositions toward developing certain diseases and act in kind, modifying behavior or even designing a la carte drugs. We are convinced that the IX Symposium of the CRG has successfully drawn attention to new technologies in genomic sequencing and, above all, has helped us to appreciate the great impact that these technologies will have on the development of personalised medicine in the near future.

Scientific Content

Revolutionary developments in genome sequencing technologies that are already available enable us to sequence an entire human genome at an affordable price and within a short time frame. At present, high-throughput sequencing technology is increasingly being applied in basic biomedical science and is being validated for diagnostic sequencing of a small numbers of established disease genes. When applied more widely this approach has the potential to elucidate the full genetic background of a given disease, which will be of major importance for the accurate classification of disease and for the design of therapeutic strategies, bringing personalised genomic medicine (PGM) closer to reality. There is a great need to establish a pan-European network of experts in PGM. These experts come together from a great variety of different biomedical fields and include (but is not limited to) clinicians, human geneticists, sequencing experts, bioinformatics experts and industrial stakeholders. A strong European network in this field will contribute to ensure a front-running position of European laboratories, clinics and commercial enterprises in the competitive field of Genomic Medicine. In order to achieve this, a European initiative to build a virtual platform for the joint programming of Genomic Medicine Research in Europe has been initiated in 2008. This initiative, called GEUVADIS (Genetic EUropean VAriation in DISease), was presented to the European Science Foundation and other stakeholders at the EuroBioFund III meeting. One of the goals of GEUVADIS is to encourage PGM collaborations at the European level. The GEUVADIS initiative, now supported by the European Commission as a Concerted Action, launched its first conference in a series aiming at shaping PGM development in Europe.

The meeting “MEDICAL GENOME SEQUENCING: UNDERSTANDING THE GENOMES OF DISEASE” has been the first in a series of meetings focused on developments in next-generation sequencing (NGS) technology and its implications for Genomic Medicine. Several members of the GEUVADIS consortium participated in the sessions, which were an excellent forum for European leaders (scientists, pharmaceutics, or biotechnologists) and stakeholders involved in developing PGM. Sessions at the meeting provided an overview of medical applications resulting from next-generation sequence technology,
facilitated to establish a strong multidisciplinary and internally sustainable “Medical
Genome Sequencing” network consisting of clinicians, sequencing and bioinformatics experts, and industrial scientists, allowing to build extensive knowledge and expertise in medical sequencing applications, to accelerate implementation of this technology in routine DNA diagnostics laboratories, for successful translation of sequencing results to clinically relevant genomic applications.

This first symposium was organised in two main sessions: Thursday 28 October –
Defining the Framework of Genomic Analysis, and Friday 29 October – Genomic Dissection of Phenotypes. The meeting allowed the investigators for each of the players involved in the process of PGM (i.e. researchers, clinicians, pharmaceuticals and biotech companies) to express their hopes and concerns about PGM.

Assessment of the results & impact of the event

In its first day, the symposium analysed the potential of new technologies in genome sequencing. Over the course of the day, various international experts spoke about their work in the field of sequencing the genome of complex human diseases. All over the world new initiatives and databases have emerged to catalogue structural changes, insertions, mutations and anomalies in DNA that are allowing for diseases as complex as cancer to be catalogued. Additionally, these efforts are also identifying the mutations that cause monogenetic diseases such as Crohn’s disease and chronic lymphocytic leukemia (CLL).

The second day of the symposium revolved around the analysis of genome expression and regulation. Advances in the knowledge of the epigenetics and genetics of cellular populations are permitting a better understanding of the genetic basis for certain diseases. We are seeing that in some cases not only is the presence or absence of a mutation in a single gene important, but that the pattern of genome activation in the cells, its chromosomal compression and even the process of splicing are also relevant.
Together, all of these advances are placing increasing downward pressure on the costs of DNA sequencing, allowing us to quickly and cheaply make available all of the information contained in our genome. Thanks to this, we will be able to know our individual predispositions toward developing certain diseases and act in kind, modifying behavior or even designing a la carte drugs. We are convinced that the IX Symposium of the CRG has successfully drawn attention to new technologies in genomic sequencing and, above all, has helped us to appreciate the great impact that these technologies will have on the development of personalised medicine in the near future.

On the website created specifically for the Symposium (http://2010symposium.crg.eu) you can find all kinds of material that we have been compiling over the course of the two-day meeting.
Videos of the presentations: Luca Pagani, Paul Fliceck, Victor Solovyev, Emmanouil T. Dermitzakis, Mireia Jordà, Sarah NG, Joris Veltman and Roderic Guigó. (http://2010symposium.crg.eu/streaming)
Detailed day-by-day reports with both articles and video summaries (http://2010symposium.crg.eu/noticias).

