Comparative physical mapping of targeted regions of the rat genome

The comparative mapping and sequencing of vertebrate genomes is now a key p riority for the Human Genome Project. In addition to finishing the human ge nome sequence and generating a 'working draft' of the mouse genome sequence , significant attention is rapidly turning to the analysis of other model o rganisms, such as the laboratory rat (Rattus norvegicus). As a complement t o genome-wide mapping and sequencing efforts, it is often important to gene rate detailed maps and sequence data for specific regions of interest. Usin g an adaptation of our previously described approach for constructing mouse comparative and physical maps, we have established a general strategy for targeted mapping of the rat genome. Specifically, we constructed a framewor k comparative map of human Chromosome (Chr) 7 and the orthologous regions o f the rat genome, as well as two large (>1-Mb) P1-derived artificial chromo some (PAC)-based physical maps. Generation of these physical maps involved the use of mouse-derived probes that cross-hybridized with rat PAC clones. The first PAC map encompasses the cystic fibrosis transmembrane conductance regulator gene (Cftr), while the second map allows a three-species compari son of a genomic region containing intra- and inter-chromosomal evolutionar y rearrangements. The studies reported here further demonstrate that cross- species hybridization between related animals, such as rat and mouse, can b e readily used for the targated construction of clone-based physical maps, thereby accelerating the analysis of biologically interesting regions of ve rtebrate genomes.