Shockley and Churchill, 2006 SUPPLEMENTAL MATERIAL Table

Shockley and Churchill, 2006

SUPPLEMENTAL MATERIAL

Table S1. NetAffx Mapping of Probe Set IDs to Chromosomal Location CHR Number of Unique Probe IDs 1 2,667 2 3,396 3 2,132 4 2,445 5 2,559 6 2,304 7 2,711 8 2,032 9 2,234 10 1,927 11 3,152 12 1,547 13 1,580 14 1,478 15 1,619 16 1,415 17 1,692 18 1,197 19 1,398 X 1,255 Y 8 M 1 Un 152

Total Unique 40,901 Total Probe IDs 45,101

Non-Unique or 4,200 Missing Probe IDs Gene mapping was performed with the Affymetrix tool NetAffx (available at http://www.affymetrix.com/analysis/index.affx). “M” refers to mitochondria; “Un” is unknown location.

Gene Expression in Mouse Chromosome Substitution Strains 1

Shockley and Churchill, 2006

Table S2. Over-representation of Canonical Pathways in Mouse Liver from Ingenuity Systems Database p-value NAME Description FC q B.A1 Arginine and Proline Metabolism 0.04 ODC1 ornithine decarboxylase 1 -2.1 0.01 P4HA2 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide II -2.2 0.01

B.A2 Sulfur Metabolism 0.00 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.8 0.00 SULT1B1 sulfotransferase family, cytosolic, 1B, member 1 1.8 0.00 Bile Acid Biosynthesis 0.01 ALDH4A1 aldehyde dehydrogenase -1.5 0.00 CYP7A1 cytochrome P450, family 7, subfamily A, polypeptide 1 2.3 0.00 LIPA lipase A -3.6 0.01 Histidine Metabolism 0.04 ALDH4A1 aldehyde dehydrogenase -1.5 0.00 FTCD formiminotransferase cyclodeaminase -2.5 0.01

B.A3 Sulfur Metabolism 0.03 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.5 0.00 JAK/Stat Signaling 0.04 CISH cytokine inducible SH2-containing protein -1.8 0.01 SOCS2 suppressor of cytokine signaling 2 -1.8 0.01 Death Receptor Signaling 0.04 APAF1 apoptotic protease activating factor -1.2 0.00 TNFSF10 tumor necrosis factor (ligand) superfamily, member 10 2.5 0.00 Taurine and Hypotaurine Metabolism -0.05 CSAD cysteine sulfinic acid decarboxylase -2.0 0.01 Purine Metabolism 0.00 ADCY1 adenylate cyclase 1 (brain) 1.3 0.00 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.5 0.00 POLR2A polymerase (RNA) II (DNA directed) polypeptide A, 220kDa -1.5 0.01 SPAST spastin -1.5 0.00

B.A4 Phenylalanine Metabolism 0.02 GOT1 glutamic-oxaloacetic transaminase 1, soluble 1.6 0.00 MAOA monoamine oxidase A -1.3 0.01 Tyrosine Metabolism 0.03 GOT1 glutamic-oxaloacetic transaminase 1, soluble 1.6 0.00 MAOA monoamine oxidase A -1.3 0.01 Nucleotide Excision Repair Pathway 0.04 RAD23B RAD23 homolog B (S. cerevisiae) -1.7 0.00 XPA xeroderma pigmentosum, complementation group A 1.3 0.00

B.A5 Selenoamino Acid Metabolism 0.00 GGT1 gamma-glutamyl transferase 1 -1.2 0.01 MAT1A methionine adenosyltransferase I, alpha 1.2 0.01 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.0 0.00 Fatty Acid Metabolism 0.01 ACAD10 Acyl-Coenzyme A dehydrogenase family 1.6 0.00 ACOX1 acyl-Coenzyme A oxidase 1, palmitoyl 1.8 0.01 ALDH1A1 aldehyde dehydrogenase 1 family, member A1 2.0 0.00 CYP2B6 cytochrome P450, family 2, subfamily B, polypeptide 6 1.8 0.00 CYP3A7 cytochrome P450 -3.6 0.00 Gluthionone Metabolism 0.02 GGT1 gamma-glutamyl transferase 1 -1.2 0.01 GSTM2 glutathione S-transferase M2 (muscle) 1.5 0.00 GSTT3 glutathione S-transferase theta-3 1.4 0.01 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, N-Glycan Biosynthesis 0.03 B4GALT1 polypeptide 1 -1.3 0.01 MAN1A2 mannosidase, alpha, class 1A, member 2 1.3 0.00 MGAT3 mannosyl (beta-1,4-)-glycoprotein beta-1,4-N- acetylglucosaminyltransferase -1.2 0.00 Arginine and Proline Metabolism 0.03 ALDH1A1 aldehyde dehydrogenase 1 family, member A1 2.0 0.00 P4HA2 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide II -1.6 0.01 procollagen-proline, 2-oxoglutarate 4-dioxygenase P4HB (proline 4-hydroxylase), beta polypeptide (protein disulfide isomerase-associated 1) 1.8 0.01

Gene Expression in Mouse Chromosome Substitution Strains 2

Shockley and Churchill, 2006

B.A6 None

B.A7 Aminosugars Metabolism 0.01 DIA1 diaphorase (NADH) (cytochrome b-5 reductase) 3.5 0.01 NANS N-acetylneuraminic acid synthase (sialic acid synthase) -1.5 0.00 PDGF Signaling 0.01 EIF2AK2 eukaryotic translation initiation factor 2-alpha kinase 2 1.5 0.00 PDGFRB platelet-derived growth factor receptor, beta polypeptide -1.7 0.00 STAT1 signal transducer and activator of transcription 1, 91kDa 1.4 0.01 Sulfur Metabolism 0.04 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 3.1 0.00

B.A8 Sulfur Metabolism 0.02 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 3.2 0.00 Methane Metabolism 0.05 PRDX2 peroxiredoxin 2 -4.0 0.00

B.A9 Alanine and Aspartate Metabolism 0.00 ASL argininosuccinate lyase 1.4 0.01 ASS argininosuccinate synthetase 1.2 0.01 GOT1 glutamic-oxaloacetic transaminase 1, soluble 1.5 0.01 GPT2 glutamic pyruvate transaminase (alanine aminotransferase) 2 1.6 0.01 PC pyruvate carboxylase 2.0 0.01 Sulfur Metabolism 0.00 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 3.0 0.00 SULT1B1 sulfotransferase family, cytosolic, 1B, member 1 1.3 0.01 SUOX sulfite oxidase 1.4 0.01 Integrin Signaling 0.00 ACTB actin, beta 1.8 0.01 AKT2 v-akt murine thymoma viral oncogene homolog 2 1.9 0.01 ARF3 ADP-ribosylation factor 3 1.5 0.01 CAPN1 calpain 1, (mu/I) large subunit 1.8 0.00 GRB7 growth factor receptor-bound protein 7 1.7 0.00 PARVA parvin, alpha 1.7 0.00 PXN paxillin 2.0 0.00 RAP2B RAP2B, member of RAS oncogene family 1.3 0.00 RAPGEF1 Rap guanine nucleotide exchange factor (GEF) 1 1.5 0.01 SHC1 SHC (Src homology 2 domain containing) transforming protein 1 2.0 0.01 Gluthionone Metabolism 0.00 GSTM2 glutathione S-transferase M2 (muscle) 1.7 0.01 GSTM3 glutathione S-transferase M3 (brain) 1.7 0.00 GSTM6 glutathione S-transferase, mu 6 1.6 0.00 GSTT3 glutathione S-transferase, theta 3 2.0 0.00 Urea Cycle and Metabolism of Amino Groups 0.00 ACY1 aminoacylase 1 1.9 0.00 ASL argininosuccinate lyase 1.4 0.01 ASS argininosuccinate synthetase 1.2 0.01 Arginine and Proline Metabolism 0.00 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 1.4 0.00 ASL argininosuccinate lyase 1.4 0.01 ASS argininosuccinate synthetase 1.2 0.01 GOT1 glutamic-oxaloacetic transaminase 1, soluble 1.5 0.01 One Carbon Pool by Folate 0.00 FTCD formiminotransferase cyclodeaminase -2.1 0.01 SHMT1 serine hydroxymethyltransferase 1 (soluble) 1.4 0 SHMT2 serine hydroxymethyltransferase 2 (mitochondrial) 1.9 0.01 Lysine Degradation 0.01 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 1.4 0.00 BAT8 euchromatic histone-lysine N-methyltransferase 2 1.6 0.01 SHMT1 serine hydroxymethyltransferase 1 (soluble) 1.4 0 SHMT2 serine hydroxymethyltransferase 2 (mitochondrial) 1.9 0.01 VEGF Signaling 0.01 ACTB actin, beta 1.8 0.01 AKT2 v-akt murine thymoma viral oncogene homolog 2 1.9 0.01 BCLDL1 BCL2-like 1 1.8 0.01 PXN paxillin 2.0 0.00 SHC1 SHC (Src homology 2 domain containing) transforming protein 1 2.0 0.01 Glutamate Metabolism 0.02 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 1.4 0.00

