A User's Guide to the Human Genome. Question 12. How does a user find characterized mouse mutants corresponding to human genes?

The NCBI provides a set of maps that show chromosomal regions homologous between mouse and human. This resource can be accessed directly at http://www.ncbi.nlm.nih.gov/Homol-ogy/. For this example using a known, mapped human gene, however, it is easier to start the search from the LocusLink entry for tyrosinase. The LocusLink 10 query page can be found at Human from the Organism pull-down menu, enter 'tyrosinase' into the Query box and click Go. To view the entry for tyrosinase (TYR), click on its LocusLink ID, 7299. On the resulting page (Fig. 12.1), links to the mouse homology maps are in the section of the LocusLink summary page marked Relationships. In this case, there are four maps available for TYR showing mouse alignments: NCBI vs MGD aligns the current NCBI assembly of the human genome with the MGD (Mouse Genome Database 21 , at The Jackson Laboratory) genetic map, UCSC vs. MGD aligns the current UCSC genome assembly with the MGD genetic map, NCBI vs. EST-based RH Map aligns the NCBI assembly with the Whitehead–MRC RH map, and UCSC vs. Hudson et al. aligns the 7 October 2001 UCSC assembly with the Whitehead–MRC RH Map 22. The Hs and Mm links adjacent to each map name show the mouse–human homology map with the master chromosome as human or mouse, respectively. Click on the Hs link next to the NCBI vs. MGD map. The resulting mouse–human map shows the mouse genes that are the likely orthologs of human genes on human chromosome 11 (Fig. 12.2). Depending on the browser being used, one may have to click the View as text box to obtain the output; the resulting output will appear in text format, slightly different from what is shown in Fig. 12.2. Chromosomal locations of the mouse genes are shown, where known. The green circles link to the UniSTS entry for each locus; those on the left link to the human UniSTS entry, whereas those on the right link to the mouse UniSTS entry. The cytogenetic positions are hyperlinked to either the human or mouse Map Viewer, as appropriate. Gene symbols are linked to LocusLink 10. The tyrosinase gene, highlighted in pink, maps to mouse chromosome 7 at 44 cM, a piece of information that will be needed in the next step. The mouse models themselves are described at the Mouse Genome Informatics site at the Jackson Laboratory. Go to the Mouse Genome Informatics …