Glatt et al. 10.1073/pnas.0507666102. |
Fig. 2. Relationships among ontology terms overrepresented by differentially expressed genes in dorsolateral prefrontal cortex (DLPFC) in schizophrenia (SZ). Of the 177 genes differentially expressed in DLPFC in SZ, 25 were linked to one or more significantly overrepresented terms in the Biological Process (A) and/or Molecular Function (B) ontology. Colored ovals represent ontology terms that were significantly overrepresented among the genes differentially expressed in the DLPFC in SZ (pink, P < 0.05; red, P < 0.01).
Table 4. Genes differentially expressed in DLPFC in SZ
Accession number | Gene symbol | Gene product | Chromosomal locus* | Fold change in SZ | P | |
AF003114 | CYR61 | Cysteine-rich, angiogenic inducer, 61 | 1p31-p22 | 1.39 | 0.02990 | |
201445_at | NM_001839 | CNN3 | Calponin 3, acidic | 1p22-p21 | 1.37 | 0.01660 |
208859_s_at | AI650257 | ATRX | Alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae) | Xq13.1-q21.1 | 1.36 | 0.00980 |
215338_s_at | AI688640 | NKTR | Natural killer-tumor recognition sequence | 3p23-p21 | 1.33 | 0.00280 |
216563_at | X80821 | ANKRD12 | Ankyrin repeat domain 12 | 18p11.22 | 1.32 | 0.01470 |
216609_at | AF065241 | TXN | Thioredoxin | 9q31 | 1.32 | 0.01980 |
208993_s_at | AW340788 | PPIG | Peptidyl-prolyl isomerase G (cyclophilin G) | 2q31.1 | 1.30 | 0.03260 |
209655_s_at | AI803181 | TM4SF10 | Transmembrane 4 superfamily member 10 | Xp11.4 | 1.30 | 0.01260 |
203548_s_at | BF672975 | LPL | Lipoprotein lipase | 8p22* | 1.28 | 0.02680 |
217820_s_at | NM_018212 | ENAH | Enabled homolog (Drosophila) | 1q42.12 | 1.28 | 0.00620 |
211997_x_at | NM_005324 | H3F3B | H3 histone, family 3B (H3.3B) | 17q25 | 1.26 | 0.00280 |
214212_x_at | AI928241 | PLEKHC1 | Pleckstrin homology domain containing, family C (with FERM domain) member 1 | 14q22.1 | 1.26 | 0.04640 |
218930_s_at | NM_018374 | FLJ11273 | Hypothetical protein FLJ11273 | 7p21.3 | 1.26 | 0.01520 |
202619_s_at | AI754404 | PLOD2 | Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase) 2 | 3q23-q24 | 1.25 | 0.02280 |
202412_s_at | AW499935 | USP1 | Ubiquitin specific protease 1 | 1p32.1-p31.3 | 1.23 | 0.04030 |
209069_s_at | BC001124 | H3F3B | H3 histone, family 3B (H3.3B) | 17q25 | 1.23 | 0.00480 |
207014_at | NM_000807 | GABRA2 | Gamma-aminobutyric acid (GABA) A receptor, alpha 2 | 4p12 | 1.22 | 0.01050 |
204964_s_at | NM_005086 | SSPN | Sarcospan (Kras oncogene-associated gene) | 12p11.2 | 1.21 | 0.04060 |
212649_at | AL079292 | DHX29 | DEAH (Asp-Glu-Ala-His) box polypeptide 29 | 5q11.2 | 1.21 | 0.04200 |
215450_at | W87901 | SNRPE | Small nuclear ribonucleoprotein polypeptide E | 1q32 | 1.21 | 0.03350 |
217936_at | AW044631 | ARHGAP5 | Rho GTPase activating protein 5 | 14q12* | 1.21 | 0.03890 |
208920_at | AV752215 | SRI | Sorcin | 7q21.1 | 1.20 | 0.02480 |
209024_s_at | AI472757 | SYNCRIP | Synaptotagmin binding, cytoplasmic RNA interacting protein | 6q14-q15 | 1.20 | 0.01850 |
209600_s_at | S69189 | ACOX1 | Acyl-Coenzyme A oxidase 1, palmitoyl | 17q24-q25* | 1.20 | 0.00480 |
212044_s_at | BE737027 | RPL27A | Hypothetical protein MGC10850 | 11p15 | 1.20 | 0.02780 |
218490_s_at | NM_018443 | ZNF302 | Zinc finger protein 302 | 19q13.11 | 1.20 | 0.03440 |
200943_at | NM_004965 | HMGN1 | High-mobility group nucleosome binding domain 1 | 21q22.3 | 1.19 | 0.00920 |
222035_s_at | AI984479 | PAPOLA | Poly(A) polymerase alpha | 14q32.31 | 1.19 | 0.02600 |
203202_at | AI950314 | HRB2 | HIV-1 rev binding protein 2 | 12q21.1 | 1.18 | 0.02550 |
203628_at | H05812 | IGF1R | Insulin-like growth factor 1 receptor | 15q26.3 | 1.18 | 0.03650 |
205475_at | NM_007281 | SCRG1 | Scrapie responsive protein 1 | 4q31-q32 | 1.18 | 0.02860 |
218859_s_at | NM_016649 | C20orf6 | Chromosome 20 open reading frame 6 | 20p12.1* | 1.18 | 0.03300 |
201965_s_at | NM_015046 | KIAA0625 | Senataxin | 9q34.13 | 1.17 | 0.01070 |
203549_s_at | NM_000237 | LPL | Lipoprotein lipase | 8p22* | 1.17 | 0.04020 |
208990_s_at | AF132362 | HNRPH3 | Heterogeneous nuclear ribonucleoprotein H3 (2H9) | 10q22 | 1.17 | 0.01960 |
210970_s_at | AF235049 | IBTK | Inhibitor of Bruton agammaglobulinemia tyrosine kinase | 6q14.1 | 1.17 | 0.04700 |
212179_at | AW157501 | C6orf111 | Chromosome 6 open reading frame 111 | 6q16.3* | 1.17 | 0.04900 |
212689_s_at | AA524505 | JMJD1A | Jumonji domain containing 1A | 2p11.2* | 1.17 | 0.01230 |
214352_s_at | BF673699 | KRAS2 | v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog | 12p12.1 | 1.17 | 0.00330 |
221960_s_at | AI189609 | RAB2 | RAB2, member RAS oncogene family | 8q12.1 | 1.17 | 0.02270 |