Gene Expression in Mouse Chromosome Substitution Strains 3

Shockley and Churchill, 2006

GOT1 glutamic-oxaloacetic transaminase 1, soluble 1.5 0.01 GPT2 glutamic pyruvate transaminase (alanine aminotransferase) 2 1.6 0.01 Methane Metabolism 0.02 SHMT1 serine hydroxymethyltransferase 1 (soluble) 1.4 0 SHMT2 serine hydroxymethyltransferase 2 (mitochondrial) 1.9 0.01 Pyruvate Metabolism 0.02 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 1.4 0.00 ME1 malic enzyme 1, NADP(+)-dependent, cytosolic -1.5 0.01 PC pyruvate carboxylase 2.0 0.01 PKLR pyruvate kinase, liver and RBC 2.2 0.00 Insulin Receptor Signaling 0.03 AKT2 v-akt murine thymoma viral oncogene homolog 2 1.1 0.01 PDPK1 3-phosphoinositide dependent protein kinase-1 -1.5 0.01 RAPGEF1 Rap guanine nucleotide exchange factor (GEF) 1 1.5 0.01 SHC1 SHC (Src homology 2 domain containing) transforming protein 1 2.0 0.01 TSC2 tuberous sclerosis 2 1.7 0.01 P13K/AKT Signaling 0.03 AKT2 v-akt murine thymoma viral oncogene homolog 2 1.1 0.01 BCL2L1 BCL2-like 1 1.8 0.01 PDPK1 3-phosphoinositide dependent protein kinase-1 -1.5 0.01 TP53 tumor protein p53 (Li-Fraumeni syndrome) 2.0 0.00 TSC2 tuberous sclerosis 2 1.7 0.01 IL-2 Signaling 0.04 AKT2 v-akt murine thymoma viral oncogene homolog 2 1.1 0.01 SHC1 SHC (Src homology 2 domain containing) transforming protein 1 2.0 0.01 STAT5A signal transducer and activator of transcription 5A 2.1 0.01 Hypoxia Signaling in the Cardiovascular System 0.05 TP53 tumor protein p53 (Li-Fraumeni syndrome) 2.0 0.00 ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, UBE2D1 yeast) 1.7 0.00 UBE2L6 ubiquitin-conjugating enzyme E2L 6 2.1 0.01

B.A10 Nicotinate and Nicotinamide Metabolism 0.00 ENPP1 ectonucleotide pyrophosphatase/phosphodiesterase 1 -1.6 0.00 ENPP3 ectonucleotide pyrophosphatase/phosphodiesterase 3 -1.5 0.01 NT5C3 5'-nucleotidase, cytosolic III -1.5 0.01 PBEF1 pre-B-cell colony enhancing factor 1 -1.4 0.00

B.A11 Pyruvate Metabolism 0.01 ALDH1B1 aldehyde dehydrogenase family 1 1.6 0.01 NKD1 naked cuticle homolog 1 (Drosophila) 1.3 0.00 PCK1 phosphoenolpyruvate carboxykinase 1 -1.7 0.00 Gluthionone Metabolism 0.02 ALDH1B1 aldehyde dehydrogenase family 1 1.6 0.01 NKD1 naked cuticle homolog 1 (Drosophila) 1.3 0.00 PCK1 phosphoenolpyruvate carboxykinase 1 -1.7 0.00 Lysine Degradation 0.03 ALDH1B1 aldehyde dehydrogenase family 1 1.6 0.01 SHMT1 serine hydroxymethyltransferase 1 (soluble) 1.9 0.00 Sulfur Metabolism 0.04 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 3.3 0.00

B.A12 Cell Cycle: G1/S Checkpoint Regulation 0.01 E2F6 E2F transcription factor -1.9 0.00 SKP1A S-phase kinase associated protein 1A -1.1 0.00 Phototransduction Pathway 0.03 GUCA2B guanylate cyclase activator 2B (uroguanylin) 1.2 0.01

B.A13 Jak/Stat Signaling 0.03 JAK1 Janus kinase 1 (a protein tyrosine kinase) 2.1 0.00

B.A14 Arginine and Proline Metabolism 0.00 ALDH3A2 aldehyde dehydrogenase 3 family, member A2 -1.7 0.01 ALDH4A1 aldehyde dehydrogenase family 4, member A1 1.4 0.00 AMD1 adenosylmethionine decarboxylase 1 -1.6 0.01 ASS argininosuccinate synthetase 1.3 0.01 procollagen-proline, 2-oxoglutarate 4-dioxygenase P4HB (proline 4-hydroxylase), beta polypeptide (protein disulfide isomerase-associated 1) 1.5 0.01

Gene Expression in Mouse Chromosome Substitution Strains 4

Shockley and Churchill, 2006

Glycerolipid Metabolism 0.00 ALDH3A2 aldehyde dehydrogenase 3 family, member A2 -1.7 0.01 ALDH4A1 aldehyde dehydrogenase family 4, member A1 1.4 0.00 DGKD diacylglycerol kinase, delta 130kDa 1.5 0.01 LIPA lipase A, lysosomal acid, cholesterol esterase (Wolman disease) -2.3 0.00 SPHK2 sphingosine kinase 2 1.6 0.01 One Carbon Pool by Folate 0.00 FTCD formiminotransferase cyclodeaminase -2.0 0.01 SARDH sarcosine dehydrogenase 1.5 0.00 SHMT2 serine hydroxymethyltransferase 2 (mitochondrial) 2.0 0.00 Sulfur Metabolism 0.00 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.7 0.00 SUOX sulfite oxidase 1.3 0.01 Histidine Metabolism 0.00 ALDH3A2 aldehyde dehydrogenase 3 family, member A2 -1.7 0.01 ALDH4A1 aldehyde dehydrogenase family 4, member A1 1.4 0.00 FTCD formiminotransferase cyclodeaminase -2.0 0.01 Bile Acid Biosynthesis 0.00 ALDH3A2 aldehyde dehydrogenase 3 family, member A2 -1.7 0.01 ALDH4A1 aldehyde dehydrogenase family 4, member A1 1.4 0.00 LIPA lipase A, lysosomal acid, cholesterol esterase (Wolman disease) -2.3 0.00 Sterol Biosynthesis 0.01 MVK mevalonate kinase 1.7 0.00 SC5DL sterol-C5-desaturase (ERG3 delta-5-desaturase homolog, fungal)-like -2.2 0.01 Lysine Degradation 0.01 ALDH3A2 aldehyde dehydrogenase 3 family, member A2 -1.7 0.01 ALDH4A1 aldehyde dehydrogenase family 4, member A1 1.4 0.00 SHMT2 serine hydroxymethyltransferase 2 (mitochondrial) 2.0 0.00 Angrogen and Estrogen Metabolism 0.03 SULF2 sulfatase 2 1.7 0.00 UGT2B7 UDP glycosyltransferase 2 family, polypeptide B7 -1.9 0.01

B.A15 Fatty Acid Metabolism 0.00 ACADL acyl-Coenzyme A dehydrogenase, long chain -1.9 0.01 ADHFE1 alcohol dehydrogenase, iron containing, 1 -2.3 0.01 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 Cyp4a10 cytochrome P450, family 4, subfamily a, polypeptide 10 -2.6 0.01 CYP51A1 cytochrome P450, family 51, subfamily A, polypeptide 1 -2.8 0.01 EHHADH enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase -2.1 0.01 FLJ1292 putative acyl-CoA dehydrogenase -2.3 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- HADHB Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit -2.4 0.00 HADHSC L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain -2.1 0.01 PECI peroxisomal D3,D2-enoyl-CoA isomerase -2.9 0.00 Valine, Leucine and Isoleucine Metabolism 0.00 ACADL acyl-Coenzyme A dehydrogenase, long chain -1.9 0.01 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme EHHADH A dehydrogenase -2.1 0.01 FLJ1292 putative acyl-CoA dehydrogenase -2.3 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- Coenzyme A thiolase/enoyl-Coenzyme A hydratase HADHB (trifunctional protein), beta subunit -2.4 0.00 L-3-hydroxyacyl-Coenzyme A dehydrogenase, short HADHSC chain -2.1 0.01 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 HMGCS1 (soluble) -3.0 0.01 MCCC1 methylcrotonoyl-Coenzyme A carboxylase 1 (alpha) -2.0 0.01 Lysine Degradation 0.00 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 BAT8 euchromatic histone-lysine N-methyltransferase 2 1.8 0.00 EHHADH enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase -2.1 0.01

