2009 Vienna - European Society of Human Genetics

Concurrent Sessions
showers’ and (iii) numerous highly informative ‘homocoordinate’ mutations.
Using the proportion of CpG substitution as a crude indicator
of the relative likelihood of transient hypermutability, we also present
evidence to suggest that CSMMs comprising at least one pair of mutations
separated by 300 genes, and the DMuDB diagnostic database
(http://ngrl.man.ac.uk/dmudb)
Our current focus extends into areas such as grid-based services, and
systems for providing universal IDs for all biomedical research data
and entities on the internet, including individual researchers. This will
revolutionise the potential for holistic data integration, and ensure fair
and equitable use of sensitive G2P information.
Acknowledgements: GEN2PHEN is funded by the European Community’s
Seventh Framework Programme (FP7/2007-2013) under grant
agreement 200754.
c15.6
Establishing a link between microRNAs, genes and hereditary
diseases : the miRiFix database
A. Henrion Caude 1 , C. Mugnier 2 , S. Bandiera 1 , M. Girard 1 , M. Le Merrer 1 , A.
Munnich 1 , S. Lyonnet 1 ;
1 INSERM U781, Paris, France, 2 University Paris Descartes, Paris, France.
Identification and analysis of microRNAs (miRs) enhance our understanding
of the important roles that small RNAs play in complex
regulatory networks. However, there are still few data supporting the
involvement of miRs in Mendelian disease inheritance other than cancer.
MiRs may be regarded either as candidate gene within a disease
locus, or as putative modifier gene, which can regulate the expression
of a given disease-causing gene. At this latter level, single nucleotide
polymorphisms (SNPs) within the target gene add a supplemental layer
of complexity. Herein, we present a comprehensive resource, aimed
at linking miRs and hereditary diseases : mirifix.com. MiRiFix is an
easy-to-use, web-accessible framework of tool and data integration.
Our model crosses up-to-date information on human miRs and the
Genatlas database, which provides integrated data on gene mapping
and genetic diseases. MiRiFix enables to systematically explore the
computational involvement of miRs in the pathogenesis of diseases,
and retrieves : (i) miR as a candidate gene from a locus, using the updated
compendium of human miRs and their mapping information, (ii)
a set of miRs predicted to regulate a disease-causing gene, in both its
3’-UTR and coding sequence, using distinct algorithms, and finally (iii)
a set of SNPs predicted to be functional in terms of miR regulation. We
will present the efficiency of miRiFix in predicting previously established
links, but also in retrieving novel data on mapped diseases orphan of
identified genes. Our web resource provides a unique integrated way
to assess computational roles of miRs in hereditary disease.
c16.1
the Effect of translocation-induced Nuclear Re-organization on
Gene Expression
L. Harewood 1 , F. Schütz 1,2,3 , S. Boyle 4 , P. Perry 4 , M. Delorenzi 2,3 , W. A. Bickmore
4 , A. Reymond 1 ;
1 Center for Integrative Genomics, Lausanne, Switzerland, 2 National Center of
Competence in Research (NCCR) “Molecular Oncology”, Lausanne, Switzerland,
3 Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland, 4 MRC
Human Genetics Unit, Edinburgh, United Kingdom.
Chromosome organization in the nucleus is thought to impact on gene
expression. To study the effect of balanced chromosomal rearrangements
on gene expression, we compared the transcriptomes of cell
lines from control and t(11;22)(q23;q11) individuals. This translocation
between chromosomes 11 and 22 is the only recurrent constitutional
non-Robertsonian translocation in humans. The number of differentially
expressed transcripts between the translocated and control cohorts
is significantly higher than that observed between control samples
alone, suggesting that balanced rearrangements have a greater
effect on gene expression than normal variation. Altered expression
on translocation chromosomes is limited to chromosome 11-mapping
genes. Consistently, we show that the nuclear position of the derivative
chromosome 11, but not that of the derivative chromosome 22, is
significantly altered compared to its normal counterpart, suggesting
that expression changes of chromosome 11 genes are potentially due
to their transposition into an anomalous chromatin environment. Our