Introduction
Materials and methods
Study subjects
Microarray analysis
Microarray data normalization and quality control
Identification of differentially expressed probes
Disease-specific gene expression analyses
Functional analysis of differentially expressed genes
Real-time polymerase chain reaction analysis
Results
Microarray differential expression analysis
Accession | Annotation | Fold changea | Pvalueb | FDR | Function/Category |
---|---|---|---|---|---|
Increased expression in probands | |||||
TNFAIP6
| Tumor necrosis factor-alpha-induced protein 6 | 2.2 | 1.5 × 10-5 | 0.051 | Co-factor, immune |
HP
| Haptoglobin | 2.2 | 2.0 × 10-5 | 0.051 | Carrier, transport |
HPR
| Haptoglobin-related protein | 2.3 | 3.5 × 10-5 | 0.059 | Carrier, transport |
ANXA3
| Annexin A3 | 2.8 | 5.1 × 10-5 | 0.074 | Regulation, signaling |
APOBEC3A
| Apolipoprotein B mRNA editing enzyme 3A | 1.4 | 5.8 × 10-5 | 0.074 | Regulation, translation |
EIF2AK2
| Eukaryotic translation initiation factor 2-alpha kinase 2 | 2.4 | 7.1 × 10-5 | 0.074 | Regulation, translation |
BMX
| Non-receptor tyrosine kinase | 2.2 | 8.6 × 10-5 | 0.074 | Kinase, signaling |
CEACAM6
| Carcinoembryonic Ag-related cell adhesion molecule 6 | 4.7 | 8.7 × 10-5 | 0.074 | Receptor, targeting |
PLSCR1
| Phospholipid scramblase 1 | 2.3 | 1.0 × 10-4 | 0.074 | Regulation, immune |
LTF
| Lactotransferrin | 2.3 | 1.1 × 10-4 | 0.074 | Regulation, immune |
TNFSF10
| Tumor necrosis factor ligand 10 | 1.6 | 1.4 × 10-4 | 0.074 | Cytokine, immune |
OASL
| 2'-5'-Oligoadenylate synthetase-like | 2.2 | 1.7 × 10-4 | 0.074 | Binding, thyroid receptor |
MAP2K6
| Mitogen-activated protein kinase kinase 6 | 1.4 | 2.2 × 10-4 | 0.080 | Kinase, signaling |
ZCCHC2
| Zinc finger protein | 1.5 | 2.4 × 10-4 | 0.082 | Unknown, signaling |
INHBB
| Inhibin, beta B | 2.3 | 2.7 × 10-4 | 0.085 | Ligand, signaling |
DEFA4
| Defensin, alpha 4, corticostatin | 2.3 | 2.9 × 10-4 | 0.088 | Ligand, signaling |
IFI27
| Interferon, alpha-inducible protein 27 | 7.2 | 3.0 × 10-4 | 0.088 | Unknown, immune |
SLC22A4
| Solute carrier family 22, member 4 | 1.7 | 3.3 × 10-4 | 0.088 | Transport |
IL1RN
| Interleukin 1 receptor antagonist | 1.7 | 3.4 × 10-4 | 0.088 | Ligand, immune |
RRAGD
| Ras-related GTP-binding protein D | 1.3 | 3.4 × 10-4 | 0.088 | Ligand, signaling |
DEGS1
| Degenerative spermatocyte homolog 1 | 1.1 | 3.9 × 10-4 | 0.093 | Enzyme, metabolism |
PGAP1
| GPI deacylase | 1.3 | 3.9 × 10-4 | 0.093 | Enzyme, signaling |
F5
| Coagulation factor V | 1.4 | 4.2 × 10-4 | 0.094 | Ligand, coagulation |
CDS2
| CDP-diacylglycerol synthase | 1.2 | 4.6 × 10-4 | 0.097 | Enzyme, metabolism |
HIST1H2AB
| Histone 1, H2ab | 1.3 | 4.7 × 10-4 | 0.097 | Chromatin, structural |