Gene Expression in Mouse Chromosome Substitution Strains 5

Shockley and Churchill, 2006

hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- HADHB Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit -2.4 0.00 HADHSC L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain -2.1 0.01 SHMT2 serine hydroxymethyltransferase 2 (mitochondrial) 2.3 0.01 TMLHE trimethyllysine hydroxylase, epsilon 0.01 Propanoate Metabolism 0.01 ACADL acyl-Coenzyme A dehydrogenase, long chain -1.9 0.01 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 EHHADH enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase -2.1 0.01 FLJ1292 putative acyl-CoA dehydrogenase -2.3 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- Coenzyme A thiolase/enoyl-Coenzyme A hydratase HADHB (trifunctional protein), beta subunit -2.4 0.00 LDHB lactate dehydrogenase B 1.3 0.01 Glycerolipid Metabolism 0.01 ADHFE1 alcohol dehydrogenase, iron containing, 1 -2.3 0.01 AGPAT2 1-acylglycerol-3-phosphate O-acyltransferase 2 (lysophosphatidic acid acyltransferase, beta) 1.9 0.01 AKR7A2 aldo-keto reductase family 7, member A2 (aflatoxin aldehyde reductase) 2.0 0.01 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 DGKZ diacylglycerolkinase zeta 2.0 0.00 LIPA lipase A, lysosomal acid, cholesterol esterase (Wolman disease) -4.3 0.00 SPHK2 sphingosine kinase 2 1.8 0.01 β-Alanine Metabolism 0.01 ACADL acyl-Coenzyme A dehydrogenase, long chain -1.9 0.01 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme EHHADH A dehydrogenase -2.1 0.01 FLJ1292 putative acyl-CoA dehydrogenase -2.3 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- Coenzyme A thiolase/enoyl-Coenzyme A hydratase HADHB (trifunctional protein), beta subunit -2.4 0.00 Bile Acid Biosynthesis 0.01 ADHFE1 alcohol dehydrogenase, iron containing, 1 -2.3 0.01 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- Coenzyme A thiolase/enoyl-Coenzyme A hydratase HADHB (trifunctional protein), beta subunit -2.4 0.00 LIPA lipase A, lysosomal acid, cholesterol esterase (Wolman disease) -4.3 0.00 Butanoate Metabolism 0.01 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 EHHADH enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase -2.1 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- HADHB Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit -2.4 0.00 HADHSC L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain -2.1 0.01 HMGCS1 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (soluble) -3.0 0.01 Histidine Metabolism 0.02 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 FTCD formiminotransferase cyclodeaminase -2.6 0.01 HARS histidyl-tRNA synthetase -2.3 0.01 TGF-β Signaling 0.02 MAP3K7 mitogen-activated protein kinase kinase kinase 7 -1.7 0.01 PIAS4 protein inhibitor of activated STAT, 4 1.6 0.01

Gene Expression in Mouse Chromosome Substitution Strains 6

Shockley and Churchill, 2006

SMAD2 SMAD, mothers against DPP homolog 2 (Drosophila) -1.9 0.01 SMAD5 SMAD, mothers against DPP homolog 5 (Drosophila) -1.7 0.00 SMAD6 SMAD, mothers against DPP homolog 6 (Drosophila) 2.1 0.00 SMURF2 SMAD specific E3 ubiquitin protein ligase 2 -2.8 0.00 TGFB1 transforming growth factor, beta 1 (Camurati-Engelmann disease) 1.8 0.01 Retinol Metabolism 0.03 Rdh6 retinol dehydrogenase 16 -2.6 0.00 Rdh9 retinol dehydrogenase 9 -3.5 0.00 Sterol Biosynthesis 0.04 IDI1 isopentenyl-diphosphate delta isomerase -4.0 0.00 MVK mevalonate kinase (mevalonic aciduria) 1.8 0.00 SC5DL sterol-C5-desaturase (ERG3 delta-5-desaturase homolog, fungal)-like -3.5 0.01 AKR7A2 aldo-keto reductase family 7, member A2 (aflatoxin Pyruvate Metabolism 0.04 aldehyde reductase) 2.0 0.01 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 FLJ1292 putative acyl-CoA dehydrogenase -2.3 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- HADHB Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit -2.4 0.00 LDHB lactate dehydrogenase B 1.3 0.01 PCK1 phosphoenolpyruvate carboxykinase 1 (soluble) -1.6 0.00 Arginine and Proline Metabolism 0.04 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 DKFZp727A071 -- 1.6 0.01 GAMT guanidinoacetate N-methyltransferase 1.9 0.00 OAT ornithine aminotransferase (gyrate atrophy) -1.7 0.01 EHHADH enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme Fatty Acid Metabolism (Path 2) 0.04 A dehydrogenase -2.1 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- HADHB Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit -2.4 0.00 HADHSC L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain -2.1 0.01 Tryptophan Metabolism 0.05 ALDH3A2 alcohol dehydrogenase 3 family, member A2 -2.9 0.00 ALDH5A1 aldehyde dehydrogenase, 5 family, member A1 -2.1 0.01 CYP51A1 cytochrome P450, family 51, subfamily A, polypeptide 1 -2.8 0.01 EHHADH enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase -2.1 0.01 hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl- HADHB Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta subunit -2.4 0.00 HADHSC L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain -2.1 0.01

B.A16 Taurine and Hypotaurine Metabolism 0.02 CSAD cysteine sulfinic acid decarboxylase -1.6 0.01

B.A17 Antigen Presentation Pathway 0.00 H2-BL histocompatibility 2, blastocyst 1.6 0.00 H2-D1 histocompatibility 2, D region locus 1 41.8 0.00 HLA-A major histocompatibility complex, class I, A -5.6 0.00 HLA-E major histocompatibility complex, class I, E 2.2 0.00 Sulfur Metabolism 0.00 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.9 0.00 SULT1B sulfotransferase family, cytosolic, 1B, member 1 1.3 0.00 Arginine and Proline Metabolism 0.01 CKM creatine kinase, muscle 1.9 0.00 GOT1 glutamic-oxaloacetic transaminase 1, soluble (aspartate aminotransferase 1) 1.6 0.00 Inositol Phosphate Metabolism 0.03 IHPK2 inositol hexaphosphate kinase 2 -1.4 0.01 PLCL2 phospholipase C-like 2 -1.7 0.01 GOT1 glutamic-oxaloacetic transaminase 1, soluble (aspartate Cysteine Metabolism 0.04 aminotransferase 1) 1.6 0.00

Gene Expression in Mouse Chromosome Substitution Strains 7

Shockley and Churchill, 2006

B.A18 Tryptophan Metabolism 0.00 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 2.1 0.00 CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1 -1.1 0.01 Fatty Acid Metabolism 0.00 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 2.1 0.00 CYP1B1 cytochrome P450, family 1, subfamily B, polypeptide 1 -1.1 0.01 Sulfur Metabolism 0.01 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.2 0.01 Selenoamino Acid Metabolism 0.02 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.2 0.01 Histidine Metabolism 0.03 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 2.1 0.00 Bile Acid Biosynthesis 0.03 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 2.1 0.00 Purine Metabolism 0.02 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.2 0.01 PRPSIL1 phosphoribosyl pyrophosphate synthetase 1-like 1 -1.2 0.01 b-Alanine Metabolism 0.05 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 2.1 0.00 Arginine and Proline Metabolism 0.05 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 2.1 0.00 Butanoate Metabolism 0.05 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 2.1 0.00

B.A19 Arginine and Proline Metabolism 0.04 CKM creatine kinase, muscle 1.9 0.00 GOT1 glutamic-oxaloacetic transaminase 1, soluble 1.6 0.00 Sulfur Metabolism 0.04 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 3.2 0.00

B.AX Sulfur Metabolism 0.01 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 1.9 0.01 Selenoamino Acid Metabolism 0.05 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 1.9 0.01

B.AY Sulfur Metabolism 0.02 PAPSS2 3'-phosphoadenosine 5'-phosphosulfate synthase 2 2.5 0.01 PPAR Signaling 0.02 NRIP1 nuclear receptor interacting protein 1 1.9 0.01 PPARBP PPAR binding protein 1.2 0.00

B6.AJ Tryptophan Metabolism 0.00 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 1.9 0.00 CAT catalase -2.1 0.00 CYP2C37 cytochrome P450 -7.1 0.00 CYP2c38 cytochrome P450 2.1 0.00 CYP3A7 cytochrome P450 -2.9 0.00 CYP51A1 cytochrome P450 -1.9 0.00 KYNU kynureninase -1.4 0.01 MAOA monoamine oxidase A -1.6 0.00 WARS tryptophanyl-tRNA synthetase -1.6 0.01 Inositol Phosphate Metabolism 0.01 IMPA2 inositol(myo)-1(or 4)-monophosphatase 2 -1.2 0.01 INPP5A inositol polyphosphate-5-phosphatase, 40kDa 1.3 0.01 ITPK inositol 1,4,5-trisphosphate 3-kinase A 1.5 0.01 PI4KII phosphatidylinositol 4-kinase type II -1.9 0.00 PIK3C2G phosphoinositide-3-kinase, class 2, gamma polypeptide 1.6 0.00 PIK4CB phosphatidylinositol 4-kinase, catalytic, beta polypeptide 2.4 0.00 PLCL2 phospholipase C-like 2 -1.6 0.00 PTPMT1 protein tyrosine phosphatase, mitochondrial 1 -1.6 0.00 SYNJ2 synaptojanin 2 1.7 0.01 Urea Cycle and Metabolism of Amino Groups 0.01 ALDH18A1 aldehyde dehydrogenase 18 family, member A1 -1.2 0.00 ASS argininosuccinate synthetase 1.8 0.01 OAT ornithine aminotransferase (gyrate atrophy) -1.5 0.00 ODC1 ornithine decarboxylase 1 -1.6 0.01 Bile Acid Biosynthesis 0.01 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 1.9 0.00 CYP27A1 cytochrome P450, family 27, subfamily A, polypeptide 1 -1.2 0.00 CYP7A1 cytochrome P450, family 7, subfamily A, polypeptide 1 3.5 0.00 LIPA lipase A, lysosomal acid, cholesterol esterase (Wolman disease) 1.8 0.00 SRD5A1 steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1) -1.6 0.00 Antigen Presentation Pathway 0.01 H2-BL histocompatibility 2, blastocyst 1.7 0.00 H2-D1 histocompatibility 2, D region locus 1 29.6 0.00

