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Adipose Liver Muscle Brain Adipose Liver 30 8 25 6 20 LOD 15 LOD 4 10 2 5 0 0 1 2 3 4 5 6 7 8 9 10111213141516171819X 1 2 3 4 5 6 7 8 9 10111213141516171819X Chromosome Chromosome Muscle Brain 60 30 50 40 20 LOD LOD 30 20 10 10 0 0 1 2 3 4 5 6 7 8 9 10111213141516171819X 1 2 3 4 5 6 7 8 9 10111213141516171819X Chromosome Chromosome Supplementary Figure 1. Bicc1 eQTL plots in adipose, liver, muscle and brain tissue from the BXH F2 cross. Bicc1+/+ Males A B C Bicc1+/jcpk Males 50 50 120 0 0 4 4 100 jcpk / + 80 30 30 Bicc1 60 0 0 Weight (g) 2 2 Adiposity (%) 40 Percent of 0 0 1 1 20 0 0 0 P K Cl Ca Na BUN Albumin Supplementary Figure 2. Body weight (A), adiposity (B) and markers of kidney function (C) in 28 week-old Bicc1+/jcpk and Bicc1+/+ male mice. Data presented are means + standard errors. None of the measurements in Bicc1+/jcpk differ statistically from Bicc1+/+ mice. Supplementary Figure 3. Bicc1 expression levels across 96 different mouse tissues and cell-types. Micoarray data are from N=2/tisssue cell-type. Data for three different microarray probe sets are presented. Images were downloaded from www.biogps.org. Supplementary Figure 4. Pkd2 expression levels across 96 different mouse tissues and cell-types. Micoarray data are from N=2/tisssue cell-type.Data for three different microarray probe sets are presented. Images were downloaded from www.biogps.org. Empty PKD2 Vector PKD2 Pkd2_1 siRNA Pkd2_1 SC siRNA PKD2 ACTIN ACTIN 100 250 80 200 60 150 40 100 PKD2/ACTIN PKD2/ACTIN 20 50 0 0 Pkd2 SC siRNA Pkd2_1 siRNA Emphty Vector Supplementary Figure 5. Quantification of Pkd2 protein levels. PKD2 levels are reduced by ~20% by the Pkd2_1 siRNA and increased by ~260% by overexpressing Pkd2. Blot in the top left shows PKD2 and ACTIN levels in osteoblats 48 hours after transfection with Pkd2_1 or scrambled control (SC). Sample were run on the same gel but not in contigious lanes. Barchart in bottom left provides quantification of PKD2 from two seperate blots. Top right blot demonstrates an increase in PKD2 levels upon Pkd2 overexpression in osteoblasts. Bottom right provides quantification of band densities (N=3). Supplementary Figure 6. VISTA genome comparison plot for human BICC1. Shown is the ~15 Kbp region surrounding rs10740740 which is associated >50% Base genome: Human Feb. 2009 Chromosome: chr10 60,372,850-60,392,050 BICC1 100% Calc. Window: 100 bp Cons. Width: 100 bp Cons. Identity: 70% 50% 100% Calc. Window: 100 bp Cons. Width: 100 bp Cons. Identity: 70% 50% 60,372.88k 60,373.38k 60,373.88k 60,374.38k 60,374.88k 60,375.38k 60,375.88k 60,376.38k 60,376.88k 60,377.38k Annotations: BICC1 Gene UTR Exon CNS Repeats: 100% LINE RNA LTR DNA SINE Other 50% SNPs: SNP 100% Contigs: Contig Overlap 50% 60,377.68k 60,378.18k 60,378.68k 60,379.18k 60,379.68k 60,380.18k 60,380.68k 60,381.18k 60,381.68k 60,382.18k 1. Mouse Jul. 2007 (SLAGAN) 2. Mouse Jul. 2007 (SLAGAN) page 1 of 2 Base genome: Human Feb. 2009 Chromosome: chr10 60,372,850-60,392,050 BICC1 100% Calc. Window: 100 bp Location of rs10740740 Cons. Width: 100 bp Cons. Identity: 70% 50% 100% Calc. Window: 100 bp Cons. Width: 100 bp Cons. Identity: 70% 50% 