KR102333647B1 - Biomarker composition for diagnosing massive perivillous fibrin deposition and use thereof - Google Patents

Abstract

The present invention relates to a biomarker composition for diagnosing abortion placental fibrin hyperdeposition and uses thereof. The protein included as an active ingredient in the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is specifically found only in the blood of a mother diagnosed with fibrin-type MPFD (f-MPFD), so it is useful for diagnosis with f-MPFD. It can be utilized and can prevent habitual miscarriage according to f-MPFD in advance. In addition, through the MPFD diagnosis, there is an opportunity to detect MPFD-related blood hypercoagulation diseases in advance by additional testing for MPFD-related blood hypercoagulation diseases in mothers diagnosed with MPFD, and it is possible to prevent and treat serious complications caused by blood hypercoagulation diseases.

Description

Biomarker composition for diagnosing abortion placental fibrin hyperdeposition and use thereof

The present invention relates to a biomarker composition for diagnosing abortion placental fibrin hyperdeposition and uses thereof.

The placenta is an organ that connects the uterine wall between the fetus and the mother to supply nutrients, exchange gas, and discharge waste. Most of the placenta, which mediates the exchange of substances necessary for the survival and growth of the fetus between the fetus and the mother, is tissue derived from the fetus, and the tissue formed in the mother is attached to the bottom of the placenta. Specifically, a part of a fertilized egg implanted in the uterine wall grows and changes into the chorion responsible for material transfer from the placenta, and a part of the uterus changes into the decidua surrounding the outermost part of the placenta (Sarah K, et al., 2015). .

As such, the mother's spiral artery enters the outer part of the placenta, which is responsible for the core function necessary for the growth of the fetus through material exchange at the borderline between the mother and the fetus, and spurts blood through the placenta. The villi in the placenta are immersed in the spurted maternal blood. When observing the villi submerged in blood under a microscope, there are blood vessels of the fetus inside the villi and the blood of the fetus flows, and the blood of the mother exists outside the villi. Nutrients including carbon dioxide and oxygen move between maternal blood and fetal blood that exist inside and outside the villi.

On the other hand, there is a case in which fibrinoids are over-deposited around the villi that separate the maternal and fetal blood, this is called placental fibrin hyper-deposition (massive perivillous fibrin deposition, MPFD). When the placenta is filled with fibrinoids, the placenta turns yellow and the maternal-fetal interface is lost due to the fibrinoids filled in the intervilli space, preventing the exchange of gas and nutrients between the fetus and mother, resulting in complete loss of placental function. will do

Fetuses of mothers with MPFD have developmental delay in 24 to 100%, death in 13 to 50%, and premature birth in 26 to 60%. Even if the fetus survives and is delivered, severe brain damage may occur. The frequency of MPFD is a rare disease of 0.005 to 0.5%, but in the case of MPFD, there are cases where the fetus suddenly dies in the second half of pregnancy without any specific signs during pregnancy. There are cases where this happens. In the case of surviving children, serious brain damage may occur, and the pediatrician may be questioned for medical negligence.

However, to date, the cause of MPFD has not been well elucidated, and MPFD in early pregnancy miscarriage has hardly been studied worldwide.

Sarah K, et al. Placental structure, function and drug transfer. Continuing Education in Anaesthesia, Critical Care & Pain. 2015. pp. 84-89.

Accordingly, while the present inventors were studying a method for diagnosing placental fibrin hyperdeposition in the placenta of a mother who had abortion, the present inventors discovered specific proteins expressed only in the blood of mothers diagnosed with fibrin-type MPFD (f-MPFD). The invention was completed.

It is an object of the present invention to provide a biomarker composition for diagnosing placental fibrin hyperdeposition associated with abortion.

In order to achieve the above object, the present invention provides a group consisting of CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN, LGALS1 and IGFBP4. It provides a biomarker composition for diagnosing abortion placental fibrin hyperdeposition or habitual abortion comprising any one or more proteins selected from among as an active ingredient.

In addition, the present invention is composed of CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN, LGALS1 and IGFBP4 blood collected from mothers. Measuring the detection amount of any one or more proteins selected from the group; And it provides a method of providing information necessary for diagnosing MPFD or habitual abortion, comprising determining the mother as MPFD or habitual abortion when the detection amount of the protein is higher than the detection amount of the protein present in the normal maternal blood.

In addition, the present invention comprises the steps of measuring the degree of sensitization (sensitization) to HLA (human leukocyte antigen) in blood collected from the mother; comparing the degree of sensitization to HLA with the degree of sensitization to HLA of normal maternal blood; And when the degree of sensitization to HLA is higher than the degree of sensitization to HLA of normal maternal blood, it provides a method of providing information necessary for diagnosing MPFD, comprising determining the mother as MPFD.

In addition, the present invention comprises the steps of performing C4d (Complement component 4d) immunostaining on blood collected from a mother determined to be MPFD by performing the method for providing information necessary for diagnosing MPFD; And it provides a method of providing information necessary for diagnosing recurrent miscarriage, including determining the mother as recurrent miscarriage when the immunostaining result is C4d positive (C4d immunopositive).

In addition, the present invention provides any one selected from the group consisting of CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN, LGALS1 and IGFBP4. It provides a kit for diagnosing MPFD or habitual abortion comprising an antibody or fragment thereof binding to the above protein as an active ingredient.

The protein included as an active ingredient in the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is specifically found only in the blood of a mother diagnosed with fibrin-type MPFD (f-MPFD), so it is useful for diagnosis with f-MPFD. It can be utilized and can prevent habitual miscarriage according to f-MPFD in advance. In addition, through the MPFD diagnosis, there is an opportunity to detect MPFD-related blood hypercoagulation diseases in advance by additional testing for MPFD-related blood hypercoagulation diseases in mothers diagnosed with MPFD, and it is possible to prevent and treat serious complications caused by blood hypercoagulation diseases.

1 shows the MPFD diagnostic criteria together with placental microscopic images.
Figure 2 shows the H&E staining of the mother's placenta diagnosed with MPFD and observed under a microscope. Fibrin is shown in pink, and it can be seen that fibrin is over-deposited around the placental villi.
Figure 3 shows the automatic image analysis of the mother's placenta diagnosed with MPFD. In this case, Bg means the background of the digital slide image during H&E staining, and v is an abbreviation of "villi" and means placental villi.
4 shows the placenta of a normal mother and the placenta of a mother diagnosed with MPFD together with microscopic images.
5 is a microscopic image showing the results of positive and negative reactions upon C4d immunochemical staining.
6 is a graph showing whether repeated abortion according to the C4d immunostaining reaction of the abortion group mothers.
7A and 7B are microscopic observations of the mother's placenta stained with H&E, fibrin and C4d at the time of diagnosis of the 6th and 7th miscarriage of a mother diagnosed with fibrin-type MPFD who showed a positive reaction as a result of C4d immunostaining.
8A and 8B are graphs showing whether the mother was sensitized to HLA antigen (human leukocyte antigen) through pregnancy and generated antibodies to the HLA antigen through the HLA panel.
Figure 9a shows the results of observing the blood of mothers diagnosed with fibrin-type MPFD by staining them with H&E, anti-fibrin antibody, or anti-collagen-type IV antibody at different magnifications (x40 and x200) under a microscope.
Figure 9b shows the results of observing the blood of mothers diagnosed with matrix-type MPFD by staining with H&E, anti-fibrin antibody, or anti-collagen type IV antibody and observing it under a microscope at different magnifications (x40 and x200).
10 is a graph showing the probability of habitual miscarriage among mothers diagnosed with MPFD and increased intervillous fibrin (IIF).
11 is a graph showing the probability of repeated miscarriage according to the MPFD type.
12 is a graph showing the results of testing for placental chromosomal abnormalities in mothers diagnosed with f-MPFD, m-MPFD, and abortion without fibrin deposition.
13 is a Venn diagram showing the results of proteomic analysis of plasma obtained from f-MPFD, MC (miscarriage control) and NC (normal control) groups.
14 is a volcano plot showing that, as a result of quantitative analysis of proteins by LFQ (Label free quantification), the p value is statistically less than 0.05 and the amount of protein differs more than twice between groups.

In one aspect, the present invention provides an aspect selected from the group consisting of CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN, LGALS1 and IGFBP4. Provided is a biomarker composition for diagnosing abortion placental fibrin hyperdeposition or habitual abortion comprising any one or more proteins as an active ingredient.

In this case, the CCT3 is a polypeptide having the amino acid sequence of SEQ ID NO: 1, the CCT7 is a polypeptide having the amino acid sequence of SEQ ID NO: 3, the PSMA2 is a polypeptide having the amino acid sequence of SEQ ID NO: 5, or the HSPA4 is The polypeptide having the amino acid sequence of SEQ ID NO: 7, the RAD23B is the polypeptide having the amino acid sequence of SEQ ID NO: 9, the UBE2D3 is the polypeptide having the amino acid sequence of SEQ ID NO: 11, or the HNRNPC is the amino acid of SEQ ID NO: 13 is a polypeptide having the sequence, wherein the EFTUD2 is a polypeptide having the amino acid sequence of SEQ ID NO: 15, the MBP is a polypeptide having the amino acid sequence of SEQ ID NO: 17, or the AHNAK is a polypeptide having the amino acid sequence of SEQ ID NO: 19 Or, the HSD17B10 is a polypeptide having the amino acid sequence of SEQ ID NO: 21, the IL18 is a polypeptide having the amino acid sequence of SEQ ID NO: 23, the RPL22 is a polypeptide having the amino acid sequence of SEQ ID NO: 25, or the SERBP1 is SEQ ID NO: 27 is a polypeptide having the amino acid sequence of SEQ ID NO: 27, the PCOLCE is a polypeptide having the amino acid sequence of SEQ ID NO: 29, the ACAA2 is a polypeptide having the amino acid sequence of SEQ ID NO: 31, or the FASN is the amino acid of SEQ ID NO: 33 It may be a polypeptide having the sequence, the LGALS1 may be a polypeptide having the amino acid sequence of SEQ ID NO: 35, or the IGFBP4 may be a polypeptide having the amino acid sequence of SEQ ID NO: 37.

As used herein, the term “CCT3” is an abbreviation of “chaperonin containing TCP1, subunit 3” and is also known as CCTG, PIG48, TRIC5, CCT-gamma, or TCP-1-gamma. The CCT3 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 1, and the CCT3 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 1. . Meanwhile, the gene encoding the CCT3 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 1, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 2. The nucleotide sequence encoding the CCT3 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 2.

The term “CCT7” used herein is an abbreviation of “chaperonin containing TCP1, subunit 7” and is also called CCTH, CCTETA, NIP7-1, or TCP1ETA. The CCT7 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 3, and the CCT7 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 3 . Meanwhile, the gene encoding the CCT7 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 3, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 4. The nucleotide sequence encoding the CCT7 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 4.

As used herein, the term “PSMA2” is an abbreviation of “proteasome subunit alpha type 2” and is also called MU, HC3, PSC2 or PMSA2. The PSMA2 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 5, and the PSMA2 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 5. . Meanwhile, the gene encoding the PSMA2 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 5, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 6. The nucleotide sequence encoding the PSMA2 protein may have about 70%, 80%, 90%, or 95% or more homology to the nucleotide sequence of SEQ ID NO: 6.

As used herein, the term "HSPA4" is an abbreviation of "heat shock protein family A member 4" and is also known as RY, APG-2, HSPH2, hsp70, hsp70RY, HEL-S-5a or HS24/P52. The HSPA4 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 7, and the HSPA4 protein may have about 70%, 80%, 90% or 95% or more homology to the amino acid sequence of SEQ ID NO: 7 . Meanwhile, the gene encoding the HSPA4 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 7, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 8. The nucleotide sequence encoding the HSPA4 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 8.

As used herein, the term “RAD23B” is an abbreviation of “RAD23 homolog B, nucleotide excision repair protein” and is also called P58, HR23B, or HHR23B. The RAD23B protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 9, and the RAD23B protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 9. . Meanwhile, the gene encoding the RAD23B protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 9, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 10. The nucleotide sequence encoding the RAD23B protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 10.

As used herein, the term “UBE2D3” is an abbreviation of “ubiquitin-conjugating enzyme E2 D 3” and is also called UBC4/5, UBCH5C or E2(17)KB3. The UBE2D3 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 11, and the UBE2D3 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 11. . Meanwhile, the gene encoding the UBE2D3 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 11, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 12. The nucleotide sequence encoding the UBE2D3 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 12.

As used herein, the term “HNRNPC” is an abbreviation of “heterogeneous nuclear ribonucleoprotein C (C1/C2)” and is also called C1, C2, HNRNP, HNRPC or SNRPC. The HNRNPC protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 13, and the HNRNPC protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 13. . Meanwhile, the gene encoding the HNRNPC protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 13, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 14. The nucleotide sequence encoding the HNRNPC protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 14.

As used herein, the term “EFTUD2” is an abbreviation of “elongation factor Tu GTP binding domain containing 2” and is also known as MFDM, MFDGA, Snu114, Snrp116, SNRNP116, or U5-116KD. The EFTUD2 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 15, and the EFTUD2 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 15. . Meanwhile, the gene encoding the EFTUD2 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 15, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 16. The nucleotide sequence encoding the EFTUD2 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 16.

The term "MBP" used herein is an abbreviation of "myelin basic protein", and the MBP protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 17. In addition, the MBP protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 17. Meanwhile, the gene encoding the MBP protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 17, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 18. The nucleotide sequence encoding the MBP protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 18.

As used herein, the term “AHNAK” is an abbreviation of “AHNAK nucleoprotein” and is also called PM227 or AHNAKRS. The AHNAK protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 19. The AHNAK protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 19. Meanwhile, the gene encoding the AHNAK protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 19, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 20. The nucleotide sequence encoding the AHNAK protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 20.

As used herein, the term "HSD17B10" is an abbreviation of "hydroxysteroid 17-beta dehydrogenase 10", and is ABAD, CAMR, ERAB, HCD2, MHBD, HADH2, MRPP2, MRX17, MRX31, SCHAD, MRXS10, SDR5C1, HSD10MD, 17b-HSD10 or Also known as DUPXp11.22. The HSD17B10 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 21, and the HSD17B10 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 21. . Meanwhile, the gene encoding the HSD17B10 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 21, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 22. The nucleotide sequence encoding the HSD17B10 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 22.

As used herein, the term “IL18” is an abbreviation of “interleukin 18” and is also known as IGIF, IL-18, IL-1g or IL1F4. The IL18 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 23, and the IL18 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 23 . Meanwhile, the gene encoding the IL18 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 23, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 24. The nucleotide sequence encoding the IL18 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 24.

As used herein, the term “RPL22” is an abbreviation of “ribosomal protein L22” and is also called EAP, L22, HBP15, or HBP15/L22. The RPL22 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 25, and the RPL22 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 25. . Meanwhile, the gene encoding the RPL22 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 25, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 26. The nucleotide sequence encoding the RPL22 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 26.

The term "SERBP1" used herein is an abbreviation of "SERPINE1 mRNA binding protein 1" and is also known as CGI-55, CHD3IP, HABP4L, PAIRBP1 or PAI-RBP1. The SERBP1 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 27, and the SERBP1 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 27. . Meanwhile, the gene encoding the SERBP1 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 27, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 28. The nucleotide sequence encoding the SERBP1 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 28.

As used herein, the term “PCOLCE” is an abbreviation of “procollagen C-endopeptidase enhancer” and is also called PCPE, PCPE1, or PCPE-1. The PCOLCE protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 29, and the PCOLCE protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 29. . Meanwhile, the gene encoding the PCOLCE protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 29, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 30. The nucleotide sequence encoding the PCOLCE protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 30.

As used herein, the term “ACAA2” is an abbreviation of “acetyl-CoA acyltransferase 2” and is also known as DSAEC. The ACAA2 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 31, and the ACAA2 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 31. . Meanwhile, the gene encoding the ACAA2 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 31, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 32. The nucleotide sequence encoding the ACAA2 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 32.

As used herein, the term "FASN" is an abbreviation of "fatty acid synthase" and is also called FAS, OA-519, or SDR27X1. The FASN protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 33, and the FASN protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 33. . Meanwhile, the gene encoding the FASN protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 33, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 34. The nucleotide sequence encoding the FASN protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 34.

As used herein, the term "LGALS1" is an abbreviation of "lectin, galactoside-binding, soluble, 1", and the LGALS1 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 35. In addition, the LGALS1 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 35. Meanwhile, the gene encoding the LGALS1 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 35, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 36. The nucleotide sequence encoding the LGALS1 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 36.

The term "IGFBP4" used herein is an abbreviation of "insulin-like growth factor binding protein 4" and is also known as BP-4, IBP4, IGFBP-4 or HT29-IGFBP. The IGFBP4 protein of the present invention may be a polypeptide having the amino acid sequence of SEQ ID NO: 37, and the IGFBP4 protein may have about 70%, 80%, 90%, or 95% or more homology to the amino acid sequence of SEQ ID NO: 37. . Meanwhile, the gene encoding the IGFBP4 protein, which is a polypeptide having the amino acid sequence of SEQ ID NO: 37, may be a polynucleotide having the nucleotide sequence of SEQ ID NO: 38. The nucleotide sequence encoding the IGFBP4 protein may have about 70%, 80%, 90%, or 95% or more homology with the nucleotide sequence of SEQ ID NO: 38.

Specifically, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2 , may include any one protein selected from the group consisting of LGALS1 and IGFBP4 as an active ingredient. For example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3 as an active ingredient, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any two proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3 and PCOLCE as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any three proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3, CCT7 and PCOLCE as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any four proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. As an example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3, CCT7, ACAA2 and PCOLCE as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any five proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include UBE2D3, HNRNPC, EFTUD2, LGALS1 and IGFBP4 as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any six proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3, UBE2D3, HNRNPC, EFTUD2, LGALS1 and IGFBP4 as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any seven proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3 and FASN as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any eight proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK and HSD17B10 as active ingredients.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any nine proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2 and MBP as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any ten proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP and IGFBP4 as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any eleven proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18 and RPL22 as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any twelve proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. For example, the biomarker composition for diagnosis of MPFD of the present invention may include PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22 and IGFBP4 as active ingredients, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any thirteen proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. As an example, the biomarker composition for diagnosis of MPFD of the present invention may include UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN and LGALS1 as active ingredients, but is limited thereto. no.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any 14 proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. As an example, the biomarker composition for diagnosis of MPFD of the present invention may include UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN, LGALS1, and IGFBP4 as active ingredients. Not limited.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any fifteen proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. In one example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, PCOLCE, ACAA2, FASN, LGALS1 and IGFBP4 as active ingredients, However, the present invention is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any sixteen proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. In one example, the biomarker composition for diagnosis of MPFD of the present invention may include CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, PCOLCE, HSD17B10, ACAA2, FASN, LGALS1 and IGFBP4 as active ingredients. However, it is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any seventeen proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. In one example, the biomarker composition for diagnosis of MPFD of the present invention includes CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN and LGALS1 as active ingredients. can, but is not limited thereto.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, Any 18 proteins selected from the group consisting of LGALS1 and IGFBP4 may be included as active ingredients. In one example, the biomarker composition for MPFD diagnosis of the present invention contains CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN and LGALS1 as active ingredients. It may include, but is not limited to.

In addition, the biomarker composition for diagnosing abortion placental fibrin hyperdeposition according to the present invention is CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, LGALS1 and IGFBP4 proteins may be included as active ingredients. When the biomarker composition for diagnosing MPFD of the present invention includes all 19 proteins according to the present invention as active ingredients, it can be used as a more effective biomarker for diagnosing MPFD than a combination of other proteins.

As used herein, the term "placental fibrin deposition (massive perivillous fibrin deposition, MPFD)" refers to a case in which fibrinoids are over-deposited around the villi that separates maternal and fetal blood. The MPFD is classified into a fibrin type and a matrix type. In the case of mothers diagnosed with fibrin type MPFD, the villi in the placenta are deposited with fibrin having a function of blood coagulation. In addition, in the case of a mother diagnosed with matrix type MPFD, the villi in the placenta are deposited with an extracellular matrix such as collagen type IV and glycoprotein secreted from the trophoblast, which is a placental cell. In many embodiments of the present invention, the mother diagnosed with the fibrin-type MPFD was named f-MPFD, and the mother diagnosed with the matrix-type MPFD was named m-MPFD.

As used herein, the term "biomarker" is an anatomical, physiological, biochemical or molecular parameter associated with the presence of a particular physiological state or progression. Biomarkers are detectable and measurable by a variety of methods, including laboratory assays and medical imaging. When a biomarker is indicative of or indicative of abnormal progression or disease or other condition in an individual, the biomarker is generally indicative of or indicative of normal progression or absence of a disease or other condition in the individual, the expression level or value of the biomarker. compared to over-expressed or under-expressed.

