Map Integration: From a Genetic Map to a Physical Gene Map and Ultimately to the Sequence Map

The full integration of the cytogenetic, genetic, and physical maps together with the search to identify all the genes of an organism and the effort to position them on the corresponding integrated map, has long been a key issue in genetics. In all three fields of mapping, enormous progress has been made over the past two decades through either the development of new reagents or innovations in technology. The use of sequence tag sites (STSs) as markers (1 ) however, could be singled out as the major tool toward map integration. Currently, genetic maps of complex genomes such as the human, mouse, and rat (2 –4 ) are all based on microsatellite STS markers, also referred to as single sequence length polymorphisms, which in turn have been used to isolate yeast artificial chromosome, bacterial artificial chromosome (BAC), or P1 artificial chromosome (PAC) clones and build physical maps at increasing levels of resolution (5 –8 ). The construction of high-resolution physical maps has also been accelerated by the use of whole genome radiation hybrid (RH) mapping (9 ). RH mapping provides a means to localize any STS to a defined map position in the genome, by the use of polymerase chain reaction (PCR). Thus, STS-based markers provide a means to integrate genetic (2 –4 ), RH (4 ,10 –12 ), and clone maps (5 –8 ). EST-based STS markers have also been used to integrate the genetic, physical, and transcript maps by means of RH (6 ,10 –11 ,13 ) and/or landmark contig (i.e., a set of overlapping clones) mapping.