Gene Expression in Mouse Chromosome Substitution Strains 8

Shockley and Churchill, 2006

HLA-A major histocompatibility complex, class I, A -9.2 0.00 HLA-DQA1 major histocompatibility complex, class II, DQ alpha -1.7 0.01 HLA-E major histocompatibility complex, class I, E -2.0 0.00 Arginine and Proline Metabolism 0.01 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 1.9 0.00 ASS argininosuccinate synthetase 1.8 0.01 MAOA monoamine oxidase A -1.6 0.00 OAT ornithine aminotransferase (gyrate atrophy) -1.5 0.00 ODC1 ornithine decarboxylase 1 -1.6 0.01 Fatty Acid Metabolism 0.02 ACAD10 acetyl-Coenzyme A dehydrogenase family, member 10 1.8 0.00 ACOX1 acyl-Coenzyme A oxidase 1, palmitoyl -1.9 0.00 ALDH7A1 aldehyde dehydrogenase, 7 family, member A1 1.9 0.00 CYP2C37 cytochrome P450 -7.1 0.00 CYP2c38 cytochrome P450 2.1 0.00 CYP3A7 cytochrome P450 -2.9 0.00 CYP51A1 cytochrome P450 -1.9 0.00 IVD isovaleryl Coenzyme A dehydrogenase -1.4 0.01 Methane Metabolism 0.02 CAT catalase -2.1 0.00 PRDX2 peroxiredoxin -3.3 0.00 SHMT1 serine hydroxymethyltransferase 1 (soluble) 2.0 0.00 Androgen Metabolism 0.03 HSD17B7 hydroxysteroid (17-beta) dehydrogenase 7 1.2 0.01 HSPC105 NAD(P) dependent steroid dehydrogenase-like 1.6 0.01 SRD5A1 steroid-5-alpha-reductase, alpha polypeptide 1 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 1) -1.6 0.00 SULF2 sulfatase 2 2.1 0.00

B.A6 - REPEATS Fructose and Mannose Metabolism 0.00 ALDOA-PS1 aldolase 1, A isoform, pseudogene 1 1.4 0.00 ALDOC aldolase C, fructose-bisphosphate -1.4 0.00 GCK glucokinase (hexokinase 4, maturity onset diabetes of the young 2) 2.1 0.00 PFKFB3 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 2.5 0.00 Retinol Metabolism 0.01 Rdh6 retinol dehydrogenase 16 -1.9 0.00 RDH11 retinol dehydrogenase 11 (all-trans and 9-cis) -1.9 0.01 Integrin Signaling 0.02 ACTB actin, beta -1.5 0.00 ARHGAP26 Rho GTPase activating protein 26 1.5 0.00 FN1 fibronectin 1 -1.6 0.01 PAK1 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast) -1.2 0.00 RHOU ras homolog gene family, member U -1.4 0.01 RND3 Rho family GTPase 3 -1.6 0.00 TM4FS7 tetraspanin 4 1.2 0.00 Phenylalanine, Tyrosine and Tryptophan FARSLB Biosynthesis 0.03 phenylalanine-tRNA synthetase-like, beta subunit -1.7 0.00 TAT tyrosine aminotransferase 1.7 0.00 Glycolysis/Gluconeogenesis 0.05 ALDOA-PS1 aldolase 1, A isoform, pseudogene 1 1.4 0.00 ALDOC aldolase C, fructose-bisphosphate -1.4 0.00 GCK glucokinase (hexokinase 4, maturity onset diabetes of the young 2) 2.1 0.00 PKLR pyruvate kinase, liver and RBC 1.3 0.00 Toll-like Receptor Signaling 0.0 JUN v-jun sarcoma virus 17 oncogene homolog (avian) -2.0 0.00 MAP2K6 mitogen-activated protein kinase kinase 6 1.7 0.00 NFKBIA nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha 1.4 0.01

B.A15 - REPEATS Tryptophan Metabolism 0.0 ALDH2 aldehyde dehydrogenase 2 family (mitochondrial) -1.3 0.00 ALDH1A1 aldehyde dehydrogenase 1 family, member A1 -2.0 0.00 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 -1.3 0.00 CAT catalase -1.8 0.00 CYP2A13 cytochrome P450, family 2, subfamily A, polypeptide 13 -1.4 0.01 CYP2B6 cytochrome P450, family 2, subfamily B, polypeptide 6 -1.9 0.00 Cyp2c37 cytochrome P450, family 2. subfamily c, polypeptide 37 -1.3 0.01

Gene Expression in Mouse Chromosome Substitution Strains 9

Shockley and Churchill, 2006

Cyp2c38 cytochrome P450, family 2, subfamily c, polypeptide 38 -1.5 0.00 CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 -1.4 0.00 Cyp2j5 cytochrome P450, family 2, subfamily j, polypeptide 5 -1.3 0.00 DDC dopa decarboxylase (aromatic L-amino acid decarboxylase) 2.0 0.00 INMT indolethylamine N-methyltransferase -1.3 0.00 WARS tryptophanyl-tRNA synthetase 1.3 0.00 PPAR Signaling 0.0 AIP aryl hydrocarbon receptor interacting protein 1.2 0.01 CREBBP CREB binding protein (Rubinstein-Taybi syndrome) -2.0 0.00 HSPCA heat shock 90kDa protein 1, alpha 1.7 0.00 HSPCB heat shock 90kDa protein 1, beta 1.2 0.00 JUN v-jun sarcoma virus 17 oncogene homolog (avian) -1.4 0.01 MAPK1 mitogen-activated protein kinase kinase 6 -1.9 0.00 NCOR1 nuclear receptor co-repressor 1 -2.2 0.00 NR1H3 nuclear receptor subfamily 1, group H, member 3 1.3 0.00 PDGFRB platelet-derived growth factor receptor, beta polypeptide 1.3 0.00 PPARBP PPAR binding protein -1.6 0.00 PPARG peroxisome proliferative activated receptor, gamma -1.3 0.01 PPARGC1A peroxisome proliferative activated receptor, gamma, coactivator 1, alpha -1.3 0.01 SOS1 son of sevenless homolog 1 (Drosophila) -1.3 0.01 SOS2 son of sevenless homolog 2 (Drosophila) -1.4 0.00 STAT5A signal transducer and activator of transcription 5A 1.4 0.00 AGPAT2 1-acylglycerol-3-phosphate O-acyltransferase 2 Glycerolipid Metabolism 0.01 (lysophosphatidic acid acyltransferase, beta) 1.4 0.00 AKR7A2 aldo-keto reductase family 7, member A2 (aflatoxin aldehyde reductase) 1.3 0.01 ALDH2 aldehyde dehydrogenase 2 family (mitochondrial) -1.3 0.00 ALDH1A1 aldehyde dehydrogenase 1 family, member A1 -2.0 0.00 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 -1.3 0.00 DGKD diacylglycerol kinase, delta 130kDa -1.3 0.00 DGKH diacylglycerol kinase, eta -1.3 0.01 LIPA lipase A, lysosomal acid, cholesterol esterase (Wolman disease) 1.6 0.00 LIPG lipase, endothelial -1.5 0.00 MGLL monoglyceride lipase 1.3 0.00 PNLIPRP2 pancreatic lipase-related protein 2 1.6 0.01 PPAP2B phosphatidic acid phosphatase type 2B -1.5 0.00 SPHK2 sphingosine kinase 2 1.4 0.00 Retinol Metabolism 0.02 BCMO1 beta-carotene 15,15'-monooxygenase 1 -1.2 0.01 Rdh6 retinol dehydrogenase 1 -1.5 0.01 Rdh9 retinol dehydrogenase 9 -1.6 0.00 Wnt/β-catenin Signaling 0.02 APC adenomatosis polyposis coli -1.4 0.00 CDH1 cadherin 1, type 1, E-cadherin (epithelial) 1.4 0.00 CDH2 cadherin 2, type 1, N-cadherin (neuronal) -1.3 0.00 CREBBP CREB binding protein (Rubinstein-Taybi syndrome) -2.0 0.00 CSNK1A1 casein kinase 1, alpha 1 -1.4 0.00 DVL2 dishevelled, dsh homolog 2 (Drosophila) -1.3 0.00 FRAT1 frequently rearranged in advanced T-cell lymphomas 1.4 0.00 FZD10 frizzled homolog 10 (Drosophila) 1.4 0.00 GNAQ guanine nucleotide binding protein (G protein), q polypeptide -1.4 0.00 GSK3B glycogen synthase kinase 3 beta -1.6 0.00 KREMEN1 kringle containing transmembrane protein 1 -1.3 0.00 LRP5 low density lipoprotein receptor-related protein 5 1.5 0.00 MAP4K1 mitogen-activated protein kinase kinase kinase kinase 1 1.4 0.00 PPP2R4 protein phosphatase 2A, regulatory subunit B' (PR 53) 1.4 0.00 PPP2R3A protein phosphatase 2 (formerly 2A), regulatory subunit B'', alpha -1.2 0.01 PPP2R3B protein phosphatase 2, regulatory subunit B (B56), beta isoform 1.4 0.00 RARA retinoic acid receptor, alpha 1.3 0.01

