The rat is a useful and sometimes unique model for the study of many physiological traits and diseases.
In contrast to its central role in physiology, biochemistry, toxicology, transplantation research, cancer research, neurobiology and other fields, the rat has lagged behind the mouse as a genetic model organism. Molecular biology has catalysed the convergence of physiology and genetics, and consequently there is an increasing need for genetic studies in the rat. In the past few years there has been very significant progress in rat genome analysis. While almost no reliable gene assignment was available in the early 80'es, some 600 rat genes have now been assigned to specific chromosomes, and a genetic map with some 650 markers is also available. Teams participating in the present project have been intimately involved in this development, contributing about half of the chromosome assignments and also to the construction of the linkage maps. Furthermore, the participating teams have developed the only existing international rat genetic database (RATMAP). Thus European teams have a strong tradition in rat gene mapping, and our proposal is to generate mapping resources and information necessary to take advantage of the rat for the identification of genes underlying traits relevant to mammalian physiology, behaviour and complex disease, such as diabetes, hypertension, susceptibility to cancer or stress, drug addiction etc.
The genetic basis of such traits could be understood if the rat genome was better known.
The proposed project contains two parts: mapping the rat genome on the one hand and analysis of multifactorial traits on the other.
The mapping work will include:
- genetic linkage work of transcribed genes,especially "anchored reference loci" for comparative mapping, and of anonymous markers, using molecular methods that have already been implemented in the participating labs, and with rat strains and strain crosses already available, generation of new markers (e.g. AFLP, RAPD)
- chromosome and cytogenetic mapping of genes using cell hybrids and fluorescence in situ hybridization (FISH), including orientation of the linkage groups with respect to the chromosomes and amalgamation of the genetic linkage and the cytogenetic maps
- isolation of whole genome radiation hybrids to generate a high resolution map of active genes, even if they are devoid of genetic polymorphism - construction of new genomic DNA libraries
- ensuring availability of the generated data as well as those linkage data disseminated in the literature to the scientific community via expansion of the already implemented rat genome database and the rat encyclopedia which is being implemented.
The analysis of multifactorial traits will deal with cancer, neurological and psychiatric disorders, autoimmune diseases and the dissection of the rat MHC, metabolic studies, hypertension and morphogenesis. This work will be greatly facilitated by the collaborations established within the proposed project, and by the flow of new information among the groups.
Funding SchemeCSC - Cost-sharing contracts
128 00 Praha 2
142 20 Praha 4