201129_at | NM_006276 | SFRS7 | Splicing factor, arginine/serine-rich 7, 35kDa | 2p22.1 | 1.16 | 0.03180 |
201918_at | AI927944 | FLJ10618 | Hypothetical protein FLJ10618 | 3q23 | 1.16 | 0.04000 |
207010_at | NM_000812 | GABRB1 | Gamma-aminobutyric acid (GABA) A receptor, beta 1 | 4p12 | 1.16 | 0.04360 |
209763_at | AL049176 | CHRDL1 | Chordin-like 1 | Xq23 | 1.16 | 0.03340 |
212368_at | AA972711 | ZNF292 | Zinc finger protein 292 | 6q15* | 1.16 | 0.04620 |
213792_s_at | AA485908 | INSR | Insulin receptor | 19p13.3-p13.2 | 1.16 | 0.01300 |
214433_s_at | NM_003944 | SELENBP1 | Selenium binding protein 1 | 1q21-q22 | 1.16 | 0.04510 |
218183_at | NM_013399 | C16orf5 | Chromosome 16 open reading frame 5 | 16p13.3 | 1.16 | 0.03280 |
218595_s_at | NM_018072 | FLJ10359 | Hypothetical protein FLJ10359 | 1q43 | 1.16 | 0.01920 |
202258_s_at | U50532 | PFAAP5 | Phosphonoformate immuno-associated protein 5 | 13q12-q13 | 1.15 | 0.02060 |
211929_at | AA527502 | HNRPA3 | Heterogeneous nuclear ribonucleoprotein A3 | 2q31.2 | 1.15 | 0.01410 |
219819_s_at | NM_014018 | MRPS28 | Mitochondrial ribosomal protein S28 | 8q21.1-q21.2 | 1.15 | 0.00580 |
200616_s_at | BC000371 | KIAA0152 | KIAA0152 gene product | 12q24.31 | 1.14 | 0.02490 |
AL535380 | BTG1 | B-cell translocation gene 1, anti-proliferative | 12q22 | 1.14 | 0.04020 | |
201138_s_at | BG532929 | SSB | Sjogren syndrome antigen B (autoantigen La) | 2q31.1 | 1.14 | 0.00570 |
201637_s_at | NM_005087 | FXR1 | Fragile X mental retardation, autosomal homolog 1 | 3q28 | 1.14 | 0.04690 |
201831_s_at | BE875592 | VDP | Vesicle docking protein p115 | 4q21.1 | 1.14 | 0.02890 |
202324_s_at | NM_022735 | ACBD3 | Acyl-Coenzyme A binding domain containing 3 | 1q42.12 | 1.14 | 0.04460 |
203526_s_at | M74088 | APC | Adenomatosis polyposis coli | 5q21-q22 | 1.14 | 0.02510 |
207557_s_at | NM_001035 | RYR2 | Ryanodine receptor 2 (cardiac) | 1q42.1-q43 | 1.14 | 0.01030 |
208663_s_at | AI652848 | TTC3 | Tetratricopeptide repeat domain 3 | 21q22.2 | 1.14 | 0.04010 |
209049_s_at | BC001004 | PRKCBP1 | Protein kinase C binding protein 1 | 20q13.12 | 1.14 | 0.03340 |
212332_at | BF110947 | RBL2 | Retinoblastoma-like 2 (p130) | 16q12.2* | 1.14 | 0.04480 |
216039_at | D38503 | PMS2L1 | Postmeiotic segregation increased 2-like 1 | 7q22.1 | 1.14 | 0.03510 |
217975_at | NM_016303 | WBP5 | WW domain binding protein 5 | Xq22.2 | 1.14 | 0.02620 |
200944_s_at | NM_004965 | HMGN1 | High-mobility group nucleosome binding domain 1 | 21q22.3 | 1.13 | 0.02050 |
201773_at | NM_015339 | ADNP | Activity-dependent neuroprotector | 20q13.13 | 1.13 | 0.01290 |
203133_at | NM_006808 | SEC61B | Sec61 beta subunit | 9q22.32-q31.3 | 1.13 | 0.00260 |
208921_s_at | L12387 | SRI | Sorcin | 7q21.1 | 1.13 | 0.02490 |
210588_x_at | L32610 | HNRPH3 | Heterogeneous nuclear ribonucleoprotein H3 (2H9) | 10q22 | 1.13 | 0.04050 |
211930_at | AW080932 | HNRPA3 | Heterogeneous nuclear ribonucleoprotein A3 | 2q31.2 | 1.13 | 0.02060 |
212519_at | AL518159 | UBE2E1 | Ubiquitin-conjugating enzyme E2E 1 (UBC4/5 homolog, yeast) | 3p24.2* | 1.13 | 0.03680 |
216399_s_at | AK025663 | ZNF291 | Zinc finger protein 291 | 15q24 | 1.13 | 0.00080 |
218435_at | NM_013238 | DNAJD1 | DnaJ (Hsp40) homolog, subfamily D, member 1 | 13q14.1 | 1.13 | 0.01580 |
55692_at | W22924 | ELMO2 | Engulfment and cell motility 2 (ced-12 homolog, C. elegans) | 20q13 | 1.13 | 0.03650 |
202299_s_at | NM_006402 | HBXIP | Hepatitis B virus x interacting protein | 1p13.3* | 1.12 | 0.04400 |
207543_s_at | NM_000917 | P4HA1 | Procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide I | 10q21.3-q23.1 | 1.12 | 0.03640 |
209180_at | U49245 | RABGGTB | Rab geranylgeranyltransferase, beta subunit | 1p31 | 1.12 | 0.02210 |
211784_s_at | BC006181 | SFRS1 | Splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) | 17q21.3-q22* | 1.12 | 0.02460 |
211828_s_at | AF172268 | TNIK | TRAF2 and NCK interacting kinase | 3q26.2 | 1.12 | 0.04840 |
221613_s_at | AL136598 | ZA20D3 | Zinc finger, A20 domain containing 3 | 15q25.1 | 1.12 | 0.04060 |
200020_at | NM_007375 | TARDBP | TAR DNA binding protein | 1p36.22 | 1.11 | 0.04070 |
200063_s_at | BC002398 | NPM1 | Nucleophosmin (nucleolar phosphoprotein B23, numatrin) | 5q35 | 1.11 | 0.03260 |
202266_at | NM_016614 | TTRAP | TRAF and TNF receptor associated protein | 6p22.3-p22.1* | 1.11 | 0.04520 |
202301_s_at | BE396879 | FLJ11021 | Similar to splicing factor, arginine/serine-rich 4 | 12q24.31 | 1.11 | 0.02420 |
209059_s_at | AB002282 | EDF1 | Endothelial differentiation-related factor 1 | 9q34.3 | 1.11 | 0.02090 |
