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Construction of a high resolution map of chromosome 21 integrating genetic, physical, overlap and transcriptional data

Objective



A new molecular cytogenetic approach, termed "comparative genomic in situ hybridization" (CGH) has recently been developped by a few groups in Europe and the USA(Kallioniemi et al., 1992, Science 258:818).
In Europe, the laboratories of T.Cremer, P.Lichter and M.Robert-Nicoud have pioneered this development (du Manoir et al.Hum.Genet.
1993, in press ; Joos et al.1993, Hum.Genet., in press).
CGH allows to rapidly map disease specific gains and losses of genetic material, e.g.in solid tumors or fetal cells.
In contrast to other molecular genetic techniques and conventional chromosome banding, CGH is a fast and cost-effective approach, since it requires only a single two color fluorescence in situ hybridization (FISH) experiment.
It can be applied in cases where genomic DNA from suspected cells is the only material available and appears ideally suited for automation. In this proposal, european researchers and companies leading in the fields of molecular cytogenetics, fluorescence microscopy and digital image analysis, including automated chromosome analyses, have combined their expertise to enable the further development and standardization of CGH for large scale applications.
We propose (i) to increase the sensitivity of the CGH test for the detection of small genetic changes and to make it applicable to the analysis of small numbers of cells for (e.g.
nuclei isolated from bioptic samples, body fluids, as well as nuclei from paraffinembedded tissue sections) (T.
Cremer, Heidelberg, F.R.G.), (ii) to develop image analysis procedures for improved sensitivity and automated analysis of CGH-experiments (M. RobertNicoud, Grenoble, France, in collaboration with ALCATEL-TITN-ANSWARE, Grenoble, France, and the Carl ZEISS GmbH, Oberkochen, F.R.G.) and (iii) to extensively test the potential of this new approach at each level of this development to identify specific gains and losses of genetic materials in a variety of malignant tumors and clinical specimens (P.Malet, Clermont-Ferrand, France ; D.Taruscio, Rome, Italy ; D.Leroux, Grenoble, France). At the end of this project a dedicated instrument will have been evaluated by the laboratories partners of the project in a significant number of cancer types.
It can be already envisaged that this instrument will be subject to an industrial phase in order to make a commercial product that will be requested by potential users of CGH.
This would contribute to palliate a main weakness of the european industry with respect to economical criteria and to feedback to advanced research technology, i.e.
the lack of integration between the microscope technology and the image processing technology.
Finally, we expect that CGH will have far reaching applications in tumor research and diagnostics, as well as in clinical cytogenetics.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Centre National de la Recherche Scientifique
Address
Rue De Sèvres
75743 Paris
France

Participants (11)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Route De Mende 1919
34293 Montpellier
Centre Médical Universitaire
Switzerland
Address
9,Avenue De Champel
1211 Genève
Centre National de la Recherche Scientifique
France
Address
Avenue De La Terrasse
91198 Gif-sur-yvette
Fundación Bosch i Gimpera de la Universidad de Barcelona
Spain
Address
643,Diagonal
08028 Barcelona
Hospital Duran I Reynals
Spain
Address
Ctra. Castelldefels K.m. 2.7
08907 Barcelona
IMPERIAL CANCER RESEARCH FUND
United Kingdom
Address
Lincoln's Inn Fields 44
WC2A 3PX London
Institute of Child Health
Greece
Address

11527 Athens
St Mary's Hospital Medical School
United Kingdom
Address
Norfolk Place
W2 1PG London
THE SCHOOL OF PHARMACY, UNIVERSITY OF LONDON
United Kingdom
Address
Brunswick Square 29-39
London
Universitaire Instelling Antwerpen - Universiteit Antwerpen
Belgium
Address
1,Universiteitsplein 1
2610 Wilrijk
Università Cattolica del Sacro Cuore
Italy
Address
Largo Francesco Vito 1
00168 Roma