As used herein, the term "diagnosis" refers to determining the susceptibility of an individual to a particular disease or condition, determining whether an individual currently has a particular disease or disorder, or having a particular disease or disorder. Determining the prognosis of an individual, or therametrics (eg, monitoring the condition of an individual to provide information about the efficacy of treatment).

In another aspect, the present invention provides CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN, LGALS1 and IGFBP4 in blood collected from the mother. Measuring the detection amount of any one or more proteins selected from the group consisting of; And it provides a method of providing information necessary for diagnosing MPFD or habitual abortion, comprising determining the mother as MPFD or habitual abortion when the detection amount of the protein is higher than the detection amount of the protein present in the normal maternal blood.

In this case, the detection amount of the protein may be measured by a liquid chromatography-mass spectrometry (LC-MS) technique or an enzyme-linked immunosorbent assay (ELISA) technique.

In addition, the present invention provides a method for diagnosing MPFD, comprising the steps of: 1) measuring the degree of sensitization to HLA (human leukocyte antigen) in blood collected from the mother; 2) comparing the degree of sensitization to HLA with the degree of sensitization to HLA of normal maternal blood; and 3) determining that the mother is MPFD when the degree of sensitization to HLA is higher than that of normal maternal blood to HLA.

In one embodiment of the present invention, in order to check whether the mother is sensitized to the HLA antigen through pregnancy and generates an antibody to the HLA antigen, blood is collected from a panel consisting of HLA class I and HLA class II and reacted As a result of the experiment, mothers diagnosed with MPFD had an increase in HLA panel reactive antibody (PRA) than mothers of other groups, and it was found that the amount of HLA PRA could be a criterion for diagnosing MPFD.

In addition, the present invention provides a method for diagnosing habitual abortion, comprising the steps of: 1) performing C4d (Complement component 4d) immunostaining on blood collected from mothers determined to be MPFD by the diagnostic method according to the present invention; and 2) when the immunostaining result is C4d positive (C4d immunopositive), the step of determining the mother of step 1) as recurrent miscarriage may be additionally performed.

In one embodiment of the present invention, it was hypothesized that the cause of MPFD would be rejection of the fetus, and to confirm the hypothesis, immunostaining was performed using C4d, a marker related to organ transplant rejection, in abortion mothers. As a result of the experiment, all mothers diagnosed with fibrin-type MPFD who showed a positive result of C4d immunostaining experienced three or more repeated abortions, whereas all mothers diagnosed with fibrin-type MPFD who showed a negative C4d test experienced repeated abortions. did not experience Through this, it was found that mothers who were diagnosed with fibrin-type MPFD and showed a positive result as a result of C4d immunostaining had a very high possibility of repeated abortion.

In another aspect, the present invention is selected from the group consisting of CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN, LGALS1 and IGFBP4. It provides a kit for diagnosing MPFD or habitual abortion comprising an antibody or fragment thereof that binds to any one or more proteins as an active ingredient.

As used herein, the term “antibody” is a term known in the art and refers to a specific immunoglobulin directed against an antigenic site. Antibodies in the present invention are from the group consisting of CCT3, CCT7, PSMA2, HSPA4, RAD23B, UBE2D3, HNRNPC, EFTUD2, MBP, AHNAK, HSD17B10, IL18, RPL22, SERBP1, PCOLCE, ACAA2, FASN, LGALS1 and IGFBP4 of the present invention. It refers to an antibody that specifically binds to any one or more selected proteins, and the antibody can be prepared according to a conventional method in the art. The form of the antibody includes polyclonal antibodies or monoclonal antibodies, and all immunoglobulin antibodies are included. The antibody refers to a complete form having two full-length light chains and two full-length heavy chains. Moreover, the said antibody also includes special antibodies, such as a humanized antibody.

In addition, the kit of the present invention includes an antibody that specifically binds to a marker component, a secondary antibody conjugate to which a label that develops color by reaction with a substrate is conjugated, a chromogenic substrate solution to react with the label, a washing solution, and It may include an enzyme reaction stop solution, etc., and may be manufactured in a number of separate packaging or compartments containing the reagent components used. Specifically, the kit may be a lateral flow kit, and more specifically, a rapid kit, but is not limited thereto.

The rapid kit may include a sample pad to which a liquid sample is applied, a membrane to which an antibody is immobilized, and an absorbent pad capable of absorbing a liquid sample, but is not limited thereto. The liquid sample may be mother's whole blood, serum, plasma, saliva, other body fluids (urine, etc.), and specifically may be mother's plasma, but is not limited thereto.

Hereinafter, the present invention will be described in detail by the following preparation examples and examples. However, the following preparation examples and examples are only for illustrating the present invention, and the present invention is not limited thereto.

Example 1. Collection of a heritage group

A miscarriage cohort was established by collecting aborted placenta and maternal blood from the abortion clinic of Hamchoon Women's Clinic. Specifically, from March 2012 to June 2016, we collected cases of miscarriage and curettage at Hamchun Women's Clinic, and 582 samples from mothers with 562 miscarriages over 4 years and 4 months were collected through curettage. obtained. A pathology cassette was prepared from the specimen obtained by curettage, which was fixed with formalin and embedded in paraffin. In addition, the mother's blood in which abortion was found was separated into plasma and serum and stored at -80°C.

Example 2. Classification of abortion groups

The abortion group collected in Example 1 was classified into three groups as follows. First, among mothers diagnosed with abortion placental fibrin hyperplasia, 7 women (Hamchun Women's Clinic) who were fibrin type and normal placental chromosomes were selected as the first group, and this group was named f-MPFD. did At this time, a case in which fibrin was deposited in more than 25% of all villi in the placenta was diagnosed as MPFD (Katzman PJ, Dev Pathol, 2002). This is shown in FIG. 1 . In order to more objectively measure fibrin deposition, an automated imaging analysis technique was used. A case in which fibrin was over-deposited around the villi in the placenta is shown in FIG. 2 , and the results of the automatic image analysis are shown in FIG. 3 . In addition, the placenta of a normal mother and the placenta of a mother diagnosed with MPFD are shown in FIG. 4 .

In addition, 18 mothers (Hamchun Women's Clinic) whose mother's age, number of miscarriages, and gestational weeks were matched and placental chromosomes were normal were selected as the second group as a miscarriage control, This group was named MC. This is shown in Table 1 below. Finally, two healthy mothers who were undergoing prenatal examination at Asan Medical Center in Seoul and had no specific diseases were selected as the third group as a normal control, and this group was named NC.

[Table 1]

Experimental Example 1. C4d immunochemical staining

Since pregnancy is a type of organ transplantation, we hypothesized that the cause of MPFD might be rejection of the fetus. In the abortion group of Example 2, immunostaining was performed using C4d, a marker related to organ transplant rejection. The results of C4d positive and negative are shown in FIG. 5 .

In addition, as a result of confirming the relationship between the C4d immune response and recurrent miscarriage, all mothers diagnosed with fibrin-type MPFD who showed a positive C4d immunostaining result experienced three or more repeated miscarriages. On the other hand, all mothers diagnosed with fibrin-type MPFD who were C4d negative did not experience recurrent miscarriage. This is shown in FIG. 6 . Through this, it was found that mothers who were diagnosed with fibrin-type MPFD and showed a positive result as a result of C4d immunostaining had a very high possibility of repeated abortion.

On the other hand, when a mother diagnosed with fibrin-type MPFD, which showed a positive result as a result of C4d immunostaining as described above, was diagnosed with the 6th and 7th abortion, the mother's placenta was stained with H&E, fibrin and C4d and observed under a microscope. 7a and 7b. As shown in FIGS. 7A and 7B , two mothers diagnosed with fibrin-type MPFD who showed a positive result of C4d immunostaining showed the same pathological pattern in both the 6th and 7th abortions.

Experimental Example 2. HLA antibody screening

In order to confirm the hypothesis that the cause of MPFD established in Experimental Example 1 is rejection of the fetus, maternal blood was rejected by the fetus using human leukocyte antigen (HLA), a histocompatibility antigen used for organ transplantation. It was confirmed that there is This experiment was conducted in the f-MPFD and MC groups among the abortion groups classified in Example 2. In addition, for this experiment, the abortion cohort was divided into three groups as follows: 14 mothers diagnosed with MPFD, 7 mothers with increased intervillous fibrin (IIF), and abortion control mothers. 18 people.

In order to determine whether the mothers of each group were sensitized to HLA antigen through pregnancy and generated antibodies to HLA antigen, blood was collected from a panel consisting of HLA class I and HLA class II (LABScreen Mixed class I). and II assay (Luminex Corporation, Austin, Texas); Luminex LX 200 (Luminex Corporation, Austin, Texas)). At this time, in order to determine whether the HLA antibody is generated, LABScreen Mixed Class I and II analysis technique (Luminex Corporation, Austin, Texas, US) and Luminex LX 200 (Luminex Corporation, Austin, Texas, US) were used. The results are shown in FIGS. 8A and 8B.

As shown in FIGS. 8A and 8B , the HLA panel reactive antibody (PRA) increased in mothers diagnosed with MPFD than mothers with IIF. In addition, mothers diagnosed with f-MPFD in the abortion group classified in Example 2 had a significantly increased HLA panel reactive antibody than mothers in the MC group. In addition, the mothers diagnosed with f-MPFD in Example 2, that is, the seven mothers (Hamchun Women's Clinic) with normal chromosomes of the placenta diagnosed with fibrin type MPFD, all showed a positive result as a result of C4d immunostaining. At the same time as shown, it showed a positive reaction of the HLA panel reactive antibody.

Experimental Example 3. Relationship between MPFD disease and repeated abortion

Through the 562 abortion-discovered mothers recruited in Example 1, the MPFD incidence rate and the recurrent miscarriage rate in women diagnosed with MPFD were confirmed.

Among the 562 abortions, 15 were diagnosed with MPFD, and the MPFD incidence rate was 2.7%. In addition, among the 15 mothers diagnosed with MPFD, 11 mothers diagnosed with fibrin-type MPFD (f-MPFD) accounted for 73% of the mothers diagnosed with MPFD. In addition, among the 15 mothers diagnosed with MPFD, 4 mothers diagnosed with matrix-type MPFD (m-MPFD) accounted for 27% of the mothers diagnosed with MPFD. H&E, anti-fibrin antibody (anti fibrin ab, Biorbyt, Cambridge, UK) or anti-collagen type IV antibody (anti collagen type IV ab, Biorbyt, Cambridge, UK) and observed under a microscope according to magnifications (x40 and x200) are shown in FIGS. 9a and 9b. Through this, it was found that the anti-fibrin antibody and the anti-collagen type IV antibody are markers that can easily distinguish the type of MPFD.

On the other hand, 7 mothers with increased fibrin deposition between the villi (IIF) showed an incidence of IIF of 1.25% among the mothers with abortion. Among them, 4 patients had fibrin type IIF and 3 patients had matrix type IIF.

In addition, among the 15 mothers diagnosed with MPFD, 12 mothers who had experienced two miscarriages before and this was their third miscarriage accounted for 80% of the mothers diagnosed with MPFD. In addition, among the 7 mothers diagnosed with IIF, 2 women who had experienced two miscarriages before and this was their third miscarriage accounted for 28.6% of the mothers diagnosed with IIF. This is shown in FIG. 10 .

The chance of an accidental repeat of two or more miscarriages is less than 1%, with three miscarriages indicating that the miscarriage is and will be repeated. In the medical field, this is called habitual abortion, and it was found that 80% of mothers diagnosed with MPFD were such habitual abortion through this experiment.

Experimental Example 3.1. The relationship between MPFD disease and recurrent miscarriage by type

The repeated miscarriage rate according to MPFD type was confirmed in mothers diagnosed with MPFD. Among 11 mothers diagnosed with fibrin-type MPFD (f-MPFD), 6 women had more than 4 miscarriages. That is, the incidence of habitual miscarriage was 54.5% in mothers diagnosed with f-MPFD. On the other hand, among the four mothers diagnosed with matrix-type MPFD (m-MPFD), none of the mothers had more than four miscarriages. This is shown in FIG. 11 . Through this, it was found that mothers diagnosed with f-MPFD are more likely to have repeated miscarriages.

Experimental Example 3.2. Relationship between MPFD and placental chromosomal abnormalities

In Experimental Example 3, mothers diagnosed with a miscarriage without f-MPFD, m-MPFD, and fibrin deposition were tested for placental chromosomal abnormalities, and the results are shown in FIG. 12 . As shown in FIG. 12 , placental chromosomes were found to be normal in 7 out of 10 mothers diagnosed with f-MPFD, that is, placental chromosomes were found to be normal in mothers diagnosed with f-MPFD with a 70% probability. In addition, placental chromosomes were found to be normal in 2 out of 3 mothers diagnosed with m-MPFD. In other words. In mothers diagnosed with m-MPFD, placental chromosomes were normal with a 66.7% probability. In general, considering that more than 50% of miscarriages are caused by placental chromosomal abnormalities, it was found that miscarriages caused by MPFD have a completely different disease-generating mechanism from normal miscarriages.

Experimental Example 4. Relationship between MPFD disease and blood hypercoagulation disease

The medical history of the mother diagnosed with MPFD was investigated. This is shown in Table 2 below.

[Table 2]

As shown in Table 2, blood hypercoagulation diseases were found in 36% of mothers diagnosed with MPFD.

Through the above results, it was found that if a mother can diagnose whether or not MPFD is present during miscarriage, there is an opportunity to detect the disease in advance by performing a blood hypercoagulation disease test on the mother diagnosed with MPFD. Since serious complications such as pulmonary arterial embolism and deep vein thrombosis may occur when blood hypercoagulation disease occurs, prevention and treatment of blood hypercoagulation disease by additional examination through MPFD diagnosis is more beneficial to maternal health. It is important.

Experimental Example 5. Biomarker selection for MPFD diagnosis

Experimental Example 5.1. Selection of proteins specific to f-MPFD

By pooling the blood of the f-MPFD (7 people), MC (18 people) and NC (2 people) groups classified in Example 2, 7 plasma of the f-MPFD group and 18 plasma of the MC group and two plasmas of the NC group were prepared. Then, in order to cut the protein in the prepared plasma, a process of denaturing by treatment with urea and DTT, that is, reduction and alkylation reactions were performed. Thereafter, a process of cleaving the protein using trypsin, that is, a filter-aided sample preparation (FASP) process was performed. Then, C18 resin (Thermo Scientific) was used to wash urea and DTT previously used in the denaturation process. Then, LC-MS (liquid chromatography-mass spectrometry) was performed using Q Exactive Plus Nano LC (Thermo Fisher Scientific), and the protein was qualitatively analyzed using Proteome Discoverer 2.2 (Thermo Fisher Scientific). Proteins were quantitatively analyzed by label free quantification (LFQ).

As a result of protein analysis, Venn diagrams for proteins found in the three groups are shown in FIG. 13 . As shown in FIG. 13 , a total of 771 proteins were found in the f-MPFD group, and 156 proteins specific to MPFD were found. In addition, among the LFQ results, statistically, the p value was 0.05 or less and the difference in the amount of protein between the groups more than twice was displayed as a volcano plot. The number of proteins indicated in the volcano diagram was 268.

As a result of the above experiment, among the proteins simultaneously expressed in the MC and f-MPFD groups, 24 proteins increased more than 2 fold in the MPFD group, and increased more than 2 fold in the MPFD group among the proteins simultaneously expressed in the NC and f-MPFD groups. Among the proteins simultaneously expressed in the NC, MC and f-MPFD groups, 68 proteins increased more than twice in the MPFD group.

In addition, compared to the NC group, the f-MPFD group showed 237 proteins that were significantly higher than that of the NC group, and 69 proteins were expressed less. In addition, compared to the MC group, the f-MPFD group showed 216 proteins that were significantly more than twice as high and 72 proteins that were less expressed. This is shown in FIG. 14 . Through the above results, it was confirmed that proteins expressed significantly more than twice in the f-MPFD group than in other groups can be utilized as biomarkers for MPFD diagnosis.

Experimental Example 5.2. Selection of biomarkers for f-MPFD diagnosis

As shown in Experimental Example 5.1, among 771 proteins expressed in the f-MPFD group, 156 proteins specifically expressed only in the f-MPFD group. In order to confirm whether the 156 proteins are found in plasma, the human plasma atlas of the plasma proteome database was used. After mapping the 156 proteins using the human plasma atlas, 45 proteins to be mapped were selected.

Then, among the 45 selected proteins, 19 proteins having a function related to the pathogenesis of f-MPFD discovered through the Uniprot database and having a large amount found in the f-MPFD group were selected. Information on the finally selected 19 biomarker candidate groups is shown in Table 3 below.

[Table 3]

In Table 3, CCT3, CCT7, PSMA2, HSPA4, RAD23B and UBE2D3 are molecular chaperones, heat shock proteins, ubiquitins and proteasomes associated with protein misfolding. (proteasome). In addition, HNRNPC and EFTUD2 are proteins involved in RNA splicing. MBP, AHNAK and HSD17B10 are proteins involved in neural development.

