MoKa - Molecular Karyotyping

From 01-10-2007 to 30-09-2011

Description

This research proposal aims to push the technical limits of Array CGH.  By advancing the potential of molecular karyotyping, both by improving technology and data analysis 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.
These advances will not only enable to answer new basic questions, but change human genetic diagnosis.  Single cell array CGH analysis will improve preimplantation genetic diagnosis and possibly the diagnosis of certain types of tumors. Mosaicism detection will influence and change the fields of prenatal and postnatal diagnosis of constitutional and acquired disorders. It is well known that epigenetic processes play an important role in both constitutional and acquired diseases. The potential of arrays to get a genomewide overview of epigenetic changes might be tremendous. In particular, for the diagnosis of several types of cancers, the lack of a genomewide screening tool has been limiting the diagnostic potential. Finally, we foresee that the huge amount of novel (biological) information coming from these analyses will require bioinformatics approaches to aid clinicians and laboratory directors in decision making and help researchers in understanding their findings. Since each application might use the different proposed technological fields, data storage, visualization and analysis tools will be shared among applications.

Team

• Yves Moreau, Co-promoter
• Joris Vermeesch, Promoter (External)
• Bert Coessens, Team member
• Steven Van Vooren, Team member

Financing

Funding: IWT - Agentschap voor Innovatie door Wetenschap en Technologie 

Program/Grant Type: IWT SBO - IWT Projects Strategic Basic Research