2008 Barcelona - European Society of Human Genetics

Therapy for genetic disease 0
processes and IT support for quality management .
Since 2005, 156 different participants, from 85 institutes and 27 countries
worldwide, have participated in the 8 workshops organized to
date .
In addition to the training sessions, an electronic survey was sent to all
participating institutes in order to get a more detailed view on the progress
laboratories make towards accreditation and the implementation
of different quality aspects such as document control, performing internal
audits and tracking non-conformities . Furthermore, the value of
training in the improvement of a quality system was surveyed . The
answers received from more than 50 institutes have been analysed .
This survey gives us insight into the reaction of laboratories to the increasing
pressure to develop their investment in continuous improvement
and accreditation . Moreover, we will anticipate and address topics
on quality in future workshops, particularly adapted to the needs of
the genetic testing laboratories .
P09.72
Genetic counsulting of families when one of the members is the
carrier of balanced translocation
R. Sereikiene, V. Abraitis, D. Strazdienė;
KAUNAS MEDICAL UNIVERSITY HOSPITAL, KAUNAS, Lithuania.
Infertility in the family is one of most common courses of genetic consulting
. Between 266 consulted families we found 4 families with carrier
of balanced translocation . By the example of these families we’ll try
show the specific features of their genealogies and ethical aspects of
genetic consulting . Translocation examples in the families:
1 . Male/Female: 46 XY, t (1;4) (p36 .2; q32)/ 46 XX .
2 . Male/Female: 46 XY/ 46 XX, t (4;9) (p15 .3; q12) .
3 . Male/Female: 45 XY; -13; -14; +t (13;14)/ 46 XX .
4 . Male/Female: 46 XY/ 46 XX, t (6;10) (q23; p13) .
Genealogies of these families had some characteristic features:
1 . Sterility .
2 . Spontaneous abortions and miscarriages .
3 . Stillborns .
4 . Different anomalies of fetus .
5 . The cases of mental retardation of unclear etiology between relatives
.
Some ethical problems rise during genetic counseling of these families:
1 . Who must say the results of chromosomal examination for healthy
spouse - doctor or translocation suffering husband or wife?
2 . What tactic should keep the doctor in cases when translocation carriers
don’t agree inform other member of family?
3. The examination of first line relatives (parents, brothers, sisters and
children) and other relatives sometimes needs to avoid more fetal
anomalies . What tactic must be of the doctor in case when couple
doesn’t want informing others? Is it ethical to hide information which
knows the doctor from relatives who might be interested in?
4 . How explain family the results of examination in correct way to avoid
conflicts and sometimes divorces of the families?
P09.73
towards practical guidelines for the validation of genetic
diagnostic tests
E. Swinnen 1,2 , E. Bakker 3 , D. E. Barton 4 , S. Berwouts 1,2 , P. Bossuyt 5 , J. Camajova
6,1 , A. Corveleyn 1,2 , E. Dequeker 1,2 , T. Janssens 1,2 , M. Macek Jr. 6,1 , I. Mann 7 ,
C. Mattocks 8 , M. Morris 9 , C. Müller 10 , V. Pratt 11 , I. Salden 2 , H. Scheffer 12 , A.
Stambergova 6,1 , A. Wallace 13 , J. A. Wilson 14 , M. Zoccoli 15 , G. Matthijs 1,2 ;
1 Eurogentest Network of Excellence, Leuven, Belgium, 2 KUL, UZ Leuven,
Leuven, Belgium, 3 Leiden University Medical Center, Leiden, The Netherlands,
4 Our Lady’s Children’s Hospital, Dublin, Ireland, 5 University of Amsterdam,
Amsterdam, The Netherlands, 6 Charles University, Prague, Czech Republic,
7 Swiss Accreditation Service, Lausanne, Switzerland, 8 Salisbury District Hospital,
Salisbury, United Kingdom, 9 University Hospital Geneva, Geneva, Switzerland,
10 University of Würzburg, Würzburg, Germany, 11 Nichols Institute, Chantilly,
VA, United States, 12 University Medical Centre Nijmegen, Nijmegen, The
Netherlands, 13 St Mary’s Hospital, Manchester, United Kingdom, 14 Sequenom, San
Diego, CA, United States, 15 Celera Diagnostics, Alameda, CA, United States.
