Comparative Genome Mapping in the Sequence-based Era: Early Experience with Human Chromosome 7

The rapid advances and monumental achievements of the Human Genome Project are igniting a new era in biomedical research. The availability of the complete genomic sequence for the model organism Caenorhabditis elegans (The C. elegans Sequencing Consortium 1998), in conjunction with the impending completion of the Drosophila and human genomic sequences, provides an unprecedented view of the genetic essence of multicellular organisms. In the coming century, interpretation and utilization of complete genome sequences will provide new insights into old problems and inspire the development and testing of novel hypotheses. Adapting to a scientific environment with such rapidly changing and powerful new resources presents a significant but rewarding challenge to those studying biology. Genome mapping is historically dependent on species-specific resources and reagents as well as species-independent technologies. For instance, genome mapping in mouse has been performed principally with genetic mapping methods using inbred strains (Reeves & D'Eustachio 1999). This valuable mouse-specific resource combined with technological advances (e.g., PCR) has increased the number of available genetic markers (Dietrich et al. 1992; Dietrich et al. 1994; Dietrich et al. 1996) and the rate at which they can be assembled into maps. The recent development of radiation hybrid mapping (Cox et al. 1990; Matise et al. 1999) and markers that are conserved between species (Lyons et al. 1997) reduces the dependence on species-specific resources, thereby increasing the number of genomes amenable to systematic mapping. The complete sequence of the human genome will provide a reference vertebrate ‘genetic blueprint’ and, as such, should accelerate the mapping of other genomes. Here we provide a general overview of the approaches we are developing and implementing to exploit available human genomic sequence for the purpose of mapping a related mammal, the mouse. Importantly, our preliminary results demonstrate how genomic sequence greatly enhances comparative genome analyses.