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

Genomics, technology, bioinformatics
models includes genes involved, their function, site and timing of expression
and sequence data. Over 1,900 mutant phenotypes currently
are associated with human disease phenotypes, representing approximately
12% of OMIM terms with one or more associated mouse
models. These data and new mouse model data that continue to accumulate
provide fertile ground for selecting appropriate experimental
mice, as well as identifying potential mouse targets that may be used
to explore new models.
Supported by NIH grant HG000330.
P1244. Specific features of dermatoglyphics problems in
different diseases
D. Noje, I. Tomulescu, E. Laslo, C. Pusta;
University of Oradea, Oradea, Romania.
This paper is an application of the concept of a Genetic Algorithm,
modified to approximate certain functions. The classical problem of
the dermathogliphic recognition has a settlement in different modes
existing at this time very strong real time applications.
What we want to bring something new in this article is a possible solution
of the dermatoglyphic recognition even if they are damaged by
some typical diseases or lightly damaged by will.
The application has been built on a certain method of recognition of
some essential items in the symbolism of the human dermatoglyphics
those through genetic approximation techniques we complete those if
there is the case and that follows a search in the data base to identify
the owner.
P1245. Development of TaqMan ® SNP and DME Genotyping
Assays on TaqMan ® Low Density Arrays
T. Hartshorne, R. Padilla, J. Au-Young, T. Ceccardi, J. Ziegle;
Applied Biosystems, Foster City, CA, United States.
Applied Biosystems’ TaqMan® Low Density Arrays (TLDAs) are 384well
micro fluidic cards that provide a convenient low- to mediumthroughput
platform for TaqMan® Gene Expression Assay panels.
TLDAs are pre-loaded with assays, which greatly reduces experiment
preparation time and eliminates the need for liquid-handling robots or
multi-channel pipettors. Towards the goal of providing TaqMan® DME
Genotyping Assay panels on TLDAs, we conducted benchmark tests
to compare the performance of genotyping assays run on TLDAs and
on conventional 384-well plates. TLDA cards contained 8 x 48 distinct
TaqMan® Validated SNP and Drug Metabolism (DME) Assays, which
were previously validated on sample sets including 45 Caucasian and
45 African American Coriell genomic DNAs. These same sample sets
were run on the TLDAs and the resulting genotyping data were compared
to data from the 384-well plate assay validation studies. Assay
performance was found to be equivalent between platforms: all assays
performed successfully on TLDAs (100% pass rate), call rate was
greater than 99.0%, and accuracy was greater than 99.6%. Experiments
are underway to define the lower limit number of DNA samples
required for sample clustering and accurate genotyping in the absence
or presence of control DNA samples. An interactive data analysis software
tool, Autocaller software, is also in development. This software
tool enables overlaying and viewing cluster plots from multiple plates
or cards and is used to facilitate analysis of genotyping data from TLDA
cards. Genotyping DME SNPs using TLDAs will streamline studies of
drug metabolism and response variation among patients.
P1246. Fast, reliable and very cost-effective method for DNA
extraction from bioptic specimen
J. Ramic, L. Kapur, N. Lojo, D. Macic, N. Pojskic, A. Durmic-Pasic, K. Bajrovic;
Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and
Herzegovina.
Procedure of DNA isolation is a basic step for molecular-genetics research
as well as for archiving for future reference. Therefore, the protocols
that guarantee optimum quality and quantity should be used in
order to ensure long-term storage of DNA samples.
Three diferent protocols for DNA extraction from tumor tissue specimen
obtained in biopsy, have been compared trough evaluation of
following parameters: time-consumption, feasibility, DNA quality and
quantity and cost of procedure.
Protocol for DNA isolation using salting out method by Miller et al.
(1987) that was modified in our lab showed to be the fast, reliable in
terms of DNA quality, quantity and long-term stability as well as highly
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cost-effective and applicable for archiving of DNA for future research
using large-scale genetic analysis technology.
P1247. CpG islet methylation in the human genome
N. C. Wong, M. Qazag, P. Canham, J. M. Craig, K. A. Choo, R. Saffery;
The Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne,
Australia.
