Figure 17 of Geisert, Mol Vis 2009; 15:1730-1763.


Figure 17. Corneal QTL networks identified using variation in Aldh3a1 expression level. Notice the distinct vertical QTL bands shared by nearly all transcripts. Chromosomes are numbered at the bottom. Above the red line are transcripts that correlate with the expression of Adh3a1. Below the red line are transcripts and genes associated with strong cis QTLs that may cause the transband on distal Chr 1. These genes include Cenpf, Nek2, Slc30a1, Traf5, Rcor3, Kcnh1, and G0s2. Notice that two of these transcripts (Cenpf and Nek2) have the same banding pattern as well known corneal signature genes (above the red line). Cenpf and Nek2 are therefore particularly good candidates that may control expression of the corneal network. How to examine a region of a chromosome (Chr 1) to define candidate genes: 'The Advanced Search' function as described in Figure 2 illustrates complex searches that can be used to find probe sets with low expression, but good signal-to-noise ratio. The Advanced Search query is a string of search parameters that first limits the search to genes with a significant QTL. The first command entered into the ANY box is LRS=(20 200). This limits the search to genes with LRS scores between 20 and 200; thus search results identified 6,451 probe sets. When you run this search an error message occurs indicating that you have generated a list of over 2,000 genes and request that you modify the search to generate a list of fewer than 2,000 genes. Ignore this message and modify the search to limit it to genes within the immediate vicinity of the peak LSR score. The next command cisLRS=(20 200 20) will limit the search to significant LRS scores where the gene lies within 20 Mb of the peak LRS score. Within the HEIMED there are 4,580 probe sets that meet this criterion. The results of this search also generate an error because over 2,000 probe sets were found. Finally, the last command limits the genomic region to distal Chr 1 using Mb=(Chr1 190 200). This search produces 117 probe sets. Finally, if we combine all these search criteria as LRS=(20 200) CisLRS=(20 200 20) mb=(chr1 190 200), the result is 18 probe sets. These candidate genes include Cenpf, Nek2, Slc30a1, Traf5, Rcor3, Rd3, Kcnh1, and G0s2. Select these genes by clicking on the box next to their probe set and select 'Add to Collection'. At the BXD Trait Collection page you will find a list of the genes’ probe sets. Click the 'Select All' button and then select the 'QTL Heat Map' function. The QTL Heat Map will compute two transcripts, Cenpf and Nek2, which have a similar QTL signature as Aldh3a1.