Sex Specific Gene Regulation . ... Table 2. Correlations of expression data for chromosome 1 hotspot cis eQTLs with 308 trans eQTLs in males. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... Probe mega- Marker mega- Average ...Probe base base LOD Correlation (R) Gene Name Description . ... 1435475_at 36.37 46.54 10.71 0.30 Lman2l lectin, mannose-binding 2-like . ... 1417293_at 36.01 48.59 6.36 0.29 Hs6st1 heparan sulfate 6-O-sulfotransferase 1 .... 1416931_at 58.39 52.97 8.43 0.26 Nif3l1 Ngg1 interacting factor 3-like 1 (S. pombe) ... 1459679_s_at 51.69 51.87 7.60 20.24 Myo1b myosin IB . ... 1436984_at 60.42 58.35 14.01 20.24 Abi2 abl-interactor 2 . ... 1434422_at 57.33 58.35 8.18 0.23 Unknown Unknown ... 1434303_at 60.43 48.59 9.90 20.21 Raph1 Ras association (RalGDS/AF-6) and pleckstrin homology domains 1 . ... 1428425_at 42.99 48.59 7.60 0.21 Tgfbrap1 transforming growth factor, beta receptor associated protein 1 . ... 1421982_a_at 37.37 55.71 6.60 20.21 Unc50 unc-50 homolog (C. elegans) . . .. (Only probes with average expression value greater than 150 used in correlations) . .. doi:10.1371/journal.pone.0001435.t002 . ... Table 3. Correlations of expression data for chromosome 16 hotspot cis eQTLs with 379 trans eQTLs in males. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...Probe Probe mega-base Marker mega- base LOD Average Correlation (R) Gene Name Description . . ... 1435969_at 3.89 7.64 6.09 0.34 Btbd12 BTB (POZ) domain containing 12 .... 1435439_at 18.17 7.64 5.55 0.31 Dgcr8 DiGeorge syndrome critical region gene 8 ... 1437524_x_at 4.54 5.27 8.92 20.22 Coro7 coronin 7 . . . .. doi:10.1371/journal.pone.0001435.t003 . ... Table 4. eQTLs shared by male and female F2 mice. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... Count Ave. LOD female Ave. LOD male % female shared % male shared . . ... LOD 3.0 .... Total shared eQTLs 1,599 10.31 13.17 17.2 13.0 ... Cis shared eQTLs 1,285 (80.2%) 10.47 11.90 69.1 64.6 . ... Trans shared eQTLs 71 (4.6%) 4.07 4.13 1.2 0.82 .... Ambiguous shared eQTLs 243 (15.2%) 11.35 12.70 18.2 13.9 ... LOD 4.3 . ... Total shared eQTLs 1,151 12.65 14.36 52.9 38.5 . ... Cis shared eQTLs 965 (83.8%) 12.45 14.09 73.1 66.8 .... Trans shared eQTLs 9 (0.8%) 5.97 6.82 1.7 0.83 ... Ambiguous shared eQTLs 177 (15.4%) 14.05 16.21 53.6 38.6 . . .. . doi:10.1371/journal.pone.0001435.t004 males, respectively), indicating that most of these ambiguous eQTLs were actually cis eQTLs, but their probes were not uniquely assigned to the mouse genome (Supplemental Table S6). Significant eQTLs We repeated the eQTL analysis using a significant LOD threshold of 4.3, yielding a nominal p value of 561025 [16]. Permutation analysis revealed that the LOD 4.3 threshold yielded a genome wide p-value of 0.02 in both males and females. In the females, 2,177 eQTLs met this LOD threshold, with 1,321 cis eQTLs, representing 61% of the total eQTLs, and 526 trans eQTLs, representing 24% of the total eQTLs (Table 1). There were also 330 ambiguous eQTLs (15% of the total eQTLs) that had a very high average LOD score of 10.13. Again, this indicates that the majority of these ambiguous eQTLs were actually due to strongly associated cis eQTLs, but their probes were not uniquely assigned to the mouse genome. Of the suggestive female cis eQTLs that met the LOD.3.0 threshold, 71% met the LOD 4.3 threshold cutoff, while only 8.6% of the female suggestive trans eQTLs were maintained at this LOD stringency, again indicating the relative strength of the cis eQTLs compared to the trans eQTLs. In the males, 2,988 eQTLs met the LOD 4.3 threshold that mapped to the autosomes and the X chromosome, with 1,445 cis eQTLs, representing 48% of the total eQTLs, and 1,086 trans eQTLs, representing 36% of the total eQTLs (Table 1). There were also 457 ambiguous eQTLs (15% of the total eQTLs) that had a very high average LOD score of 9.6. Of the suggestive male cis eQTLs that met the LOD.3.0 threshold, 73% met the LOD 4.3 threshold cutoff, while only 13% of the trans eQTLs were maintained at this LOD stringency. There were also 334 male eQTLs that mapped to the Y chromosome that met the LOD 4.3 threshold, with 30% of the LOD 3.0 threshold trans eQTLs PLoS ONE | www.plosone.org 4 January 2008 | Issue 1 | e1435