<110> University of Ulsan Foundation For Industry Cooperation THE ASAN FOUNDATION <120> BIOMARKER COMPOSITION FOR DIAGNOSING MASSIVE PERIVILLOUS FIBRIN DEPOSITION AND USE THEREOF <130> FPD/202108-0052 <150> KR 10-2018-0119600 <151> 2018-10-08 <160> 38 <170> KoPatentIn 3.0 <210> 1 <211> 545 <212> PRT <213> Artificial Sequence <220> <223> CCT3 <400> 1 Met Met Gly His Arg Pro Val Leu Val Leu Ser Gln Asn Thr Lys Arg 1 5 10 15 Glu Ser Gly Arg Lys Val Gln Ser Gly Asn Ile Asn Ala Ala Lys Thr 20 25 30 Ile Ala Asp Ile Ile Arg Thr Cys Leu Gly Pro Lys Ser Met Met Lys 35 40 45 Met Leu Leu Asp Pro Met Gly Gly Ile Val Met Thr Asn Asp Gly Asn 50 55 60 Ala Ile Leu Arg Glu Ile Gln Val Gln His Pro Ala Ala Lys Ser Met 65 70 75 80 Ile Glu Ile Ser Arg Thr Gln Asp Glu Glu Val Gly Asp Gly Thr Thr 85 90 95 Ser Val Ile Ile Leu Ala Gly Glu Met Leu Ser Val Ala Glu His Phe 100 105 110 Leu Glu Gln Gln Met His Pro Thr Val Val Ile Ser Ala Tyr Arg Lys 115 120 125 Ala Leu Asp Asp Met Ile Ser Thr Leu Lys Lys Ile Ser Ile Pro Val 130 135 140 Asp Ile Ser Asp Ser Asp Met Met Leu Asn Ile Ile Asn Ser Ser Ile 145 150 155 160 Thr Thr Lys Ala Ile Ser Arg Trp Ser Ser Leu Ala Cys Asn Ile Ala 165 170 175 Leu Asp Ala Val Lys Met Val Gln Phe Glu Glu Asn Gly Arg Lys Glu 180 185 190 Ile Asp Ile Lys Lys Tyr Ala Arg Val Glu Lys Ile Pro Gly Gly Ile 195 200 205 Ile Glu Asp Ser Cys Val Leu Arg Gly Val Met Ile Asn Lys Asp Val 210 215 220 Thr His Pro Arg Met Arg Arg Tyr Ile Lys Asn Pro Arg Ile Val Leu 225 230 235 240 Leu Asp Ser Ser Leu Glu Tyr Lys Lys Gly Glu Ser Gln Thr Asp Ile 245 250 255 Glu Ile Thr Arg Glu Glu Asp Phe Thr Arg Ile Leu Gln Met Glu Glu 260 265 270 Glu Tyr Ile Gln Gln Leu Cys Glu Asp Ile Ile Gln Leu Lys Pro Asp 275 280 285 Val Val Ile Thr Glu Lys Gly Ile Ser Asp Leu Ala Gln His Tyr Leu 290 295 300 Met Arg Ala Asn Ile Thr Ala Ile Arg Arg Val Arg Lys Thr Asp Asn 305 310 315 320 Asn Arg Ile Ala Arg Ala Cys Gly Ala Arg Ile Val Ser Arg Pro Glu 325 330 335 Glu Leu Arg Glu Asp Asp Val Gly Thr Gly Ala Gly Leu Leu Glu Ile 340 345 350 Lys Lys Ile Gly Asp Glu Tyr Phe Thr Phe Ile Thr Asp Cys Lys Asp 355 360 365 Pro Lys Ala Cys Thr Ile Leu Leu Arg Gly Ala Ser Lys Glu Ile Leu 370 375 380 Ser Glu Val Glu Arg Asn Leu Gln Asp Ala Met Gln Val Cys Arg Asn 385 390 395 400 Val Leu Leu Asp Pro Gln Leu Val Pro Gly Gly Gly Ala Ser Glu Met 405 410 415 Ala Val Ala His Ala Leu Thr Glu Lys Ser Lys Ala Met Thr Gly Val 420 425 430 Glu Gln Trp Pro Tyr Arg Ala Val Ala Gln Ala Leu Glu Val Ile Pro 435 440 445 Arg Thr Leu Ile Gln Asn Cys Gly Ala Ser Thr Ile Arg Leu Leu Thr 450 455 460 Ser Leu Arg Ala Lys His Thr Gln Glu Asn Cys Glu Thr Trp Gly Val 465 470 475 480 Asn Gly Glu Thr Gly Thr Leu Val Asp Met Lys Glu Leu Gly Ile Trp 485 490 495 Glu Pro Leu Ala Val Lys Leu Gln Thr Tyr Lys Thr Ala Val Glu Thr 500 505 510 Ala Val Leu Leu Leu Arg Ile Asp Asp Ile Val Ser Gly His Lys Lys 515 520 525 Lys Gly Asp Asp Gln Ser Arg Gln Gly Gly Ala Pro Asp Ala Gly Gln 530 535 540 Glu 545 <210> 2 <211> 2107 <212> DNA <213> Artificial Sequence <220> <223> CCT3 <400> 2 ctaacttgtc tggccgttct tgcgtagggg gcgggactaa ggctgtcaat tggtctgttt 60 ttgtgccgat caatgagatg ggtgcggtga ttggcgacta ccttgagagt agcgggttga 120 ggtgtaagcc ctgaggaggc agcgttttct gggcttctgt ctggttctct ctctccagaa 180 ggttctgccg gttcccccag ctctgggtac ccggctctgc atcgcgtcgc catgatgggc 240 catcgtccag tgctcgtgct cagccagaac acaaagcgtg aatccggaag aaaagttcaa 300 tctggaaaca tcaatgctgc caagactatt gcagatatca tccgaacatg tttgggaccc 360 aagtccatga tgaagatgct tttggaccca atgggaggca ttgtgatgac caatgatggc 420 aatgccattc ttcgagagat tcaagtccag catccagcgg ccaagtccat gatcgaaatt 480 agccggaccc aggatgaaga ggttggagat gggaccacat cagtaattat tcttgcaggg 540 gaaatgctgt ctgtagctga gcacttcctg gagcagcaga tgcacccaac agtggtgatc 600 agtgcttacc gcaaggcatt ggatgatatg atcagcaccc taaagaaaat aagtatccca 660 gtcgacatca gtgacagtga tatgatgctg aacatcatca acagctctat tactaccaaa 720 gccatcagtc ggtggtcatc tttggcttgc aacattgccc tggatgctgt caagatggta 780 cagtttgagg agaatggtcg gaaagagatt gacataaaaa aatatgcaag agtggaaaag 840 atacctggag gcatcattga agactcctgt gtcttgcgtg gagtcatgat taacaaggat 900 gtgacccatc cacgtatgcg gcgctatatc aagaaccctc gcattgtgct gctggattct 960 tctctggaat acaagaaagg agaaagccag actgacattg agattacacg agaggaggac 1020 ttcacccgaa ttctccagat ggaggaagag tacatccagc agctctgtga ggacattatc 1080 caactgaagc ccgatgtggt catcactgaa aagggcatct cagatttagc tcagcactac 1140 cttatgcggg ccaatatcac agccatccgc agagtccgga agacagacaa taatcgcatt 1200 gctagagcct gtggggcccg gatagtcagc cgaccagagg aactgagaga agatgatgtt 1260 ggaacaggag caggcctgtt ggaaatcaag aaaattggag atgaatactt tactttcatc 1320 actgactgca aagaccccaa ggcctgcacc attctcctcc ggggggctag caaagagatt 1380 ctctcggaag tagaacgcaa cctccaggat gccatgcaag tgtgtcgcaa tgttctcctg 1440 gaccctcagc tggtgccagg gggtggggcc tccgagatgg ctgtggccca tgccttgaca 1500 gaaaaatcca aggccatgac tggtgtggaa caatggccat acagggctgt tgcccaggcc 1560 ctagaggtca ttcctcgtac cctgatccag aactgtgggg ccagcaccat ccgtctactt 1620 acctcccttc gggccaagca cacccaggag aactgtgaga cctggggtgt aaatggtgag 1680 acgggtactt tggtggacat gaaggaactg ggcatatggg agccattggc tgtgaagctg 1740 cagacttata agacagcagt ggagacggca gttctgctac tgcgaattga tgacatcgtt 1800 tcaggccaca aaaagaaagg cgatgaccag agccggcaag gcggggctcc tgatgctggc 1860 caggagtgag tgctaggcaa ggctacttca atgcacagaa ccagcagagt ctcccctttt 1920 cctgagccag agtgccagga acactgtgga cgtctttgtt cagaagggat caggttgggg 1980 ggcagccccc agtccctttc tgtcccagct cagttttcca aaagacactg acatgtaatt 2040 cttctctatt gtaaggtttc catttagttt gcttccgatg attaaatcta agtcatttga 2100 gaaagtt 2107 <210> 3 <211> 543 <212> PRT <213> Artificial Sequence <220> <223> CCT7 <400> 3 Met Met Pro Thr Pro Val Ile Leu Leu Lys Glu Gly Thr Asp Ser Ser 1 5 10 15 Gln Gly Ile Pro Gln Leu Val Ser Asn Ile Ser Ala Cys Gln Val Ile 20 25 30 Ala Glu Ala Val Arg Thr Thr Leu Gly Pro Arg Gly Met Asp Lys Leu 35 40 45 Ile Val Asp Gly Arg Gly Lys Ala Thr Ile Ser Asn Asp Gly Ala Thr 50 55 60 Ile Leu Lys Leu Leu Asp Val Val His Pro Ala Ala Lys Thr Leu Val 65 70 75 80 Asp Ile Ala Lys Ser Gln Asp Ala Glu Val Gly Asp Gly Thr Thr Ser 85 90 95 Val Thr Leu Leu Ala Ala Glu Phe Leu Lys Gln Val Lys Pro Tyr Val 100 105 110 Glu Glu Gly Leu His Pro Gln Ile Ile Ile Arg Ala Phe Arg Thr Ala 115 120 125 Thr Gln Leu Ala Val Asn Lys Ile Lys Glu Ile Ala Val Thr Val Lys 130 135 140 Lys Ala Asp Lys Val Glu Gln Arg Lys Leu Leu Glu Lys Cys Ala Met 145 150 155 160 Thr Ala Leu Ser Ser Lys Leu Ile Ser Gln Gln Lys Ala Phe Phe Ala 165 170 175 Lys Met Val Val Asp Ala Val Met Met Leu Asp Asp Leu Leu Gln Leu 180 185 190 Lys Met Ile Gly Ile Lys Lys Val Gln Gly Gly Ala Leu Glu Asp Ser 195 200 205 Gln Leu Val Ala Gly Val Ala Phe Lys Lys Thr Phe Ser Tyr Ala Gly 210 215 220 Phe Glu Met Gln Pro Lys Lys Tyr His Asn Pro Lys Ile Ala Leu Leu 225 230 235 240 Asn Val Glu Leu Glu Leu Lys Ala Glu Lys Asp Asn Ala Glu Ile Arg 245 250 255 Val His Thr Val Glu Asp Tyr Gln Ala Ile Val Asp Ala Glu Trp Asn 260 265 270 Ile Leu Tyr Asp Lys Leu Glu Lys Ile His His Ser Gly Ala Lys Val 275 280 285 Val Leu Ser Lys Leu Pro Ile Gly Asp Val Ala Thr Gln Tyr Phe Ala 290 295 300 Asp Arg Asp Met Phe Cys Ala Gly Arg Val Pro Glu Glu Asp Leu Lys 305 310 315 320 Arg Thr Met Met Ala Cys Gly Gly Ser Ile Gln Thr Ser Val Asn Ala 325 330 335 Leu Ser Ala Asp Val Leu Gly Arg Cys Gln Val Phe Glu Glu Thr Gln 340 345 350 Ile Gly Gly Glu Arg Tyr Asn Phe Phe Thr Gly Cys Pro Lys Ala Lys 355 360 365 Thr Cys Thr Phe Ile Leu Arg Gly Gly Ala Glu Gln Phe Met Glu Glu 370 375 380 Thr Glu Arg Ser Leu His Asp Ala Ile Met Ile Val Arg Arg Ala Ile 385 390 395 400 Lys Asn Asp Ser Val Val Ala Gly Gly Gly Ala Ile Glu Met Glu Leu 405 410 415 Ser Lys Tyr Leu Arg Asp Tyr Ser Arg Thr Ile Pro Gly Lys Gln Gln 420 425 430 Leu Leu Ile Gly Ala Tyr Ala Lys Ala Leu Glu Ile Ile Pro Arg Gln 435 440 445 Leu Cys Asp Asn Ala Gly Phe Asp Ala Thr Asn Ile Leu Asn Lys Leu 450 455 460 Arg Ala Arg His Ala Gln Gly Gly Thr Trp Tyr Gly Val Asp Ile Asn 465 470 475 480 Asn Glu Asp Ile Ala Asp Asn Phe Glu Ala Phe Val Trp Glu Pro Ala 485 490 495 Met Val Arg Ile Asn Ala Leu Thr Ala Ala Ser Glu Ala Ala Cys Leu 500 505 510 Ile Val Ser Val Asp Glu Thr Ile Lys Asn Pro Arg Ser Thr Val Asp 515 520 525 Ala Pro Thr Ala Ala Gly Arg Gly Arg Gly Arg Gly Arg Pro His 530 535 540 <210> 4 <211> 1948 <212> DNA <213> Artificial Sequence <220> <223> CCT7 <400> 4 atagagtagc ggaagtggtc cgttctcttt ctctcccggc ccaagcttct gggtatttct 60 attgcgcgag gcattgtggg ttgctgggcg gcccggtctc ggagaagagg ggagagtggc 120 gggccgctga ataagcttcc aaaatgatgc ccacaccagt tatcctattg aaagagggga 180 ctgatagctc ccaaggcatc ccccagcttg tgagtaacat cagtgcctgc caggtgattg 240 ctgaggctgt aagaactacc ctgggtcccc gtggcatgga caagcttatt gtagatggca 300 gaggcaaagc aacaatttct aatgatgggg ccacaattct gaaacttctt gatgttgtcc 360 atcctgcagc aaagactttg gtagacattg ccaaatccca agatgctgag gtgggtgatg 420 gcaccacctc agtgaccttg ctggctgcag agtttctgaa gcaggtgaaa ccctatgtgg 480 aggaaggttt acacccccag atcatcattc gagctttccg cacagccacc cagctggcag 540 ttaacaagat caaagagatt gctgtgaccg tgaagaaggc agataaagtg gagcagagga 600 agctgctgga aaagtgtgcc atgaccgctc tgagctccaa gctgatctcc cagcagaaag 660 ctttctttgc taagatggtg gtggatgcag tgatgatgct cgatgatttg ctgcagctta 720 aaatgattgg aatcaagaag gtacagggtg gagccctcga ggattctcag ctggtagctg 780 gtgttgcatt caagaagact ttctcttacg ctgggtttga aatgcaaccc aaaaagtacc 840 acaatcccaa gattgccctt ttgaatgtcg agctcgagtt gaaagctgag aaagacaatg 900 ctgagataag agtccacaca gttgaggatt atcaggcaat tgttgatgct gagtggaaca 960 ttctctatga caagttagag aagatccatc attctggagc caaagttgtc ttgtccaaac 1020 tccccattgg ggatgtggcc acccagtact ttgctgacag ggacatgttc tgtgctggcc 1080 gagtacctga ggaggatctg aagaggacaa tgatggcctg tggaggctca atccagacca 1140 gtgtgaatgc tctgtcagca gatgtgctgg gtcgatgcca ggtgtttgaa gagacccaga 1200 ttggaggcga gaggtacaat ttttttactg gctgccccaa ggccaagaca tgcaccttca 1260 ttctccgtgg cggcgccgag cagtttatgg aggagacaga gcggtccctg catgatgcca 1320 tcatgatcgt caggagggcc atcaagaatg attcagtggt ggctggtggc ggggccattg 1380 agatggaact ctccaagtac ctgcgggatt actcaaggac tattccagga aaacagcagc 1440 tgttgattgg ggcatatgcc aaggccttgg agattatccc acgccagctg tgtgacaatg 1500 ctggctttga tgccacaaac attctcaaca agctgcgggc tcggcatgcc caggggggta 1560 catggtatgg agtagacatc aacaacgagg acattgctga caactttgaa gctttcgtgt 1620 gggagccagc tatggtgcgg atcaatgcgc tgacagcagc ctctgaggct gcgtgcctga 1680 tcgtgtctgt agatgaaacc atcaagaacc cccgctcgac tgtggatgct cccacagcag 1740 caggccgggg ccgtggtcgt ggccgccccc actgagaggc accccaccca tcacatggct 1800 ggctggctgc tgggtgcact taccctcctt ggcttggtta cttcatttta caaggaaggg 1860 gtagtaattg gcccactctc ttcttactgg aggctattta aataaaatgt aagacttcag 1920 ataactttgt aaattaaaaa aaaaaaaa 1948 <210> 5 <211> 234 <212> PRT <213> Artificial Sequence <220> <223> PSMA2 <400> 5 Met Ala Glu Arg Gly Tyr Ser Phe Ser Leu Thr Thr Phe Ser Pro Ser 1 5 10 15 Gly Lys Leu Val Gln Ile Glu Tyr Ala Leu Ala Ala Val Ala Gly Gly 20 25 30 Ala Pro Ser Val Gly Ile Lys Ala Ala Asn Gly Val Val Leu Ala Thr 35 40 45 Glu Lys Lys Gln Lys Ser Ile Leu Tyr Asp Glu Arg Ser Val His Lys 50 55 60 Val Glu Pro Ile Thr Lys His Ile Gly Leu Val Tyr Ser Gly Met Gly 65 70 75 80 Pro Asp Tyr Arg Val Leu Val His Arg Ala Arg Lys Leu Ala Gln Gln 85 90 95 Tyr Tyr Leu Val Tyr Gln Glu Pro Ile Pro Thr Ala Gln Leu Val Gln 100 105 110 Arg Val Ala Ser Val Met Gln Glu Tyr Thr Gln Ser Gly Gly Val Arg 115 120 125 Pro Phe Gly Val Ser Leu Leu Ile Cys Gly Trp Asn Glu Gly Arg Pro 130 135 140 Tyr Leu Phe Gln Ser Asp Pro Ser Gly Ala Tyr Phe Ala Trp Lys Ala 145 150 155 160 Thr Ala Met Gly Lys Asn Tyr Val Asn Gly Lys Thr Phe Leu Glu Lys 165 170 175 Arg Tyr Asn Glu Asp Leu Glu Leu Glu Asp Ala Ile His Thr Ala Ile 180 185 190 Leu Thr Leu Lys Glu Ser Phe Glu Gly Gin Met Thr Glu Asp Asn Ile 195 200 205 Glu Val Gly Ile Cys Asn Glu Ala Gly Phe Arg Arg Leu Thr Pro Thr 210 215 220 Glu Val Lys Asp Tyr Leu Ala Ala Ile Ala 225 230 <210> 6 <211> 1466 <212> DNA <213> Artificial Sequence <220> <223> PSMA2 <400> 6 ggccacagtg cgcatgtgtg cggctgtgct ttggctcttc gggtaaagat ggcggagcgc 60 gggtacagct tttcgctgac tacattcagc ccgtctggta aacttgtcca gattgaatat 120 gctttggctg ctgtagctgg aggagccccg tccgtgggaa ttaaagctgc aaatggtgtg 180 gtattagcaa ctgagaaaaa acagaaatcc attctgtatg atgagcgaag tgtacacaaa 240 gtagaaccaa ttaccaagca tataggtttg gtgtacagtg gcatgggccc cgattacaga 300 gtgcttgtgc acagagctcg aaaactagct caacaatact atcttgtgta ccaagaaccc 360 attcctacag ctcagctggt acagagagta gcttctgtga tgcaagaata tactcagtca 420 ggtggtgttc gtccatttgg agtttcttta cttatttgtg gttggaatga gggacgacca 480 tatttatttc agtcagatcc atctggagct tactttgcct ggaaagctac agcaatggga 540 aagaactatg tgaatgggaa gactttcctt gagaaaagat ataatgaaga tctggaactt 600 gaagatgcca ttcatacagc catcttaacc ctaaaggaaa gctttgaagg gcaaatgaca 660 gaggataaca tagaagttgg aatctgcaat gaagctggat ttaggaggct tactccaact 720 gaagttaagg attacttggc tgccatagca taacaatgaa gtgactgaaa aatccagaat 780 ttcagataat ctatctactt aaacatgttt aaagtatgtt ttgttttgca gactttttgc 840 atacttattt ctacatggtt taaatcgact gtttttaaaa tgacacttat aaatcctaat 900 aaactgttaa acccaccttc cagcctttta ggagttgcta aaattttaac agttatttcc 960 tgctttttat cacagttgat ttctgaagac tacattgcca agcagaatga tgaaatgact 1020 ttttcgttgt caggcaattt tggttaagtc aaatcttaat gccctcttcg ctatcagatg 1080 ttgcctgtgt ttccataaag caaaatgctg attttggtaa aaaacatgac tgcttctaga 1140 gctgggagga tctgcagact ttcacggatt catggaacaa gaaaagaagc ataggtactt 1200 ttaggtgcca ttaggtattg atcagtgaaa tcctagggtg ctctatgaga ttgtactagg 1260 cctatgaaga gtggtaagcc aaataggtct ccatgggaga tacattatgt aaataaataa 1320 