The fusion of somatic cells from different species to create somatic cell hybrids has provided an exceptionally useful tool for mapping of genes to particular chromosomes because the chromosomes of one species are always progressively lost in such interspecific somatic cell hybrids (1). Using hybrid cell lines, it is also possible to use recognizable chromosome breakpoints to localize genetic loci more accurately. This process is greatly facilitated by inducing chromosome breaks with radiation (2). This technique uses a somatic cell hybrid between a rodent and a human cell that contains a single human chromosome, all of the rodent chromosomes, and a selectable marker that confers resistance to the antibiotic neomycin. The chromosomes in this hybrid cell line are fragmented by irradiation such that cell death normally occurs. However, the irradiated hybrid cell line is rescued by fusion with another rodent cell line that is neomycin-sensitive. Growth in neomycin allows selection to operate in favor of the resulting radiation hybrid cell lines, rather than the neomycin-sensitive unfused cell line. Fragments of the human chromosomes are retained and incorporated into the rodent cell chromosomes. The different radiation hybrid cell lines generated in this way can be examined for the presence or absence of molecular markers from the human chromosome.
The production of radiation hybrids has provided a useful methodology for mapping how close genes are in the human chromosome. Two genes that are close together remain together following radiation, whereas those that are far apart are separated. By estimating the frequency of separation, it is possible to build up a physical map of the chromosome providing gene order and distance (3).
