The rat remains a major model for biomedical research within both academia and industry. The strength of the rat is the long history of physiological, pharmacological, and biochemical studies that characterizes this model system. However, until recently the rat has not been a major """"""""genetic system."""""""" With the success of the Human Genome Project in mapping and identifying genes responsible for monogenic diseases, there has been a shift towards the multifactorial disorders. The rat offers a distinct advantage in that there are more than 140 inbred strains of rats, most of which are model systems for these multifactorial disorders (1). The broad utility of the rat is perhaps best illustrated by the large number of NIH Institutes, Centers and Office of the Director that provide the support for the rat genome project and this RFA. Generation of a cDNA or expressed sequence tag sites (ESTs) project will further accelerate the development of the rat as a """"""""genetic system"""""""". In order to make the ESTs useful to the whole research community, the ESTs need to be arrayed, sequenced and attached to the rat gene map. With a large number of genes and ESTs mapped a conserved gene order map is derived linking the rat genome to the genomes of the human and the mouse, in which the sequence and therefore all the genes are known. Using the principles of conserved gene order between mammalian species, investigators can use this gene order as the first approximation of the gene order in the rat. For example, there are 181 conserved linkage groups between mouse and human (2). I. COMPLETE THE FRAMEWORK MAP OF THE RAT RADIATION HYBRID (RH) PANEL AND MAP A SUBSET OF ESTs. In order for the rat radiation hybrid (RH) panel to be useful as a general mapping tool, a framework map is required. The investigators will begin by II. TO ARRAY AND SEQUENCE A KIDNEY EST LIBRARY. In year 1, while the other Centers that are sequencing ESTs are coming on-line, the investigators will complete their kidney EST sequencing project using the rat cDNA library from Dr. M. Bento Soares.
|Kwitek, Anne E; Gullings-Handley, Jo; Yu, Jiaming et al. (2004) High-density rat radiation hybrid maps containing over 24,000 SSLPs, genes, and ESTs provide a direct link to the rat genome sequence. Genome Res 14:750-7|
|Twigger, Simon N; Nie, Jeff; Ruotti, Victor et al. (2004) Integrative genomics: in silico coupling of rat physiology and complex traits with mouse and human data. Genome Res 14:651-60|
|Steen, R G; Kwitek-Black, A E; Glenn, C et al. (1999) A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat. Genome Res 9:AP1-8, insert|