214053_at | AW772192 | ERBB4 | v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) | 2q33.3-q34 | 1.11 | 0.04040 |
217869_at | NM_016142 | HSD17B12 | Hydroxysteroid (17-beta) dehydrogenase 12 | 11p11.2 | 1.11 | 0.03900 |
222216_s_at | AK026857 | MRPL17 | Mitochondrial ribosomal protein L17 | 11p15.5-p15.4 | 1.11 | 0.01650 |
200977_s_at | AF090891 | TAX1BP1 | Tax1 (human T-cell leukemia virus type I) binding protein 1 | 7p15 | 1.10 | 0.03050 |
201812_s_at | NM_019059 | TOMM7 | Translocase of outer mitochondrial membrane 7 homolog (yeast) | 7p15.3 | 1.10 | 0.04140 |
203870_at | BE856374 | USP46 | Ubiquitin specific protease 46 | 4q12 | 1.10 | 0.04410 |
203880_at | NM_005694 | COX17 | COX17 homolog, cytochrome c oxidase assembly protein (yeast) | 3q13.33 | 1.10 | 0.01780 |
208726_s_at | BC000461 | EIF2S2 | Eukaryotic translation initiation factor 2, subunit 2 beta, 38kDa | 20pter-q12* | 1.10 | 0.03110 |
208895_s_at | BG530850 | DDX18 | DEAD (Asp-Glu-Ala-Asp) box polypeptide 18 | 2q14.1* | 1.10 | 0.04930 |
217724_at | AF131807 | PAI-RBP1 | PAI-1 mRNA-binding protein | 1p31-p22 | 1.10 | 0.01610 |
201157_s_at | AF020500 | NMT1 | N-myristoyltransferase 1 | 17q21.31 | 1.09 | 0.00980 |
201606_s_at | BE796924 | PWP1 | Nuclear phosphoprotein similar to S. cerevisiae PWP1 | 12q23.3 | 1.09 | 0.04390 |
203621_at | NM_002492 | NDUFB5 | NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 5, 16kDa | 3q26.33 | 1.09 | 0.02910 |
209224_s_at | BC003674 | NDUFA2 | NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8kDa | 5q31* | 1.09 | 0.02260 |
217898_at | NM_020154 | C15orf24 | Chromosome 15 open reading frame 24 | 15q14 | 1.09 | 0.01910 |
217907_at | NM_014161 | MRPL18 | Mitochondrial ribosomal protein L18 | 6q25.3 | 1.09 | 0.00370 |
218123_at | NM_017835 | C21orf59 | Chromosome 21 open reading frame 59 | 21q22.1 | 1.09 | 0.00130 |
200728_at | BE566290 | ACTR2 | Actin-related protein 2 homolog (yeast) | 2p14 | 1.08 | 0.04030 |
217774_s_at | NM_016404 | HSPC152 | Hypothetical protein HSPC152 | 11q13.1 | 1.08 | 0.02850 |
217940_s_at | NM_018210 | FLJ10769 | Hypothetical protein FLJ10769 | 13q34 | 1.08 | 0.01660 |
218142_s_at | NM_016302 | CRBN | Cereblon | 3p26.2 | 1.08 | 0.01660 |
201134_x_at | NM_001867 | COX7C | Cytochrome c oxidase subunit VIIc | 5q14 | 1.07 | 0.04030 |
203478_at | NM_002494 | NDUFC1 | NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 1, 6kDa | 4q28.2-q31.1 | 1.07 | 0.00900 |
217491_x_at | AF042165 | COX7CP1 | Cytochrome c oxidase subunit VIIc pseudogene 1 | 13q14-q21 | 1.07 | 0.03650 |
217874_at | NM_003849 | SUCLG1 | Succinate-CoA ligase, GDP-forming, alpha subunit | 2p11.2* | 1.06 | 0.02870 |
200021_at | NM_005507 | CFL1 | Cofilin 1 (non-muscle) | 11q13 | -1.06 | 0.04670 |
203929_s_at | AI056359 | MAPT | Microtubule-associated protein tau | 17q21.1 | -1.07 | 0.04770 |
211780_x_at | BC006163 | DCTN1 | Dynactin 1 (p150, glued homolog, Drosophila) | 2p13 | -1.07 | 0.03780 |
213867_x_at | AA809056 | ARHGEF10 | Rho guanine nucleotide exchange factor (GEF) 10 | 8p23 | -1.07 | 0.02110 |
201864_at | NM_001493 | GDI1 | GDP dissociation inhibitor 1 | Xq28 | -1.08 | 0.02220 |
202508_s_at | NM_003081 | SNAP25 | Synaptosomal-associated protein, 25kDa | 20p12-p11.2* | -1.08 | 0.02980 |
202752_x_at | NM_012244 | SLC7A8 | Solute carrier family 7 (cationic amino acid transporter, y+ system), member 8 | 14q11.2* | -1.08 | 0.01790 |
203103_s_at | NM_014502 | PRP19 | PRP19/PSO4 homolog (S. cerevisiae) | 11q12.2 | -1.08 | 0.01750 |
206213_at | NM_003394 | WNT10B | Wingless-type MMTV integration site family, member 10B | 12q13 | -1.08 | 0.04540 |
214626_s_at | AK026548 | GANAB | Glucosidase, alpha; neutral AB | 11q12.3 | -1.08 | 0.01490 |
221966_at | AA813194 | RH98400 | Chromosome 11 hypothetical protein ORF4 | 11cen-q22.3* | -1.08 | 0.01840 |
35265_at | U31501 | FXR2 | Fragile X mental retardation, autosomal homolog 2 | 17p13.1 | -1.08 | 0.00660 |
200758_s_at | AI361227 | NFE2L1 | Nuclear factor (erythroid-derived 2)-like 1 | 17q21.3 | -1.09 | 0.01890 |
202210_x_at | NM_019884 | GSK3A | Glycogen synthase kinase 3 alpha | 19q13.2 | -1.09 | 0.02490 |
202801_at | NM_002730 | PRKACA | Protein kinase, cAMP-dependent, catalytic, alpha | 19p13.1 | -1.09 | 0.04400 |
203906_at | AI652645 | IQSEC1 | IQ motif and Sec7 domain 1 | 3p25.2* | -1.09 | 0.04350 |
205331_s_at | NM_016606 | C5orf19 | Chromosome 5 open reading frame 19 | 5q31* | -1.09 | 0.01970 |
207366_at | NM_002251 | KCNS1 | Potassium voltage-gated channel, delayed-rectifier, subfamily S, member 1 | 20q12 | -1.09 | 0.04360 |
208390_s_at | U01104 | GLP1R | Glucagon-like peptide 1 receptor | 6p21* | -1.09 | 0.03080 |
