Facilitating haplotype analysis by fully automated analysis of all chromosomes in human-mouse hybrid cell lines

Recent evidence suggests that haplotype analysis is essential in recognizing genetic factors involved in the tendency toward a particular disease or pharmacogenetic phenotype, as well as to identify genes involved in multigenic disorders. Because of the increasing need for efficient haplotype tests, a new hybrid system, called conversion technology, was developed. Conversion technology aims at converting the diploid chromosome content into a haploid state so that hybrids contain a single copy of any desired chromosome. A number of mutations can now be identified easily, as they are no longer obscured by the normal sequence present on the other copy of the chromosome. However, the efficient use of this hybrid system depends on a complete analysis of both human and mouse chromosome complements in order to assess the stability of the hybrid cells and to accurately determine their human chromosome content. We describe a new multicolor FISH-based method capable of analyzing both genomes simultaneously in a single hybridization. This new technique should become an instrumental part of inexpensive, reliable haplotype tests.