Functional Analysis of Genetic Determinants of Human Disease

Geoff Hicks
Manitoba Inst. Cell Biology/U Manitoba
Rm ON5029
675 McDermot Ave
Winnipeg, MB R3E 0V9
Canada
telephone: 204-787-2133
fax: 204-787-2190
email: hicksgg@cc.umanitoba.ca
prestype: Platform
presenter: Geoff Hicks

The Manitoba Institute of Cell Biology Centre for Mammalian Functional Genomics (MFG) uses a novel form of gene trapping called Tagged-Sequence Mutagenesis (TSM). Through random insertion of a gene-trap vector into the genome, genes are both tagged and invariably mutated. Each mutation is studied first by direct DNA sequencing. Comparison of the sequence tags (PSTs) with the existing databases identifies disruptions of known genes or genes which may be related by homology or functional domains. As a result, ES cell lines bearing disruptions in genes of particular interest can be studied directly or used for making mutant mice. ES cells lines will be made available to the academic community at large. The MFG database currently being developed, <www.EScells.ca>, will ensure widespread public access to this resource. The Centre is also integrated with the International Gene-Trap Consortium. Future developments will focus on high throughput sequence-based screens to generate ES cell libraries for cell-type specific gene expression, and for generation of hyper- and hypo-morphic mutations. It is hoped that this resource will significantly impact on the accessibility of genetic modeling in mice to understand gene function within the context of the whole organism – a context that is critical for assessing the role of genetic determinants of disease.