208829_at | AF029750 | TAPBP | TAP binding protein (tapasin) | 6p21.3* | -1.09 | 0.02930 |
214354_x_at | T91506 | SFTPB | Surfactant, pulmonary-associated protein B | 2p12-p11.2* | -1.09 | 0.02470 |
219521_at | NM_018644 | B3GAT1 | Beta-1,3-glucuronyltransferase 1 (glucuronosyltransferase P) | 11q25 | -1.09 | 0.04350 |
220465_at | NM_024988 | FLJ12355 | Hypothetical protein FLJ12355 | 19q13.11 | -1.09 | 0.00970 |
221560_at | AB049127 | MARK4 | MAP/microtubule affinity-regulating kinase 4 | 19q13.3 | -1.09 | 0.02540 |
200001_at | NM_001749 | CAPNS1 | Calpain, small subunit 1 | 19q13.12 | -1.10 | 0.01740 |
200639_s_at | NM_003406 | YWHAZ | Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide | 8q23.1 | -1.10 | 0.03720 |
200752_s_at | NM_005186 | CAPN1 | Calpain 1, (mu/I) large subunit | 11q13 | -1.10 | 0.02210 |
202676_x_at | NM_006712 | FASTK | FAST kinase | 7q35 | -1.10 | 0.04340 |
202806_at | NM_004395 | DBN1 | Drebrin 1 | 5q35.3 | -1.10 | 0.02130 |
203618_at | AB023167 | FAIM2 | Fas apoptotic inhibitory molecule 2 | 12q13 | -1.10 | 0.02870 |
204947_at | NM_005225 | E2F1 | E2F transcription factor 1 | 20q11.2 | -1.10 | 0.00300 |
204980_at | NM_004898 | CLOCK | Clock homolog (mouse) | 4q12 | -1.10 | 0.04370 |
209229_s_at | BC002799 | KIAA1115 | KIAA1115 | 19q13.42 | -1.10 | 0.01650 |
210975_x_at | BC000377 | FASTK | FAST kinase | 7q35 | -1.10 | 0.03390 |
211677_x_at | AF062733 | IGSF4B | Immunoglobulin superfamily, member 4B | 1q21.2-q22 | -1.10 | 0.02190 |
214903_at | AF070580 | FLJ42519 | CDNA FLJ42519 fis, clone BRACE3000787 | 1q32 | -1.10 | 0.03390 |
217419_x_at | AK021586 | AGRN | Agrin | 1p36.33 | -1.10 | 0.03320 |
219400_at | NM_003632 | CNTNAP1 | Contactin associated protein 1 | 17q21 | -1.10 | 0.03850 |
221901_at | BF516072 | KIAA1644 | KIAA1644 protein | 22q13 | -1.10 | 0.03390 |
47560_at | AI525402 | LPHN1 | Latrophilin 1 | 19p13.2 | -1.10 | 0.02260 |
203151_at | AW296788 | MAP1A | Microtubule-associated protein 1A | 15q13-qter | -1.11 | 0.02680 |
203831_at | NM_014925 | KIAA1002 | KIAA1002 protein | 12q13.3 | -1.11 | 0.00700 |
205325_at | NM_014759 | PHYHIP | Phytanoyl-CoA hydroxylase interacting protein | 8p21.3* | -1.11 | 0.04680 |
208823_s_at | BE787860 | PCTK1 | PCTAIRE protein kinase 1 | Xp11.3-p11.23 | -1.11 | 0.03640 |
211240_x_at | AB002382 | CTNND1 | Catenin (cadherin-associated protein), delta 1 | 11q11 | -1.11 | 0.01540 |
217766_s_at | NM_014313 | SMP1 | Small membrane protein 1 | 1p36.11 | -1.11 | 0.01340 |
220974_x_at | NM_030971 | BA108L7.2 | Similar to rat tricarboxylate carrier-like protein | 10q24.32 | -1.11 | 0.00260 |
221535_at | AL136897 | FLJ11301 | Hypothetical protein FLJ11301 | 3q29 | -1.11 | 0.00450 |
203244_at | NM_000319 | PEX5 | Peroxisomal biogenesis factor 5 | 12p13.3 | -1.12 | 0.00890 |
203264_s_at | NM_015185 | ARHGEF9 | Cdc42 guanine nucleotide exchange factor (GEF) 9 | Xq11.2 | -1.12 | 0.03980 |
207629_s_at | NM_004723 | ARHGEF2 | Rho/rac guanine nucleotide exchange factor (GEF) 2 | 1q21-q22 | -1.12 | 0.04820 |
209435_s_at | BC000265 | ARHGEF2 | Rho/rac guanine nucleotide exchange factor (GEF) | 1q21-q22 | -1.12 | 0.00820 |
217637_at | R25692 | Unknown | Full length insert cDNA clone ZE05A03 | 20q13.1 | -1.12 | 0.04500 |
212252_at | AA181179 | CAMKK2 | Calcium/calmodulin-dependent protein kinase kinase 2, beta | 12q24.2 | -1.13 | 0.03980 |
212699_at | BE222801 | SCAMP5 | Secretory carrier membrane protein 5 | 15q23 | -1.13 | 0.04090 |
204893_s_at | NM_004799 | ZFYVE9 | Zinc finger, FYVE domain containing 9 | 1p32.3 | -1.14 | 0.04400 |
211934_x_at | W87689 | GANAB | Glucosidase, alpha; neutral AB | 11q12.3 | -1.14 | 0.01130 |
212285_s_at | AW008051 | AGRN | Agrin | 1p36.33 | -1.14 | 0.00740 |
217991_x_at | NM_018070 | SSBP3 | Single stranded DNA binding protein 3 | 1p32.3 | -1.14 | 0.01450 |
218952_at | NM_013271 | PCSK1N | Proprotein convertase subtilisin/kexin type 1 inhibitor | Xp11.23 | -1.14 | 0.03060 |
205508_at | NM_001037 | SCN1B | Sodium channel, voltage-gated, type I, beta | 19q13.1 | -1.15 | 0.00770 |
209728_at | BC005312 | HLA-DRB1 | Major histocompatibility complex, class II, DR beta 1 | 6p21.3* | -1.17 | 0.04220 |
219724_s_at | NM_014796 | KIAA0748 | KIAA0748 gene product | 12q13.2 | -1.21 | 0.00310 |
203337_x_at | NM_004763 | ITGB1BP1 | Integrin beta 1 binding protein 1 | 2p25.2 | -1.29 | 0.01930 |
217427_s_at | X75296 | HIRA | HIR histone cell cycle regulation defective homolog A (S. cerevisiae) | 22q11.2* | -1.32 | 0.00940 |
205048_s_at | NM_003832 | PSPHL | Phosphoserine phosphatase-like | 7q11.2 | -2.14 | 0.04420 |
Implicated in SZ by meta-analysis of genome-wide linkage studies (1).
