Biomarkers for diagnosis of stroke and its causes

Patent metadata

Field	Value
Publication number	US-9803243-B2
Application number	US-201615068600-A
Country	US
Kind code	B2
Filing date	Mar 13, 2016
Priority date	Jul 15, 2010
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

The present invention provides compositions and methods for the diagnosis of the occurrence and cause of stroke.

First claim

What is claimed is:

1. A solid support attached to nucleic acids that hybridize to ischemia biomarkers comprising ring finger protein 141 (RNF141), C-type lectin domain family 4, member E (CLEC4E), TIMP metallopeptidase inhibitor 2 (TIMP2), putative homeodomain transcription factor 1 (PHTF1), chemokine-like factor (CKLF), Ras-related GTP binding D (RRAGD), RhoGEF and PH domain containing 4 (FGD4), cytoplasmic polyadenylation element binding protein 2 (CPEB2), similar to hCG1994130 (LOC100290882), UBX domain protein 2B (UBXN2B), ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), bone marrow stromal cell antigen 1 (BST1), leukotriene B4 receptor (LTB4R), coagulation factor V (F5), interferon-related developmental regulator 1 (IFRD1), KIAA0319, chromatin modifying protein 1B (CHMP1B), multiple C2 domains, transmembrane 1 (MCTP1), vanin 3 (VNN3), antagonist of mitotic exit network 1 homolog (AMN1), lysosomal-associated membrane protein 2 (LAMP2), FCH domain only 2 (FCHO2), zinc finger protein 608 (ZNF608), RAS (RAD and GEM)-like GTP binding 2 (REM2), Quaking homolog, KH domain RNA binding (QKI), RNA binding motif protein 25 (RBM25), Fatty acyl CoA reductase 2 (FAR2), ST3 beta-galactoside alpha-2,3-sialyltransferase 6 (ST3GAL6), Heterogeneous nuclear ribonucleoprotein H2 (HNRNPH2), GRB2-associated binding protein 1 (GAB1), ubiquitin protein ligase E3 component n-recognin 5 (UBR5), VAMP (vesicle-associated membrane protein)-associated protein A (VAPA), phosphoglucomutase 5 (PGM5), coiled-coil domain containing 144C (CCDC144C), similar to coiled-coil domain containing 144B (LOC100134159), leukocyte cell-derived chemotaxin 2 (LECT2), short stature homeobox (SHOX), T-box 5 (TBX5), serine palmitoyltransferase, long chain base subunit 3 (SPTLC3), SNAP25-interacting protein (SNIP), RNA binding motif, single stranded interacting protein (RBMS3), prostate-specific P704P (P704P), thrombospondin, type I, domain containing 4 (THSD4), FAT tumor suppressor homolog 3 (FAT3), small nuclear ribonucleoprotein polypeptide N (SNRPN), glycine-N-acyltransferase-like 1 (GLYATL1), glutamate decarboxylase-like 1 (GADL1), coxsackie virus and adenovirus receptor (CXADR), ovo-like 2 (OVOL2), Spi-B transcription factor (Spi-1/PU.1 related) (SPIB), brix domain containing 5 (BXDC5), unc-5 homolog B (UNC5B), astrotactin 2 (ASTN2), FLJ35934, ankyrin repeat domain 28 (ANKRD28), coiled-coil domain containing 144A (CCDC144A), translocase of inner mitochondrial membrane 8 homolog A (TIMM8A), aldolase A, fructose-bisphosphate pseudogene 2 (ALDOAP2), LIM domain binding 3 (LDB3), protein tyrosine phosphatase, receptor type D (PTPRD), similar to PTPRF interacting protein binding protein 1 (LOC729222), PTPRF interacting protein, binding protein 1 (liprin beta 1) (PPFIBP1), chemokine (C-C motif) receptor-like 1 (CCRL1), heterogeneous nuclear ribonucleoprotein U-like 2(HNRNPUL2), Fc receptor-like 4 (FCRL4), embryonic lethal, abnormal vision-like 2 (ELAVL2), protogenin homolog (PRTG), distal-less homeobox 6 (DLX6), forkhead box A2 (FOXA2), stearoyl-CoA desaturase 5 (SCDS), gamma-aminobutyric acid (GABA) A receptor, beta 2 (GABRB2), Glycophorin A (MNS blood group) (GYPA), LOC283027, LOC344595, Ribosomal protein L22 (RPL22), LOC100129488 and SH3-domain GRB2-like 3 (SH3GL3), wherein the solid support is attached to 100 or fewer nucleic acids.

2. The solid support of claim 1 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Tables 13A and 13B selected from the group consisting of EBF1, GRM5, TSKS, ENPP2, AP3S2, LRRC37A3, C16orf68, LOC284751, IRF6, LHFP, BANK1, ARHGEF5, ZNF254, TFDP1, COL13A1, GSTK1, ADAMTSL4, P2RX5, LHFP, PIK3C2B, CHURC1, EXT2, HLA-DOA, OOEP, ZNF185, TMEM19, FCRL1, FLJ40125, ARHGEF12, CLEC18A, CD46, PTPN20A///PTPN20B, and C19orf28.

