It is the long term goal of this research to develop a method of orderly segmenting the human genome into 1-50 Mb fragments. This objective can be achieved by streamlining the screening process of hybrid clones generated by chromosome fragment gene transfer (CFGT). The most expeditions screening process is one which includes a dominant selectable marker near the locus of interest. Homologous recombination will be used to direct a dominant selectable marker to a specific chromosomal location allowing the targeted to become phenotypically selectable. Cells containing a correctly targeted dominant marker are an ideal donor source for Goss-Harris hybrids. The transgenomes produced by this approach will be valuable reagents for molecular and medical genetic research. They will allow for a rapid means of saturating a locus with genetic markers. In addition, the resulting enrichment of a targeted genetic disease locus will facilitate the identification of the responsible defect. At the genome level, a set of targeting vectors, each directed to chromosomal locations separated by 10-20 Mb, could generate an ordered set of "transgenome". These reagents would enhance current and future human genome mapping efforts.