QTL Hotspot on Mouse Distal Chromosome 1 Figure 4. Segregation of trans-QTLs in Qrr1. Expression of Atp5j2, Cplx2, and Nars are modulated by trans-QTLs in Qrr1 (blue plot). D allele has the positive additive effect (green plot; allele effect scale shown on the right) on the expression of Atp5j2 and Cplx2; peak LOD scores are on markers near candidate genes Ndufs2 and Kcnj10. B allele has the positive additive effect (red plot) on the expression of Nars; peak LOD score is on markers near candidate gene Fmn2. The horizontal lines indicate the genome-wide significant thresholds (p-value = 0.05). Yellow seismograph tracks the SNP density between B and D alleles. Affymetrix probe set ID for each transcript in the BXD hippocampus dataset is shown. doi:10.1371/journal.pgen.1000260.g004 set and B6D2F2 intercrosses—and in the B6 and C3H intercrosses. The feature is much weaker in the large LXS RI set and in the small CXB panel. The effect specificity demonstrates that a major source of the Qrr1 signal is generated by variations between B and D, and B and C3H alleles (H) but not by variations between the ILS and ISS alleles (L and S, respectively), and B and BALB alleles (C). This contrast can be exploited to identify sub- regions that underlie the trans-QTLs [67]. SNPs were counted for all four pairs of parental haplotypes—B vs D, B vs H, B vs C, and L vs S—and SNP profiles for the four crosses were compared (figure 6). Qrr1 is a highly polymorphic interval in the B66D2 crosses. The flanking regions, however, have few SNPs (170–172.25 Mb proximally, and 177.5–179.5 Mb distally) and are almost identical-by-descent between B6 and D2. The B66BALB crosses, despite being negative for the trans-effect, have moderate to high SNP counts in Qrr1 and share a SNP profile somewhat similar to B66D2 crosses. The B66C3H crosses also have moderate to high SNP counts in Qrr1, with a relatively higher SNP count in Qrr1d compared to Qrr1p. In contrast, in the LXS, Qrr1p is more SNP-rich than Qrr1d. Most notably, the segments that harbor the tRNAs and candidates Fmn2, Grem2, and Rgs7 are almost identical by descent between ILS and ISS. This SNP PLoS Genetics | www.plosgenetics.org 8 November 2008 | Volume 4 | Issue 11 | e1000260