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Project: Array comparative genomic hybridization (Array CGH)

project duration
01/10/07 – 30/09/11
abstract
Array comparative genomic hybridization (array CGH), also called molecular karyotyping, uses microarray technology (high-density DNA probes on a solid surface) to detect in parallel whether any of several thousands of chromosomal fragments are deleted or duplicated in a genomic DNA sample, Array CGH can thus idenify chromosomal abnormalities in patients with constitutional or acquired disorders and in embryos. This research proposal aims to push the technical limits of this novel technology. By advancing the potential of molecular karyotyping, both by improving technology and data anlysis methods, we will create novel applications in research as well as novel possibilities for genetic diagnosis. First, we will develop genomewide analysis of genomic imbalances from a single cell. This will allow us to answer long standing questions about early embryogenesis and tumor development. Second, we will push back the limits of the technology to detect low-grade mosaicisms, which are genetic imbalances in only a fraction of a mixture of cells. This in turn will allow us to investigate fetal DNA in the maternal plasma as well as improved analysis of tumors, lymphomas and leukemias and probing potentially undetected causes of recurrent miscarriages and subfertility. Third, we will investigate the role of epigenetic phenomena in X-linked chromosomal anomalies, constitutional anomalies, and cancer. Finally we will maximize the effectiveness of these advances in array CGH by developing novel data-interpretation methods. Statistical approaches, data storage and vizualisation tools developed in each of these domains wil cross-fertilize the advances in the other domains.