2008 Barcelona - European Society of Human Genetics

Plenary Lectures
ing its high throughput genotyping platforms . We have widely applied
different formats of Illumina Infinium and Affymetrix arrays. The CNG
genotyping platforms are embedded in a system of highly standardized
DNA handling and QC, LIMS, data QC, statistical analysis and
OPERON, a bioinformatic knowledge database . Our studies have delivered
many striking results, such as ORMDL3, a strong candidate
gene associated with childhood asthma, PTGER4 a candidate gene
associated with Crohn’s disease, BCL11A a strong candidate gene associated
with sickle cell disease and β-thalassemia, and others. The
identification of associated genes was accelerated by a database of
genome-wide association of global gene expression . Recently we
managed to identify an intriguing group of genes that constitute subunits
of a nicotinic acetylcholine receptor on 15q25 associated with
lung cancer susceptibility .
To gain better understanding of the regions of the genome that show
association with a phenotype we are currently using a 2nd generation
DNA sequencing platform based on Illumina Genome Analyzers . We
have adapted efficient methods for the enrichment of regions of interest
. The 2nd generation DNA sequencing methodology is well suited
for the analysis of DNA samples enriched for particular genomic regions
of interest . Due to the technical limitations of these technologies,
their application for capturing structural variation such as short range
length polymorphisms (microsatellites and minisatellites), duplications
and inversion requires work arounds . We believe that a further paradigm
shift to a 3rd generation of DNA sequencing technology will be
required for cost-effective whole genome sequencing . This technology
will have to be able to analyze clonal DNA molecules over long
distances (5 - 30 kb) . The European Community is funding an effort to
develop such a technology through its FP7 programme READNA .
PL4.1
Distinguished speaker Lecture: systems Biology and systems
medicine
L. Hood;
President, Institute for Systems Biology, Seattle, WA, United States.
The grand challenge for biology and medicine in the 21st century is
complexity . A currently emerging paradigm change is the idea that
biology is an informational science and that most biological information
is mediated by dynamical biological networks . The systems approach
to biology and medicine is a general category of approaches
that appear to be very effective in dealing both with biological circuits
and hence with biological complexity . Systems approaches require a
truly cross-disciplinary environment and the effective integration of
biology, technology and computation/mathematics . I will discuss my
views of systems biology . Then I will discuss a systems approach to
one disease, prion disease in mice, and demonstrate how it profoundly
alters our views of disease_with regard to understanding disease
pathophysiology as well as new approaches to diagnosis, therapy and
eventually prevention . Then I will talk about the emerging measurement
technologies that are the foundation of P4 medicine, as well as
some of the pioneering computational and mathematical tools that will
be necessary to usher in this revolution in medicine . The view of biology
as an information science, the systems approach to disease,
the new measurement and visualization technologies and the evolving
mathematical/computation tools will catalyze this paradigm change in
medicine. I will make five predictions: 1) our current largely reactive
medicine will be transformed to a predictive, preventive, personalized
and participatory (P4) medicine over the next 10 to 20 years, 2) this will
lead to the digitalization of medicine (extracting information from single
cells, single molecules and single individuals) with even more profound
implications for society than the digitalization of communications and
information technologies, 3) systems medicine and its digitalization
will dramatically turn around the slope of ever increasing healthcare
costs to the point that the developed world will be able to export its
P4 medicine to the developing world, 4) P4 medicine will necessitate
fundamental changes in the business plans of virtually every sector
of the healthcare industry and 5) this new world of medicine will be
propelled forward by carefully chosen strategic partnerships_across
all sectors of science_academia, industry, government laboratories, independent
research institutes, etc_and that these partnerships will be
international . ISB hopes to play an important role in catalyzing a series
of these strategic partnerships .