acaatggttt gctggttcct gttggtgtct ccacaagtag gtaaacatgt ttaaaggaac 1380 ccgggttctt agattttgtt agacttttta aactcaagga tgagcataag tgcttgaaat 1440 aaaatgctaa tacttaagtg tcaaaa 1466 <210> 7 <211> 840 <212> PRT <213> Artificial Sequence <220> <223> HSPA4 <400> 7 Met Ser Val Val Gly Ile Asp Leu Gly Phe Gln Ser Cys Tyr Val Ala 1 5 10 15 Val Ala Arg Ala Gly Gly Ile Glu Thr Ile Ala Asn Glu Tyr Ser Asp 20 25 30 Arg Cys Thr Pro Ala Cys Ile Ser Phe Gly Pro Lys Asn Arg Ser Ile 35 40 45 Gly Ala Ala Ala Lys Ser Gln Val Ile Ser Asn Ala Lys Asn Thr Val 50 55 60 Gln Gly Phe Lys Arg Phe His Gly Arg Ala Phe Ser Asp Pro Phe Val 65 70 75 80 Glu Ala Glu Lys Ser Asn Leu Ala Tyr Asp Ile Val Gln Leu Pro Thr 85 90 95 Gly Leu Thr Gly Ile Lys Val Thr Tyr Met Glu Glu Glu Arg Asn Phe 100 105 110 Thr Thr Glu Gln Val Thr Ala Met Leu Leu Ser Lys Leu Lys Glu Thr 115 120 125 Ala Glu Ser Val Leu Lys Lys Pro Val Val Asp Cys Val Val Ser Val 130 135 140 Pro Cys Phe Tyr Thr Asp Ala Glu Arg Arg Ser Val Met Asp Ala Thr 145 150 155 160 Gln Ile Ala Gly Leu Asn Cys Leu Arg Leu Met Asn Glu Thr Thr Ala 165 170 175 Val Ala Leu Ala Tyr Gly Ile Tyr Lys Gln Asp Leu Pro Ala Leu Glu 180 185 190 Glu Lys Pro Arg Asn Val Val Phe Val Asp Met Gly His Ser Ala Tyr 195 200 205 Gln Val Ser Val Cys Ala Phe Asn Arg Gly Lys Leu Lys Val Leu Ala 210 215 220 Thr Ala Phe Asp Thr Thr Leu Gly Gly Arg Lys Phe Asp Glu Val Leu 225 230 235 240 Val Asn His Phe Cys Glu Glu Phe Gly Lys Lys Tyr Lys Leu Asp Ile 245 250 255 Lys Ser Lys Ile Arg Ala Leu Leu Arg Leu Ser Gln Glu Cys Glu Lys 260 265 270 Leu Lys Lys Leu Met Ser Ala Asn Ala Ser Asp Leu Pro Leu Ser Ile 275 280 285 Glu Cys Phe Met Asn Asp Val Asp Val Ser Gly Thr Met Asn Arg Gly 290 295 300 Lys Phe Leu Glu Met Cys Asn Asp Leu Leu Ala Arg Val Glu Pro Pro 305 310 315 320 Leu Arg Ser Val Leu Glu Gln Thr Lys Leu Lys Lys Glu Asp Ile Tyr 325 330 335 Ala Val Glu Ile Val Gly Gly Ala Thr Arg Ile Pro Ala Val Lys Glu 340 345 350 Lys Ile Ser Lys Phe Phe Gly Lys Glu Leu Ser Thr Thr Leu Asn Ala 355 360 365 Asp Glu Ala Val Thr Arg Gly Cys Ala Leu Gln Cys Ala Ile Leu Ser 370 375 380 Pro Ala Phe Lys Val Arg Glu Phe Ser Ile Thr Asp Val Val Pro Tyr 385 390 395 400 Pro Ile Ser Leu Arg Trp Asn Ser Pro Ala Glu Glu Gly Ser Ser Asp 405 410 415 Cys Glu Val Phe Ser Lys Asn His Ala Ala Pro Phe Ser Lys Val Leu 420 425 430 Thr Phe Tyr Arg Lys Glu Pro Phe Thr Leu Glu Ala Tyr Tyr Ser Ser 435 440 445 Pro Gln Asp Leu Pro Tyr Pro Asp Pro Ala Ile Ala Gln Phe Ser Val 450 455 460 Gln Lys Val Thr Pro Gln Ser Asp Gly Ser Ser Ser Lys Val Lys Val 465 470 475 480 Lys Val Arg Val Asn Val His Gly Ile Phe Ser Val Ser Ser Ala Ser 485 490 495 Leu Val Glu Val His Lys Ser Glu Glu Asn Glu Glu Pro Met Glu Thr 500 505 510 Asp Gln Asn Ala Lys Glu Glu Glu Lys Met Gln Val Asp Gln Glu Glu 515 520 525 Pro His Val Glu Glu Gln Gln Gln Gln Thr Pro Ala Glu Asn Lys Ala 530 535 540 Glu Ser Glu Glu Met Glu Thr Ser Gln Ala Gly Ser Lys Asp Lys Lys 545 550 555 560 Met Asp Gln Pro Pro Gln Ala Lys Lys Ala Lys Val Lys Thr Ser Thr 565 570 575 Val Asp Leu Pro Ile Glu Asn Gln Leu Leu Trp Gln Ile Asp Arg Glu 580 585 590 Met Leu Asn Leu Tyr Ile Glu Asn Glu Gly Lys Met Ile Met Gln Asp 595 600 605 Lys Leu Glu Lys Glu Arg Asn Asp Ala Lys Asn Ala Val Glu Glu Tyr 610 615 620 Val Tyr Glu Met Arg Asp Lys Leu Ser Gly Glu Tyr Glu Lys Phe Val 625 630 635 640 Ser Glu Asp Asp Arg Asn Ser Phe Thr Leu Lys Leu Glu Asp Thr Glu 645 650 655 Asn Trp Leu Tyr Glu Asp Gly Glu Asp Gln Pro Lys Gln Val Tyr Val 660 665 670 Asp Lys Leu Ala Glu Leu Lys Asn Leu Gly Gln Pro Ile Lys Ile Arg 675 680 685 Phe Gln Glu Ser Glu Glu Arg Pro Lys Leu Phe Glu Glu Leu Gly Lys 690 695 700 Gln Ile Gln Gln Tyr Met Lys Ile Ile Ser Ser Phe Lys Asn Lys Glu 705 710 715 720 Asp Gln Tyr Asp His Leu Asp Ala Ala Asp Met Thr Lys Val Glu Lys 725 730 735 Ser Thr Asn Glu Ala Met Glu Trp Met Asn Asn Lys Leu Asn Leu Gln 740 745 750 Asn Lys Gln Ser Leu Thr Met Asp Pro Val Val Lys Ser Lys Glu Ile 755 760 765 Glu Ala Lys Ile Lys Glu Leu Thr Ser Thr Cys Ser Pro Ile Ile Ser 770 775 780 Lys Pro Lys Pro Lys Val Glu Pro Pro Lys Glu Glu Gln Lys Asn Ala 785 790 795 800 Glu Gln Asn Gly Pro Val Asp Gly Gln Gly Asp Asn Pro Gly Pro Gln 805 810 815 Ala Ala Glu Gln Gly Thr Asp Thr Ala Val Pro Ser Asp Ser Asp Lys 820 825 830 Lys Leu Pro Glu Met Asp Ile Asp 835 840 <210> 8 <211> 3385 <212> DNA <213> Artificial Sequence <220> <223> HSPA4 <400> 8 gctctggtgc tgcggctccg ctctcgtcgc aacgagatct ttcgagatct tctccgcccc 60 cgctaccggc gcctcctctg cggccactga gccggagccg gcctgagcag cgctctcggt 120 tgcagtaccc actggaagga cttaggcgct cgcgtggaca ccgcaagccc ctcagtagcc 180 tcggcccaag aggcctgctt tccactcgct agccccgccg ggggtccgtg tcctgtctcg 240 gtggccggac ccgggcccga gcccgagcag tagccggcgc catgtcggtg gtgggcatag 300 acctgggctt ccagagctgc tacgtcgctg tggcccgcgc cggcggcatc gagactatcg 360 ctaatgagta tagcgaccgc tgcacgccgg cttgcatttc ttttggtcct aagaatcgtt 420 caattggagc agcagctaaa agccaggtaa tttctaatgc aaagaacaca gtccaaggat 480 ttaaaagatt ccatggccga gcattctctg atccatttgt ggaggcagaa aaatctaacc 540 ttgcatatga tattgtgcag ttgcctacag gattaacagg tataaaggtg acatatatgg 600 aggaagagcg aaattttacc actgagcaag tgactgccat gcttttgtcc aaactgaagg 660 agacagccga aagtgttctt aagaagcctg tagttgactg tgttgtttcg gttccttgtt 720 tctatactga tgcagaaaga cgatcagtga tggatgcaac acagattgct ggtcttaatt 780 gcttgcgatt aatgaatgaa accactgcag ttgctcttgc atatggaatc tataagcagg 840 atcttcctgc cttagaagag aaaccaagaa atgtagtttt tgtagacatg ggccactctg 900 cttatcaagt ttctgtatgt gcatttaata gaggaaaact gaaagttctg gccactgcat 960 ttgacacgac attgggaggt agaaaatttg atgaagtgtt agtaaatcac ttctgtgaag 1020 aatttgggaa gaaatacaag ctagacatta agtccaaaat ccgtgcatta ttacgactct 1080 ctcaggagtg tgagaaactc aagaaattga tgagtgcaaa tgcttcagat ctccctttga 1140 gcattgaatg ttttatgaat gatgttgatg tatctggaac tatgaataga ggcaaatttc 1200 tggagatgtg caatgatctc ttagctagag tggagccacc acttcgtagt gttttggaac 1260 aaaccaagtt aaagaaagaa gatatttatg cagtggagat agttggtggt gctacacgaa 1320 tccctgcggt aaaagagaag atcagcaaat ttttcggtaa agaacttagt acaacattaa 1380 atgctgatga agctgtcact cgaggctgtg cattgcagtg tgccatctta tcgcctgctt 1440 tcaaagtcag agaattttct atcactgatg tagtaccata tccaatatct ctgagatgga 1500 attctccagc tgaagaaggg tcaagtgact gtgaagtctt ttccaaaaat catgctgctc 1560 ctttctctaa agttcttaca ttttatagaa aggaaccttt cactcttgag gcctactaca 1620 gctctcctca ggatttgccc tatccagatc ctgctatagc tcagttttca gttcagaaag 1680 tcactcctca gtctgatggc tccagttcaa aagtgaaagt caaagttcga gtaaatgtcc 1740 atggcatttt cagtgtgtcc agtgcatctt tagtggaggt tcacaagtct gaggaaaatg 1800 aggagccaat ggaaacagat cagaatgcaa aggaggaaga gaagatgcaa gtggaccagg 1860 aggaaccaca tgttgaagag caacagcagc agacaccagc agaaaataag gcagagtctg 1920 aagaaatgga gacctctcaa gctggatcca aggataaaaa gatggaccaa ccaccccaag 1980 ccaagaaggc aaaagtgaag accagtactg tggacctgcc aatcgagaat cagctattat 2040 ggcagataga cagagagatg ctcaacttgt acattgaaaa tgagggtaag atgatcatgc 2100 aggataaact ggagaaggag cggaatgatg ctaagaacgc agtggaggaa tatgtgtatg 2160 aaatgagaga caagcttagt ggtgaatatg agaagtttgt gagtgaagat gatcgtaaca 2220 gttttacttt gaaactggaa gatactgaaa attggttgta tgaggatgga gaagaccagc 2280 caaagcaagt ttatgttgat aagttggctg aattaaaaaa tctaggtcaa cctattaaga 2340 tacgtttcca ggaatctgaa gaacgaccaa aattatttga agaactaggg aaacagatcc 2400 aacagtatat gaaaataatc agctctttca aaaacaagga ggaccagtat gatcatttgg 2460 atgctgctga catgacaaag gtagaaaaaa gcacaaatga agcaatggag tggatgaata 2520 acaagctaaa tctgcagaac aagcagagtt tgaccatgga tccagttgtc aagtcaaaag 2580 agattgaagc taaaattaag gagctgacaa gtacttgtag ccctataatt tcaaagccca 2640 aacccaaagt ggaacctcca aaagaggaac aaaaaaatgc agagcagaat ggaccagtgg 2700 atggacaagg agacaaccca ggcccccagg ctgctgagca gggtacagac acagctgtgc 2760 cttcggattc agacaagaag cttcctgaaa tggacattga ttgattccaa cacttgtttc 2820 tattaaaaca gactattata aagctttaag ttgtcaactt tgttctaaat atcaactagc 2880 gcaagtgaat actgaagatt tcttagtcag tttttagggg attttcgggg aggggaaata 2940 ggtaatgtat ggagcatttt cacttctaaa tagttagata cagaaattaa gtgcattgta 3000 tctttttcat aatggtacta tttagaagcc cagttagtct tactgagctt atgcttcact 3060 cctttatgtt taaccatgtg tctacaagaa taagtttgtt ttggaaagtt gagctatagc 3120 tacagctcta gctatccagc agacttttca ttatgactta catggcagga gctctaatta 3180 tgctttaaaa atctgttgtg gagattgctt taaatgctcc ctgcctggtg tggggatggg 3240 gtccccctct ttgtgagggc tggagcatgg cacggcatgg attaacacgg cagaggaaca 3300 aaggtgtgct ctgagcttct tcatatttca ccttcaccct cacctgtgtt ctcttccctc 3360 tctcccaata aaagggctcc catta 3385 <210> 9 <211> 409 <212> PRT <213> Artificial Sequence <220> <223> RAD23B <400> 9 Met Gln Val Thr Leu Lys Thr Leu Gln Gln Gln Thr Phe Lys Ile Asp 1 5 10 15 Ile Asp Pro Glu Glu Thr Val Lys Ala Leu Lys Glu Lys Ile Glu Ser 20 25 30 Glu Lys Gly Lys Asp Ala Phe Pro Val Ala Gly Gln Lys Leu Ile Tyr 35 40 45 Ala Gly Lys Ile Leu Asn Asp Asp Thr Ala Leu Lys Glu Tyr Lys Ile 50 55 60 Asp Glu Lys Asn Phe Val Val Val Met Val Thr Lys Pro Lys Ala Val 65 70 75 80 Ser Thr Pro Ala Pro Ala Thr Thr Gln Gln Ser Ala Pro Ala Ser Thr 85 90 95 Thr Ala Val Thr Ser Ser Thr Thr Thr Thr Val Ala Gln Ala Pro Thr 100 105 110 Pro Val Pro Ala Leu Ala Pro Thr Ser Thr Pro Ala Ser Ile Thr Pro 115 120 125 Ala Ser Ala Thr Ala Ser Ser Glu Pro Ala Pro Ala Ser Ala Ala Lys 130 135 140 Gln Glu Lys Pro Ala Glu Lys Pro Ala Glu Thr Pro Val Ala Thr Ser 145 150 155 160 Pro Thr Ala Thr Asp Ser Thr Ser Gly Asp Ser Ser Arg Ser Asn Leu 165 170 175 Phe Glu Asp Ala Thr Ser Ala Leu Val Thr Gly Gln Ser Tyr Glu Asn 180 185 190 Met Val Thr Glu Ile Met Ser Met Gly Tyr Glu Arg Glu Gln Val Ile 195 200 205 Ala Ala Leu Arg Ala Ser Phe Asn Asn Pro Asp Arg Ala Val Glu Tyr 210 215 220 Leu Leu Met Gly Ile Pro Gly Asp Arg Glu Ser Gln Ala Val Val Asp 225 230 235 240 Pro Pro Gln Ala Ala Ser Thr Gly Ala Pro Gln Ser Ser Ala Val Ala 245 250 255 Ala Ala Ala Ala Thr Thr Thr Ala Thr Thr Thr Thr Thr Ser Ser Gly 260 265 270 Gly His Pro Leu Glu Phe Leu Arg Asn Gln Pro Gln Phe Gln Gln Met 275 280 285 Arg Gln Ile Ile Gln Gln Asn Pro Ser Leu Leu Pro Ala Leu Leu Gln 290 295 300 Gln Ile Gly Arg Glu Asn Pro Gln Leu Leu Gln Gln Ile Ser Gln His 305 310 315 320 Gln Glu His Phe Ile Gln Met Leu Asn Glu Pro Val Gln Glu Ala Gly 325 330 335 Gly Gln Gly Gly Gly Gly Gly Gly Gly Gly Ser Gly Gly Ile Ala Glu Ala 340 345 350 Gly Ser Gly His Met Asn Tyr Ile Gln Val Thr Pro Gln Glu Lys Glu 355 360 365 Ala Ile Glu Arg Leu Lys Ala Leu Gly Phe Pro Glu Gly Leu Val Ile 370 375 380 Gln Ala Tyr Phe Ala Cys Glu Lys Asn Glu Asn Leu Ala Ala Asn Phe 385 390 395 400 Leu Leu Gln Gln Asn Phe Asp Glu Asp 405 <210> 10 <211> 4167 <212> DNA <213> Artificial Sequence <220> <223> RAD23B <400> 10 atccccccag gtttttcgcg tgggggaggg ggcacgtctc ggcgagtcac gatgatggcg 60 gccaccatcc tgtggtgagc tagcggattc cctgcttgtc tcgccgaccc cctcgcgcct 120 tctgcagact ccgtggctgg cgctcggcgc gtgaggaagc acggcggccc gagttcgcgg 180 ggaaggccgc agtcgcggag gcagcggcgc ggtccggggc acgggctggg ggagaggccg 240 ctccgctggg cgaatgtgac aagccccccac ccccaccgcc ttcctcccca gagcgcgagg 300 agcgcgggcg accccggggc cccgccaggc cacagacccc gcccagcggc cagcacccgg 360 cgcaggcccg gcagccgagc tgcgcggcgg caccatgcag gtcaccctga agaccctcca 420 gcagcagacc ttcaagatag acattgaccc cgaggagacg gtgaaagcac tgaaagagaa 480 gattgaatct gaaaagggga aagatgcctt tccagtagca ggtcaaaaat taatttatgc 540 aggcaaaatc ctcaatgatg atactgctct caaagaatat aaaattgatg agaaaaactt 600 tgtggtggtt atggtgacca aacccaaagc agtgtccaca ccagcaccag ctacaactca 660 gcagtcagct cctgccagca ctacagcagt tacttcctcc accaccacaa ctgtggctca 720 ggctccaacc cctgtccctg ccttggcccc cacttccaca cctgcatcca tcactccagc 780 atcagcgaca gcatcttctg aacctgcacc tgctagtgca gctaaacaag agaagcctgc 840 agaaaagcca gcagagacac cagtggctac tagcccaaca gcaactgaca gtacatcggg 900 tgattcttct cggtcaaacc tttttgaaga tgcaacgagt gcacttgtga cgggtcagtc 960 ttacgagaat atggtaactg agatcatgtc aatgggctat gaacgagagc aagtaattgc 1020 agccctgaga gccagtttca acaaccctga cagagcagtg gagtatcttt taatgggaat 1080 ccctggagat agagaaagtc aggctgtggt tgacccccct caagcagcta gtactggggc 1140 tcctcagtct tcagcagtgg ctgcagctgc agcaactacg acagcaacaa ctacaacaac 1200 aagttctgga ggacatcccc ttgaattttt acggaatcag cctcagtttc aacagatgag 1260 acaaattatt cagcagaatc cttccttgct tccagcgtta ctacagcaga taggtcgaga 1320 gaatcctcaa ttacttcagc aaattagcca acaccaggag cattttattc agatgttaaa 1380 tgaaccagtt caagaagctg gtggtcaagg aggaggaggt ggaggtggca gtggaggaat 1440 tgcagaagct ggaagtggtc atatgaacta cattcaagta acacctcagg aaaaagaagc 1500 tatagaaagg ttaaaggcat taggatttcc tgaaggactt gtgatacaag cgtattttgc 1560 ttgtgagaag aatgagaatt tggctgccaa ttttcttcta cagcagaact ttgatgaaga 1620 ttgaaaggga cttttttata tctcacactt cacaccagtg cattacacta acttgttcac 1680 tggattgtct gggatgactt gggctcatat ccacaatact tggtataagg tagtagattg 1740 ttgggggtgg ggagggaggg atctaggata cagggcaggg ataaatacag tgcatgtctg 1800 cttcaattag cagatgccgc aactccacac agtgtgtaaa atatatacaa ccaaaaatca 1860 gcttttgcag gtctttattt cttctgtaaa acagtaggta acttttccta ggtttcactc 1920 tttttagtgt actagatcca gaaacttagt gtaatgccct gctttatatt tctttgactt 1980 aacattggtt tcagaaagaa tcttagctac ctagaattta cagtctctgt ttcatggcaa 2040 cactggataa tggctttgtg aaatttaaaa aatttttgta gcgactgtaa acagaaatgc 2100 caaattgatg gttaattgtt gctgcttcaa aaataagtat aaaattaata tgtaaggaag 2160 cccattcttt catgttaaat acttggggtg ggaggggaga aagggaacct tttcttaaaa 2220 tgaaaataat tactgctatt ttaaaatttc ttgatcattg aatgtgagac ccttctaaca 2280 tgatttgaga agctgtacaa gtataggcag agttattttc ctgtttacat tttttttttg 2340 ttttggggaa aaaattggta ggtgtctaat tactgtttac ttcattgtta tattgcagta 2400 aaagttttaa aacaaccatt gcatgtttgc ttttgatgta tccctttgtg aaattagcac 2460 