Gene Expression in Mouse Chromosome Substitution Strains 10

Shockley and Churchill, 2006

SMO smoothened homolog (Drosophila) 1.2 0.01 SOX7 SRY (sex determining region Y)-box 7 1.2 0.01 TCF4 transcription factor 4 1.3 0.00 WNT1 wingless-type MMTV integration site family, member 1 -1.2 0.01 WNT6 wingless-type MMTV integration site family, member 6 1.4 0.00 WNT5B wingless-type MMTV integration site family, member 5B 1.7 0.00 Bile Acid Biosynthesis 0.02 ALDH2 aldehyde dehydrogenase 2 family (mitochondrial) -1.3 0.00 ALDH1A1 aldehyde dehydrogenase 1 family, member A1 -2.0 0.00 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 -1.3 0.00 CYP7A1 cytochrome P450, family 7, subfamily A, polypeptide 1 -2.2 0.00 LIPA lipase A, lysosomal acid, cholesterol esterase (Wolman disease) 1.6 0.00 SOAT1 sterol O-acyltransferase (acyl-Coenzyme A: cholesterol acyltransferase) 1 -1.2 0.01 SOAT2 sterol O-acyltransferase 2 -1.4 0.00 Insulin Receptor Signaling 0.03 CRK v-crk sarcoma virus CT10 oncogene homolog (avian) -1.2 0.01 EIF2B2 eukaryotic translation initiation factor 2B, subunit 2 beta, 39kDa 1.3 0.00 EIF4E eukaryotic translation initiation factor 4E 1.2 0.01 GSK3B glycogen synthase kinase 3 beta -1.6 0.00 GYS2 glycogen synthase 2 (liver) -1.6 0.00 IRS2 insulin receptor substrate 2 -1.4 0.00 MAPK1 mitogen-activated protein kinase 1 -1.9 0.00 NCK1 NCK adaptor protein 1 -1.4 0.00 PDPK1 3-phosphoinositide dependent protein kinase-1 -1.5 0.00 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (p85 alpha) -1.6 0.00 PPP1R11 protein phosphatase 1, regulatory (inhibitor) subunit 11 1.3 0.00 PPP1R14C protein phosphatase 1, regulatory (inhibitor) subunit 14C 1.3 0.00 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) -1.4 0.00 RHOQ ras homolog gene family, member Q -1.3 0.00 SOS1 son of sevenless homolog 1 (Drosophila) -1.3 0.01 SOS2 son of sevenless homolog 2 (Drosophila) -1.4 0.00 STXBP4 syntaxin binding protein 4 1.3 0.00 VAMP2 vesicle-associated membrane protein 2 (synaptobrevin 2) -1.2 0.00 Integrin Signaling ACTB actin, beta -1.4 0.00 ACTN1 actinin, alpha 1 -1.3 0.00 ACTN4 actinin, alpha 4 1.2 0.00 ARF1 ADP-ribosylation factor 1 1.2 0.00 ARF3 ADP-ribosylation factor 3 -1.3 0.01 ARHGAP26 Rho GTPase activating protein 26 2.0 0.00 BCAR3 breast cancer anti-estrogen resistance 3 1.3 0.00 BRAF v-raf murine sarcoma viral oncogene homolog B1 -1.3 0.00 COL4A3 collagen, type IV, alpha 3 (Goodpasture antigen) -1.4 0.00 DDEF1 development and differentiation enhancing factor 1 -1.4 0.00 GRB7 growth factor receptor-bound protein 7 1.3 0.00 GSKB3 glycogen synthase kinase 3 beta -1.6 0.00 ITGA3 integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor) 1.3 0.00 ITGB integrin, beta 5 1.3 0.00 LAMB2 laminin, beta 2 (laminin S) 1.5 0.00 LAMB3 laminin, beta 3 1.2 0.01 MAPK1 mitogen-activated protein kinase 1 -1.9 0.00 MRCL3 myosin regulatory light chain MRCL3 2.0 0.00 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (p85 alpha) -1.6 0.00 PTEN phosphatase and tensin homolog (mutated in multiple advanced cancers 1) -1.4 0.00 RHOC ras homolog gene family, member C 1.3 0.01 RHOQ ras homolog gene family, member Q -1.3 0.00 RND2 Rho family GTPase 2 1.3 0.01

Gene Expression in Mouse Chromosome Substitution Strains 11

Shockley and Churchill, 2006

SOS1 son of sevenless homolog 1 (Drosophila) -1.3 0.01 SOS2 son of sevenless homolog 2 (Drosophila) -1.4 0.00 TNK2 tyrosine kinase, non-receptor, 2 1.4 0.00 PI3K/AKT Signaling 0.03 CCND1 cyclin D1 (PRAD1: parathyroid adenomatosis 1) -1.5 0.00 CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) 1.3 0.00 EIF4E eukaryotic translation initiation factor 4E 1.2 0.01 GSK3B glycogen synthase kinase 3 beta -1.6 0.00 GYS2 glycogen synthase 2 (liver) -1.6 0.00 HSPCA heat shock 90kDa protein 1, alpha 1.7 0.00 HSPCB heat shock 90kDa protein 1, beta 1.2 0.00 MAPK1 mitogen-activated protein kinase 1 -1.9 0.00 PDPK1 3-phosphoinositide dependent protein kinase-1 -1.5 0.00 PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (p85 alpha) -1.6 0.00 PPP2R4 protein phosphatase 2A, regulatory subunit B' (PR 53) 1.4 0.00 PPP2R3A protein phosphatase 2 (formerly 2A), regulatory subunit B'', alpha -1.2 0.01 PPP2R5B protein phosphatase 2, regulatory subunit B (B56), beta isoform 1.36 0.00 PTEN phosphatase and tensin homolog (mutated in multiple - advanced cancers 1) 1.38 0.00 SFN stratifin 1.37 0.00 SOS1 son of sevenless homolog 1 (Drosophila) -1.3 0.01 SOS2 son of sevenless homolog 2 (Drosophila) -1.4 0.00 YWHAC tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide 1.34 0.00 ACOX1 - Fatty Acid Metabolism 0.04 acyl-Coenzyme A oxidase 1, palmitoyl 1.45 0.00 ALDH2 aldehyde dehydrogenase 2 family (mitochondrial) -1.3 0.00 ALDH1A1 aldehyde dehydrogenase 1 family, member A1 -2.0 0.00 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 -1.3 0.00 CYP2A13 cytochrome P450, family 2, subfamily A, polypeptide 13 -1.4 0.01 CYP2B6 cytochrome P450, family 2, subfamily B, polypeptide 6 -1.9 0.00 CYP2C37 cytochrome P450, family 2. subfamily c, polypeptide 37 -1.3 0.01 CYP2C38 cytochrome P450, family 2, subfamily c, polypeptide 38 -1.5 0.00 CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 -1.4 0.00 CYP2J5 - cytochrome P450, family 2, subfamily j, polypeptide 5 1.35 0.00 CYP4A10 - cytochrome P450, family 4, subfamily a, polypeptide 10 1.65 0.00 PECI - peroxisomal D3,D2-enoyl-CoA isomerase 1.30 0.00 Arginine and Proline Metabolism 0.05 ALDH2 aldehyde dehydrogenase 2 family (mitochondrial) -1.3 0.00 ALDH1A1 aldehyde dehydrogenase 1 family, member A1 -2.0 0.00 ALDH4A1 aldehyde dehydrogenase 4 family, member A1 -1.3 0.00 ARG2 arginase, type II 1.34 0.00 ODC1 ornithine decarboxylase 1 1.47 0.00 P4HA2 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide II 1.24 0.00 PYCR2 pyrroline-5-carboxylate reductase family, member 2 1.23 0.00 SPR sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase) 1.23 0.00

Gene Expression in Mouse Chromosome Substitution Strains 12

Shockley and Churchill, 2006

Table S3. Over-representation of Canonical Pathways in Mouse Kidney from Ingenuity Systems Database p-value NAME Description FC q B.A1 None ------

B.A6 0.02 ALAS2 aminolevulinate, delta-synthase 2 (sideroblastic/hyperchronic -1.9 0.00 Glycine, Serine and Threonine Metabolism anemia) PISD phosphatidyl serine decarboxylase -1.6 0.00

B.A15 0.00 ALAS2 aminolevulinate, delta-synthase 2 (sideroblastic/hyperchronic -1.8 0.00 Glycine, Serine and Threonine Metabolism anemia) BHMT betaine-homocysteine methyltransferase -1.5 0.00 PISD phosphatidyl serine decarboxylase -1.3 0.00

Taurine and Hypotaurine Metabolism 0.03 CSAD cysteine sulfinic acid decarboxylase -1.7 0.00

Gene Expression in Mouse Chromosome Substitution Strains 13

Shockley and Churchill, 2006

Table S4. Functional Category Over-representation from EASE in Mouse Liver Gene Category EASE score Bon