Decreased expression in probands
| |||||
PACSIN1
| Protein kinase C substrate 1 in neurons | -1.4 | 3.3 × 10-6 | 0.042 | Kinase, signaling |
KRTCAP2
| Keratinocyte-associated protein 2 | -1.2 | 5.9 × 10-6 | 0.042 | Enzyme, structural |
FCER1A
| Fc fragment of high affinity IgE receptor | -1.9 | 9.2 × 10-6 | 0.042 | Receptor, immune |
FYN
| Oncogene | -1.3 | 9.8 × 10-6 | 0.042 | Kinase, signaling |
SYTL2
| Synaptotagmin-like 2 | -1.5 | 1.0 × 10-5 | 0.042 | Unknown, immune |
CD99
| MIC2, single-chain type-1 glycoprotein | -1.2 | 1.8 × 10-5 | 0.051 | Receptor, immune |
PECI
| Peroxisomal D3,D2-enoyl-CoA isomerase | -1.3 | 3.3 × 10-5 | 0.059 | Enzyme, metabolism |
CD81
| Target of antiproliferative antibody 1 | -1.2 | 3.4 × 10-5 | 0.059 | Receptor, immune |
PBX4
| Pre-B-cell leukemia transcription factor 4 | -1.4 | 7.7 × 10-5 | 0.074 | Regulation, transcription |
DYRK2
| Tyrosine-phosphorylation regulated kinase 2 | -1.2 | 8.1 × 10-5 | 0.074 | Kinase, signaling |
ZBTB5
| Zinc finger and BTB domain containing 5 | -1.2 | 9.4 × 10-5 | 0.074 | Regulation, transcription |
PABPC3
| Poly(A)-binding protein 3 | -1.3 | 9.8 × 10-5 | 0.074 | Regulation, translation |
NELL2
| NEL-like 2 | -1.3 | 1.0 × 10-4 | 0.074 | Mitogen, cell division |
LOC100133315
| Unknown cation channel/receptor | -1.2 | 1.0 × 10-4 | 0.074 | Receptor, signaling |
DNAJA3
| DnaJ (Hsp40) homolog A3 | -1.3 | 1.2 × 10-4 | 0.074 | Chaperone, transport |
EIF3S6IP
| Eukaryotic translation initiation factor 3, subunit 6 | -1.3 | 1.2 × 10-4 | 0.074 | Regulation, translation |
EIF3S8
| Eukaryotic translation initiation factor 3, subunit 8 | -1.2 | 1.2 × 10-4 | 0.074 | Regulation, translation |
RBMX
| RNA-binding motif protein | -1.1 | 1.2 × 10-4 | 0.074 | Regulation, transcription |
GZMK
| Granzyme K | -1.4 | 1.3 × 10-4 | 0.074 | Enzyme, immune |
DNMT1
| DNA (cytosine 5)-methyltransferase 1 | -1.3 | 1.3 × 10-4 | 0.074 | Enzyme, metabolism |
ZNF219
| Zinc finger protein 219 | -1.2 | 1.3 × 10-4 | 0.074 | Regulation, transcription |
DVL1
| Dishevelled homologue (Drosophila) | -1.2 | 1.4 × 10-4 | 0.074 | Mitosis, signaling |
IMP3
| U3 small ribonucleoprotein homologue (yeast) | -1.2 | 1.5 × 10-4 | 0.074 | Structural, translation |
ANAPC5
| Anaphase promoting complex subunit 5 | -1.2 | 1.5 × 10-4 | 0.074 | Enzyme, cell cycle |
AOF2
| Amine oxidase (flavin containing) domain 2 | -1.2 | 1.6 × 10-4 | 0.074 | Regulation, transcription |
GPRASP1
| G protein-coupled receptor | -1.4 | 1.6 × 10-4 | 0.074 | Receptor, signaling |
LTK
| Leukocyte tyrosine kinase | -1.3 | 1.6 × 10-4 | 0.074 | Kinase, immune |
MTA1
| Metastasis-associated 1 | -1.2 | 1.6 × 10-4 | 0.074 | Regulation, transcription |
