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Definition of a genetic network involved in congenital heart disease

Objective

This application focuses on transcriptional networks that govern the development of a heart region commonly affected by congenital heart disease (CHD). The major goal is to provide the clinical and basic science research communities with a validated list of interconnected genes required for normal heart development. To achieve this goal, we have recruited 6 European groups of scientists strongly committed to CHD research. The participants bring to the consortium significant resources and credible synergy. The entry point for the interrogation and perturbation of cardiogenic gene networks will be the transcription factor Tbx1, the major gene for 22q11.2 deletion syndrome, a common genetic cause of CHD. The project has three specific aims: 1) To define the roles and interactions of T-box transcription factors in cardiac outflow tract (OFT) development. Our hypothesis is that a critical balance of Tbx1, 2, and 3 is required to regulate homeostasis of a specific population of cardiac progenitors and their interactions with non-cardiogenic cells. 2) To define gene networks perturbed in OFT developmental defects. Innovative approaches will identify the transcriptional targets and protein interactors of Tbx1. Candidate genes will be validated in vitro and in vivo using mouse and zebrafish models. In addition, we will perform extensive transcriptome analyses using biopsy material from CHD patients in order to integrate animal and patient data. 3) To integrate gene expression, cell lineage distribution and phenotype data. Normal heart morphology is achieved through a concerted gene expression program and the integration of molecular signals and tissue interactions. Aided by 3-dimensional reconstruction of gene expression patterns and phenotypic information, we will integrate different types of data to develop models of CHD pathogenesis. Teamwork will be enhanced by shared technologies that provide homogeneity and comparability of data between the participating labs.
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Coordinator

FONDAZIONE TELETHON

Address

Via Varese 16/B
00185 Roma

Italy

Activity type

Research Organisations

EU Contribution

€ 667 502

Administrative Contact

Irene Mearelli (Ms.)

Participants (6)

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UNIVERSITY COLLEGE LONDON

United Kingdom

EU Contribution

€ 485 280

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM

Netherlands

EU Contribution

€ 473 877

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

United Kingdom

EU Contribution

€ 322 415

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France

EU Contribution

€ 471 644

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany

EU Contribution

€ 217 001,46

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Germany

EU Contribution

€ 42 280,54

Project information

Grant agreement ID: 223463

Status

Closed project

  • Start date

    1 March 2009

  • End date

    28 February 2013

Funded under:

FP7-HEALTH

  • Overall budget:

    € 3 929 129,91

  • EU contribution

    € 2 680 000

Coordinated by:

FONDAZIONE TELETHON

Italy