B.A1 cellular metabolism 8.38E-03 1.00E+00 regulation of metabolism 1.00E-02 1.00E+00 primary metabolism 1.28E-02 1.00E+00 nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 1.37E-02 1.00E+00 regulation of transcription\, DNA-dependent 1.46E-02 1.00E+00 transcription\, DNA-dependent 1.72E-02 1.00E+00 regulation of transcription 1.76E-02 1.00E+00 regulation of nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 1.84E-02 1.00E+00 regulation of biological process 2.33E-02 1.00E+00 transcription 2.45E-02 1.00E+00 regulation of cellular metabolism 2.65E-02 1.00E+00 regulation of physiological process 3.22E-02 1.00E+00 metabolism 3.22E-02 1.00E+00 spermatogenesis 3.29E-02 1.00E+00 male gamete generation 3.29E-02 1.00E+00 regulation of cellular process 4.84E-02 1.00E+00 B.A2 cell cycle 2.65E-03 1.00E+00 regulation of cell cycle 4.43E-03 1.00E+00 sexual reproduction 2.08E-02 1.00E+00 reproduction 2.08E-02 1.00E+00 protein localization 3.01E-02 1.00E+00 regulation of biological process 3.25E-02 1.00E+00 gametogenesis 3.38E-02 1.00E+00 fatty acid biosynthesis 4.22E-02 1.00E+00 forebrain development 4.25E-02 1.00E+00 protein transport 4.53E-02 1.00E+00 establishment of protein localization 4.83E-02 1.00E+00 B.A3 regulation of biological process 2.55E-02 1.00E+00 regulation of metabolism 2.66E-02 1.00E+00 cellular metabolism 3.33E-02 1.00E+00 regulation of physiological process 3.66E-02 1.00E+00 cellular process 4.31E-02 1.00E+00 regulation of transcription 4.65E-02 1.00E+00 regulation of nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 4.83E-02 1.00E+00 B.A4 cellular physiological process 2.70E-02 1.00E+00 physiological process 3.77E-02 1.00E+00 regulation of metabolism 4.84E-02 1.00E+00 B.A5 protein modification 1.18E-02 1.00E+00 B.A6 N/A B.A7 metabolism 9.39E-03 1.00E+00 physiological process 1.15E-02 1.00E+00 B.A8 N/A

Gene Expression in Mouse Chromosome Substitution Strains 14

Shockley and Churchill, 2006

B.A9 cellular physiological process 7.06E-04 7.11E-01 cellular process 3.80E-03 1.00E+00 physiological process 4.70E-03 1.00E+00 cellular metabolism 1.17E-02 1.00E+00 phosphate metabolism 2.77E-02 1.00E+00 phosphorus metabolism 2.77E-02 1.00E+00 metabolism 3.30E-02 1.00E+00 protein amino acid phosphorylation 4.08E-02 1.00E+00 phosphorylation 4.17E-02 1.00E+00 B.A10 cellular protein metabolism 1.24E-02 1.00E+00 protein metabolism 1.45E-02 1.00E+00 cell fate commitment 2.74E-02 1.00E+00 ubiquitin-dependent protein catabolism 2.75E-02 1.00E+00 modification-dependent protein catabolism 3.00E-02 1.00E+00 cellular macromolecule metabolism 3.67E-02 1.00E+00 B.A11 cellular metabolism 1.06E-03 6.60E-01 primary metabolism 3.68E-03 1.00E+00 DNA metabolism 4.37E-03 1.00E+00 metabolism 5.80E-03 1.00E+00 regulation of cell cycle 1.30E-02 1.00E+00 biopolymer metabolism 1.79E-02 1.00E+00 physiological process 2.27E-02 1.00E+00 cellular physiological process 3.11E-02 1.00E+00 carboxylic acid metabolism 3.16E-02 1.00E+00 organic acid metabolism 3.16E-02 1.00E+00 response to DNA damage stimulus 3.34E-02 1.00E+00 amino acid activation 3.37E-02 1.00E+00 tRNA aminoacylation 3.37E-02 1.00E+00 tRNA aminoacylation for protein translation 3.37E-02 1.00E+00 nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 3.53E-02 1.00E+00 response to endogenous stimulus 3.67E-02 1.00E+00 tRNA modification 3.86E-02 1.00E+00 regulation of physiological process 4.33E-02 1.00E+00 regulation of metabolism 4.99E-02 1.00E+00 B.A12 N/A B.A13 regulation of transcription from RNA polymerase II promoter 1.26E-02 1.00E+00 regulation of cellular process 2.12E-02 1.00E+00 cellular physiological process 2.45E-02 1.00E+00 transcription from RNA polymerase II promoter 2.49E-02 1.00E+00 regulation of cellular physiological process 3.11E-02 1.00E+00 negative regulation of metabolism 4.16E-02 1.00E+00 cellular macromolecule metabolism 4.25E-02 1.00E+00 negative regulation of microtubule depolymerization 4.28E-02 1.00E+00 regulation of microtubule depolymerization 4.28E-02 1.00E+00 regulation of microtubule polymerization or depolymerization 4.28E-02 1.00E+00 negative regulation of microtubule polymerization or depolymerization 4.28E-02 1.00E+00

Gene Expression in Mouse Chromosome Substitution Strains 15

Shockley and Churchill, 2006

primary metabolism 4.28E-02 1.00E+00 microtubule polymerization or depolymerization 4.75E-02 1.00E+00 microtubule depolymerization 4.75E-02 1.00E+00 regulation of biological process 4.91E-02 1.00E+00 regulation of physiological process 4.95E-02 1.00E+00 B.A14 cellular macromolecule metabolism 7.24E-03 1.00E+00 cellular protein metabolism 8.08E-03 1.00E+00 protein metabolism 8.98E-03 1.00E+00 primary metabolism 1.40E-02 1.00E+00 macromolecule metabolism 1.60E-02 1.00E+00 protein amino acid phosphorylation 1.66E-02 1.00E+00 sexual reproduction 1.84E-02 1.00E+00 reproduction 1.84E-02 1.00E+00 transmembrane receptor protein serine/threonine kinase signaling pathway 2.12E-02 1.00E+00 phosphorylation 2.94E-02 1.00E+00 cellular metabolism 3.42E-02 1.00E+00 gametogenesis 3.86E-02 1.00E+00 phosphorus metabolism 4.02E-02 1.00E+00 phosphate metabolism 4.02E-02 1.00E+00 B.A15 cellular physiological process 8.60E-04 1.00E+00 phosphorus metabolism 1.36E-03 1.00E+00 phosphate metabolism 1.36E-03 1.00E+00 primary metabolism 3.36E-03 1.00E+00 phosphorylation 3.52E-03 1.00E+00 physiological process 3.65E-03 1.00E+00 protein modification 3.90E-03 1.00E+00 cellular protein metabolism 4.09E-03 1.00E+00 cellular metabolism 4.82E-03 1.00E+00 protein metabolism 5.25E-03 1.00E+00 cellular macromolecule metabolism 6.24E-03 1.00E+00 protein amino acid phosphorylation 7.03E-03 1.00E+00 macromolecule metabolism 7.14E-03 1.00E+00 translation 1.63E-02 1.00E+00 metabolism 2.09E-02 1.00E+00 deoxyribonucleotide biosynthesis 2.28E-02 1.00E+00 regulation of growth 2.54E-02 1.00E+00 establishment of protein localization 3.36E-02 1.00E+00 protein localization 3.43E-02 1.00E+00 protein biosynthesis 4.35E-02 1.00E+00 protein transport 4.52E-02 1.00E+00 regulation of cell growth 4.87E-02 1.00E+00 enzyme linked receptor protein signaling pathway 4.91E-02 1.00E+00 B.A16 metabolism 4.94E-03 1.00E+00 cellular metabolism 8.02E-03 1.00E+00 primary metabolism 1.66E-02 1.00E+00 cellular macromolecule metabolism 1.68E-02 1.00E+00

Gene Expression in Mouse Chromosome Substitution Strains 16

Shockley and Churchill, 2006

macromolecule metabolism 2.38E-02 1.00E+00 cellular protein metabolism 3.11E-02 1.00E+00 protein metabolism 3.25E-02 1.00E+00 phosphate metabolism 3.77E-02 1.00E+00 phosphorus metabolism 3.77E-02 1.00E+00 B.A17 N/A B.A18 N/A B.A19 cellular physiological process 8.13E-03 1.00E+00 physiological process 1.48E-02 1.00E+00 enzyme linked receptor protein signaling pathway 2.06E-02 1.00E+00 one-carbon compound metabolism 3.28E-02 1.00E+00 transforming growth factor beta receptor signaling pathway 4.31E-02 1.00E+00 B.AX N/A B.AY physiological process 1.42E-02 1.00E+00 regulation of biological process 3.20E-02 1.00E+00 B.AJ cellular metabolism 7.31E-04 1.00E+00 cellular macromolecule metabolism 2.42E-03 1.00E+00 primary metabolism 2.44E-03 1.00E+00 G-protein signaling\, adenylate cyclase inhibiting pathway 3.46E-03 1.00E+00 cellular process 3.49E-03 1.00E+00 metabolism 3.79E-03 1.00E+00 cellular physiological process 4.63E-03 1.00E+00 cAMP-mediated signaling 4.65E-03 1.00E+00 macromolecule metabolism 4.98E-03 1.00E+00 protein metabolism 5.57E-03 1.00E+00 cellular protein metabolism 8.03E-03 1.00E+00 cyclic-nucleotide-mediated signaling 8.28E-03 1.00E+00 biopolymer metabolism 9.27E-03 1.00E+00 G-protein signaling\, coupled to cAMP nucleotide second messenger 1.04E-02 1.00E+00 G-protein signaling\, coupled to cyclic nucleotide second messenger 1.82E-02 1.00E+00 protein catabolism 3.45E-02 1.00E+00 biopolymer catabolism 3.70E-02 1.00E+00 nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 3.78E-02 1.00E+00 folic acid and derivative metabolism 4.22E-02 1.00E+00 ubiquitin-dependent protein catabolism 4.37E-02 1.00E+00 macromolecule catabolism 4.59E-02 1.00E+00 cellular protein catabolism 4.85E-02 1.00E+00 proteolysis and peptidolysis 4.85E-02 1.00E+00 modification-dependent protein catabolism 4.88E-02 1.00E+00 B.A6_ind regulation of cellular process 1.42E-05 1.58E-02 regulation of biological process 2.32E-05 2.58E-02 regulation of cellular physiological process 3.10E-05 3.46E-02 regulation of cellular metabolism 7.84E-05 8.74E-02 regulation of physiological process 9.22E-05 1.03E-01 regulation of metabolism 1.23E-04 1.38E-01 negative regulation of transcription\, DNA-dependent 1.39E-04 1.55E-01