UXT
| Ubiquitously expressed transcript | -1.2 | 1.6 × 10-4 | 0.074 | Regulation, transcription |
KLRB1
| Killer cell lectin-like receptor B1 | -1.6 | 1.7 × 10-4 | 0.074 | Receptor, immune |
SEMA4C
| Semaphorin 4C | -1.3 | 1.7 × 10-4 | 0.074 | Neural development |
STMN3
| Stathmin-like 3 | -1.4 | 2.0 × 10-4 | 0.079 | Cytoskeletal, signaling |
ATP1A1
| ATPase Na+/K+ transporter | -1.2 | 2.0 × 10-4 | 0.079 | Transporter, signaling |
PSBP
| Prostatic steroid-binding protein | -1.3 | 2.2 × 10-4 | 0.080 | Receptor, signaling |
RPL18
| Ribosomal protein L18 | -1.3 | 2.2 × 10-4 | 0.080 | Structural, translation |
RNF220
| Ring finger protein | -1.1 | 2.2 × 10-4 | 0.080 | Unknown |
SPOCK2
| Sparc/osteonectin/proteoglycan (testican) 2 | -1.2 | 2.3 × 10-4 | 0.081 | Extracellular, structural |
DDX28
| DEAD box polypeptide | -1.2 | 2.3 × 10-4 | 0.081 | RNA helicase, transcription |
SRP46
| Splicing factor, arginine/serine-rich, 46 kDa | -1.3 | 2.4 × 10-4 | 0.082 | Regulation, transcription |
EIF3S7
| Eukaryotic translation initiation factor 3S7 | -1.2 | 2.5 × 10-4 | 0.084 | Regulation, translation |
TNFRSF25
| Tumor necrosis factor receptor 25 | -1.3 | 2.6 × 10-4 | 0.085 | Receptor, immune |
MYBL1
| v-Myb myeloblastosis viral oncogene homolog | -1.4 | 2.7 × 10-4 | 0.085 | Regulation, transcription |
UBE2I
| Ubiquitin-conjugating enzyme E2I | -1.1 | 2.8 × 10-4 | 0.087 | Enzyme, regulation |
PABPC1
| Poly(A)-binding protein | -1.3 | 3.0 × 10-4 | 0.088 | Regulation, translation |
LDOC1L
| Leucine zipper, downregulated in cancer 1-like | -1.4 | 3.1 × 10-4 | 0.088 | Unknown |
LGR6
| Leucine-rich repeat-containing G protein receptor 6 | -1.6 | 3.1 × 10-4 | 0.088 | Receptor, signaling |
AES
| Amino-terminal enhancer of split | -1.1 | 3.2 × 10-4 | 0.088 | Regulation, transcription |
CXCR3
| Chemokine receptor 3 | -1.3 | 3.2 × 10-4 | 0.088 | Receptor, immune |
ATP5G2
| ATP synthase, mitochondrial F0 complex | -1.2 | 3.3 × 10-4 | 0.088 | Enzyme, metabolism |
RPLP2
| Ribosomal protein P2 | -1.3 | 3.3 × 10-4 | 0.088 | Structural, translation |
TC2N
| Membrane targeting C2 domain | -1.4 | 3.6 × 10-4 | 0.090 | Unknown, signaling |
ERGIC3
| Breast cancer antigen 84 | -1.2 | 3.8 × 10-4 | 0.092 | Unknown, cell growth |
GPR183
| Epstein-Barr virus induced gene 2 | -1.5 | 3.9 × 10-4 | 0.093 | Receptor, signaling |
CSNK1E
| Casein kinase 1, epsilon | -1.2 | 4.1 × 10-4 | 0.094 | Kinase, regulation |
CRIP1
| Cysteine-rich protein 1 | -1.3 | 4.1 × 10-4 | 0.094 | Zn-binding, transport |
ARIH2
| Ariadne homolog 2 | -1.1 | 4.2 × 10-4 | 0.094 | Ubiquitin ligase, regulation |
POLS
| DNA polymerase sigma | -1.2 | 4.2 × 10-4 | 0.094 | Enzyme, metabolism |