ttttggggcc aatggagaaa tgcagcattc actctccctg tcttttcccc ttccctcagc 2520 agaaacgtgt ttatcagcaa gtcgtgagtc aaactgctgc cttttaaaaa acccacaaaa 2580 tgctgattca gttcaaaatt aatgcaaatg tttcaaaact gggtttctga tatttgtaaa 2640 tgtgtttctt tattagataa gagtgtatta ccattaaagt cattagtata atattgcttt 2700 caaaaagaaa tggtagacaa aactataatc cagcatcttt tattgcattg gaaagactgg 2760 caaagtcttt tggatgggtt gggagatgtg gctggaaagt actttggaaa atatacaatc 2820 aagatatctc atggcatatt aaaagaaaaa tcttaatagc agtgttggct tttatttgga 2880 ttttttcatc tcagtttttt ctgtggaatc tccttcattg gcattgttat ttaatcataa 2940 acggggcaga tgtctacttg ttcagttttt caaatctgtt ttcctgagta taaataagag 3000 tattaaaga aataatttgg attgcttttt ttttttgttt cctttttttt aaccatctga 3060 tactaagaag atgaatttgc acagatttct ctgcataatt tctcaatatc tttagcacag 3120 tatggtgatg atgactttta agcatttaca tcacgtactc ataacctatt atgaaaataa 3180 atgaaactgg ctgggtatgg tggctcatgc ctataatccc agcactttgg gaggccgagg 3240 tgggcagatc acttgaggcc aggagattga gaccagcctg accgtcatgg cgaaaccccg 3300 tctatactaa aaatacaaaa aatagccagg catggtggcg cacgcctgtg gtcccagcta 3360 cttgggaggc tgaggcatga gaattgcttg aacccgggaa gtgaaggttg ccgtgagctg 3420 agatcacacc actgccataa acatgacagg cttttggact ttgtattacc tgtatgtttt 3480 ataatggatc atgcataatt tctcaggaga ataaaatgag aattcatata tacgttcatc 3540 tttcaagtca gagcaatgag ttgggaaaag aggtggcatt tctgatcgga taatggaata 3600 ctctcattta ttttatgaca ttctctgtct actcagatca tagtgaaaac tggaaacaaa 3660 aaaaaaaaac agcctcttct tggaaagtga cagcagaagg tggcatggag cttgtgtcct 3720 tggacaacaa atctggatat actaggatta attatcagaa gacagctcag gccaagtttt 3780 gatcgttcca tacagtacct tgtttatctg cttcttaaag aatcagccga gacaccataa 3840 aagaaatagg ctttttgtgc cttttgctgt taatgtttaa tttacaaact gttttggtaa 3900 atctcttaat gtaagtagct atttgacttt ggaattttgc attcgaggta tactgtcatt 3960 tcttgaaatc tttttctcgt ttagttgctc tgtgggaaat gtgaggaagc ctaagtttgt 4020 atttgtaaat ttcttatgcc atcctctagt caaatttttt ttcattgttt aaaaatacgg 4080 aagtgttcca atataatttt ttcctgtact ggatggctag gattctagag aattgattat 4140 aaaatatttt caatacatcc aaaaaaa 4167 <210> 11 <211> 147 <212> PRT <213> Artificial Sequence <220> <223> UBE2D3 <400> 11 Met Ala Leu Lys Arg Ile Asn Lys Glu Leu Ser Asp Leu Ala Arg Asp 1 5 10 15 Pro Pro Ala Gln Cys Ser Ala Gly Pro Val Gly Asp Asp Met Phe His 20 25 30 Trp Gln Ala Thr Ile Met Gly Pro Asn Asp Ser Pro Tyr Gln Gly Gly 35 40 45 Val Phe Phe Leu Thr Ile His Phe Pro Thr Asp Tyr Pro Phe Lys Pro 50 55 60 Pro Lys Val Ala Phe Thr Thr Arg Ile Tyr His Pro Asn Ile Asn Ser 65 70 75 80 Asn Gly Ser Ile Cys Leu Asp Ile Leu Arg Ser Gln Trp Ser Pro Ala 85 90 95 Leu Thr Ile Ser Lys Val Leu Leu Ser Ile Cys Ser Leu Leu Cys Asp 100 105 110 Pro Asn Pro Asp Asp Pro Leu Val Pro Glu Ile Ala Arg Ile Tyr Lys 115 120 125 Thr Asp Arg Asp Lys Tyr Asn Arg Ile Ser Arg Glu Trp Thr Gln Lys 130 135 140 Tyr Ala Met 145 <210> 12 <211> 4184 <212> DNA <213> Artificial Sequence <220> <223> UBE2D3 <400> 12 accaagtgag gaaactgggg gacgctgtgg ggaggggcgt ggggctggat cgcgcagcgg 60 ctgcttcctt taccttcctc ccatggtctc cttccggttc tcgatgcttc tctgagccta 120 agggtttccg ccactcgttc accctccccc cagctcatga tcctcctccc tccccccgccc 180 tcctggtcca atctccgatc tgtttagtaa gaaggtgctg ttccgagaag aaggaaaagg 240 gcttgacacg tattcactcg gccccggacg tgggaagcaa gccgtctggc ttcggcctca 300 catcggtctt gtgctcggga cggcggcgtt ggcggactga tccgcggcgg tgaagagagg 360 ccgggaagtt aaacttgtag ccaccacctc cgctcttccc gtcaccctcg cccccacttc 420 gggccgaaag cacggtacag aggctgttgg tggctttgcc acgccacccc acccaccccg 480 gatcgcggct gtcttaaggg acctggattc atcaggggct cttcggggcc tgtgcgagtg 540 ctgatctgct ccgtttttgc aaaaggcgcc tgtgtctggc agagctggtg tgagacgaga 600 caatcctgcc ccgccgccgg gataatcaag agttttggcc ggacctttga gcatacaccg 660 agagagtgag gagccagacg acaagcacac actatggcgc tgaaacggat taataaggaa 720 cttagtgatt tggcccgtga ccctccagca caatgttctg caggtccagt tggggatgat 780 atgtttcatt ggcaagccac aattatggga cctaatgaca gcccatatca aggcggtgta 840 ttctttttga caattcattt tcctacagac taccccttca aaccacctaa ggttgcattt 900 acaacaagaa tttatcatcc aaatattaac agtaatggca gcatttgtct cgatattcta 960 agatcacagt ggtcgcctgc tttaacaatt tctaaagttc ttttatccat ttgttcactg 1020 ctatgtgatc caaacccaga tgacccccta gtgccagaga ttgcacggat ctataaaaca 1080 gacagagata agtacaacag aatatctcgg gaatggactc agaagtatgc catgtgatgc 1140 taccttaaag tcagaataac ctgcattata gctggaataa actttaaatt actgttcctt 1200 ttttgatttt cttatccggc tgctccccta tcagacctca tcttttttaa ttttattttt 1260 tgtttacctc cctccattca ttcacatgct catctgagaa gacttaagtt cttccagctt 1320 tggacaataa ctgcttttag aaactgtaaa gtagttacaa gagaacagtt gcccaagact 1380 cagaattttt aaaaaaaaaa atggagcatg tgtattatgt ggccaatgtc ttcactctaa 1440 cttggttatg agactaaaac cattcctcac tgctctaaca tgctgaagaa atcatctgag 1500 ggggagggag atggatgctc agttgtcaca tcaaaggata cagcattatt ctagcagcat 1560 ccattcttgt ttaagccttc cactgttaga gatttgaggt tacatgatat gctttatgct 1620 cataactgat gtggctggag aattggtatt gaatttatag catcagcaga acagaaaatg 1680 tgatgtattt tatgcatgtc aataaaggaa tgacctgttc ttgttctaca gagaatggaa 1740 attggaagtc aaacaccctt tgtattccaa aatagggtct caaacatttt gtaattttca 1800 tttaaattgt taggaggctt ggagctatta gttaatctat cttccaatac actgtttaat 1860 atagcactga ataaatgatg caagttgtca atggatgagt gatcaactaa tagctctgct 1920 agtaattgat ttatttttct tcaataaagt tgcataaacc aatgagttag ctgcctggat 1980 taatcagtat gggaaacaat cttttgtaaa tgcaaagctg ttttttgtat atactgttgg 2040 gatttgcttc attgtttgac atcaaatgat gatgtaaagt tcgaaagagt gaatattttg 2100 ccatgttcag ttaaagtgca cagtctgtta caggttgaca cattgcttga cctgatttat 2160 gcagaattaa taagctattt ggatagtgta gctttaatgt gctgcacatg atactggcag 2220 ccctagagtt catagatgga cttttgggac ccagcagttt tgaaatgtgt ttatggagtt 2280 taagaaattt attttccagg tgcagcccct gtctaactga aatttctctt caccttgtac 2340 acttgacagc tgaaaaaaaa caacatggga gtaataatgg gtcaaaattt gcaaaataaa 2400 gtactgtttt ggtgtgggag ttgtcatgag gctgtgttga agtgacttat ctatgtggga 2460 tattgagtat ccattgaaat ggatttgttc agccatttac attaatgagc atttaaatgc 2520 aacagatatc atttcaggtg acttaacatg aatgaataaa agtcaatgct attggattgt 2580 tttttgtttg acaagtgcta tctgtgccac tgatttaact tctgtagtaa caagggcatt 2640 accattcttc acctttccta attctgatcc catagtttta catttttcct gtttattttg 2700 attttgttca ctgctttatt tcttaaagtt ctagcacatc tgtgactcct ccacttccac 2760 atttttgcac tgcttacact tacgtgcaat cttattcctt gtctgcacac acatgtggaa 2820 agctagaaat aaatgttaaa acttactttt tataaacatt ttaatatgta gtttggacat 2880 gatttattga cttaaggttc ttctctaaac tggaagtgaa atgcatgcct tctgaagatg 2940 ttctggcttt gttaattctg taatcatttc attggggaaa aaaccagcta cgcagttttt 3000 ccaatgagtg aattttttca ttttgtgttt tgcttaaaac ggctccttca gggtagatgt 3060 catactgcat aacttttttg gattcaaatt atgaatgaga aattagttaa cattctgctc 3120 cacaaggtaa gaaaaactgc tctttggctc tattttcaaa attacttctg agatgcatat 3180 agtctcaaaa taacagcttt agtaggcata tcacttcttg aaagccaaac atgagtgtaa 3240 gacactttta tgaaacacgg tggatcccta actggctttc aaattgacct ttatagcctt 3300 agacaaccct taggtattta cggagatgac ttctttgatt gtcataacaa ttagtggatg 3360 tgtccagttc tctgtatctt tgacttgatg ctttatacat catttcattt gttgcttcta 3420 agggaataag ccatagaggc ttctccaggt ttaaaagaac agtaaagtac ctggaaaacc 3480 aacatttttg aatgtatgga cactggacat gagatatgta caatgaaatc ttaaaagaat 3540 ctaagaattt gccctctttg ccccactcca cccagtaatt tgacattact agtgccatgt 3600 ataggaccca actgagtatt agaatcagtt ttgactatgt ctttgtattt cctaaatctt 3660 ttaatgcata aaccgaatta gggtccagtt ggcctgttaa tggtaaattt acatttaaa 3720 tgactcagtt tgtttttcct gggcgagttt gcaatgtgat aatcagattt tttaaaactg 3780 attaatttgc tttcttgtgt gggtgtactc acatttaaa gtatgaacca cagttaacta 3840 gtggtctcag gggtagtgaa acactcactt ttttttttgt ttgttttttt ttgtttgttg 3900 aaatggctta gttgaagtat acttaaggta ctgatcatgc tgtgttagta atttgggcgg 3960 ggaggggggt aactcagcca tgttttgtgt tggcataaca aaactgttaa tgattgttga 4020 ttacactttt aagtgaattt gtcttttatg aggaacccag tgcaagtcac taaatattgt 4080 ctaatagtga catctgcata agacttgtaa tagctgaagt taattgagct taaaggaatt 4140 gttaccata aagtctgtgt ttaaagacaa aaaaaaaaaa aaaa 4184 <210> 13 <211> 306 <212> PRT <213> Artificial Sequence <220> <223> HNRNPC <400> 13 Met Ala Ser Asn Val Thr Asn Lys Thr Asp Pro Arg Ser Met Asn Ser 1 5 10 15 Arg Val Phe Ile Gly Asn Leu Asn Thr Leu Val Val Lys Lys Ser Asp 20 25 30 Val Glu Ala Ile Phe Ser Lys Tyr Gly Lys Ile Val Gly Cys Ser Val 35 40 45 His Lys Gly Phe Ala Phe Val Gln Tyr Val Asn Glu Arg Asn Ala Arg 50 55 60 Ala Ala Val Ala Gly Glu Asp Gly Arg Met Ile Ala Gly Gln Val Leu 65 70 75 80 Asp Ile Asn Leu Ala Ala Glu Pro Lys Val Asn Arg Gly Lys Ala Gly 85 90 95 Val Lys Arg Ser Ala Ala Glu Met Tyr Gly Ser Val Thr Glu His Pro 100 105 110 Ser Pro Ser Pro Leu Leu Ser Ser Ser Phe Asp Leu Asp Tyr Asp Phe 115 120 125 Gln Arg Asp Tyr Tyr Asp Arg Met Tyr Ser Tyr Pro Ala Arg Val Pro 130 135 140 Pro Pro Pro Pro Ile Ala Arg Ala Val Val Pro Ser Lys Arg Gln Arg 145 150 155 160 Val Ser Gly Asn Thr Ser Arg Arg Gly Lys Ser Gly Phe Asn Ser Lys 165 170 175 Ser Gly Gln Arg Gly Ser Ser Lys Ser Gly Lys Leu Lys Gly Asp Asp 180 185 190 Leu Gln Ala Ile Lys Lys Glu Leu Thr Gln Ile Lys Gln Lys Val Asp 195 200 205 Ser Leu Leu Glu Asn Leu Glu Lys Ile Glu Lys Glu Gln Ser Lys Gln 210 215 220 Ala Val Glu Met Lys Asn Asp Lys Ser Glu Glu Glu Gln Ser Ser Ser 225 230 235 240 Ser Val Lys Lys Asp Glu Thr Asn Val Lys Met Glu Ser Glu Gly Gly 245 250 255 Ala Asp Asp Ser Ala Glu Glu Gly Asp Leu Leu Asp Asp Asp Asp Asn 260 265 270 Glu Asp Arg Gly Asp Asp Gln Leu Glu Leu Ile Lys Asp Asp Glu Lys 275 280 285 Glu Ala Glu Glu Gly Glu Asp Asp Arg Asp Ser Ala Asn Gly Glu Asp 290 295 300 Asp Ser 305 <210> 14 <211> 921 <212> DNA <213> Artificial Sequence <220> <223> HNRNPC <400> 14 atggccagca acgttaccaa caagacagat cctcgctcca tgaactcccg tgtattcatt 60 gggaatctca acactcttgt ggtcaagaaa tctgatgtgg aggcaatctt ttcgaagtat 120 ggcaaaattg tgggctgctc tgttcataag ggctttgcct tcgttcagta tgttaatgag 180 agaaatgccc gggctgctgt agcaggagag gatggcagaa tgattgctgg ccaggtttta 240 gatattaacc tggctgcaga gccaaaagtg aaccgaggaa aagcaggtgt gaaacgatct 300 gcagcggaga tgtacgggtc agtaacagaa cacccttctc cgtcccctct actcagctcc 360 tcttttgact tggactatga ctttcaacgg gactattatg ataggatgta cagttaccca 420 gcacgtgtac ctcctcctcc tcctattgct cgggctgtag tgccctcgaa acgtcagcgt 480 gtatcaggaa acacttcacg aaggggcaaa agtggcttca attctaagag tggacagcgg 540 ggatcttcca agtctggaaa gttgaaagga gatgaccttc aggccattaa gaaggagctg 600 acccagataa aacaaaaagt ggattctctc ctggaaaacc tggaaaaaat tgaaaaggaa 660 cagagcaaac aagcagtaga gatgaagaat gataagtcag aagaggagca gagcagcagc 720 tccgtgaaga aagatgagac taatgtgaag atggagtctg aggggggtgc agatgactct 780 gctgaggagg gggacctact ggatgatgat gataatgaag atcggggggga tgaccagctg 840 gagttgatca aggatgatga aaaagaggct gaggaaggag aggatgacag agacagcgcc 900 aatggcgagg atgactctta a 921 <210> 15 <211> 972 <212> PRT <213> Artificial Sequence <220> <223> EFTUD2 <400> 15 Met Asp Thr Asp Leu Tyr Asp Glu Phe Gly Asn Tyr Ile Gly Pro Glu 1 5 10 15 Leu Asp Ser Asp Glu Asp Asp Asp Glu Leu Gly Arg Glu Thr Lys Asp 20 25 30 Leu Asp Glu Met Asp Asp Asp Asp Asp Asp Asp Asp Asp Val Gly Asp His 35 40 45 Asp Asp Asp His Pro Gly Met Glu Val Val Leu His Glu Asp Lys Lys 50 55 60 Tyr Tyr Pro Thr Ala Glu Glu Val Tyr Gly Pro Glu Val Glu Thr Ile 65 70 75 80 Val Gln Glu Glu Asp Thr Gln Pro Leu Thr Glu Pro Ile Ile Lys Pro 85 90 95 Val Lys Thr Lys Lys Phe Thr Leu Met Glu Gln Thr Leu Pro Val Thr 100 105 110 Val Tyr Glu Met Asp Phe Leu Ala Asp Leu Met Asp Asn Ser Glu Leu 115 120 125 Ile Arg Asn Val Thr Leu Cys Gly His Leu His His Gly Lys Thr Cys 130 135 140 Phe Val Asp Cys Leu Ile Glu Gln Thr His Pro Glu Ile Arg Lys Arg 145 150 155 160 Tyr Asp Gln Asp Leu Cys Tyr Thr Asp Ile Leu Phe Thr Glu Gln Glu 165 170 175 Arg Gly Val Gly Ile Lys Ser Thr Pro Val Thr Val Val Leu Pro Asp 180 185 190 Thr Lys Gly Lys Ser Tyr Leu Phe Asn Ile Met Asp Thr Pro Gly His 195 200 205 Val Asn Phe Ser Asp Glu Val Thr Ala Gly Leu Arg Ile Ser Asp Gly 210 215 220 Val Val Leu Phe Ile Asp Ala Ala Glu Gly Val Met Leu Asn Thr Glu 225 230 235 240 Arg Leu Ile Lys His Ala Val Gln Glu Arg Leu Ala Val Thr Val Cys 245 250 255 Ile Asn Lys Ile Asp Arg Leu Ile Leu Glu Leu Lys Leu Pro Pro Thr 260 265 270 Asp Ala Tyr Tyr Lys Leu Arg His Ile Val Asp Glu Val Asn Gly Leu 275 280 285 Ile Ser Met Tyr Ser Thr Asp Glu Asn Leu Ile Leu Ser Pro Leu Leu 290 295 300 Gly Asn Val Cys Phe Ser Ser Ser Gln Tyr Ser Ile Cys Phe Thr Leu 305 310 315 320 Gly Ser Phe Ala Lys Ile Tyr Ala Asp Thr Phe Gly Asp Ile Asn Tyr 325 330 335 Gln Glu Phe Ala Lys Arg Leu Trp Gly Asp Ile Tyr Phe Asn Pro Lys 340 345 350 Thr Arg Lys Phe Thr Lys Lys Ala Pro Thr Ser Ser Ser Gln Arg Ser 355 360 365 Phe Val Glu Phe Ile Leu Glu Pro Leu Tyr Lys Ile Leu Ala Gln Val 370 375 380 Val Gly Asp Val Asp Thr Ser Leu Pro Arg Thr Leu Asp Glu Leu Gly 385 390 395 400 Ile His Leu Thr Lys Glu Glu Leu Lys Leu Asn Ile Arg Pro Leu Leu 405 410 415 Arg Leu Val Cys Lys Lys Phe Phe Gly Glu Phe Thr Gly Phe Val Asp 420 425 430 Met Cys Val Gln His Ile Pro Ser Pro Lys Val Gly Ala Lys Pro Lys 435 440 445 Ile Glu His Thr Tyr Thr Gly Gly Val Asp Ser Asp Leu Gly Glu Ala 450 455 460 Met Ser Asp Cys Asp Pro Asp Gly Pro Leu Met Cys His Thr Thr Lys 465 470 475 480 Met Tyr Ser Thr Asp Asp Gly Val Gln Phe His Ala Phe Gly Arg Val 485 490 495 Leu Ser Gly Thr Ile His Ala Gly Gln Pro Val Lys Val Leu Gly Glu 500 505 510 Asn Tyr Thr Leu Glu Asp Glu Glu Asp Ser Gln Ile Cys Thr Val Gly 515 520 525 Arg Leu Trp Ile Ser Val Ala Arg Tyr His Ile Glu Val Asn Arg Val 530 535 540 Pro Ala Gly Asn Trp Val Leu Ile Glu Gly Val Asp Gln Pro Ile Val 545 550 555 560 Lys Thr Ala Thr Ile Thr Glu Pro Arg Gly Asn Glu Glu Ala Gln Ile 565 570 575 Phe Arg Pro Leu Lys