Gene Expression in Mouse Chromosome Substitution Strains 17

Shockley and Churchill, 2006 negative regulation of metabolism 2.09E-04 2.33E-01 regulation of transcription from RNA polymerase II promoter 2.19E-04 2.44E-01 negative regulation of cellular metabolism 2.96E-04 3.30E-01 negative regulation of transcription 3.86E-04 4.31E-01 regulation of transcription 4.15E-04 4.63E-01 regulation of nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 4.61E-04 5.14E-01 regulation of transcription\, DNA-dependent 5.15E-04 5.74E-01 negative regulation of nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 5.57E-04 6.21E-01 transcription\, DNA-dependent 7.43E-04 8.29E-01 transcription 9.08E-04 1.00E+00 negative regulation of transcription from RNA polymerase II promoter 1.38E-03 1.00E+00 transcription from RNA polymerase II promoter 1.39E-03 1.00E+00 negative regulation of cellular process 1.92E-03 1.00E+00 negative regulation of biological process 2.56E-03 1.00E+00 positive regulation of transcription from RNA polymerase II promoter 5.78E-03 1.00E+00 blood vessel development 5.99E-03 1.00E+00 vasculature development 6.33E-03 1.00E+00 hexose metabolism 7.83E-03 1.00E+00 monosaccharide metabolism 8.24E-03 1.00E+00 heart development 8.57E-03 1.00E+00 transmembrane receptor protein tyrosine kinase signaling pathway 8.67E-03 1.00E+00 negative regulation of cellular physiological process 8.90E-03 1.00E+00 positive regulation of biological process 9.55E-03 1.00E+00 glucose metabolism 1.09E-02 1.00E+00 cell proliferation 1.10E-02 1.00E+00 regulation of development 1.17E-02 1.00E+00 positive regulation of cellular process 1.18E-02 1.00E+00 morphogenesis 1.23E-02 1.00E+00 alcohol metabolism 1.34E-02 1.00E+00 blood vessel morphogenesis 1.43E-02 1.00E+00 nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 1.50E-02 1.00E+00 positive regulation of transcription\, DNA-dependent 1.51E-02 1.00E+00 positive regulation of cellular physiological process 1.56E-02 1.00E+00 enzyme linked receptor protein signaling pathway 1.58E-02 1.00E+00 histogenesis 1.71E-02 1.00E+00 regulation of cell growth 1.76E-02 1.00E+00 negative regulation of physiological process 1.79E-02 1.00E+00 response to external biotic stimulus 1.89E-02 1.00E+00 positive regulation of physiological process 1.89E-02 1.00E+00 development 1.90E-02 1.00E+00 response to pest\, pathogen or parasite 2.46E-02 1.00E+00 cellular carbohydrate metabolism 2.48E-02 1.00E+00 metabolism 2.56E-02 1.00E+00 cell growth 2.95E-02 1.00E+00 rhythmic process 3.00E-02 1.00E+00 primary metabolism 3.01E-02 1.00E+00 regulation of cell size 3.26E-02 1.00E+00

Gene Expression in Mouse Chromosome Substitution Strains 18

Shockley and Churchill, 2006

cellular morphogenesis 3.49E-02 1.00E+00 positive regulation of cellular metabolism 3.54E-02 1.00E+00 heme oxidation 3.74E-02 1.00E+00 angiogenesis 3.77E-02 1.00E+00 positive regulation of metabolism 3.90E-02 1.00E+00 circadian rhythm 4.01E-02 1.00E+00 positive regulation of transcription 4.08E-02 1.00E+00 positive regulation of nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 4.08E-02 1.00E+00 regulation of cell proliferation 4.40E-02 1.00E+00 regulation of growth 4.51E-02 1.00E+00 MAPKKK cascade 4.51E-02 1.00E+00 B.A15_ind response to unfolded protein 1.93E-03 1.00E+00 circadian rhythm 2.92E-03 1.00E+00 chromosome organization and biogenesis 7.37E-03 1.00E+00 establishment and/or maintenance of chromatin architecture 9.55E-03 1.00E+00 serine family amino acid metabolism 1.17E-02 1.00E+00 regulation of lymphocyte proliferation 1.19E-02 1.00E+00 adipocyte differentiation 1.23E-02 1.00E+00 rhythmic process 1.41E-02 1.00E+00 negative regulation of metabolism 1.78E-02 1.00E+00 DNA packaging 1.81E-02 1.00E+00 protein folding 1.85E-02 1.00E+00 epithelial cell differentiation 1.97E-02 1.00E+00 organelle organization and biogenesis 1.99E-02 1.00E+00 response to temperature 2.23E-02 1.00E+00 amino acid biosynthesis 2.69E-02 1.00E+00 lymphocyte proliferation 2.69E-02 1.00E+00 chromatin modification 2.93E-02 1.00E+00 sulfur amino acid biosynthesis 3.00E-02 1.00E+00 L-serine metabolism 3.00E-02 1.00E+00 chromatin assembly or disassembly 3.18E-02 1.00E+00 sulfur amino acid metabolism 3.29E-02 1.00E+00 B-cell proliferation 3.29E-02 1.00E+00 response to heat 3.72E-02 1.00E+00 positive regulation of nucleobase\, nucleoside\, nucleotide and nucleic acid metabolism 3.73E-02 1.00E+00 positive regulation of transcription 3.73E-02 1.00E+00 chromosome organization and biogenesis (sensu Eukaryota) 3.75E-02 1.00E+00 heart development 3.91E-02 1.00E+00 positive regulation of lymphocyte proliferation 4.17E-02 1.00E+00 aromatic compound metabolism 4.18E-02 1.00E+00 regulation of metabolism 4.29E-02 1.00E+00 regulation of epithelial cell differentiation 4.41E-02 1.00E+00 mRNA metabolism 4.79E-02 1.00E+00 negative regulation of cellular metabolism 4.84E-02 1.00E+00

Gene Expression in Mouse Chromosome Substitution Strains 19

Shockley and Churchill, 2006

Table S5. EASE Functional Category Analysis in Mouse Kidney Gene Category EASE score Bon

B.A1 cellular lipid metabolism 7.75E-04 6.12E-01 organic acid biosynthesis 9.35E-04 7.37E-01 carboxylic acid biosynthesis 9.35E-04 7.37E-01 cellular biosynthesis 1.14E-03 9.01E-01 fatty acid metabolism 2.23E-03 1.00E+00 organic acid metabolism 2.51E-03 1.00E+00 carboxylic acid metabolism 2.51E-03 1.00E+00 lipid metabolism 3.35E-03 1.00E+00 biosynthesis 3.66E-03 1.00E+00 lipid biosynthesis 7.32E-03 1.00E+00 fatty acid biosynthesis 7.42E-03 1.00E+00 positive regulation of transport 1.46E-02 1.00E+00 organismal physiological process 2.18E-02 1.00E+00 microtubule cytoskeleton organization and biogenesis 3.53E-02 1.00E+00 regulation of cell activation 4.03E-02 1.00E+00 regulation of lymphocyte activation 4.03E-02 1.00E+00 steroid metabolism 4.09E-02 1.00E+00 transport 4.65E-02 1.00E+00 establishment of localization 4.71E-02 1.00E+00 immune response 4.83E-02 1.00E+00 cholesterol metabolism 4.92E-02 1.00E+00 B.A6 negative regulation of cell adhesion 1.01E-03 5.69E-01 regulation of cell adhesion 5.94E-03 1.00E+00 negative regulation of cellular process 8.99E-03 1.00E+00 positive regulation of cellular physiological process 1.05E-02 1.00E+00 positive regulation of physiological process 1.17E-02 1.00E+00 positive regulation of cellular process 1.48E-02 1.00E+00 negative regulation of biological process 1.55E-02 1.00E+00 regulation of cellular process 2.12E-02 1.00E+00 positive regulation of biological process 3.14E-02 1.00E+00 gas transport 4.75E-02 1.00E+00 oxygen transport 4.75E-02 1.00E+00 regulation of biological process 4.91E-02 1.00E+00 B.A15 oxygen transport 0.03698052 1.00E+00 gas transport 0.03698052 1.00E+00 endoderm development 0.0478126 1.00E+00

