2008 Barcelona - European Society of Human Genetics

Genomics, technology, bioinformatics
clusters of transcripts in humans . The developed database revealed
a signicant number of sense—antisense pairs consisting of one EST
cluster expressed predominantly in normal tissues and another cluster
with tumor-specic expression . The role of antisense transcripts in
the regulation of oncogenes and tumor suppressor genes warrants
functional research . Here we describe and characterize an antisense
mRNA asAFAP overlapping human AFAP1 gene .
AFAP1 encodes for an actin filament binding protein, which serves as
a modificator of actin filament structure and integrity. It also is able to
relay a signal from receptor tyrosine kinases through PKCα to Src protein
kinase . It has been shown that AFAP1 is overexpressed in prostate
cancer and contributes to tumorigenic growth . We hypothesized that
the transcription of asAFAP antisense mRNA may lead to suppression
of sense AFAP1 gene expression and a compensatory restrain added
to one of the mitogenic signaling pathway that is unlikely to be supported
by natural selection in the tumor cell population . To study the
intriguing phenomenon of tumor-specic asAFAP antisense expression
we performed detailed in silico analysis of asAFAP sequences and
experimentally quantified this transcript in normal and tumor human
tissues .
We have specified the exon-intronic structure of asAFAP antisense
transcript and carried out the expression analysis of AFAP1 sense—
antisense pair in normal and tumor human tissues .
P08.04
High-resolution breakpoint mapping of human chromosome 21
segmental aneuploidies for genotype-phenotype correlation and
identification of underlying genomic architecture
A. Hoischen, B. van Bon, L. E. L. M. Vissers, C. F. H. A. Gilissen, S. Keijzers-
Vloet, N. de Leeuw, B. B. A. de Vries, H. G. Brunner, J. A. Veltman;
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
As part of the European FP6-sponsored AnEUploidy consortium we
are involved with work package 2: Genotype-phenotype correlations
in human aneuploidies . The objective of this work package is to study
the phenotypic consequences of gene dosage imbalance in the human
population .
One of our roles in this project is the characterization of segmental
aneuploidies of HSA 21 . Until now we collected 19 cases with detailed
clinical information, enabled by using a standardized phenotypic
list . Cell lines and/or DNA are available for all patients . Karyotyping
as well as additional analysis (FISH, microarray-based high-resolution
genome profiling) were performed for the majority of cases. We
have used a chromosome 21 specific oligo-array with 385,000 oligonucleotides
to further delineate the genomic rearrangements in this
cohort. Breakpoint fine mapping of approximately 1kb accuracy has
been performed for the most cases, enabling breakpoint sequencing
as a next step . For one case with a partial chromosome 21 deletion
(46,XY,del(21)(q11 .2q21 .3)) the rearrangement coincide with bordering
segmental duplications (SDs) that have identical orientation and
high (>95%) similarity . This suggests that recurring deletions and/or
corresponding duplications of similar size that are mediated by NAHR
(non-allelic homologous recombination) may exist . These analysis of
the underlying genomic-architecture are enabled by in-house developed
software tools .
Detailed genotype-phenotype correlations are ongoing for all patients
to get a better insight into the underlying gene dosage imbalances . Expansion
of the patient cohort and transcriptome analysis are planned
as joined efforts of the consortium .
P08.05
Artificial intelligence applied in finger prints identification
E. Laslo, I. Tomulescu;
Faculty of Sciences, Oradea, Romania.
In this paper we propose a new database search method with results
in finding the most nearest existing data. The searching method is
based on the artificial intelligence concepts named Genetic Algorithms
combined with polynomial approximation .
In the first stage of the process for each record in the database we
create an algebraic polynominal named characteristic function and we
update the database with the polynominal coefficients.
For the second stage we process the input data also to create an algebraic
polynomial approximation . This method was used in our previous
research in numerical approximation with Genetic Algorithms .
In the last stage we search all the polynominals created in the first
stage which approximate the minimum requirement of the polynominal
representing the input data .
If the difference doesn’t satisfy the minimal requirement, we consider
this data inexistent in the original database and we could save this
data like a new record .
We applied this method to interpret the 2d coordinates of the points
which represent the particularities of the finger prints.
P08.06
Genomic profiling to identify novel genetic risk factors for
Behçet’s disease
J. M. Xavier1 , T. Krug1 , B. V. Fonseca1 , F. Barcelos2 , G. Jesus3 , A. Bernardino3 ,
M. Coutinho3 , C. Neves3 , J. Vedes4 , M. Salgado5 , J. Crespo3 , J. Vaz Patto2 , S.
A. Oliveira1 ;
1 2 Instituto Gulbenkian de Ciencia, Oeiras, Portugal, Instituto Portugues de
Reumatologia, Lisboa, Portugal, 3Hospital Infante D. Pedro, Aveiro, Portugal,
4 5 Hospital de Sousa Martins, Guarda, Portugal, Hospital Pediatrico de Coimbra,
Coimbra, Portugal.
Introduction: Behçet’s disease (BD) is a multisystemic immuno-inflammatory
disorder characterized by a generalized vasculitis, particularly
at oral and genital mucosa and eye (uveitis) . Although there is evidence
for environmental risk factors, epidemiological and family studies
strongly support the existence of genetic risk factors for BD . The
only established genetic predisposition for BD is the HLA-B*51 alelle
on chr . 6p21, which explains only 19% of its overall genetic susceptibility
. Furthermore, a recent linkage study on Turkish families found
strong evidence for linkage with BD at 6p22-24 and 12p12-13 . Casecontrol
association studies on biological candidate genes have so far
mostly been inconclusive . To identify new susceptibility genes for BD,
we are conducting the “genomic convergence” approach, which combines
data from whole genome linkage screens with expression studies
to determine which genes will be tested in association studies .
Methods & Materials: We performed gene expression profiling in
peripheral blood mononuclear cells of carefully matched cases and
controls using Affymetrix GeneChip Human Genome U133 Plus 2 .0
microarrays .
Results: Preliminary analyses identified 131 genes differentially expressed
among 11 cases and 11 controls (1 .2 fold-change cutoff and
p-value