Continuous advances in human genetics and biotechnological developments
have led to a rapid growth of nucleic acid-based diagnostic
testing in medical laboratories . To further improve the quality of genetic
testing, it is necessary to support the implementation of reliable tests .
Several quality assurance measures are demanded by regulatory organizations
and accreditation bodies as outlined in published standards
and guidelines (e .g . ISO 15189 standard, the IVD Directive 98/79/EC,
the OECD Quality Assurance Guideline) .
However, proper instructions or the know-how to fulfil these requirements,
especially for the validation of genetic tests, are lacking .
A working group was created within EuroGentest, that aims to develop
practical guidelines for - to begin with - the analytical validation of molecular
genetic tests .
Through brainstorming meetings in Leuven (2007) and Prague (2008),
literature studies and with the help of external experts, a background
document was generated . It includes a consensus glossary of terms
(applicable to molecular genetic testing), a categorization of the variable
array of genetic test methods, discussions on the meaning of critical
performance characteristics for genetic tests and several generic
aids, such as a flowchart to guide the user to appropriate instructions,
a generic validation SOP and a template file for the validation report.
Future plans include the experimental design of test validations, a statistical
evaluation of ‘numbers’ in validation experiments, interlaboratory
(collaborative) trials and clinical validation .
The document will be posted and submitted to a public and expert
consultation during the summer of 2008 .
P10. Therapy for genetic disease
P10.01
comparative sequence analysis, structure prediction, primer
design of ApolipoproteinE protein in Alzheimer’s disease
K. Mahdieh1 , K. R. Rupesh2 ;
1 2 Special Medical Center, Tehran, Islamic Republic of Iran, IFREMER, Plouzane,
France.
Alzheimer’s disease (AD), neurodegenerative disease, is common
cause of dementia, characterized clinically by progressive intellectual
deterioration together with declining activities of daily living and
neuropsychiatric symptoms or behavioral changes . Researchers have
identified increased risk of developing late-onset AD to the apolipoprotein
E (apoE) gene found on chromosome 19 . In this study we have
compared the ApoE gene and its protein in different organisms to understand
the mechanism of expression of ApoE . Multiple sequence
alignment (MSA) of the apoE gene revealed that it is analogous to all
the other 16 organisms whereas the apoE protein is found to be 66%
homologous . On analysis of apoE (NM_000041), it was found that
ORF region was between 84-1034 position. Specific primers for the
apoE coding region were designed which resulted in product size 1109
bp . The apoE protein analysis showed that it was hydrophilic . 13 antigenic
determinants were found when the apoE protein was analysed
for Antigenic prediction sites which could be used as potential targets .
The positions of alpha helix and b-sheets in the secondary structure of
the proteins were predicted along with 3D structure prediction of apoE .
The degenerate primers designed could be used as a diagnostic tool
for identifying apoE protein expression in AD patients . The predicted
antigenic sites on the apoE proteins could be used as an effective
target for interaction with candidate drugs for the control of the expression
of the apoE in AD patients, this has to be further evaluated using
in vitro and in vivo methods .
P10.02
Anthracyclines, an antiobiotic family with anti-proliferating
activity, can elevate γ-globin expression in vitro and increase
HbF production in human erythtoid cells
P. N. Spyrou1 , L. Kythreotis2 , A. Kirri2 , S. Christou2 , M. Kleanthous1 ;
1 2 The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus, Makarios
Hospital, Nicosia, Cyprus.
Anthracyclines are a family of natural products produced by microorganisms
of the actinomycetes group . Some members of the anthracycline
group of antibiotics show pharmacological and mostly anticancer
activities . Their biological activities are proposed to be the result of
drug-induced damage or structural alterations to DNA due to inhibition
of enzymes that are involved in the DNA synthesis like topoisomerase
II .
In this study we investigate whether some anthraclyclines could be
HbF inducers due to their DNA binding properties and the formation
of stable complexes with it . A group of other DNA binding agents were