European Human Genetics Conference 2007 June 16 – 19, 2007 ...

Concurrent Symposia
Concurrent Symposia
S01. The increasing impact of internet on genetic services
S. Aymé, A. Rath, V. Thibaudeau, V. Fonteny, B. Urbero, K. Marazova, M.
Levi-Strauss;
INSERM sc11, Paris, France.
With the widespread dissemination of the internet and the multiplication
of web-based information services, the question of to what extent
this affects the behaviour of the stakeholders needs to be addressed.
For the patients, potential benefits are a better understanding of their
disease and its mode of inheritance, improved dialogue with health
care professionals, the ability to more easily locate the expert service
that they can be referred to, and occasionally to be able to participate
in clinical research. For the patients support groups, the benefits are
improved visibility, which leads to an expansion of their membership
and allows them to help more people. For the non-specialised healthcare
professional, the benefits are similar to those for the patients with
the ultimate benefit being to deliver better care. At the beginning of
the internet era, experts feared they would no longer be consulted,
due to the wide availability of what they considered as their specific
added-value. Experience shows that this fear was unfounded. Taking
Orphanet (www.orpha.net) as an example of a website, and looking at
the behaviour of the site visitors during the past ten years and at the
impact in terms of referral to listed services, it seems like the positive
effects outweigh the negative ones. Additional services are expected
from the community. The physicians and biologists would like to access
mutation databases by population, the physicians are expecting
more practical information and the patients would like to be partners
in the development of an encyclopaedia concerning their own experience.
S02. Is there a role for the Human Geneticist in the genomic
revolution
C. J. Epstein;
University of California, San Francisco, Department of Pediatrics and Institute
for Human Genetics, San Francisco, CA, United States.
With the completion of the human genome project, the belief that virtually
all human diseases and responses to therapy are the products
of both genetic and environmental factors has firmly taken hold, and
an extensive search for mutations/variants that influence susceptibility
to disease and the efficacy and toxicity of drugs is well underway.
The anticipated outcomes of this research are a better understanding
of disease pathogenesis and the development of genetic tests to
predict who will be at risk for what. It is believed by many that genetic
risk assessment or profiling will lead to a genomic or “personalized”
medicine in which individualized strategies will be used to prevent the
onset of disease and to improve the efficacy of therapeutic agents. Although
human geneticists will certainly be involved in the research, the
role of the medical (clinical) geneticist in the delivery of this genomic
medicine, if it actually comes to pass, is less certain. Given their small
numbers, medical geneticists would certainly not be in a position to become
the principal providers of genetic testing and risk assessment for
the greater population, and this responsibility would fall to others. Nevertheless,
geneticists do have a special knowledge of genetics and human
disease that should be brought to bear on the provision of these
services. This can be accomplished by playing a role in the education
in genetics of other physicians and health providers and by serving as
designated referral sources for problems that may be too complex for
those without substantial knowledge of genetics to handle alone. At
the same time, medical geneticists need to continue to provide and,
indeed, to expand the services that are uniquely theirs to give: the
diagnosis, management (including treatment), and counseling of patients
and families with Mendelian, chromosomal, and mitochondrial
disorders, malformations, and syndromes.
S03. What use the 1000 euro genome?
M. E. Pembrey;
Institute of Child Health, University College London, United Kingdom.
Whatever this use of the word ‘genome’ includes in terms of coverage
and DNA sequence information, the 1000 euro genome will detect a
vast amount of personal genetic variation including rare mutations. It
will become commercially available in less than 20 years was the conclusion
of a 2005 UK report on genetic profiling by a group chaired by
John Sulston (www.hgc.gov.uk/Client/news_item.asp?NewsId=38) and
probably used by individuals, although not as state-funded screening.
However being used is not the same as being useful! Software claiming
to interpret your genome will become the new palmistry. There is
a pressing need to develop research programmes within existing and
in new cohort studies that include intermediate as well as disease
phenotypes and environmental exposures to discover what it means
prospectively to carry a particular genotype. The cheap genotyping
techniques behind the drive for the 1000 euro genome will help in this
research although more useful in epidemiology may be selected gene
by gene sequencing of many thousands of samples in parallel. The
first fruits of such cohort research could be the introduction of clinically
useful newborn genetic screens sequencing 100 genes or so. Detection
of filaggrin null mutations might be an example where simple strategies
might prevent eczema related allergies. One of the problems
with the idea of genetic profiling at birth, or at any other time for that
matter, is that most genetic effects are likely to be conditional on the
person’s developmental experience and/or the prevailing environment.
Thus the value of knowing just one’s genotype is also conditional. By
the time the 1000 euro genome arrives we may have more useful tests
based on epigenetic/methylation profiling to detect prenatal developmental
programming or based on gene expression patterns in peripheral
blood cells under challenge from specific stressors.
S04. Better education for medical geneticists and nongeneticists
in the new genomics era
R. M. Harden;
Tay Park House, Dundee, United Kingdom.
No abstract available as per date of printing. Please check www.eshg.
org for updates in the online database.
S05. MicroRNAs as oncogenes and tumor suppressors
S. M. Hammond;
Department of Cell and Developmental Biology, University of North Carolina,
Chapel Hill, NC, United States.
MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally
regulate gene expression. Over 450 miRNA genes have been
identified in the human genome. We have undertaken the study of
miRNA function in mammals. Using a custom microarray platform, we
investigated miRNA expression patterns in mammalian development
and in cancer. We found that many miRNAs are down-regulated in
tumor cell lines. This downregulation is not due to decreased transcription,
but is due to reduced maturation during miRNA biogenesis. On
the other hand, several miRNA genes are over-expressed in tumor
cell lines and primary tumors. Seven of these cancer-associated miR-
NAs are clustered in a single primary transcript termed chr13orf 25 or
OncomiR-1. This cluster is located in a region amplified in lymphoma
and several solid malignancies. Ectopic expression of these miRNAs
in a mouse model of lymphoma accelerated disease progression. In
addition, the lymphomas had reduced apoptosis and were more disseminated
into secondary regions. This work establishes non-coding
RNAs, and specifically miRNAs, as oncogenes in human cancers.
S06. Small RNAs in gametogenesis
A. Girard, A. Aravin, R. Sachidanandam, M. Carmell, G. Hannon;
Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Cold
Spring Harbor, NY, United States.
Argonaute proteins and associated small RNAs have critical role in
development by regulating messenger RNA stability, protein synthesis,
chromatin organization and genome structure. In animals, Argonaute
proteins segregate into two subfamilies. Ubiquitously expressed members
of Argonaute subfamily bind 21-23 nt RNA and act in RNA interference
and in microRNA-mediated gene regulation. The Piwi subfamily
is involved in germline-specific events such as germline stem cell
maintenance and meiosis. Particularly, three members of the Piwi subfamily
in mouse are critical for successful spermatogenesis. Recently
we identified a new class of 25-30 nt RNAs (piRNAs) as a binding
partner of Piwi proteins in the mammalian male germ cells. piRNAs are
highly abundant in germ cells and accumulate at the onset of meiosis.
Thousands of identified piRNAs show distinctive localization patterns
in the genome, being predominantly grouped into 20-90-kilobase clusters
scattered throughout genome. We explore biogenesis of piRNAs
and function of Piwi-piRNA complexes in the mammalian germline.