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Content archived on 2024-05-29

AnEUploidy: understanding the importance of gene dosage imbalance in human health using genetics, functional genomics and systems biology

Objective

Aneuploidy refers to abnormal copy number of genomic elements, and is one of the most common cause in morbidity and mortality in human populations. The importance of Aneuploidy is often neglected because most of its effects occur in the embryonic and fetal period. The prototype of extra genomic material is trisomy 21 (Down syndrome), and some common microdeletion syndromes are the models of monosomies. It is likely that numerous other unknown pathologic conditions (including common phenotypes) are due to segmental aneuploidies. In addition, an extensive variability of the copy number of numerous genomic regions is polymorphic in human populations. Aneuploidy is related to gene expression perturbation and abnormalities, but the molecular pathogenesis of the numerous aneuploid disorders is largely unknown.

This grant proposal has the ambitious goals of contributing to the understanding of the molecular basis and pathogenetic mechanisms of aneuploidies. The experimental strategies proposed use the recent achievements of human genome sequencing, comparative genome analysis, genome variation, mouse transgenesis, technological platforms for transcriptome and genotypic analysis, bioinformatics tools, and systems biology.

The specific goals of this interdisciplinary project are to: i) link abnormal phenotypes with gene copy number alterations; ii) identify novel conditions due to aneuploidy; iii) study the gene overexpression and transcriptome dysregulation in mouse embryonic stem cells; iv) produce and study mouse models of aneuploidy; v) identify functional genomic elements that are important for aneuploidy; v) integrate and interpret the results of genome dysregulation.

In addition, this proposal builds on the excellence and competitiveness of European laboratories in the field of Aneuploidy. The deliverables of this proposal will build a knowledge infrastructure that will benefit millions of Europeans and their families affected by the consequences of Aneuploidy.

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Call for proposal

FP6-2005-LIFESCIHEALTH-6
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Coordinator

UNIVERSITY OF GENEVA
EU contribution
No data
Address
Rue du General-Dufour 24
GENEVA
Switzerland

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Total cost
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Participants (15)