QTL Hotspot on Mouse Distal Chromosome 1 Figure 6. SNP comparison between crosses. SNPs in Qrr1 were counted for (A) C57BL/6J (B6)6DBA/2J (D2), (B) B66BALB/cBy (BALB), (C) B66C3H/HeJ (C3H), and (D) ILS6ISS. The SNP distribution profiles were generated by plotting the number of SNPs in 250 kb bins. Vertical red lines mark the approximate positions of recombination (corresponds to figure 2). Region covered by Qrr1p (horizontal line), candidate genes in Qrr1d (yellow bars), and position of tRNA clusters (triangles) are shown above the graphs. The B66D2, B66BALB, and B66C3H crosses have moderate to high SNP counts throughout Qrr1. In the ILSxISS cross, Qrr1p is relatively SNP-rich but Qrr1d is SNP-sparse. doi:10.1371/journal.pgen.1000260.g006 Both Fmn2 and Rgs7 are almost exclusively expressed in the CNS and are high priority candidates for the CNS specific trans- QTLs. A point of distinction between the two candidates is that while expression of Rgs7 maps as a cis-QTL only in the B66D2 and B66C3H crosses, expression of Fmn2 maps as a cis-QTL in B66D2 and B66C3H crosses, and in the CXB RI strains in which the trans-effect is not detected (table 3). Based on the pattern of specificity of cis-QTLs in multiple crosses, Rgs7 is a more appealing candidate. However, Fmn2 has known missense SNPs that segregate in the B66D2 (Glu610Asp, Pro1077Leu, Asp1431Glu) and B66C3H crosses (Val372Ala). There are no known missense mutations in Fmn2 in the CXB and LXS RI strains, and no known missense mutation in Rgs7 in any of the four crosses. Partial Correlation Analysis Linkage disequilibrium (LD) is a major confounding factor that limits fine-scale discrimination among physically linked candidates in a QTL. To further evaluate the two high-priority candidates in PLoS Genetics | www.plosgenetics.org 10 November 2008 | Volume 4 | Issue 11 | e1000260