Phe Asn Thr Thr Ser Val Ile Lys Ile Ala Val 580 585 590 Glu Pro Val Asn Pro Ser Glu Leu Pro Lys Met Leu Asp Gly Leu Arg 595 600 605 Lys Val Asn Lys Ser Tyr Pro Ser Leu Thr Thr Lys Val Glu Glu Ser 610 615 620 Gly Glu His Val Ile Leu Gly Thr Gly Glu Leu Tyr Leu Asp Cys Val 625 630 635 640 Met His Asp Leu Arg Lys Met Tyr Ser Glu Ile Asp Ile Lys Val Ala 645 650 655 Asp Pro Val Val Thr Phe Cys Glu Thr Val Val Glu Thr Ser Ser Leu 660 665 670 Lys Cys Phe Ala Glu Thr Pro Asn Lys Lys Asn Lys Ile Thr Met Ile 675 680 685 Ala Glu Pro Leu Glu Lys Gly Leu Ala Glu Asp Ile Glu Asn Glu Val 690 695 700 Val Gln Ile Thr Trp Asn Arg Lys Lys Leu Gly Glu Phe Phe Gln Thr 705 710 715 720 Lys Tyr Asp Trp Asp Leu Leu Ala Ala Arg Ser Ile Trp Ala Phe Gly 725 730 735 Pro Asp Ala Thr Gly Pro Asn Ile Leu Val Asp Asp Thr Leu Pro Ser 740 745 750 Glu Val Asp Lys Ala Leu Leu Gly Ser Val Lys Asp Ser Ile Val Gln 755 760 765 Gly Phe Gln Trp Gly Thr Arg Glu Gly Pro Leu Cys Asp Glu Leu Ile 770 775 780 Arg Asn Val Lys Phe Lys Ile Leu Asp Ala Val Val Ala Gln Glu Pro 785 790 795 800 Leu His Arg Gly Gly Gly Gln Ile Ile Pro Thr Ala Arg Arg Val Val 805 810 815 Tyr Ser Ala Phe Leu Met Ala Thr Pro Arg Leu Met Glu Pro Tyr Tyr 820 825 830 Phe Val Glu Val Gln Ala Pro Ala Asp Cys Val Ser Ala Val Tyr Thr 835 840 845 Val Leu Ala Arg Arg Arg Gly His Val Thr Gln Asp Ala Pro Ile Pro 850 855 860 Gly Ser Pro Leu Tyr Thr Ile Lys Ala Phe Ile Pro Ala Ile Asp Ser 865 870 875 880 Phe Gly Phe Glu Thr Asp Leu Arg Thr His Thr Gln Gly Gln Ala Phe 885 890 895 Ser Leu Ser Val Phe His His Trp Gln Ile Val Pro Gly Asp Pro Leu 900 905 910 Asp Lys Ser Ile Val Ile Arg Pro Leu Glu Pro Gln Pro Ala Pro His 915 920 925 Leu Ala Arg Glu Phe Met Ile Lys Thr Arg Arg Arg Lys Gly Leu Ser 930 935 940 Glu Asp Val Ser Ile Ser Lys Phe Phe Asp Asp Pro Met Leu Leu Glu 945 950 955 960 Leu Ala Lys Gln Asp Val Val Leu Asn Tyr Pro Met 965 970 <210> 16 <211> 4167 <212> DNA <213> Artificial Sequence <220> <223> EFTUD2 <400> 16 atcctcagct ctcaccctct ttggagcagc ccacgtcttg ggctactcgt cttggggacc 60 cgctactccg ccttgccagt ccgcggcggg catacctcgg aactggtcct caggcagagg 120 gttgtcctcc cgggcagaaa ggcgacagcg gcgtctgcgg ggtccttcct ggcggcgggc 180 gcaggcgttt cctcggcgtg gggcggaagc acgatctccg gcagcggcct gggaactctt 240 agctgagcag gcgagagcat catggatacc gacttatatg atgagtttgg gaattatatt 300 ggaccagagc ttgattctga tgaagatgat gatgaattgg gtagagagac caaagatctt 360 gatgagatgg atgatgatga cgacgacgat gacgtaggag atcatgacga tgaccaccct 420 gggatggagg tggtgctgca tgaggacaag aagtactacc caacagccga ggaggtgtat 480 ggtcctgagg tggagaccat agttcaagag gaagacactc agcctctcac agaacccatt 540 attaagccag tgaaaaccaa gaaattcact ctgatggagc agacattacc tgttacggtg 600 tatgagatgg atttcttggc ggatctgatg gataactcag agctcatcag aaatgtgacc 660 ctttgtggac atctccacca tggcaagaca tgttttgtgg attgtttaat tgaacagact 720 cacccggaaa tcagaaagcg ctatgaccaa gatctgtgct atactgacat cctcttcaca 780 gagcaagaga gaggtgtagg catcaaaagc actcctgtga cagtggtctt gccagacacc 840 aaaggaaaat cttatctctt caatatcatg gacactccag gacatgtgaa tttctctgat 900 gaggtcacag ctggcttgcg catctcagat ggagtggtcc ttttcattga tgctgctgag 960 ggggtgatgc tgaacacaga gcggctgatc aagcatgcgg tgcaggagag gctggcagtc 1020 actgtgtgca tcaacaagat tgaccggctg atcctggagc tgaagctgcc tccaactgat 1080 gcttattaca agctgcgcca cattgtggat gaggtcaatg gattaataag catgtattcc 1140 actgatgaga acctgatcct ttccccactc ctgggtaacg tctgcttctc cagctcccag 1200 tacagcatct gcttcacgct gggctccttt gccaagatct atgccgacac ctttggtgac 1260 attaattacc aagaatttgc taaaagactc tggggtgaca tctacttcaa ccctaagacg 1320 cgaaagttca ccaaaaaggc cccaactagc agctcccaga gaagtttcgt ggagtttatc 1380 ttggagcctc tttataagat cctcgcccag gttgtaggtg acgtggacac cagcctccca 1440 cggaccctag acgagcttgg catccacctg acgaaggagg agctgaagct gaacatccgc 1500 cccttgctca ggctggtctg caaaaagttc tttggcgagt tcacaggctt tgtggacatg 1560 tgtgtgcagc atatcccttc tccaaaggtg ggcgccaagc ccaagattga gcacacctac 1620 accggtggtg tggactccga cctcggcgag gctatgagtg actgtgaccc tgatggcccc 1680 ctgatgtgcc acactactaa gatgtacagc acagatgatg gagtccagtt tcacgccttt 1740 ggccgggtgc tgagtggcac cattcatgct gggcagcctg tgaaggtact gggggagaac 1800 tacaccctgg aggatgagga agactcccag atatgcaccg tgggccgcct ttggatctct 1860 gtggccaggt accacatcga ggtgaaccgt gttcctgctg gcaactgggt tctgattgaa 1920 ggtgttgatc aaccaattgt gaagacagca accataaccg aaccccgagg caatgaggag 1980 gctcagattt tccgaccctt gaagttcaat accacatctg ttatcaagat tgctgtggag 2040 ccagtcaacc cctcagagct gcccaagatg cttgatggcc tgcgcaaggt caacaagagc 2100 tatccatccc tcaccaccaa ggtggaggag tctggcgagc atgtgatcct gggcactggg 2160 gagctctacc tggactgtgt gatgcatgat ttgcggaaga tgtactcaga gatagacatc 2220 aaggtggctg acccagttgt cacgttttgt gagacggtgg tggaaacatc ctccctcaag 2280 tgctttgctg aaacgcctaa taagaagaac aagatcacca tgattgctga gcctcttgag 2340 aagggcctgg cagaggacat agagaatgag gtggtccaga ttacgtggaa caggaagaag 2400 ctgggagagt tcttccagac caagtacgat tgggatctgc tggctgcccg ttccatctgg 2460 gcttttggcc ctgatgcgac tggccccaac attctggtgg atgatactct gccctctgag 2520 gtggacaagg ctcttcttgg ttcagtgaag gacagcatcg ttcaaggttt ccagtgggga 2580 accagggagg gccccctctg tgatgaattg attcggaatg tcaagtttaa gatcctggat 2640 gcggtggttg cccaggagcc cctgcaccgg ggcgggggcc agatcatccc cacagccagg 2700 agagtcgtct actctgcctt cctcatggct actcctcgtc tgatggagcc ttactacttt 2760 gtagaggtcc aggcccctgc agattgcgtc tctgcagttt ataccgtcct ggccaggcgc 2820 aggggggcacg tgactcagga tgcacccatc ccaggctccc ctctgtacac catcaaagct 2880 tttatcccgg ccatcgactc ttttggcttt gagactgatc tccggactca cacccaggga 2940 caagcctttt ctctgtctgt cttccaccac tggcagattg tgcctggtga tcccctggac 3000 aagagcattg tcatccgccc cttggagcca cagccagctc ctcacctggc ccgggaattc 3060 atgatcaaaa cccgccgtag gaagggcctc agtgaagatg tgagcatcag caaattcttc 3120 gatgatccta tgttgctgga acttgccaaa caggatgttg tgctcaatta ccccatgtga 3180 gtgcgtggac tcctgggagc tcctgctccc tacagtgggc tgcaactcct gtacttgaag 3240 ctgagacctc atatgacgtg gccttcgtgt tgtcagagag tgtctggaag ctgctgttgc 3300 catcttgaac aactcaccaa cctccaaccc agagccccag tgagagagga gcatttggcc 3360 tcctgcttcc ttctgtggcc tctgccgggc tccattccca aggaaaagag aggagcttgg 3420 gctcacagaa agagaagggg atgaaacccc aaggggccct atctttggga tttacatgga 3480 attttatttt ctacaagttt gaccttagcc atggtttgca agtgaacaga acattctgac 3540 ctctgtcttg ctctgctcct ttcatcctcg tctcccctgc cccgtctggt gcttacattc 3600 tgaatatatg tcatctccca agaggcttca ctgcctctgc ttccagctgc agcctccttc 3660 ctgcctgggt ccccagggaa gccgcctgcc ttttaattca gtgttcccat gagcgccaag 3720 gccccattat tgcccccttg ctcccactcc atgctgcttc tgggtggaac ctaagatggc 3780 ttgggagttg ttgggttcct gcgatcagaa gtctacccca ccacctcctc aggaaactgc 3840 tgcctcccct aagaatcttc cttgccctgg agtagggggc cagagcactt tgatttccag 3900 ccatttactc caagtcctct ccccagctac caccagtccc ttactctgtt ctcccccagt 3960 gaaaaagagt ctgttgattt tcctcaaaac tgctttatta ggaatgtacc agggattgag 4020 ttaggggagt tggacagccc cggctcctat aggagtccta cttctctcca gcatcctgtg 4080 ccatcctctt gacgtaatcg ctgtacattg tgtacacagc acctgtgtga gagaaaagaa 4140 ataatgcccc ttggcatcaa acccttc 4167 <210> 17 <211> 186 <212> PRT <213> Artificial Sequence <220> <223> MBP <400> 17 Met Ala Ser Gln Lys Arg Pro Ser Gln Arg His Gly Ser Lys Tyr Leu 1 5 10 15 Ala Thr Ala Ser Thr Met Asp His Ala Arg His Gly Phe Leu Pro Arg 20 25 30 His Arg Asp Thr Gly Ile Leu Asp Ser Ile Gly Arg Phe Phe Gly Gly 35 40 45 Asp Arg Gly Ala Pro Lys Arg Gly Ser Gly Lys Val Pro Trp Leu Lys 50 55 60 Pro Gly Arg Ser Pro Leu Pro Ser His Ala Arg Ser Gln Pro Gly Leu 65 70 75 80 Cys Asn Met Tyr Lys Asp Ser His His Pro Ala Arg Thr Ala His Tyr 85 90 95 Gly Ser Leu Pro Gln Lys Ser His Gly Arg Thr Gln Asp Glu Asn Pro 100 105 110 Val Val His Phe Phe Lys Asn Ile Val Thr Pro Arg Thr Pro Pro Pro 115 120 125 Ser Gln Gly Lys Gly Ala Glu Gly Gln Arg Pro Gly Phe Gly Tyr Gly 130 135 140 Gly Arg Ala Ser Asp Tyr Lys Ser Ala His Lys Gly Phe Lys Gly Val 145 150 155 160 Asp Ala Gln Gly Thr Leu Ser Lys Ile Phe Lys Leu Gly Gly Arg Asp 165 170 175 Ser Arg Ser Gly Ser Pro Met Ala Arg Arg 180 185 <210> 18 <211> 2267 <212> DNA <213> Artificial Sequence <220> <223> MBP <400> 18 ggacaacacc ttcaaagaca ggccctctga gtccgacgag ctccagacca tccaagaaga 60 cagtgcagcc acctccgaga gcctggatgt gatggcgtca cagaagagac cctcccagag 120 gcacggatcc aagtacctgg ccacagcaag taccatggac catgccaggc atggcttcct 180 cccaaggcac agagacacgg gcatccttga ctccatcggg cgcttctttg gcggtgacag 240 gggtgcgccc aagcggggct ctggcaaggt accctggcta aagccgggcc ggagccctct 300 gccctctcat gcccgcagcc agcctgggct gtgcaacatg tacaaggact cacaccaccc 360 ggcaagaact gctcactacg gctccctgcc ccagaagtca cacggccgga cccaagatga 420 aaaccccgta gtccacttct tcaagaacat tgtgacgcct cgcacaccac ccccgtcgca 480 gggaaagggg gccgaaggcc agagaccagg atttggctac ggaggcagag cgtccgacta 540 taaatcggct cacaagggat tcaagggagt cgatgcccag ggcacgcttt ccaaaatttt 600 taagctggga ggaagagata gtcgctctgg atcacccatg gctagacgct gaaaacccac 660 ctggttccgg aatcctgtcc tcagcttctt aatataactg ccttaaaact ttaatcccac 720 ttgcccctgt tacctaatta gagcagatga cccctcccct aatgcctgcg gagttgtgca 780 cgtagtaggg tcaggccacg gcagcctacc ggcaatttcc ggccaacagt taaatgagaa 840 catgaaaaca gaaaacggtt aaaactgtcc ctttctgtgt gaagatcacg ttccttcccc 900 cgcaatgtgc ccccagacgc acgtgggtct tcagggggcc aggtgcacag acgtccctcc 960 acgttcaccc ctccaccctt ggactttctt ttcgccgtgg ctgcggcacc cttgcgcttt 1020 tgctggtcac tgccatggag gcacacagct gcagagacag agaggacgtg ggcggcagag 1080 aggactgttg acatccaagc ttcctttgtt tttttttcct gtccttctct cacctcctaa 1140 agtagacttc atttttccta acaggattag acagtcaagg agtggcttac tacatgtggg 1200 agcttttggt atgtgacatg cgggctgggc agctgttaga gtccaacgtg gggcagcaca 1260 gagagggggc cacctcccca ggccgtggct gccccacacac cccaattagc tgaattcgcg 1320 tgtggcagag ggaggaaaag gaggcaaacg tgggctgggc aatggcctca cataggaaac 1380 agggtcttcc tggagatttg gtgatggaga tgtcaagcag gtggcctctg gacgtcaccg 1440 ttgccctgca tggtggcccc agagcagcct ctatgaacaa cctcgtttcc aaaccacagc 1500 ccacagccgg agagtccagg aagacttgcg cactcagagc agaagggtag gagtcctcta 1560 gacagcctcg cagccgcgcc agtcgcccat agacactggc tgtgaccggg cgtgctggca 1620 gcggcagtgc acagtggcca gcactaaccc tccctgagaa gataaccggc tcattcactt 1680 cctcccagaa gacgcgtggt agcgagtagg cacaggcgtg cacctgctcc cgaattactc 1740 accgagacac acgggctgag cagacggccc cgtggatgga gacaaagagc tcttctgacc 1800 atatccttct taacacccgc tggcatctcc tttcgcgcct ccctccctaa cctactgacc 1860 caccttttga ttttagcgca cctgtgattg ataggccttc caaagagtcc cacgctggca 1920 tcaccctccc cgaggacgga gatgaggagt agtcagcgtg atgccaaaac gcgtcttctt 1980 aatccaattc taattctgaa tgtttcgtgt gggcttaata ccatgtctat taatatatag 2040 cctcgatgat gagagagtta caaagaacaa aactccagac acaaacctcc aaatttttca 2100 gcagaagcac tctgcgtcgc tgagctgagg tcggctctgc gatccatacg tggccgcacc 2160 cacacagcac gtgctgtgac gatggctgaa cggaaagtgt acactgttcc tgaatattga 2220 aataaaacaa taaactttta atggtaaaaa aaaaaaaaaa aaaaaaa 2267 <210> 19 <211> 149 <212> PRT <213> Artificial Sequence <220> <223> AHNAK <400> 19 Met Glu Lys Glu Glu Thr Thr Arg Glu Leu Leu Leu Pro Asn Trp Gln 1 5 10 15 Gly Ser Gly Ser His Gly Leu Thr Ile Ala Gln Arg Asp Asp Gly Val 20 25 30 Phe Val Gln Glu Val Thr Gln Asn Ser Pro Ala Ala Arg Thr Gly Val 35 40 45 Val Lys Glu Gly Asp Gln Ile Val Gly Ala Thr Ile Tyr Phe Asp Asn 50 55 60 Leu Gln Ser Gly Glu Val Thr Gln Leu Leu Asn Thr Met Gly His His 65 70 75 80 Thr Val Gly Leu Lys Leu His Arg Lys Gly Asp Arg Ser Pro Glu Pro 85 90 95 Gly Gln Thr Trp Thr Arg Glu Val Phe Ser Ser Cys Ser Ser Glu Val 100 105 110 Val Leu Asn Thr Pro Gln Pro Ser Ala Leu Glu Cys Lys Asp Gln Asn 115 120 125 Lys Gln Lys Glu Ala Ser Ser Gln Ala Gly Ala Val Ser Val Ser Thr 130 135 140 Pro Asn Ala Gly Leu 145 <210> 20 <211> 1096 <212> DNA <213> Artificial Sequence <220> <223> AHNAK <400> 20 agacccgccc gcccgagccg gagttacaag agccgcctcc gcgcacgggg gcccggccac 60 tcggagctgc tctgccgcgg ggactgcacc gcccgccctg ccagacccgc ccggaacggg 120 gctcgtcgcc gccagtagcc gcagcaccgc agccttgggc ctcgcgccgg ctatggccgt 180 gccctggggc tgagccctca ggttgtgacc gagattcccg acgagagaga ctgaggggaa 240 gagaggaagg aggggcgggc tcctggcaag gcattcgctc ctgagcggaa tcctgcaaag 300 atggagaagg aggagacaac ccgggagctg ctgctgccca actggcaggg tagtggctcc 360 cacgggctga ccatcgccca gagggacgac ggcgtctttg tgcaggaggt gacgcagaac 420 tcccctgcgg cccgcactgg ggtggtcaag gagggggacc agattgtggg tgccaccatc 480 tactttgaca acctgcagtc gggtgaggtg acccagctgc tgaacaccat ggggcaccac 540 acggtgggcc tgaagctgca ccgcaagggg gaccgctctc ccgagcctgg ccagacctgg 600 acccgtgaag tcttcagctc ctgcagctct gaagtggttc tgaacacacc acagccatca 660 gcactggaat gcaaagacca gaacaaacag aaggaagcca gcagccaagc cggggcagtt 720 tcagtctcca ccccaaatgc aggactgtag aagcggccag gaagaaaacc accccctctt 780 aaggttgttt ttgtgaccgt tctttggagc attgttctaa aaatgggaaa ttacatattg 840 ctgtgccaag ggcaacaaac acctgcagtt aaaggaatac cttccgcgag gcggcttttc 900 ggagcatgca tgtttatagc tccagccagg ccagaccgag ggctgctgca taagccctgc 960 ttggtgcatt tctttacttg caaggggaca gagtgtgggc ttaggtttgg gactagaggg 1020 ggctttggca actatggtgc tcaggtgatt atccttcgct cgtttatcca ataaacattt 1080 atcaagcatc tgaaaa 1096 <210> 21 <211> 261 <212> PRT <213> Artificial Sequence <220> <223> HSD17B10 <400> 21 Met Ala Ala Ala Cys Arg Ser Val Lys Gly Leu Val Ala Val Ile Thr 1 5 10 15 Gly Gly Ala Ser Gly Leu Gly Leu Ala Thr Ala Glu Arg Leu Val Gly 20 25 30 Gln Gly Ala Ser Ala Val Leu Leu Asp Leu Pro Asn Ser Gly Gly Glu 35 40 45 Ala Gln Ala Lys Lys Leu Gly Asn Asn Cys Val Phe Ala Pro Ala Asp 50 55 60 Val Thr Ser Glu Lys Asp Val Gln Thr Ala Leu Ala Leu Ala Lys Gly 65 70 75 80 Lys Phe Gly Arg Val Asp Val Ala Val Asn Cys Ala Gly Ile Ala Val 85 90 95 Ala Ser Lys Thr Tyr Asn Leu Lys Lys Gly Gin Thr His Thr Leu Glu 100 105 110 Asp Phe Gln Arg Val Leu