60,382.48k 60,382.98k 60,383.48k 60,383.98k 60,384.48k 60,384.98k 60,385.48k 60,385.98k 60,386.48k 60,386.98k Annotations: BICC1 Gene UTR Exon CNS Repeats: 100% LINE RNA LTR DNA SINE Other 50% SNPs: SNP 100% Contigs: Contig Overlap 50% 60,387.28k 60,387.78k 60,388.28k 60,388.78k 60,389.28k 60,389.78k 60,390.28k 60,390.78k 60,391.28k 60,391.78k 1. Mouse Jul. 2007 (SLAGAN) 2. Mouse Jul. 2007 (SLAGAN) page 2 of 2 Supplementary Table 1. M6 genes. ProbesetID TargetId Gene Description Chr Mb GeneId Module ME6 ILM102850603 scl24190.1_328-S Nfib nuclear factor I/B 4 81.936287 18028 6 0.903329275 ILM2260440 scl0226154.4_125-S Lzts2 leucine zipper, putative tumor suppressor 2 19 45.101336 226154 6 0.896270055 ILM3440373 scl31155.10_11-S Mfge8 milk fat globule-EGF factor 8 protein 7 86.278779 17304 6 0.890811618 ILM3170605 scl054324.3_167-S Arhgef5 Rho guanine nucleotide exchange factor (GEF) 5 6 43.2391 54324 6 0.890623985 ILM4670390 scl27505.17_595-S Pkd2 polycystic kidney disease 2 5 104.934692 18764 6 0.88414764 ILM4920184 scl016779.32_71-S Lamb2 laminin, beta 2 9 108.392456 16779 6 0.882162484 ILM2190333 scl00101476.1_284-S Plekha1 pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1 7 138.056746 101476 6 0.880910004 ILM5720450 scl0056490.1_199-S Zbtb20 zinc finger and BTB domain containing 20 (hippocampus expression signature) 16 43.619062 56490 6 0.877503114 ILM4730025 scl16146.28_80-S Lamc1 laminin, gamma 1 1 155.066119 226519 6 0.875219135 ILM4150609 scl32699.8.1_168-S Rras Harvey rat sarcoma oncogene, subgroup R 7 52.276834 20130 6 0.871688809 ILM1340736 scl52829.1_29-S B3gnt6 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (core 3 synthase) 19 5.041059 272411 6 0.871439639 ILM6940139 scl42950.10.1_98-S 1700019E19Rik RIKEN cDNA 1700019E19 gene 12 87.503225 76411 6 0.870468312 ILM102340605 ri|5330439J01|PX00054P19|AK077362|1511-S Sobp sine oculis-binding protein homolog (Drosophila) 10 42.722966 109205 6 0.869071715 ILM1570040 scl47452.3.1_39-S Hoxc9 homeo box C9 15 102.814804 15427 6 0.866767521 ILM101190039 scl072190.1_208-S 2510009E07Rik RIKEN cDNA 2510009E07 gene 16 21.649254 72190 6 0.865834215 ILM2510687 scl0015530.1_184-S Hspg2 perlecan (heparan sulfate proteoglycan 2) 4 137.126406 15530 6 0.865028439 ILM4780068 scl00269549.2_19-S Nfib nuclear factor I/B 4 81.937262 18028 6 0.863694579 ILM2260082 scl22869.17.1_4-S Mtmr11 myotubularin related protein 11 3 95.975134 194126 6 0.862988557 ILM3850468 GI_47564089-S BC054438 cDNA sequence BC054438 17 24.785426 407831 6 0.860384914 ILM5910735 scl056149.9_314-S Grasp GRP1 (general receptor for phosphoinositides 1)-associated scaffold protein 15 101.063103 56149 6 0.859725245 ILM103850093 ri|4832408C21|PX00313I10|AK029270|3164-S Tshz2 teashirt zinc finger family member 2 2 169.598584 228911 6 0.858523219 ILM103450497 scl0269878.14_318-S Megf8 multiple EGF-like-domains 8 7 26.150862 269878 6 0.85817318 ILM6270528 scl33150.17.997_2-S Itgb1 integrin beta 1 (fibronectin receptor beta) 8 131.619177 16412 6 0.855744008 ILM1660546 scl36349.9.1_1-S Acvr2b activin receptor IIB 9 119.342486 11481 6 0.854106412 ILM5670577 scl54747.23_352-S Dlg3 discs, large homolog 3 (synapse-associated protein 102 kD) X 98.013613 