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We have used comparative genome analyses to produce annotated maps for large genomic loci. The first example is a locus on mouse chromosome 9 that is syntenic to human chromosome 15. This effort relied on draft sequences from the human genome project, our own draft sequences from mouse genomic UNA, and, more recently, from the mouse genome project. Our strategy used reiterative searches of UNA, protein, STS and EST databases, as well as genome maps. In this fashion, we were able to assemble sequence contigs over a large region that comprises 14 genes. We present our framework for data interpretation and demonstrate that unfinished sequences can be used to assemble maps of complex genomic loci with good accuracy. By focusing on one model locus, we discuss limitations and advantages of this approach and provide criteria for the implementation of automated genome annotation strategies.