1. Lewis, C. M., Levinson, D. F., Wise, L. H., DeLisi, L. E., Straub, R. E., Hovatta, I., Williams, N. M., Schwab, S. G., Pulver, A. E., Faraone, S. V., et al. (2003) Am. J. Hum. Genet. 73, 34-48.
Table 5. Genes differentially expressed in PBCs in SZ
Affymetrix probe number | Accession number | Gene symbol | Gene product | Chromosomal locus | Fold change in SZ | P |
M30646 | EPB42 | Erythrocyte membrane protein band 4.2 | 15q15-q21 | 2.35 | 0.00053 | |
211560_s_at | AF130113 | ALAS2 | Aminolevulinate, delta-, synthase 2 (sideroblastic/hypochromic anemia) | Xp11.21 | 2.34 | 0.00111 |
213524_s_at | NM_015714 | G0S2 | Putative lymphocyte G0/G1 switch gene | 1q32.2-q41 | 2.28 | 0.00146 |
219672_at | NM_016633 | ERAF | Erythroid associated factor | 16p11.2 | 2.13 | 0.00029 |
209890_at | AF065389 | TM4SF9 | Transmembrane 4 superfamily member 9 | 4q23 | 2.12 | 0.00203 |
203691_at | NM_002638 | PI3 | Protease inhibitor 3, skin-derived (SKALP) | 20q12-q13 | 2.05 | 0.00001 |
211781_x_at | BC006164 | Unknown | Hypothetical protein MGC13219 | Unknown | 2.04 | 0.00007 |
219630_at | NM_005764 | MAP17 | Membrane-associated protein 17 | 1p33 | 2.01 | 0.00011 |
205950_s_at | NM_001738 | CA1 | Carbonic anhydrase I | 8q13-q22.1 | 1.99 | 0.00049 |
210395_x_at | AF116676 | MYL4 | Myosin, light polypeptide 4, alkali; atrial, embryonic | 17q21-qter | 1.99 | 0.00003 |
204466_s_at | BG260394 | SNCA | Synuclein, alpha (non A4 component of amyloid precursor) | 4q21 | 1.95 | 0.00119 |
214433_s_at | NM_003944 | SELENBP1 | Selenium binding protein 1 | 1q21-q22 | 1.95 | 0.00093 |
201178_at | NM_012179 | FBXO7 | F-box protein 7 | 22q12-q13 | 1.91 | 0.00025 |
211475_s_at | AF116273 | BAG1 | BCL2-associated athanogene | 9p12 | 1.89 | 0.00175 |
206834_at | NM_000519 | HBD | Hemoglobin, delta | 11p15.5 | 1.86 | 0.00132 |
210088_x_at | M36172 | MYL4 | Myosin, light polypeptide 4, alkali; atrial, embryonic | 17q21-qter | 1.84 | 0.00004 |
202219_at | NM_005629 | SLC6A8 | Solute carrier family 6 (neurotransmitter transporter, creatine), member 8 | Xq28 | 1.83 | 0.00026 |
218872_at | NM_017899 | TSC | Hypothetical protein FLJ20607 | 12q24.22 | 1.83 | 0.00019 |
201161_s_at | NM_003651 | CSDA | Cold shock domain protein A | 12p13.1 | 1.81 | 0.00240 |
202387_at | NM_004323 | BAG1 | BCL2-associated athanogene | 9p12 | 1.80 | 0.00130 |
204419_x_at | NM_000184 | HBG2 | Hemoglobin, gamma G | 11p15.5 | 1.80 | 0.00501 |
204467_s_at | NM_000345 | SNCA | Synuclein, alpha (non A4 component of amyloid precursor) | 4q21 | 1.80 | 0.00256 |
216054_x_at | X58851 | MYL4 | Myosin, light polypeptide 4, alkali; atrial, embryonic | 17q21-qter | 1.79 | 0.00002 |
204187_at | NM_006877 | GMPR | Guanosine monophosphate reductase | 6p23 | 1.77 | 0.00011 |
220757_s_at | NM_025241 | UBXD1 | UBX domain containing 1 | 19p13 | 1.77 | 0.00434 |
202947_s_at | NM_002101 | GYPC | Glycophorin C (Gerbich blood group) | 2q14-q21 | 1.73 | 0.00752 |
202201_at | NM_000713 | BLVRB | Biliverdin reductase B (flavin reductase (NADPH)) | 19q13.1-q13.2 | 1.70 | 0.00390 |
204848_x_at | NM_000559 | HBG1 | Hemoglobin, gamma A | 11p15.5 | 1.69 | 0.00779 |
202859_x_at | NM_000584 | IL8 | Interleukin 8 | 4q13-q21 | 1.68 | 0.00347 |
207827_x_at | L36675 | SNCA | Synuclein, alpha (non A4 component of amyloid precursor) | 4q21 | 1.68 | 0.00061 |
211546_x_at | L36674 | SNCA | Synuclein, alpha (non A4 component of amyloid precursor) | 4q21 | 1.68 | 0.00008 |
200844_s_at | BE869583 | PRDX6 | Peroxiredoxin 6 | 1q25.1 | 1.66 | 0.00251 |
202364_at | NM_005962 | MXI1 | MAX interactor 1 | 10q24-q25 | 1.66 | 0.00005 |
204505_s_at | NM_001978 | EPB49 | Erythrocyte membrane protein band 4.9 (dematin) | 8p21.1 | 1.65 | 0.00214 |
214273_x_at | AV704353 | C16orf35 | Chromosome 16 open reading frame 35 | 16p13.3 | 1.65 | 0.00131 |
217748_at | NM_015999 | ADIPOR1 | Adiponectin receptor 1 | 1p36.13-q41 | 1.65 | 0.00138 |
220807_at | NM_005331 | HBQ1 | Hemoglobin, theta 1 | 16p13.3 | 1.62 | 0.00439 |
206207_at | NM_001828 | CLC | Charcot-Leyden crystal protein | 19q13.1 | 1.61 | 0.00009 |
210638_s_at | AF176704 | FBXO9 | F-box protein 9 | 6p12.3-p11.2 | 1.61 | 0.00001 |
202074_s_at | NM_021980 | OPTN | Optineurin | 10p13 | 1.60 | 0.00048 |
202210_x_at | NM_019884 | GSK3A | Glycogen synthase kinase 3 alpha | 19q13.2 | 1.59 | 0.00044 |
205592_at | X77737 | SLC4A1 | Solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group) | 17q21-q22 | 1.59 | 0.00400 |
221479_s_at | AF060922 | BNIP3L | BCL2/adenovirus E1B 19kDa interacting protein 3-like | 8p21 | 1.56 | 0.00543 |
201052_s_at | BG029917 | PSMF1 | Proteasome (prosome, macropain) inhibitor subunit 1 (PI31) | 20p13 | 1.55 | 0.00652 |
40850_at | L37033 | FKBP8 | FK506 binding protein 8, 38kDa | 19p12 | 1.52 | 0.00462 |
217882_at | NM_018447 | LOC55831 | 30 kDa protein | 3p25.3 | 1.51 | 0.00863 |
205863_at | NM_005621 | S100A12 | S100 calcium binding protein A12 (calgranulin C) | 1q21 | 1.50 | 0.00018 |