DNA methylation of CpG islands is widely studied in higher eukaryotes
and has been found to regulate gene expression, imprinting and
cancer progression. Yet within the human genome, only 8% of all CpG
dinucleotides reside within a CpG island. As DNA methylation is the
addition of a methyl moiety to cytosine residues within a CpG dinucleotide,
a large pool of genomic methylation resides outside of CpG
islands and remains uncharacterised. CpG islets have the same DNA
sequence characteristics as CpG islands in terms of GC-content, but
are shorter in length and are thus more abundant within the genome
(Wong et al, 2006). We have recently shown that methylation of these
islets can vary in association with modified chromatin states, however
the extent to which CpG islet methylation plays a role in other epigenetic
phenonmenon such as gene regulation or X-inactivation has yet to
be determined. To start to address this, we are investigating the relationship
between the methylation status of CpG islets associated with
known genes and expressed sequence tags (ESTs) and gene expression
level. Preliminary results implicate CpG islet methylation in the
regulation of some gene regulation, thereby suggesting an essential
role for CpG islets within the mammalian genome.
P1248. Detection and mapping of partial trisomy and partial
monosomy of HSA21 using BAC tiling arrays
R. Lyle 1 , F. Bena 2 , C. Gehrig 2 , G. Lopez 2 , S. Gagos 2 , J. M. Delabar 3 , A.
Schinzel 4 , J. Lespinasse 5 , A. Bottani 2 , S. Dahoun 2 , L. Taine 6 , M. Doco-Fenzy 7 ,
P. Cornillet-Lefebvre 8 , A. Pellet 9 , A. Toutain 10 , L. Colleaux 9 , J. Horst 11 , I. Kennerknecht
11 , L. Florentin 12 , S. Kitsiou 13 , E. Graison 14 , M. Costantine 3 , P. Sinet 14 ,
S. E. Antonarakis 2 ;
1 Ullevål University Hospital, Oslo, Norway, 2 University of Geneva Medical
School, Geneva, Switzerland, 3 EA 3508 University Paris Denis Diderot, Paris,
France, 4 Institute of Medical Genetics, Schwerzenbach, Switzerland, 5 Cytogenetic
Laboratory, General Hospital, Chambery, France, 6 Department of
Genetics, CHU Pellegrin, Bordeaux, France, 7 Department of Genetics, IFR53,
Reims, France, 8 Department of Hematology, Reims Hospital, Reims, France,
9 INSERM U781 Necker-Enfants Malades, Paris, France, 10 CHU Hôpital Bretonneau,
Tours, France, 11 Institute of Human Genetics, University of Münster,
Münster, Germany, 12 AlfaLAB Molecular Biology and Cytogenetics Center,
Athens, Greece, 13 Department of Medical Genetics, Aghia Sophia Children’s
Hospital, Athens, Greece, 14 CNRS UMR7637, Paris, France.
Down syndrome (DS) is one of the most frequent congenital birth defects,
and the most common genetic cause of mental retardation. Affected
individuals share certain clinical features such as mental retardation,
congenital heart disease and characteristic facial and physical
apparance. In most cases, DS results from the presence of an extra
copy of chromosome 21. A major goal of understanding the molecular
pathology of DS is the identification of HSA21 genes or other functional
genomics elements that contribute to specific aspects of the phenotype.
Rare cases of partial trisomy 21 could identify genomic regions
associated with specific DS phenotypes.
In order to establish high resolution mapping of pathogenic partial aneuploidies
and unbalanced translocations involving HSA21, we constructed
a BAC microarray covering 21q. The array consists of 411
HSA21 BACs with a mean overlap of 85 kb giving an approximatively
2-fold tiling path.
Our study includes identification and mapping of 45 pathogenic chromosomal
aberrations of chromosome 21 including 8 complete HSA21
trisomy and 32 partial aneuploidies for different segments of HSA21.
In each case, the size of the segmental aneuploidy has been estimated
and in 20 cases confirmed by real-time quantitative PCR. The
breakpoints have been mapped to within 200kb on average. We also
tested 5 cases with a normal karyotype on the basis of clinical findings
indicative of a Down syndrome phenotype. Correlations of partial
21q duplication and monosomies with phenotypic features will be
presented and contribute in the understanding of genotype-phenotype
correlations in Down syndrome physiopathology.