53310 6 0.853082292 ILM102120129 scl5468.1.1_137-S 2900009C16Rik RIKEN cDNA 2900009C16 gene 10 42.722325 78400 6 0.852240847 ILM3140632 scl0320398.3_8-S Lrig3 leucine-rich repeats and immunoglobulin-like domains 3 10 125.451997 320398 6 0.852212397 ILM102340008 scl47449.2_635-S Hoxc8 homeo box C8 15 102.824421 15426 6 0.85090067 ILM3140368 scl49330.22.4_270-S Chrd chordin 16 20.742354 12667 6 0.848514294 ILM106450452 scl0240024.1_128-S Mllt4 myeloid/lymphoid or mixed lineage-leukemia translocation to 4 homolog (Drosophila) 17 14.042536 17356 6 0.847829769 ILM3520438 scl0232237.7_170-S Fgd5 FYVE, RhoGEF and PH domain containing 5 6 92.025797 232237 6 0.846776889 ILM2470735 scl46265.10.1_16-S Nfatc4 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 14 56.452674 73181 6 0.841155941 ILM4230577 scl36257.10_16-S Yap1 yes-associated protein 1 9 7.932283 22601 6 0.840021636 ILM3800372 scl26735.47.1_66-S Ift172 intraflagellar transport 172 homolog (Chlamydomonas) 5 31.555655 67661 6 0.839742217 ILM4150113 scl37767.8_640-S Syde1 synapse defective 1, Rho GTPase, homolog 1 (C. elegans) 10 78.047346 71709 6 0.839353584 ILM1740575 scl35102.50_84-S Col4a1 procollagen, type IV, alpha 1 8 11.19879 12826 6 0.838760355 ILM6020095 scl0018590.2_128-S Pdgfa platelet derived growth factor, alpha 5 139.453135 18590 6 0.838416154 ILM4010239 scl018858.5_31-S Pmp22 peripheral myelin protein 11 62.972694 18858 6 0.837554388 ILM730136 scl32180.18_394-S Parva parvin, alpha 7 119.735062 57342 6 0.836166634 ILM1780301 scl31603.36.1_19-S Ltbp4 latent transforming growth factor beta binding protein 4 7 28.090439 108075 6 0.835554779 ILM2350619 scl34083.48_466-S Col4a2 procollagen, type IV, alpha 2 8 11.44916 12827 6 0.833537699 ILM2120280 scl37679.21_483-S Appl2 adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2 10 83.06288 216190 6 0.832062188 ILM3850133 scl47450.4_93-S Hoxc6 homeo box C6 15 102.842229 15425 6 0.831880629 ILM103140541 ri|9530073A13|PX00114K21|AK035591|3548-S 9530073A13Rik RIKEN 9530073A13Rik 4 58.5338 6 0.828164891 ILM103840048 scl072844.1_278-S Kctd17 potassium channel tetramerisation domain containing 17 15 78.26961 72844 6 0.82783152 ILM6940593 scl39881.7_182-S Tnfaip1 tumor necrosis factor, alpha-induced protein 1 (endothelial) 11 78.336463 21927 6 0.826121987 ILM110717 scl30961.29_228-S Inppl1 inositol polyphosphate phosphatase-like 1 7 108.971251 16332 6 0.825627285 ILM102680592 ri|9830147J19|PX00118J13|AK036665|3837-S Smad1 MAD homolog 1 (Drosophila) 8 81.871514 17125 6 0.825285898 ILM100110338 ri|C230060D01|PX00176G21|AK048773|3746-S Kcnma1 potassium large conductance calcium-activated channel, subfamily M, alpha member 1 14 24.242905 16531 6 0.824793611 ILM2480427 scl017260.8_51-S Mef2c myocyte enhancer factor 2C 13 83.802727 17260 6 0.823783795 ILM100360300 scl39327.21_224-S Caskin2 cask-interacting protein 2 11 115.660594 140721 6 0.821286181 ILM460053 scl35355.5_339-S Dag1 dystroglycan 1 9 108.108334 13138 6 0.820987366 ILM106510204 scl073159.1_61-S Dchs1 dachsous 1 (Drosophila) 7 112.901774 233651 6 0.820951159 ILM940075 scl00269593.1_72-S Luzp1 leucine zipper protein 1 4 136.104921 269593 6
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