208949_s_at | BC001120 | LGALS3 | Lectin, galactoside-binding, soluble, 3 (galectin 3) | 14q21-q22 | 1.47 | 0.00157 |
215499_at | AA780381 | MAP2K3 | Mitogen-activated protein kinase kinase 3 | 17q11.2 | 1.47 | 0.00001 |
203966_s_at | NM_021003 | PPM1A | Protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform | 14q23.1 | 1.46 | 0.00013 |
210183_x_at | AF112222 | PNN | Pinin, desmosome associated protein | 14q21.1 | 1.45 | 0.00028 |
204018_x_at | NM_000558 | HBA1 | Hemoglobin, alpha 1 | 16p13.3 | 1.43 | 0.00001 |
211699_x_at | AF349571 | HBA1 | Hemoglobin, alpha 1 | 16p13.3 | 1.43 | 0.00003 |
217756_x_at | NM_005770 | SERF2 | Small EDRK-rich factor 2 | 15q15.3 | 1.43 | 0.00132 |
200633_at | NM_018955 | UBB | Ubiquitin B | 17p12-p11.2 | 1.41 | 0.00031 |
217414_x_at | V00489 | HBA2 | Hemoglobin, alpha 2 | 16p13.3 | 1.40 | 0.00008 |
201285_at | NM_013446 | MKRN1 | Makorin, ring finger protein, 1 | 7q34 | 1.39 | 0.00044 |
209116_x_at | M25079 | HBB | Hemoglobin, beta | 11p15.5 | 1.38 | 0.00002 |
211745_x_at | BC005931 | HBA2 | Hemoglobin, alpha 2 | 16p13.3 | 1.38 | 0.00005 |
217232_x_at | AF059180 | HBB | Hemoglobin, beta | 11p15.5 | 1.36 | 0.00005 |
214271_x_at | AA281332 | RPL12 | Ribosomal protein L12 | 9q34 | 1.35 | 0.00001 |
209458_x_at | AF105974 | HBA1 | Hemoglobin, alpha 1 | 16p13.3 | 1.34 | 0.00012 |
221700_s_at | AF348700 | UBA52 | Ubiquitin A-52 residue ribosomal protein fusion product 1 | 19p13.1-p12 | 1.33 | 0.00005 |
214290_s_at | AI313324 | H2AFO | H2A histone family, member O | 1p36.13-q24.1 | 1.30 | 0.00089 |
211696_x_at | AF349114 | HBB | Hemoglobin, beta | 11p15.5 | 1.29 | 0.00002 |
217977_at | NM_016332 | SEPX1 | Selenoprotein X, 1 | 16p13.3 | 1.29 | 0.00265 |
214414_x_at | T50399 | HBA1 | Hemoglobin, alpha 1 | 16p13.3 | 1.26 | 0.00076 |
211911_x_at | L07950 | HLA-B | Major histocompatibility complex, class I, B | 6p21.3 | -1.21 | 0.00038 |
209619_at | K01144 | CD74 | CD74 antigen (invariant polypeptide of major histocompatibility complex, class II antigen-associated) | 5q32 | -1.24 | 0.00010 |
200871_s_at | NM_002778 | PSAP | Prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy) | 10q21-q22 | -1.27 | 0.00003 |
209312_x_at | U65585 | HLA-DRB1 | Major histocompatibility complex, class II, DR beta 1 | 6p21.3 * | -1.27 | 0.00007 |
200904_at | X56841 | HLA-E | Major histocompatibility complex, class I, E | 6p21.3 | -1.28 | 0.00003 |
208980_s_at | M26880 | UBC | Ubiquitin C | 12q24.3 | -1.28 | 0.00037 |
212363_x_at | AU145192 | ACTG1 | Actin, gamma 1 | 17q25 | -1.30 | 0.00045 |
205237_at | NM_002003 | FCN1 | Ficolin (collagen/fibrinogen domain containing) 1 | 9q34 | -1.33 | 0.00055 |
215193_x_at | AJ297586 | HLA-DRB1 | Major histocompatibility complex, class II, DR beta 1 | 6p21.3 | -1.33 | 0.00006 |
201368_at | U07802 | ZFP36L2 | Zinc finger protein 36, C3H type-like 2 | 2p22.3-p21 | -1.35 | 0.00018 |
200634_at | NM_005022 | PFN1 | Profilin 1 | 17p13.3 | -1.36 | 0.00001 |
200866_s_at | M32221 | PSAP | Prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy) | 10q21-q22 | -1.36 | 0.00015 |
200920_s_at | AL535380 | BTG1 | B-cell translocation gene 1, anti-proliferative | 12q22 | -1.36 | 0.00008 |
200772_x_at | BF686442 | PTMA | Prothymosin, alpha (gene sequence 28) | 2q35-q36 | -1.37 | 0.00032 |
208438_s_at | NM_005248 | FGR | Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog | 1p36.2-p36.1 | -1.38 | 0.00001 |
219505_at | NM_017424 | CECR1 | Cat eye syndrome chromosome region, candidate 1 | 22q11.2 | -1.38 | 0.00001 |
200742_s_at | BG231932 | CLN2 | Ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease) | 11p15 | -1.41 | 0.00001 |
200743_s_at | NM_000391 | CLN2 | Ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky disease) | 11p15 | -1.41 | 0.00001 |
205898_at | U20350 | CX3CR1 | Chemokine (C-X3-C motif) receptor 1 | 3p21 | -1.41 | 0.00002 |
213738_s_at | AI587323 | ATP5A1 | ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit, isoform 1, cardiac muscle | 18q12-q21 | -1.44 | 0.00008 |
211991_s_at | M27487 | HLA-DPA1 | Major histocompatibility complex, class II, DP alpha 1 | 6p21.3 | -1.48 | 0.00002 |
212192_at | AI718937 | KCTD12 | Potassium channel tetramerisation domain containing 12 | 13q22.3 | -1.49 | 0.00005 |
207419_s_at | NM_002872 | RAC2 | Ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) | 22q13.1 | -1.51 | 0.00092 |
211921_x_at | AF348514 | PTMA | Prothymosin, alpha (gene sequence 28) | 2q35-q36 | -1.52 | 0.00002 |
204912_at | NM_001558 | IL10RA | Interleukin 10 receptor, alpha | 11q23 | -1.54 | 0.00006 |
208743_s_at | BC001359 | YWHAB | Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide | 20q13.1 | -1.54 | 0.00003 |
205292_s_at | NM_002137 | HNRPA2B1 | Heterogeneous nuclear ribonucleoprotein A2/B1 | 7p15 | -1.59 | 0.00001 |
203037_s_at | NM_014751 | MTSS1 | Metastasis suppressor 1 | 8p22 | -1.60 | 0.00002 |
