The detailed characterisation of a 400 kb cosmid walk in the BRCA1 region: identification and localisation of 10 genes including a dual-specificity phosphatase

Abstract

We have produced a detailed physical and transcriptional map of a 400 kb region within the narrowest flanking markers known to contain the hereditary 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 converting the YAC clones into ordered chromosome 17-specific cosmid contigs and joining these contigs by cosmid end-walking. A detailed long-range restriction map provided a framework for the cosmid contig assembly and further refines existing physical mapping data. We have used a combined approach towards the isolation of the genes housed within these cosmids. This has resulted in the isolation and precise localisation of eight novel genes, including a novel G protein and an endogenous retrovirus related to the HERV-K family, and the previously described dual-specificity VHR phosphatase and MOX1 homeobox genes.