Programme

Thursday 28 October – Defining the Framework of Genomic Analysis
Chair: Stephan Ossowski (Center for Genomic Regulation, Spain)
9:10 – 9:50 Michael Metzker (Human Genome Sequencing Center, Baylor
College of Medicine, USA)
Next generation technologies – Basics and applications
9:50 – 10:30 Ivo Gut (National Centre of Genomic Analyses, Spain)
Applications of whole-genome sequencing
10:30 – 10:50 Mario Cáceres (Biotechnology and Biomedicine Institute UAB, Spain)
Bioinformatic prediction of non-redundant polymorphic inversions in the human genome
10:50 – 11:20 Coffee Break
11:20 – 12:00 Ann-Christine Syvanen (Uppsala University, Sweden)
Allele-specific gene expression as a guide to genes with cis-acting regulatory epigenetic and genetic factors
12:00 – 12:40 Jun Wang (Beijing Genomics Institute, China & University of Copenhagen, Denmark)
Personal genomes are personalised
12:40 – 13:00 Luca Pagani (Wellcome Trust Sanger Institute, UK)
Characterisation, through re-sequencing, of genetic variants associated with high altitude adaptation in North Caucasians
13:00 – 14:30 Lunch and Poster Session
Chair: Fyodor Kondrashov (Center for Genomic Regulation, Spain)
14:30 – 15:10 Jeffrey Barrett (Wellcome Trust Sanger Institute, UK)
The case of the missing heritability: clues so far and mysteries remaining
15:10 – 15:50 Paul Flicek (European Bioinformatics Institute, UK)
Annotating and understanding human variation
15:50 – 16:10 Victor Solovyev (University of London, UK)
A tool for reconstructing sequences and transcriptome analysis using next-generation sequencing data
16:10 – 16:40 Coffee Break
16:40 – 17:20 Xavier Estivill (Center for Genomic Regulation (CRG-UPF), Spain)
Structural variation analysis by large-scale human genome sequencing
17:20 – 18:00 Jonas Korlach (Pacific Biosciences, USA)
Applications of Single-Molecule, Real-Time (SMRT™) DNA sequencing
18:00 – 18:40 Steve Lincoln (Complete Genomics, USA)
Large-scale human genome sequencing service for advanced disease studies

Friday 29 October – Genomic Dissection of Phenotypes
Chair: Susana de la Luna (Center for Genomic Regulation, Spain)
9:00 – 9:40 Emmanouil T. Dermitzakis (University of Geneva, Switzerland)
Cellular population genomics in humans
9:40 – 10:20 Jennifer Meadows (Dept of Medical Biochemistry and Microbiology,
Uppsala University, Sweden)
The power of comparative genetics and genomics for finding genes of medical relevance
10:20 – 10:40 Mireia Jordà (Institute of Predictive Medicine and Personalised
Cancer Medicine, Spain)
Filling up gaps in epigenomic maps: the active Aluome
10:40 – 11:10 Coffee Break
11:10 – 11:50 Sarah Ng (Genome Sciences & Pediatrics, University of Washington, USA)
Next-generation Mendelian genetics by exome sequencing
11:50 – 12:30 Joris Veltman (Radboud University, Nijmegen Medical Centre, The Netherlands)
Next generation sequencing in the clinic
12:30 – 12:50 Raquel Rabionet (Center for Genomic Regulation, Spain)
Using homozygosity mapping and exome sequencing to search for a gene causing a rare articular disease
13:00 – 14:30 Lunch and Poster Session
Chair: Cedric Notredame (Center for Genomic Regulation, Spain)
14:30 – 15:10 Stephan Schreiber (Institute of Clinical & Molecular Biology, Germany)
Crohn disease, paradigm for the etiology of complex inflammatory disorders
15:10 – 15:50 Roderic Guigó (Center for Genomic Regulation (CRG-UPF), Spain)
Uncovering and understanding splicing through massively parallel sequencing
15:50 – 16:10 Yu Sun (Leiden University Medical Center, The Netherlands)
Terminal osseous dysplasia is caused by a single recurrent mutation in the FLNA gene
16:10 – 16:40 Coffee Break
16:40 – 17:20 Stylianos Antonarakis (University of Geneva, Switzerland)
Exome sequencing to identify cancer predisposing variants
17:20 – 18:00 Peter Campbell (Wellcome Trust Sanger Institute, UK)
Interrogating the architecture of cancer genomes
18:00 – 18:40 Manolis Kellis (MIT and Broad Institute, USA)
Disease epigenomics: Interpreting disease-associated non-coding variants using chromatin states and activity profiles across many human ENCODE cell types