203104_at | NM_005211 | CSF1R | Colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog | 5q33-q35 | -1.63 | 0.00001 |
56256_at | AA150165 | SIDT2 | SID1 transmembrane family, member 2 | 11q23.3 | -1.63 | 0.00001 |
201393_s_at | NM_000876 | IGF2R | Insulin-like growth factor 2 receptor | 6q26 | -1.66 | 0.00015 |
211784_s_at | BC006181 | SFRS1 | Splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing factor) | 17q21.3-q22 | -1.71 | 0.00005 |
214617_at | AI445650 | PRF1 | Perforin 1 (pore forming protein) | 10q22 | -1.71 | 0.00001 |
203741_s_at | NM_001114 | ADCY7 | Adenylate cyclase 7 | 16q12-q13 | -1.73 | 0.00002 |
213475_s_at | AC002310 | ITGAL | Integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide) | 16p11.2 | -1.73 | 0.00001 |
208988_at | BE675843 | FBOXL11 | F-box and leucine-rich repeat protein 11 | 11q13.2 | -1.75 | 0.00001 |
213872_at | BE465032 | C6orf62 | Chromosome 6 open reading frame 62 | 6p22.2 | -1.75 | 0.00014 |
218396_at | NM_017684 | VPS13C | Vacuolar protein sorting 13C (yeast) | 15q22.2 | -1.79 | 0.00002 |
209007_s_at | AF267856 | NPD014 | NPD014 protein | 1p36.13-p35.1 | -1.80 | 0.00001 |
201218_at | N23018 | CTBP2 | C-terminal binding protein 2 | 10q26.13 | -1.86 | 0.00003 |
203113_s_at | NM_001960 | EEF1D | Eukaryotic translation elongation factor 1 delta (guanine nucleotide exchange protein) | 8q24.3 | -1.86 | 0.00118 |
202663_at | AI005043 | WASPIP | Wiskott-Aldrich syndrome protein interacting protein | 2q31.1 | -1.89 | 0.00001 |
215646_s_at | R94644 | CSPG2 | Chondroitin sulfate proteoglycan 2 (versican) | 5q14.3 | -1.91 | 0.00008 |
202230_s_at | NM_006387 | CHERP | Calcium homeostasis endoplasmic reticulum protein | 19p13.1 | -1.94 | 0.00001 |
201798_s_at | NM_013451 | FER1L3 | Fer-1-like 3, myoferlin (C. elegans) | 10q24 | -1.95 | 0.00001 |
212070_at | AL554008 | GPR56 | G protein-coupled receptor 56 | 16q13 | -2.02 | 0.00001 |
204516_at | BG390306 | ATXN7 | Ataxin 7 | 3p21.1-p12 | -2.05 | 0.00001 |
214683_s_at | AI251890 | CLK1 | CDC-like kinase 1 | 2q33 | -2.07 | 0.00002 |
201088_at | NM_002266 | KPNA2 | Karyopherin alpha 2 (RAG cohort 1, importin alpha 1) | 17q23.1-q23.3 | -2.08 | 0.00002 |
208810_at | AF080569 | DNAJB6 | DnaJ (Hsp40) homolog, subfamily B, member 6 | 7q36.3 | -2.09 | 0.00001 |
211929_at | AA527502 | HNRPA3 | Heterogeneous nuclear ribonucleoprotein A3 | 2q31.2 | -2.12 | 0.00004 |
213906_at | AW592266 | MYBL1 | v-myb myeloblastosis viral oncogene homolog (avian)-like 1 | 8q22 | -2.22 | 0.00020 |
203132_at | NM_000321 | RB1 | Retinoblastoma 1 (including osteosarcoma) | 13q14.2 | -2.46 | 0.00005 |
209006_s_at | AF247168 | NPD014 | NPD014 protein | 1p36.13-p35.1 | -2.67 | 0.00001 |
221768_at | AV705803 | SFPQ | Splicing factor proline/glutamine rich (polypyrimidine tract binding protein associated) | 1p34.3 | -2.73 | 0.00051 |
202817_s_at | NM_005637 | SS18 | Synovial sarcoma translocation, chromosome 18 | 18q11.2 | -7.24 | 0.00002 |
Supporting Text
Gene Expression in Dorsolateral Prefrontal Cortex (DLPFC)
Samples
: At the Harvard Brain Tissue Resource Center (HBTRC), »50 mg of fresh frozen brain tissue was obtained from the DLPFC of each subject, and RNA was extracted using a Totally RNA Kit (Ambion, Austin, TX). RNA samples were then purified using an RNeasy Kit (Qiagen, Valencia, CA). RNA quality of each sample was verified before hybridization by examining the state of 28S and 18S ribosomal RNA by gel electrophoresis on an Agilent 2100 bioanalyzer (Agilent Technologies, Palo Alto, CA). RNA quality was very similar between samples from SZ patients and control subjects, as determined by several indices, including the mean 28S:18S RNA ratio (1.11 vs. 1.07; P = 0.790) and the mean 3':5' ratio of the RNA transcripts of the housekeeping genes G3PDH (1.57 vs. 1.44; P = 0.407) and ACTB (2.42 vs. 2.33; P = 0.728).Microarray Preparation and Data Acquisition
: Each purified and quality-assured RNA sample (8 mg) was reverse-transcribed by using a SuperScript II double-stranded cDNA synthesis kit (Invitrogen) to yield complimentary cDNAs, which were then transcribed and amplified in vitro with an Enzo-IVT kit (Affymetrix) to yield biotin-labeled cRNAs of all mRNAs present in the brain tissue sample. Samples of cRNA were then fragmented and hybridized to a GeneChip Human Genome U95A or U133A array (Affymetrix), which was stained in a GeneChip Fluidics Station 400 (Affymetrix) and scanned twice in a DNA Microarray Scanner 2500 (Agilent Technologies). Scans were then visually inspected for artifacts such as edge effects or scratches, which were detected in <5% of samples. Samples affected with such artifacts were removed from the National Brain Databank (NBD) database.microarray suite 5.0 software (Affymetrix) was then used to assess the quality of the scans. For arrays with a rate of probe detection below 35%, the entire experimental procedure was repeated from the RNA extraction step forward. If the rate of probe detection was not improved above 35%, the gene expression data for that sample was not added to the NBD database. The rates of probe detection for the samples that we obtained from the NBD were essentially equivalent between the group of schizophrenia (SZ) patients and control subjects (45.8 vs. 45.9% present; P = 0.913), and no sample had a rate of probe detection below 35%.