PUF60
| Ro-RNP-binding protein | -1.2 | 4.3 × 10-4 | 0.096 | RNP-binding, regulation |
MFNG
| Fucose-specific β-1,3-N-acetylglucosaminyltransferase | -1.2 | 4.7 × 10-4 | 0.097 | Enzyme, development |
PRPSAP2
| Phosphoribosyl pyrophosphate synthetase protein 2 | -1.2 | 4.7 × 10-4 | 0.097 | Enzyme, metabolism |
STAG3
| Stromal antigen 3 | -1.3 | 4.7 × 10-4 | 0.097 | Cohesion subunit, meiosis |
FBL
| Fibrillarin | -1.2 | 4.9 × 10-4 | 0.098 | snRNP-binding, pre-rRNA |
RPS19
| Ribosomal protein S19 | -1.3 | 4.9 × 10-4 | 0.098 | Structural, translation |
DDB1
| Damage-specific DNA-binding protein 1 | -1.2 | 5.0 × 10-4 | 0.098 | DNA repair |
FBXO21
| F-box protein 21 | -1.2 | 5.0 × 10-4 | 0.098 | Ubiquitin ligase, regulation |
PTDSS1
| Phosphatidylserine synthase 1 | -1.2 | 5.1 × 10-4 | 0.100 | Enzyme, metabolism |
AKR1B1
| Aldo-keto reductase family 1, member B1 | -1.2 | 5.2 × 10-4 | 0.100 | Enzyme, metabolism |
Immune | Signaling | Gene expression | Metabolism | Transport | Structural | Cell cycle | Other/Unknown |
---|---|---|---|---|---|---|---|
TNFAIP6
|
ANXA3
|
EIF2AK2
|
DEGS1
|
HP
|
HIST1H2AB
|
NELL2
|
ZCCHC2
|
PLSCR1
|
APOBEC3A
|
PBX4
|
CDS2
|
HPR
|
KRTCAP2
|
DVL1
|
RNF220
|
LTF
|
BMX
|
ZBTB5
|
PECI
|
SLC22A4
|
SPOCK2
|
ANAPC5
|
LDOC1L
|
TNFSF10
|
CEACAM6
|
PABPC3
|
DNMT1
|
DNAJA3
|
SEMA4C
|
DDB1
| |
IFI27
|
OASL
|
EIF3S6IP
|
ATP5G2
|
CRIP1
|
ERGIC3
| ||
IL1RN
|
MAP2K6
|
EIF3S8
|
POLS
|
STAG3
| |||
FCER1A
|
INHBB
|
RBMX
|
MFNG
| ||||
SYTL2
|
DEFA4
|
ZNF219
|
PRPSAP2
| ||||
CD99
|
RRAGD
|
IMP3
|
PTDSS1
| ||||
CD81
|
PGAP1
|
AOF2
|
AKR1B1
| ||||
GZMK
|
PACSIN1
|
MTA1
| |||||
LTK
|
FYN
|
UXT
| |||||
KLRB1
|
DYRK2
|
RPL18
| |||||
TNFRSF25
|
LOC100133315
|
DDX28
| |||||
CXCR3
|
GPRASP1
|
SRP46
| |||||
STMN3
|
EIF3S7
| ||||||
ATP1A1
|
MYBL1
| ||||||
PSBP
|
PABPC1
| ||||||
UBE2I
|
AES
| ||||||
LGR6
|
RPLP2
| ||||||
TC2N
|
FBL
| ||||||
GPR183
|
RPS19
| ||||||
CSNK1E
| |||||||
ARIH2
| |||||||
PUF60
| |||||||
FBXO21
| |||||||
F5
|
Disease subtypes
Pathway analysis
RQ-PCR validation
Gene | RQ-PCRa | Microarraya | ||
---|---|---|---|---|
Affected | Unaffected | Affected | Unaffected | |
TNFAIP6
| 3.04 | 2.17 | 2.24 | 2.15 |
TNFSF10
| 1.50 | 1.37 | 1.58 | 1.33 |
MAP2K6
| 1.20 | 1.20 | 1.38 | 1.21 |
IL1RN
| 1.37 | 1.21 | 1.67 | 1.17 |
IFI27
| 1.20 | 2.01 | 7.24 | 6.21 |
ANXA3
| 3.18 | 1.82 | 2.79 | 2.43 |
CEACAM6
| 5.70 | 1.15 | 4.70 | 1.10 |
DEFA4
| 7.01 | 1.47 | 2.32 | 1.18 |
EIF2AK2
| 2.20 | 1.12 | 2.36 | 1.70 |
FCERA1
| -1.82 | -1.48 | -1.76 | -1.22 |
SYTL2
| -1.93 | -1.61 | -1.49 | -1.10 |
LGR6
| -1.25 | -1.13 | -1.64 | -1.11 |
KRTCAP2
| -1.20 | -1.20 | -1.16 | -1.07 |
LTK
| 1.02 | 1.21 | 2.32 | 1.06 |
FYN
| 1.23 | 1.19 | -1.26 | -1.01 |