For purposes of this example, assume that the user does not already have the human sequence of interest to hand. The first step will be to locate the human gene of interest using the UCSC Genome Browser. Begin by pointing to the UCSC Genome Browser home page, at http://genome.ucsc.edu. Select Human from the Organism pull-down menu and then click on Browser; both are located on the blue navigation bar at the left side of the page. This will take the user to the Human Genome Browser Gateway. Select the Nov. 2002 version of the UCSC genome assembly, type the gene symbol 'AGPS' into the position box, and then click Submit. On the resulting page, follow the link for AGPS in the Known Genes section.
The result of the search on AGPS is shown in Fig. 11.1. In the main figure are a series of 'tracks', which are labeled along the left-hand side. The Known Gene track is for AGPS, corresponding to the query. Clicking on AGPS returns a summary of information on that gene, including the full name of the protein product (alkylglycerone phosphate synthase precursor), a link to the GeneCards database at the Weizmann Institute20 and links to the translated protein, mRNA and genomic sequences. Focus now on the track labeled Mouse Cons. What is shown in this track is the conservation between the human and mouse genomes for 50bp windows in the human genome that have at least 15 bp aligned to mouse. Higher conservation scores are indicated as higher peaks on the Mouse Cons track. Note that many of the peaks coincide with exons in the AGPS gene, although some peaks are within introns. More details about this track can be found by clicking on the Mouse Cons hyperlink found below the main graphical display.
Figure 11.1
Click anywhere within the Mouse Cons track to view the details of the alignment (Fig. 11.2). This mouse genomic sequence is 279 nt in length and aligns with the human sequence in fifteen blocks. To view the alignment itself, click on the View details of parts of alignment within browser window link. On the resulting page (Fig. 11.3), the mouse sequence is shown on top, with the region of alignment in blue. The human genomic sequence is shown next, and a side-by-side alignment of the human and mouse sequences is at the bottom of the web page (not shown).
Figure 11.2
Figure 11.3
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Question 11 An investigator has identified and cloned a human gene, but no corresponding mouse ortholog has yet been identified. How can a mouse genomic sequence with similarity to the human gene sequence be retrieved?. Nat Genet 35 (Suppl 1), 63–65 (2003). https://doi.org/10.1038/ng1199
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DOI: https://doi.org/10.1038/ng1199
