PRINCIPLES AND PITFALLS OF RADIATION HYBRID MAPPING

Department of Veterinary Pathobiology, Texas A&M University, College Station, TX 77843 USA

Recently rediscovered, radiation hybrid (RH) mapping is a powerful tool for mammalian genomics. It is applicable to any species for which somatic hybrid cells can be made and provides a most efficient route to the production of ordered maps containing nonpolymorphic or minimally polymorphic markers. Thus, it has become the method of choice for mapping expressed sequence tags (ESTs), and is equally if not even more valuable as a comparative mapping tool. We have used a bovine RH panel to construct ordered comparative maps of several bovine and human chromosomes and have defined rearrangement of gene order within segments of conserved synteny. Such parallel RH maps will be an important intermediate in the use of human genome data for comparative candidate positional cloning of bovine genes. We are in the early stages of building cattle transcript maps on the same framework. RH maps are effective for merging different linkage maps with each other and with sequences representing known genes or transcripts. The resolution attained by RH mapping is dependent on a number of factors beginning with frequency of retention of fragments of the donor genome in a given panel. We have found that retention of fragments is not consistent for all chromosomes. Typing errors lead to discrepencies in map order and therefore duplication of marker typing is essential. Despite these and other potential hazards, RH mapping is an extremely valuable tool for building ordered maps regardless of polymorphism and should be incorporated into strategies for mapping the genome of the horse as well as other domestic animals.