Asp Val Asn Leu Met Gly Thr Phe Asn Val 115 120 125 Ile Arg Leu Val Ala Gly Glu Met Gly Gln Asn Glu Pro Asp Gln Gly 130 135 140 Gly Gln Arg Gly Val Ile Ile Asn Thr Ala Ser Val Ala Ala Phe Glu 145 150 155 160 Gly Gln Val Gly Gln Ala Ala Tyr Ser Ala Ser Lys Gly Gly Ile Val 165 170 175 Gly Met Thr Leu Pro Ile Ala Arg Asp Leu Ala Pro Ile Gly Ile Arg 180 185 190 Val Met Thr Ile Ala Pro Gly Leu Phe Gly Thr Pro Leu Leu Thr Ser 195 200 205 Leu Pro Glu Lys Val Cys Asn Phe Leu Ala Ser Gln Val Pro Phe Pro 210 215 220 Ser Arg Leu Gly Asp Pro Ala Glu Tyr Ala His Leu Val Gln Ala Ile 225 230 235 240 Ile Glu Asn Pro Phe Leu Asn Gly Glu Val Ile Arg Leu Asp Gly Ala 245 250 255 Ile Arg Met Gln Pro 260 <210> 22 <211> 963 <212> DNA <213> Artificial Sequence <220> <223> HSD17B10 <400> 22 atccccatcc cgtggagtgg ccggcgacaa gatggcagca gcgtgtcgga gcgtgaaggg 60 cctggtggcg gtaataaccg gaggagcctc gggcctgggc ctggccacgg cggagcgact 120 tgtggggcag ggagcctctg ctgtgcttct ggacctgccc aactcgggtg gggaggccca 180 agccaagaag ttaggaaaca actgcgtttt cgccccagcc gacgtgacct ctgagaagga 240 tgtgcaaaca gctctggctc tagcaaaagg aaagtttggc cgtgtggatg tagctgtcaa 300 ctgtgcaggc atcgcggtgg ctagcaagac gtacaactta aagaagggcc agacccatac 360 cttggaagac ttccagcgag ttcttgatgt gaatctcatg ggcaccttca atgtgatccg 420 cctggtggct ggtgagatgg gccagaatga accagaccag ggaggccaac gtggggtcat 480 catcaacact gccagtgtgg ctgccttcga gggtcaggtt ggacaagctg catactctgc 540 ttccaagggg ggaatagtgg gcatgacact gcccattgct cgggatctgg ctcccatagg 600 tatccgggtg atgaccattg ccccaggtct gtttggcacc ccactgctga ccagcctccc 660 agagaaagtg tgcaacttct tggccagcca agtgcccttc cctagccgac tgggtgaccc 720 tgctgagtat gctcacctcg tacaggccat catcgagaac ccattcctca atggagaggt 780 catccggctg gatggggcca ttcgtatgca gccttgaagg gagaaggcag agaaaacaca 840 cgctcctctg cccttccttt ccctggggta ctactctcca gcttgggagg aagcccagta 900 gccattttgt aactgcctac cagtcgccct ctgtgcctaa taaagtctct ttttctcaca 960 gag 963 <210> 23 <211> 193 <212> PRT <213> Artificial Sequence <220> <223> IL18 <400> 23 Met Ala Ala Glu Pro Val Glu Asp Asn Cys Ile Asn Phe Val Ala Met 1 5 10 15 Lys Phe Ile Asp Asn Thr Leu Tyr Phe Ile Ala Glu Asp Asp Glu Asn 20 25 30 Leu Glu Ser Asp Tyr Phe Gly Lys Leu Glu Ser Lys Leu Ser Val Ile 35 40 45 Arg Asn Leu Asn Asp Gln Val Leu Phe Ile Asp Gln Gly Asn Arg Pro 50 55 60 Leu Phe Glu Asp Met Thr Asp Ser Asp Cys Arg Asp Asn Ala Pro Arg 65 70 75 80 Thr Ile Phe Ile Ile Ser Met Tyr Lys Asp Ser Gln Pro Arg Gly Met 85 90 95 Ala Val Thr Ile Ser Val Lys Cys Glu Lys Ile Ser Thr Leu Ser Cys 100 105 110 Glu Asn Lys Ile Ile Ser Phe Lys Glu Met Asn Pro Pro Asp Asn Ile 115 120 125 Lys Asp Thr Lys Ser Asp Ile Ile Phe Phe Gln Arg Ser Val Pro Gly 130 135 140 His Asp Asn Lys Met Gln Phe Glu Ser Ser Ser Tyr Glu Gly Tyr Phe 145 150 155 160 Leu Ala Cys Glu Lys Glu Arg Asp Leu Phe Lys Leu Ile Leu Lys Lys 165 170 175 Glu Asp Glu Leu Gly Asp Arg Ser Ile Met Phe Thr Val Gln Asn Glu 180 185 190 Asp <210> 24 <211> 1163 <212> DNA <213> Artificial Sequence <220> <223> IL18 <400> 24 attctctccc cagcttgctg agccctttgc tcccctggcg actgcctgga cagtcagcaa 60 ggaattgtct cccagtgcat tttgccctcc tggctgccaa ctctggctgc taaagcggct 120 gccacctgct gcagtctaca cagcttcggg aagaggaaag gaacctcaga ccttccagat 180 cgcttcctct cgcaacaaac tatttgtcgc aggaataaag atggctgctg aaccagtaga 240 agacaattgc atcaactttg tggcaatgaa atttattgac aatacgcttt actttatagc 300 tgaagatgat gaaaacctgg aatcagatta ctttggcaag cttgaatcta aattatcagt 360 cataagaaat ttgaatgacc aagttctctt cattgaccaa ggaaatcggc ctctatttga 420 agatatgact gattctgact gtagagataa tgcaccccgg accatattta ttataagtat 480 gtataaagat agccagccta gaggtatggc tgtaactatc tctgtgaagt gtgagaaaat 540 ttcaactctc tcctgtgaga acaaaattat ttcctttaag gaaatgaatc ctcctgataa 600 catcaaggat acaaaaagtg acatcatatt ctttcagaga agtgtcccag gacatgataa 660 taagatgcaa tttgaatctt catcatacga aggatacttt ctagcttgtg aaaaagagag 720 agaccttttt aaactcattt tgaaaaaaga ggatgaattg ggggatagat ctataatgtt 780 cactgttcaa aacgaagact agctattaaa atttcatgcc gggcgcagtg gctcacgcct 840 gtaatcccag ccctttggga ggctgaggcg ggcagatcac cagaggtcag gtgttcaaga 900 ccagcctgac caacatggtg aaacctcatc tctactaaaa atacaaaaaa ttagctgagt 960 gtagtgacgc atgccctcaa tcccagctac tcaagaggct gaggcaggag aatcacttgc 1020 actccggagg tagaggttgt ggtgagccga gattgcacca ttgcgctcta gcctgggcaa 1080 caacagcaaa actccatctc aaaaaataaa ataaataaat aaacaaataa aaaattcata 1140 atgtgaaaaa aaaaaaaaaa aaa 1163 <210> 25 <211> 128 <212> PRT <213> Artificial Sequence <220> <223> RPL22 <400> 25 Met Ala Pro Val Lys Lys Leu Val Val Lys Gly Gly Lys Lys Lys Lys Lys 1 5 10 15 Gln Val Leu Lys Phe Thr Leu Asp Cys Thr His Pro Val Glu Asp Gly 20 25 30 Ile Met Asp Ala Ala Asn Phe Glu Gln Phe Leu Gln Glu Arg Ile Lys 35 40 45 Val Asn Gly Lys Ala Gly Asn Leu Gly Gly Gly Val Val Thr Ile Glu 50 55 60 Arg Ser Lys Ser Lys Ile Thr Val Thr Ser Glu Val Pro Phe Ser Lys 65 70 75 80 Arg Tyr Leu Lys Tyr Leu Thr Lys Lys Tyr Leu Lys Lys Asn Asn Leu 85 90 95 Arg Asp Trp Leu Arg Val Val Ala Asn Ser Lys Glu Ser Tyr Glu Leu 100 105 110 Arg Tyr Phe Gln Ile Asn Gln Asp Glu Glu Glu Glu Glu Asp Glu Asp 115 120 125 <210> 26 <211> 2099 <212> DNA <213> Artificial Sequence <220> <223> RPL22 <400> 26 gcgtctgcgt agttcgctca cctccctttc taactccgct gccgccatgg ctcctgtgaa 60 aaagcttgtg gtgaaggggg gcaaaaaaaaa gaagcaagtt ctgaagttca ctcttgattg 120 cacccaccct gtagaagatg gaatcatgga tgctgccaat tttgagcagt ttttgcaaga 180 aaggatcaaa gtgaacggaa aagctgggaa ccttggtgga ggggtggtga ccatcgaaag 240 gagcaagagc aagatcaccg tgacatccga ggtgcctttc tccaaaaggt atttgaaata 300 tctcaccaaa aaatatttga agaagaataa tctacgtgac tggttgcgcg tagttgctaa 360 cagcaaagag agttacgaat tacgttactt ccagattaac caggacgaag aagaggagga 420 agacgaggat taaatttcat ttatctggaa aattttgtat gagttcttga ataaaacttg 480 ggaaccaaaa tggtggttta tccttgtatc tctgcagtgt ggattgaaca gaaaattgga 540 aatcatagtc aaagggcttc ccttggttcg ccactcattt atttgtaact tgacttcttt 600 ttttttctgc ttaaaaattt caattctcgt ggtaatacca gagtagaagg agagggtgac 660 tttaccgaac tgacagccat tggggaggca gatgcgggtg tggaggtgtg ggctgaaggt 720 agtgactgtt tgattttaaa aagtgtgact gtcagttgta tctgttgctt ttctcaatga 780 ttcagggata caaatgggct tctctcattc attaaaagaa aacgcgacat ctttctaaga 840 ttctctgtgg gaaaatgact gtcaataaaa tgcgggtttc tgggccattc gtcttacttt 900 cattttttga ttacaaattt ctcttgacgc acacaattat gtctgctaat cctcttcttc 960 ctagagagag aaactgtgct ccttcagtgt tgctgccata aaggggtttg gggaatcgat 1020 tgtaaaagtc ccaggttcta aattaactaa atgtgtacag aaatgaacgt gtaagtaatg 1080 tttctacagg tctttgcaac aaactgtcac tttcgtctcc agcagaggga gctgtaggaa 1140 tagtgcttcc agatgtggtc tcccgtgtgg ggcccagcaa tgggggcccc tgatgccaag 1200 agctctggag gttcttgaaa gaggggacac gaaggaggag tgactgggaa gcctcccatg 1260 ccaaggaggt gggaggtgcc ctggaaatag ctgcctcatg ccacttaggc catgactgga 1320 tttaatgtca gtggtgtgcc acagtgcaga ggctagacaa ctgaaagggg ctaccaaggc 1380 tgggaaaaaa atgcaattgt tgctgtgagt gactttgaaa gactctggtg ccttgtggtg 1440 cccttctgaa attcaaacag taatgcaaaa gtgtctgcat tagaatttac ggtgtctaaa 1500 attcatgttt ttaaaagagc ttgcctacag atggtttcca cacttgaaat tgtgccctgc 1560 gagttgcata gctggaagtt caatgctcag tcctaccttg gctcccatta aacatttggt 1620 gctctgtgga ttgagttgaa cgtgttgagg ctttgcaatt tcacttgtgt taaaggctct 1680 ggcatttttc catttctatg caaatttctt tgaagcagaa ttgcttgcat atttcttctc 1740 tgccgtcaca gaaagcagag tttctttcaa acttcactga ggcatcagtt gctctttggc 1800 aatgtccctt aaccatgatt attaactaag tttgtggctt gagtttacaa attctacttg 1860 ttgcattgat gttcccatgt agtaagtcat ttttagtttg gttgtgaaaa aaccctgggc 1920 tgaagttggc atttcagtta aaagaaaaaa agaaactagt cccagatttg aaaacttgta 1980 ataaaattga aactcactgg ttttctatgt ctttttgaac tcttgtaatc gagttttgat 2040 catattttct attaaagtgg ctaacacctg gctactctta ctgtaaaaaa aaaaaaaaa 2099 <210> 27 <211> 408 <212> PRT <213> Artificial Sequence <220> <223> SERBP1 <400> 27 Met Pro Gly His Leu Gln Glu Gly Phe Gly Cys Val Val Thr Asn Arg 1 5 10 15 Phe Asp Gln Leu Phe Asp Asp Glu Ser Asp Pro Phe Glu Val Leu Lys 20 25 30 Ala Ala Glu Asn Lys Lys Lys Glu Ala Gly Gly Gly Gly Val Gly Gly 35 40 45 Pro Gly Ala Lys Ser Ala Ala Gln Ala Ala Ala Gln Thr Asn Ser Asn 50 55 60 Ala Ala Gly Lys Gln Leu Arg Lys Glu Ser Gln Lys Asp Arg Lys Asn 65 70 75 80 Pro Leu Pro Pro Ser Val Gly Val Val Asp Lys Lys Glu Glu Thr Gln 85 90 95 Pro Pro Val Ala Leu Lys Lys Glu Gly Ile Arg Arg Val Gly Arg Arg 100 105 110 Pro Asp Gln Gln Leu Gln Gly Glu Gly Lys Ile Ile Asp Arg Arg Pro 115 120 125 Glu Arg Arg Pro Pro Arg Glu Arg Arg Phe Glu Lys Pro Leu Glu Glu 130 135 140 Lys Gly Glu Gly Gly Glu Phe Ser Val Asp Arg Pro Ile Ile Asp Arg 145 150 155 160 Pro Ile Arg Gly Arg Gly Gly Leu Gly Arg Gly Arg Gly Gly Arg Gly 165 170 175 Arg Gly Met Gly Arg Gly Asp Gly Phe Asp Ser Arg Gly Lys Arg Glu 180 185 190 Phe Asp Arg His Ser Gly Ser Asp Arg Ser Ser Phe Ser His Tyr Ser 195 200 205 Gly Leu Lys His Glu Asp Lys Arg Gly Gly Ser Gly Ser His Asn Trp 210 215 220 Gly Thr Val Lys Asp Glu Leu Thr Glu Ser Pro Lys Tyr Ile Gln Lys 225 230 235 240 Gln Ile Ser Tyr Asn Tyr Ser Asp Leu Asp Gln Ser Asn Val Thr Glu 245 250 255 Glu Thr Pro Glu Gly Glu Glu His His Pro Val Ala Asp Thr Glu Asn 260 265 270 Lys Glu Asn Glu Val Glu Glu Val Lys Glu Glu Gly Pro Lys Glu Met 275 280 285 Thr Leu Asp Glu Trp Lys Ala Ile Gln Asn Lys Asp Arg Ala Lys Val 290 295 300 Glu Phe Asn Ile Arg Lys Pro Asn Glu Gly Ala Asp Gly Gln Trp Lys 305 310 315 320 Lys Gly Phe Val Leu His Lys Ser Lys Ser Glu Glu Ala His Ala Glu 325 330 335 Asp Ser Val Met Asp His His Phe Arg Lys Pro Ala Asn Asp Ile Thr 340 345 350 Ser Gln Leu Glu Ile Asn Phe Gly Asp Leu Gly Arg Pro Gly Arg Gly 355 360 365 Gly Arg Gly Gly Arg Gly Gly Arg Gly Arg Gly Gly Arg Pro Asn Arg 370 375 380 Gly Ser Arg Thr Asp Lys Ser Ser Ala Ser Ala Pro Asp Val Asp Asp 385 390 395 400 Pro Glu Ala Phe Pro Ala Leu Ala 405 <210> 28 <211> 1403 <212> DNA <213> Artificial Sequence <220> <223> SERBP1 <400> 28 gctgaagcag gcgctcttgg ctcggcgcgg cccgctgcaa tccgtggagg aacgcgccgc 60 cgagccacca tcatgcctgg gcacttacag gaaggcttcg gctgcgtggt caccaaccga 120 ttcgaccagt tatttgacga cgaatcggac cccttcgagg tgctgaaggc agcagagaac 180 aagaaaaaag aagccggcgg gggcggcgtt gggggccctg gggccaagag cgcagctcag 240 gccgcggccc agaccaactc caacgcggca ggcaaacagc tgcgcaagga gtcccagaaa 300 gaccgcaaga acccgctgcc ccccagcgtt ggcgtggttg acaagaaaga ggagacgcag 360 ccgcccgtgg cgcttaagaa agaaggaata agacgagttg gaagaagacc tgatcaacaa 420 cttcagggtg aagggaaaat aattgataga agaccagaaa ggcgaccacc tcgtgaacga 480 agattcgaaa agccacttga agaaaagggt gaaggaggcg aattttcagt tgatagaccg 540 attattgacc gacctattcg aggtcgtggt ggtcttggaa gaggtcgagg gggccgtgga 600 cgtggaatgg gccgaggaga tggatttgat tctcgtggca aacgtgaatt tgataggcat 660 agtggaagtg atagatcttc tttttcacat tacagtggcc tgaagcacga ggacaaacgt 720 ggaggtagcg gatctcacaa ctggggaact gtcaaagacg aattaacaga gtcccccaaa 780 tacattcaga aacaaatatc ttataattac agtgacttgg atcaatcaaa tgtgactgag 840 gaaacacctg aaggtgaaga acatcatcca gtggcagaca ctgaaaataa ggagaatgaa 900 gttgaagagg taaaagagga gggtccaaaa gagatgactt tggatgagtg gaaggctatt 960 caaaataagg accgggcaaa agtagaattt aatatccgaa aaccaaatga aggtgctgat 1020 gggcagtgga agaagggatt tgttcttcat aaatcaaaga gtgaagaggc tcatgctgaa 1080 gattcggtta tggaccatca tttccggaag ccagcaaatg atataacgtc tcagctggag 1140 atcaattttg gagaccttgg ccgcccagga cgtggcggca ggggaggacg aggtggacgt 1200 gggcgtggtg ggcgcccaaa ccgtggcagc aggaccgaca agtcaagtgc ttctgctcct 1260 gatgtggatg acccagaggc attcccagct ctggcttaac tggatgccat aagacaaccc 1320 tggttccttt gtgaaccctt ctgttcaaag cttttgcatg cttaaggatt ccaaacgact 1380 aagaaattaa aaaaaaaaaa aaa 1403 <210> 29 <211> 449 <212> PRT <213> Artificial Sequence <220> <223> PCOLCE <400> 29 Met Leu Pro Ala Ala Thr Ala Ser Leu Leu Gly Pro Leu Leu Thr Ala 1 5 10 15 Cys Ala Leu Leu Pro Phe Ala Gln Gly Gln Thr Pro Asn Tyr Thr Arg 20 25 30 Pro Val Phe Leu Cys Gly Gly Asp Val Lys Gly Glu Ser Gly Tyr Val 35 40 45 Ala Ser Glu Gly Phe Pro Asn Leu Tyr Pro Pro Asn Lys Glu Cys Ile 50 55 60 Trp Thr Ile Thr Val Pro Glu Gly Gin Thr Val Ser Leu Ser Phe Arg 65 70 75 80 Val Phe Asp Leu Glu Leu His Pro Ala Cys Arg Tyr Asp Ala Leu Glu 85 90 95 Val Phe Ala Gly Ser Gly Thr Ser Gly Gln Arg Leu Gly Arg Phe Cys 100 105 110 Gly Thr Phe Arg Pro Ala Pro Leu Val Ala Pro Gly Asn Gln Val Thr 115 120 125 Leu Arg Met Thr Thr Asp Glu Gly Thr Gly Gly Arg Gly Phe Leu Leu 130 135 140 Trp Tyr Ser Gly Arg Ala Thr Ser Gly Thr Glu His Gln Phe Cys Gly 145 150 155 160 Gly Arg Leu Glu Lys Ala Gln Gly Thr Leu Thr Thr Pro Asn Trp Pro 165 170 175 Glu Ser Asp Tyr Pro Pro Gly Ile Ser Cys Ser Trp His Ile Ile Ala 180 185 190 Pro Pro Asp Gln Val Ile Ala Leu Thr Phe Glu Lys Phe Asp Leu Glu 195 200 205 Pro Asp Thr Tyr Cys Arg Tyr Asp Ser Val Ser Val Phe Asn Gly Ala 210 215 220 Val Ser Asp Asp Ser Arg Arg Leu Gly Lys Phe Cys Gly Asp Ala Val 225 230 235 240 Pro Gly Ser Ile Ser Ser Glu Gly Asn Glu Leu Leu Val Gln Phe Val 245 250 255 Ser Asp Leu Ser Val Thr Ala Asp Gly Phe Ser Ala Ser Tyr Lys Thr 260 265 270 Leu Pro Arg Gly Thr Ala Lys Glu Gly Gin Gly Pro Gly Pro Lys Arg 275 280 285 Gly Thr Glu Pro Lys Val Lys Leu Pro Pro Lys Ser Gln Pro Pro Glu 290 295 300 Lys Thr Glu Glu Ser Pro Ser Ala Pro Asp Ala Pro Thr Cys Pro Lys 305 310 315 320 Gln Cys Arg Arg Thr Gly Thr Leu Gln Ser Asn Phe Cys Ala Ser Ser 325 330 335 Leu Val Val Thr Ala Thr Val Lys Ser Met Val Arg Glu Pro Gly Glu 340 345 350 Gly Leu Ala Val Thr Val Ser Leu Ile Gly Ala Tyr Lys Thr Gly Gly 355 360 365 Leu Asp Leu Pro Ser Pro Pro Thr Gly Ala Ser Leu Lys Phe Tyr Val 370 375 380 Pro Cys Lys Gln Cys Pro Pro Met Lys Lys Gly Val Ser Tyr Leu Leu 385 390 395 400 Met Gly Gln Val Glu Glu Asn Arg Gly Pro Val Leu