THE DETAILED CHARACTERIZATION OF A 400-KB COSMID WALK IN THE BRCA1 REGION - IDENTIFICATION AND LOCALIZATION OF 10 GENES INCLUDING A DUAL-SPECIFICITY PHOSPHATASE

We have produced a detailed physical and transcriptional map of a 400 kb region within the narrowest flanking markers known to contain the h ereditary breast and ovarian susceptibility gene, BRCA1. The approach described here has avoided the problems of chimaerism, instability and rearrangements commonly observed in yeast artificial chromosomes by c onverting the YAC clones into ordered chromosome 17-specific cosmid co ntigs and joining these contigs by cosmid end-walking. A detailed long -range restriction map provided a framework for the cosmid contig asse mbly and further refines existing physical mapping data. We have used a combined approach towards the isolation of the genes housed within t hese cosmids. This has resulted in the isolation and precise localisat ion of eight novel genes, including a novel G protein and an endogenou s retrovirus related to the HERV-K family, and the previously describe d dual-specificity VHR phosphatase and MOX1 homeobox genes.