Ontological Profiling
: To simplify the interpretation of the corgon-derived datasets of significantly modulated genes, we next classified genes according to the standardized ontology terms recognized by the Gene Ontology Consortium (GOC). The gene ontology (GO) classification system established and maintained by the GOC describes gene products in three domains, including Biological Process, Cellular Component, and Molecular Function. The grouping of genes based on ontological dimensions further increases the likelihood of identifying true-positive results for genes that exist within and influence the activity of a family of functionally related genes or an extended gene system that may change in synchrony in the disease state.Ontological classifications and relationships of genes were analyzed with the MicroArray Data Characterization and Profiling (MADCAP) algorithm, which is a tool for unsupervised statistical analysis of gene lists under the three separate GOs of the GOC. The algorithm finds all statistically significant ontology "terms" (of the >18,000 terms recognized by the GOC) and the genes that represent them, and creates a graphical output of the ontology highlighting significant terms. The input into MADCAP consists of two lists of genes: a reference list and a selected list. The reference list typically contains all genes detected as expressed in the corgon-analyzed microarray dataset. The selected list of genes represents a smaller group of genes selected from the reference list according to some criterion, in this case, the genes that were identified by corgon as significantly differentially expressed in the DLPFC of SZ patients and control subjects. MADCAP then identifies which, if any, biological processes, cellular components, and molecular functions are significantly represented in the selected set of genes. Each gene can be linked to several ontology terms, either directly or through daughter GO terms. The reference gene list defines a reference ontology graph as determined by connections of individual genes to ontology terms and connections of terms to other terms. The selected genes define a subgraph of the reference graph. To identify the biological processes represented by the selected genes, MADCAP searches for terms linked to an unusually high number of selected genes. Specifically, starting from the root term of the subgraph and using the known structure of the graphs, we calculate the probability for each immediate daughter term (a P value) that it be linked to as many or more selected genes than if the same number of genes was selected from the reference list at random. If the selected genes had been selected by a specific biological process (or processes) rather than at random, the process itself can be detected by an unusually large number of selected genes. This method is different from that of gominer, in that it calculates conditional P values, which allows discovery of significant terms even if they are small in size. The Fisher test used in gominer may fail to discover small significant terms if there is one large significant term, which in the clustering terminology is analogous to detecting one large cluster while neglecting smaller satellite clusters.
Gene Expression in Peripheral Blood Cells (PBCs)
Samples
: Approximately10 ml of whole blood was collected from each subject into sterile violet-capped Vacutainer tubes (Becton Dickinson) containing K3 EDTA. Each sample was temporarily stored at 4°C and processed within 6 h of collection to preserve the integrity of the mRNA and thereby more accurately reflect the in vivo conditions. Each sample was then processed by separating plasma, buffy coat, and red blood cell layers through centrifugation. Plasma was discarded, red blood cells were ruptured with lysis buffer, and each mixture was centrifuged again, yielding a pellet of white blood cells, which was briefly washed in lysis buffer. TRIzol (1 ml; Invitrogen) was then applied to extract mRNA, which was then purified and assessed for quality as described above for DLPFC samples.Microarray Preparation and Data Acquisition
: Each purified and quality-assured RNA sample (5 mg) was prepared for microarray, hybridized to either a GeneChip Human Genome U133A or U133 Plus 2.0 array, and scanned once using an Affymetrix GeneChip Scanner and Affymetrix gcos software, Ver. 1.1.1, according to the manufacturer’s published protocols (Affymetrix).