3. The solid support of claim 1 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 14 selected from the group consisting of EBF1, FLJ31945, C16orf68, SLC20A1, DOPEY2, COL13A1, LHFP, LOC284751, GRMS, LOC100144603, MTBP, SHOX2, ARHGEFS, RNF7, CLASP2, GIPC2, RANBP10, CMBL, LOC100127980, CYTH3, PROCR, LOC146880, SLC6A19, ICAM4, C12orf42, ARHGEF12, PRSS35, NTSE, LOC100271832, LHFP, NTSE and AKR1C3.

4. The solid support of claim 1 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 15 selected from the group consisting of CMTM1, COL13A1, SDC4, C6orf164, GPR176, BRUNOL6, SNORA68, MIF///SLC2A11, DUSP16, HIPK2, TTC7A, PPIE, GRLF1, MAP3K7IP1, LOC100129034, PER3, SMC1A, and LRRC43.

5. The solid support of claim 1 , further comprising a plurality of nucleic acids that hybridize to a plurality of the genes set forth in Table 16 selected from the group consisting of USP7, MAPRE2, CSNK1G2, SAFB2, PRKAR2A, PI4KB, CRTC1, HADHA, MAP1LC3B, KATS, CDC2L 1///CDC2L2, GTSE1, TCF25, CHP, LRRC40, hCG_2003956///LYPLA2///LYPLA2P1, DAXX, UBE2NL, EIF1, KCMF1, PRKRIP1, CHMP4A, TMEM184C, TINF2, PODNL1, FBXO42, LOC441258, RRP1, C10orf104, ZDHHC5, C9orf23, LRRC45, NACC1, LOC100133445///LOC115110, PEX16.

6. The solid support of claim 1 , wherein the solid support is a microarray.

7. A kit comprising a solid support of claim 1 .

8. A solid support comprising a plurality of nucleic acids that hybridize to a plurality of genes consisting of RNF141, CLEC4E, TIMP2, PHTF1, CKLF, RRAGD, CLEC4E, FGD4, CPEB2, LOC100290882, UBXN2B, ENTPD1, BST1, LTB4R, F5, IFRD1, KIAA0319, CHMP1B, MCTP1, VNN3, AMN1, LAMP2, FCHO2, ZNF608, REM2, QKI, RBM25, FAR2, ST3GAL6, HNRNPH2, GAB1, UBR5, VAPA, PGM5, CCDC144C, LOC100134159, LECT2, SHOX, TBX5, SPTLC3, SNIP, RBMS3, P704P, THSD4, FAT3, SNRPN, GLYATL1, GADL1, CXADR, OVOL2, SPIB, BXDC5, UNC5B, ASTN2, FLJ35934, ANKRD28, CCDC144A, TIMM8A, ALDOAP2, LDB3, PTPRD, LOC729222, PPFIBP1, CCRL1, HNRNPUL2, FCRL4, ELAVL2, PRTG, DLX6, FOXA2, SCD5, GABRB2, GYPA, LOC283027, LOC344595, LOC100129488, RPL22, SH3GL3, EBF1, GRM5, TSKS, ENPP2, AP3S2, LRRC37A3, C16orf68, LOC284751, IRF6, LHFP, BANK1, ARHGEF5, ZNF254, TFDP1, COL13A1, GSTK1, ADAMTSL4, P2RX5, LHFP, PIK3C2B, CHURC1, EXT2, HLA-DOA, OOEP, ZNF185, TMEM19, FCRL1, FLJ40125, ARHGEF12, CLEC18A, CD46, PTPN20A///PTPN20B, C19orf28, FLJ31945, C16orf68, SLC20A1, DOPEY2, COL13A1, LHFP, LOC284751, GRM5, LOC100144603, MTBP, SHOX2, ARHGEF5, RNF7, CLASP2, GIPC2, RANBP10, CMBL, LOC100127980, CYTH3, PROCR, LOC146880, SLC6A19, ICAM4, C12orf42, ARHGEF12, PRSS35, NT5E, LOC100271832, LHFP, NT5E, AKR1C3, CMTM1, COL13A1, SDC4, C6orf164, GPR176, BRUNOL6, SNORA68, MIF///SLC2A11, DUSP16, HIPK2, TTC7A, PPIE, GRLF1, MAP3K7IP1, LOC100129034, PER3, SMC1A, and LRRC43, USP7, MAPRE2, CSNK1G2, SAFB2, PRKAR2A, PI4KB, CRTC1, HADHA, MAP1LC3B, KATS, CDC2L1///CDC2L2, GTSE1, TCF25, CHP, LRRC40, hCG_2003956///LYPLA2///LYPLA2P1, DAXX, UBE2NL, EIF1, KCMF1, PRKRIP1, CHMP4A, TMEM184C, TINF2, PODNL1, FBXO42, LOC441258, RRP1, C10orf104, ZDHHCS, C9orf23, LRRC45, NACC1, LOC100133445///LOC115110 and PEX16.

Assignees

• Univ California

Inventors

• Sharp Frank
• Stamova Boryana
• Jickling Glen C

Classifications

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• G01N2800/2871

  Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event · CPC title

• G01N33/6896

  Neurological disorders, e.g. Alzheimer's disease · CPC title

• G01N2800/50

  Determining the risk of developing a disease · CPC title

• C12Q2600/158

  Expression markers · CPC title