Gene Expression in Mouse Chromosome Substitution Strains 20

Shockley and Churchill, 2006

Table S6. Overlaps Between Liver and Kidney Results probe set ID FDR (l) FDR (k) FC (l) FC (k) chr Symbol Description GO Biological Process B.A1 1416770_at 0.00E+00 0.00E+00 -2.6 -2.9 1 Stk25 serine/threonine kinase 25 (yeast) protein amino acid phosphorylation 1455208_at 0.00E+00 0.00E+00 -2.6 -3.0 1 Pex19 peroxisome biogenesis factor 19 peroxisome organization and biogenesis 1453074_at 5.05E-04 0.00E+00 -2.1 -1.9 1 Dusp23 dual specificity phosphatase 23 1439167_at 5.22E-04 0.00E+00 -1.9 -2.0 1 Pecr peroxisomal trans-2-enoyl-CoA reductase fatty acid biosynthesis, metabolism, lipid biosynthesis, fatty acid elongation 1431233_at 4.56E-03 0.00E+00 -1.6 -2.1 1 Cnnm4 cyclin M4 1417469_at 8.36E-03 3.28E-05 -1.6 -1.6 1 Nit1 nitrilase 1 nitrogen compound metabolism 1428023_at 2.11E-03 0.00E+00 1.6 1.5 1 3110009E18Rik RIKEN cDNA 3110009E18 gene 1419504_at 3.16E-04 3.28E-05 1.9 2.0 1 Mogat1 monoacylglycerol O-acyltransferase 1 diacylglycerol biosynthesis G-protein coupled receptor protein signaling 1420941_at 5.20E-03 0.00E+00 2.8 -1.8 1 Rgs5 pathway, negative regulation of signal regulator of G-protein signaling 5 transduction 1421551_s_at 5.05E-04 0.00E+00 6.9 2.5 1 Ifi202b interferon activated gene 202B immune response 1457666_s_at 5.96E-05 0.00E+00 20.2 4.7 1 Ifi202b interferon activated gene 202B immune response

B.A6 1446155_at 0.00E+00 0.00E+00 -4.7 -5.5 6 2700089E24Rik RIKEN cDNA 2700089E24 gene 1436240_at 8.31E-04 0.00E+00 -3.9 -23.2 6 G430041M01Rik RIKEN cDNA G430041M01 gene nuclear mRNA splicing (via spliceosome), mRNA processing 1453145_at 0.00E+00 0.00E+00 -2.4 -2.6 5 4933439C20Rik RIKEN cDNA 4933439C20 gene 1435878_at 2.68E-03 1.11E-03 -2.2 -1.4 6 Stk38l serine/threonine kinase 38 like protein amino acid phosphorylation, protein targeting apoptosis, regulation of apoptosis, positive 1417045_at 7.88E-04 4.99E-03 -2.1 -1.3 6 Bid BH3 interacting domain death agonist regulation of apoptosis regulation of transcription (DNA-dependent), regulation of transcription from RNA polymerase 1425806_a_at 2.13E-03 1.19E-03 -1.8 -1.4 6 Surb7 SRB7 (supressor of RNA polymerase B) homolog II promoter, transcription from RNA polymerase (S. cerevisiae) II promoter, positive regulation of transcription from RNA polymerase II promoter 1460603_at 5.31E-03 0.00E+00 -1.8 -1.7 6 Samd9l sterile alpha motif domain containing 9-like 1417233_at 2.32E-03 0.00E+00 -1.4 -1.6 6 Chchd4 coiled-coil-helix-coiled-coil-helix domain containing 4 1456700_x_at 4.09E-03 2.07E-03 -1.4 1.4 10 Marcks Myristoylated alanine rich protein kinase C substrate 1451891_a_at 8.71E-03 0.00E+00 -1.3 -2.5 6 Dysf dysferlin plasma membrane repair 1455215_at 9.18E-03 0.00E+00 1.3 2.1 6 C530028O21Rik RIKEN cDNA C530028O21 gene 1425003_at 3.67E-03 3.81E-04 1.7 -1.9 6 Uroc1 urocanase domain containing 1 histidine metabolism, histidine catabolism

Gene Expression in Mouse Chromosome Substitution Strains 21

Shockley and Churchill, 2006

Table S6. (Overlaps, Cont.) B.A15 1435140_at 3.97E-03 3.03E-04 -3.14 -1.48 19 Ide insulin degrading enzyme proteolysis and peptidolysis 1453145_at 1.59E-03 0.00E+00 -2.79 -2.87 5 4933439C20Rik RIKEN cDNA 4933439C20 gene 1453571_at 1.91E-03 0.00E+00 -2.71 -1.65 15 Depdc6 DEP domain containing 6 intracellular signaling cascade 1436944_x_at 6.09E-03 0.00E+00 -2.63 -1.33 5 Pisd phosphatidylserine decarboxylase phospholipid metabolism, phospholipid biosynthesis 1435838_at 1.91E-03 2.59E-03 -2.48 -1.18 15 LOC268782 similar to alanine-glyoxylate aminotransferase 2 1427981_a_at 0.00E+00 0.00E+00 -2.45 -1.65 15 Csad amino acid metabolism, L-cysteine catabolism to cysteine sulfinic acid decarboxylase taurine, taurine metabolism 1417707_at 9.04E-03 5.62E-03 -2.05 1.37 5 B230342M21Rik RIKEN cDNA B230342M21 gene 1456655_at 1.11E-04 0.00E+00 -1.93 -2.67 15 Ext1 gastrulation, endoderm development, mesoderm Exostoses (multiple) 1 development 1453287_at 8.34E-03 0.00E+00 -1.85 -1.90 15 5730557B15Rik RIKEN cDNA 5730557B15 gene 1418245_a_at 2.31E-04 0.00E+00 2.62 1.50 15 Rbm9 RNA binding motif protein 9 1439773_at 0.00E+00 2.34E-03 2.88 -1.30 15 Ly6e lymphocyte antigen 6 complex, locus E defense response

Gene Expression in Mouse Chromosome Substitution Strains 22

Shockley and Churchill, 2006

Figure S1

Figure S1. Effect of False Discovery Rate Threshold on the Determination of cis- and trans- QTL in the Mouse Liver. For various false discovery rate thresholds, cis-QTL are represented by the solid line while trans-QTL are represented by the dotted line.

Gene Expression in Mouse Chromosome Substitution Strains 23

Shockley and Churchill, 2006

Figure S2

Figures S2. Representations of the Distributions of the Ratio = (fold change B.AN/fold change A/J) in the CSS test for STRAIN for Chromosomes 1-9. In the diagrams above, cis- regulated are indicated in by the solid line and trans-regulated transcripts are shown in the dotted line for probe sets which show significant (q < 0.01) changes for both the expression differences between strains and differences between parental strains.

Gene Expression in Mouse Chromosome Substitution Strains 24

Shockley and Churchill, 2006

Figure S2

Figures S2 (cont.). Representations of the Distributions of the Ratio = (fold change B.AN/fold change A/J) in the CSS test for STRAIN for Chromosomes 10-19. In the diagrams above, cis-regulated are indicated in by the solid line and trans-regulated transcripts are shown in the dotted line for probe sets which show significant (q < 0.01) changes for both the expression differences between strains and differences between parental strains.

Gene Expression in Mouse Chromosome Substitution Strains 25

Shockley and Churchill, 2006

Figure S2

Figures S2 (cont.). Representations of the Distributions of the Ratio = (fold change B.AN/fold change A/J) in the CSS test for STRAIN for Chromosome 19. In the diagrams above, cis-regulated are indicated in by the solid line and trans-regulated transcripts are shown in the dotted line for probe sets which show significant (q < 0.01) changes for both the expression differences between strains and differences between parental strains.

Gene Expression in Mouse Chromosome Substitution Strains 26

Shockley and Churchill, 2006

Figure S3

Figure S3. Statistically Shared Overlaps between CSS Strains. (A) Results from the intersections of the Fisher’s exact test calculations to test for association between intersecting pairs of probe sets derived from the CSS strain tests in the mouse liver. The thickness of the lines represent –log(p-value). The top ten most significant intersection associations are presented in brown. (B) Intersections whose members did not show a significant association (p > 0.05) in the mouse liver.

Gene Expression in Mouse Chromosome Substitution Strains 27

Shockley and Churchill, 2006

Figure S4

Figure S4. Distribution of SNPs in C57BL/6J and A/J Mouse Strains. The bars represent the number of base pairs in the Celera SNP database for which data is available for both parent strains considered in this study broken down by chromosome. The lines represent a measure of dissimilarity between the strains in the form of the percent of single nucleotide polymorphisms between the two strains for the given number of base pairs available for analysis.

Gene Expression in Mouse Chromosome Substitution Strains 28

Figure S5 Shockley and Churchill, 2006

Gene Expression in Mouse Chromosome Substitution Strains 29

Figure S5 Shockley and Churchill, 2006

Gene Expression in Mouse Chromosome Substitution Strains 30