Pro Pro Glu Ser 405 410 415 Phe Val Val Leu His Arg Pro Asn Gln Asp Gln Ile Leu Thr Asn Leu 420 425 430 Ser Lys Arg Lys Cys Pro Ser Gln Pro Val Arg Ala Ala Ala Ser Gln 435 440 445 Asp <210> 30 <211> 1651 <212> DNA <213> Artificial Sequence <220> <223> PCOLCE <400> 30 gacctagaga ggtcccagga cacgccactg tcccgccttc cccattgccc gccccactgg 60 ccagtcccca cgcccacaca cccaaggctg ccccatctgg cgctgattat cctgctgctg 120 ccgccaccgc tgctgctgct ctgcaaaatt cagctgctgc ctctgtcttg aggaccccag 180 cgcctttccc ccggggccat gctgcctgca gccacagcct ccctcctggg gcccctcctc 240 actgcctgcg ccctgctgcc ttttgcccag ggccagaccc ccaactacac cagacccgtg 300 ttcctgtgcg gaggggatgt gaagggggaa tcaggttacg tggcaagtga ggggttcccc 360 aacctctacc cccctaataa ggagtgcatc tggaccataa cggtccccga gggccagact 420 gtgtccctct cattccgagt cttcgacctg gagctgcacc ccgcctgccg ctacgatgct 480 ctggaggtct tcgctgggtc tgggacttcc ggccagcggc tcggacgctt ttgtgggacc 540 ttccggcctg cgcccctagt cgcccccggc aaccaggtga ccctgaggat gacgacggat 600 gagggcacag gaggacgagg cttcctgctc tggtacagcg ggcgggccac ctcgggcact 660 gagcaccaat tttgcggggg gcggctggag aaggcccagg gaaccctgac cacgcccaac 720 tggcccgagt ccgattaccc cccgggcatc agctgttcct ggcacatcat cgcgcccccg 780 gaccaggtca tcgcgctgac cttcgagaag tttgacctgg agccggacac ctactgccgc 840 tatgactcgg tcagcgtgtt caacggagcc gtgagcgacg actcccggag gctggggaag 900 ttctgcggcg acgcagtccc gggctccatc tcctccgaag ggaatgaact cctcgtccag 960 ttcgtctcag atctcagtgt caccgctgat ggcttctcag cctcctacaa gaccctgccg 1020 cggggcactg ccaaagaagg gcaagggccc ggccccaaac ggggaactga gcctaaagtc 1080 aagctgcccc ccaagtccca acctccggag aaaacagagg aatctccttc agcccctgat 1140 gcacccacct gcccaaagca gtgccgccgg acaggcacct tgcagagcaa cttctgtgcc 1200 agcagccttg tggtgactgc gacagtgaag tccatggttc gggagccagg ggagggcctt 1260 gccgtgactg tcagtcttat tggtgcttat aaaactggag gactggacct gccttctcca 1320 cccactggtg cctccctgaa gttttacgtg ccttgcaagc agtgcccccc catgaagaaa 1380 gggatcagtt atctgctgat gggccaggta gaagagaaca gaggccccgt ccttcctcca 1440 gagagctttg tggttctcca ccggcccaac caggaccaga tcctcaccaa cctaagcaag 1500 aggaagtgcc cctctcaacc tgtgcgggct gctgcgtccc aggactgaga cgcaggccag 1560 ccccggcccc tagccctcag gccttctttc ttatccaaat aaatgtttct taatgaggaa 1620 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 1651 <210> 31 <211> 397 <212> PRT <213> Artificial Sequence <220> <223> ACAA2 <400> 31 Met Ala Leu Leu Arg Gly Val Phe Val Val Ala Ala Lys Arg Thr Pro 1 5 10 15 Phe Gly Ala Tyr Gly Gly Leu Leu Lys Asp Phe Thr Ala Thr Asp Leu 20 25 30 Ser Glu Phe Ala Ala Lys Ala Ala Leu Ser Ala Gly Lys Val Ser Pro 35 40 45 Glu Thr Val Asp Ser Val Ile Met Gly Asn Val Leu Gln Ser Ser Ser Ser 50 55 60 Asp Ala Ile Tyr Leu Ala Arg His Val Gly Leu Arg Val Gly Ile Pro 65 70 75 80 Lys Glu Thr Pro Ala Leu Thr Ile Asn Arg Leu Cys Gly Ser Gly Phe 85 90 95 Gln Ser Ile Val Asn Gly Cys Gln Glu Ile Cys Val Lys Glu Ala Glu 100 105 110 Val Val Leu Cys Gly Gly Thr Glu Ser Met Ser Gln Ala Pro Tyr Cys 115 120 125 Val Arg Asn Val Arg Phe Gly Thr Lys Leu Gly Ser Asp Ile Lys Leu 130 135 140 Glu Asp Ser Leu Trp Val Ser Leu Thr Asp Gln His Val Gln Leu Pro 145 150 155 160 Met Ala Met Thr Ala Glu Asn Leu Ala Val Lys His Lys Ile Ser Arg 165 170 175 Glu Glu Cys Asp Lys Tyr Ala Leu Gln Ser Gln Gln Arg Trp Lys Ala 180 185 190 Ala Asn Asp Ala Gly Tyr Phe Asn Asp Glu Met Ala Pro Ile Glu Val 195 200 205 Lys Thr Lys Lys Gly Lys Gln Thr Met Gln Val Asp Glu His Ala Arg 210 215 220 Pro Gln Thr Thr Leu Glu Gln Leu Gln Lys Leu Pro Pro Val Phe Lys 225 230 235 240 Lys Asp Gly Thr Val Thr Ala Gly Asn Ala Ser Gly Val Ala Asp Gly 245 250 255 Ala Gly Ala Val Ile Ile Ala Ser Glu Asp Ala Val Lys Lys His Asn 260 265 270 Phe Thr Pro Leu Ala Arg Ile Val Gly Tyr Phe Val Ser Gly Cys Asp 275 280 285 Pro Ser Ile Met Gly Ile Gly Pro Val Pro Ala Ile Ser Gly Ala Leu 290 295 300 Lys Lys Ala Gly Leu Ser Leu Lys Asp Met Asp Leu Val Glu Val Asn 305 310 315 320 Glu Ala Phe Ala Pro Gln Tyr Leu Ala Val Glu Arg Ser Leu Asp Leu 325 330 335 Asp Ile Ser Lys Thr Asn Val Asn Gly Gly Ala Ile Ala Leu Gly His 340 345 350 Pro Leu Gly Gly Ser Gly Ser Arg Ile Thr Ala His Leu Val His Glu 355 360 365 Leu Arg Arg Arg Gly Gly Lys Tyr Ala Val Gly Ser Ala Cys Ile Gly 370 375 380 Gly Gly Gln Gly Ile Ala Val Ile Ile Gln Ser Thr Ala 385 390 395 <210> 32 <211> 1952 <212> DNA <213> Artificial Sequence <220> <223> ACAA2 <400> 32 gtgtttaggg tgttggcgga gacaaagggg aagagtcatc gcctgtcggg gctaggatat 60 gatgggtgag aggtgtcaaa ccaaattctc tcggtttgga aacggagaaa atctaaaaat 120 gaggatgtga ggaaagagtc cgctctcaag gcgcgttgtg gtctatccga gccccgtccc 180 ctgggctccc tcgggctggg gtgaggcggg cagcgctacg cgtggggtag gaccatctta 240 cgctgggacc ccgccaagga gccccaggaa gtaggtgaaa gggcaggggc gtggctctcg 300 gggcgccacc cacgctcttg aaatctgggt gattgcgagc ggccgctcag cgtccccccac 360 accacagacc cgcgccgccg acgacccagc agccgccatg gctctgctcc gaggtgtgtt 420 tgtagttgct gctaagcgaa cgccctttgg agcttacgga ggccttctga aagacttcac 480 tgctactgac ttgtctgaat ttgctgccaa ggctgccttg tctgctggca aagtctcacc 540 tgaaacagtt gacagtgtga ttatgggcaa tgtcctgcag agttcttcag atgctatata 600 tttggcaagg catgttggtt tgcgtgtggg aatcccaaag gagaccccag ctctcacgat 660 taataggctc tgtggttctg gttttcagtc cattgtgaat ggatgtcagg aaatttgtgt 720 taaagaagct gaagttgttt tatgtggagg aaccgaaagc atgagccaag ctccctactg 780 tgtcagaaat gtgcgttttg gaaccaagct tggatcagat atcaagctgg aagattcttt 840 atgggtatca ttaacagatc agcatgtcca gctccccatg gcaatgactg cagagaatct 900 tgctgtaaaa cacaaaataa gcagagaaga atgtgacaaa tatgccctgc agtcacagca 960 gagatggaaa gctgctaatg atgctggcta ctttaatgat gaaatggcac caattgaagt 1020 gaagacaaag aaaggaaaac agacaatgca ggtagacgag catgctcggc cccaaaccac 1080 cctggaacag ttacagaaac ttcctccagt attcaagaaa gatggaactg ttactgcagg 1140 gaatgcatcg ggtgtagctg atggtgctgg agctgttatc atagctagtg aagatgctgt 1200 taagaaacat aacttcacac cactggcaag aattgtgggc tactttgtat ctggatgtga 1260 tccctctatc atgggtattg gtcctgtccc tgctatcagt ggggcactga agaaagcagg 1320 actgagtctt aaggacatgg atttggtaga ggtgaatgaa gcttttgctc cccagtactt 1380 ggctgttgag aggagtttgg atcttgacat aagtaaaacc aatgtgaatg gaggagccat 1440 tgctttgggt cacccactgg gaggatctgg atcaagaatt actgcacacc tggttcacga 1500 attaaggcgt cgaggtggaa aatatgccgt tggatcagct tgcattggag gtggccaagg 1560 tattgctgtc atcattcaga gcacagcctg aagagaccag tgagctcact gtgacccatc 1620 cttactctac ttggccaggc cacagtaaaa caagtgacct tcagagcagc tgccacaact 1680 ggccatgccc tgccattgaa acagtgatta agtttgatca agccatggtg acacaaaaat 1740 gcattgatca tgaataggag cccatgctag aagtacattc tctcagattt gaaccagtga 1800 aatatgatgt atttctgagc taaaactcaa ctatagaaga cattaaaaga aatcgtattc 1860 ttgccaagta accaccactt ctgccttaga taatatgatt ataaggaaat caaataaatg 1920 ttgccttaac ttcaaaaaaa aaaaaaaaaa aa 1952 <210> 33 <211> 2511 <212> PRT <213> Artificial Sequence <220> <223> FASN <400> 33 Met Glu Glu Val Val Ile Ala Gly Met Ser Gly Lys Leu Pro Glu Ser 1 5 10 15 Glu Asn Leu Gln Glu Phe Trp Asp Asn Leu Ile Gly Gly Val Asp Met 20 25 30 Val Thr Asp Asp Asp Arg Arg Trp Lys Ala Gly Leu Tyr Gly Leu Pro 35 40 45 Arg Arg Ser Gly Lys Leu Lys Asp Leu Ser Arg Phe Asp Ala Ser Phe 50 55 60 Phe Gly Val His Pro Lys Gln Ala His Thr Met Asp Pro Gln Leu Arg 65 70 75 80 Leu Leu Leu Glu Val Thr Tyr Glu Ala Ile Val Asp Gly Gly Ile Asn 85 90 95 Pro Asp Ser Leu Arg Gly Thr His Thr Gly Val Trp Val Gly Val Ser 100 105 110 Gly Ser Glu Thr Ser Glu Ala Leu Ser Arg Asp Pro Glu Thr Leu Val 115 120 125 Gly Tyr Ser Met Val Gly Cys Gln Arg Ala Met Met Ala Asn Arg Leu 130 135 140 Ser Phe Phe Phe Asp Phe Arg Gly Pro Ser Ile Ala Leu Asp Thr Ala 145 150 155 160 Cys Ser Ser Ser Leu Met Ala Leu Gln Asn Ala Tyr Gln Ala Ile His 165 170 175 Ser Gly Gln Cys Pro Ala Ala Ile Val Gly Gly Ile Asn Val Leu Leu 180 185 190 Lys Pro Asn Thr Ser Val Gln Phe Leu Arg Leu Gly Met Leu Ser Pro 195 200 205 Glu Gly Thr Cys Lys Ala Phe Asp Thr Ala Gly Asn Gly Tyr Cys Arg 210 215 220 Ser Glu Gly Val Val Ala Val Leu Leu Thr Lys Lys Ser Leu Ala Arg 225 230 235 240 Arg Val Tyr Ala Thr Ile Leu Asn Ala Gly Thr Asn Thr Asp Gly Phe 245 250 255 Lys Glu Gln Gly Val Thr Phe Pro Ser Gly Asp Ile Gln Glu Gln Leu 260 265 270 Ile Arg Ser Leu Tyr Gln Ser Ala Gly Val Ala Pro Glu Ser Phe Glu 275 280 285 Tyr Ile Glu Ala His Gly Thr Gly Thr Lys Val Gly Asp Pro Gln Glu 290 295 300 Leu Asn Gly Ile Thr Arg Ala Leu Cys Ala Thr Arg Gln Glu Pro Leu 305 310 315 320 Leu Ile Gly Ser Thr Lys Ser Asn Met Gly His Pro Glu Pro Ala Ser 325 330 335 Gly Leu Ala Ala Leu Ala Lys Val Leu Leu Ser Leu Glu His Gly Leu 340 345 350 Trp Ala Pro Asn Leu His Phe His Ser Pro Asn Pro Glu Ile Pro Ala 355 360 365 Leu Leu Asp Gly Arg Leu Gln Val Val Asp Gln Pro Leu Pro Val Arg 370 375 380 Gly Gly Asn Val Gly Ile Asn Ser Phe Gly Phe Gly Gly Ser Asn Val 385 390 395 400 His Ile Ile Leu Arg Pro Asn Thr Gln Pro Pro Ala Pro Ala Pro 405 410 415 His Ala Thr Leu Pro Arg Leu Leu Arg Ala Ser Gly Arg Thr Pro Glu 420 425 430 Ala Val Gln Lys Leu Leu Glu Gln Gly Leu Arg His Ser Gln Asp Leu 435 440 445 Ala Phe Leu Ser Met Leu Asn Asp Ile Ala Ala Val Pro Ala Thr Ala 450 455 460 Met Pro Phe Arg Gly Tyr Ala Val Leu Gly Gly Glu Arg Gly Gly Pro 465 470 475 480 Glu Val Gln Gln Val Pro Ala Gly Glu Arg Pro Leu Trp Phe Ile Cys 485 490 495 Ser Gly Met Gly Thr Gln Trp Arg Gly Met Gly Leu Ser Leu Met Arg 500 505 510 Leu Asp Arg Phe Arg Asp Ser Ile Leu Arg Ser Asp Glu Ala Val Lys 515 520 525 Pro Phe Gly Leu Lys Val Ser Gln Leu Leu Leu Ser Thr Asp Glu Ser 530 535 540 Thr Phe Asp Asp Ile Val His Ser Phe Val Ser Leu Thr Ala Ile Gln 545 550 555 560 Ile Gly Leu Ile Asp Leu Leu Ser Cys Met Gly Leu Arg Pro Asp Gly 565 570 575 Ile Val Gly His Ser Leu Gly Glu Val Ala Cys Gly Tyr Ala Asp Gly 580 585 590 Cys Leu Ser Gln Glu Glu Ala Val Leu Ala Ala Tyr Trp Arg Gly Gln 595 600 605 Cys Ile Lys Glu Ala His Leu Pro Gly Ala Met Ala Ala Val Gly 610 615 620 Leu Ser Trp Glu Glu Cys Lys Gln Arg Cys Pro Pro Gly Val Val Pro 625 630 635 640 Ala Cys His Asn Ser Lys Asp Thr Val Thr Ile Ser Gly Pro Gln Ala 645 650 655 Pro Val Phe Glu Phe Val Glu Gln Leu Arg Lys Glu Gly Val Phe Ala 660 665 670 Lys Glu Val Arg Thr Gly Gly Met Ala Phe His Ser Tyr Phe Met Glu 675 680 685 Ala Ile Ala Pro Pro Leu Leu Gln Glu Leu Lys Lys Val Ile Arg Glu 690 695 700 Pro Lys Pro Arg Ser Ala Arg Trp Leu Ser Thr Ser Ile Pro Glu Ala 705 710 715 720 Gln Trp His Ser Ser Leu Ala Arg Thr Ser Ser Ala Glu Tyr Asn Val 725 730 735 Asn Asn Leu Val Ser Pro Val Leu Phe Gln Glu Ala Leu Trp His Val 740 745 750 Pro Glu His Ala Val Val Leu Glu Ile Ala Pro His Ala Leu Leu Gln 755 760 765 Ala Val Leu Lys Arg Gly Leu Lys Pro Ser Cys Thr Ile Ile Pro Leu 770 775 780 Met Lys Lys Asp His Arg Asp Asn Leu Glu Phe Phe Leu Ala Gly Ile 785 790 795 800 Gly Arg Leu His Leu Ser Gly Ile Asp Ala Asn Pro Asn Ala Leu Phe 805 810 815 Pro Pro Val Glu Phe Pro Ala Pro Arg Gly Thr Pro Leu Ile Ser Pro 820 825 830 Leu Ile Lys Trp Asp His Ser Leu Ala Trp Asp Val Pro Ala Ala Glu 835 840 845 Asp Phe Pro Asn Gly Ser Gly Ser Pro Ser Ala Ala Ile Tyr Asn Ile 850 855 860 Asp Thr Ser Ser Glu Ser Pro Asp His Tyr Leu Val Asp His Thr Leu 865 870 875 880 Asp Gly Arg Val Leu Phe Pro Ala Thr Gly Tyr Leu Ser Ile Val Trp 885 890 895 Lys Thr Leu Ala Arg Ala Leu Gly Leu Gly Val Glu Gln Leu Pro Val 900 905 910 Val Phe Glu Asp Val Val Leu His Gln Ala Thr Ile Leu Pro Lys Thr 915 920 925 Gly Thr Val Ser Leu Glu Val Arg Leu Leu Glu Ala Ser Arg Ala Phe 930 935 940 Glu Val Ser Glu Asn Gly Asn Leu Val Val Ser Gly Lys Val Tyr Gln 945 950 955 960 Trp Asp Asp Pro Asp Pro Arg Leu Phe Asp His Pro Glu Ser Pro Thr 965 970 975 Pro Asn Pro Thr Glu Pro Leu Phe Leu Ala Gln Ala Glu Val Tyr Lys 980 985 990 Glu Leu Arg Leu Arg Gly Tyr Asp Tyr Gly Pro His Phe Gln Gly Ile 995 1000 1005 Leu Glu Ala Ser Leu Glu Gly Asp Ser Gly Arg Leu Leu Trp Lys Asp 1010 1015 1020 Asn Trp Val Ser Phe Met Asp Thr Met Leu Gln Met Ser Ile Leu Gly 1025 1030 1035 1040 Ser Ala Lys His Gly Leu Tyr Leu Pro Thr Arg Val Thr Ala Ile His 1045 1050 1055 Ile Asp Pro Ala Thr His Arg Gln Lys Leu Tyr Thr Leu Gln Asp Lys 1060 1065 1070 Ala Gln Val Ala Asp Val Val Val Ser Arg Trp Leu Arg Val Thr Val 1075 1080 1085 Ala Gly Gly Val His Ile Ser Gly Leu His Thr Glu Ser Ala Pro Arg 1090 1095 1100 Arg Gln Gln Glu Gln Gln Val Pro Ile Leu Glu Lys Phe Cys Phe Thr 1105 1110 1115 1120 Pro His Thr Glu Glu Gly Cys Leu Ser Glu Arg Ala Ala Leu Gln Glu 1125 1130 1135 Glu Leu Gln Leu Cys Lys Gly Leu Val Gln Ala Leu Gln Thr Lys Val 1140 1145 1150 Thr Gln Gln Gly Leu Lys Met Val Val Pro Gly Leu Asp Gly Ala Gln 1155 1160 1165 Ile Pro Arg Asp Pro Ser Gln Gln Glu Leu Pro Arg Leu Leu Ser Ala 1170 1175 1180 Ala Cys Arg Leu Gln Leu Asn Gly Asn Leu Gln Leu Glu Leu Ala Gln 1185 1190 1195 1200 Val Leu Ala Gln Glu Arg Pro Lys Leu Pro Glu Asp Pro Leu Leu Ser 1205 1210 1215 Gly Leu Leu Asp Ser Pro Ala Leu Lys Ala Cys Leu Asp Thr Ala Val 1220 1225 1230 Glu Asn Met Pro Ser Leu Lys Met Lys Val Val Glu Val Leu Ala Gly 1235 1240 1245 His Gly His Leu Tyr Ser Arg Ile Pro Gly Leu Leu Ser Pro His Pro 1250 1255 1260 Leu Leu Gln Leu Ser Tyr Thr Ala Thr Asp Arg His Pro Gln Ala Leu 1265 1270 1275 1280 Glu Ala Ala Gln Ala Glu Leu Gln Gln His Asp Val Ala Gln Gly Gln 1285 1290 1295 Trp Asp Pro Ala Asp Pro Ala Pro Ser Ala Leu Gly Ser Ala Asp Leu 1300 1305 1310 Leu Val Cys Asn Cys Ala Val Ala Ala Leu Gly Asp Pro Ala Ser Ala 1315 1320 1325 Leu Ser Asn Met Val Ala Ala Leu Arg Glu Gly Gly Phe Leu Leu Leu 1330 1335 1340 His Thr Leu Leu Arg Gly His Pro Leu Gly Asp Ile Val Ala Phe Leu 1345 1350 1355 1360 Thr Ser Thr Glu Pro Gln Tyr Gly Gln Gly Ile Leu Ser Gln Asp Ala 1365 1370 1375 Trp Glu Ser Leu Phe Ser Arg Val Ser Leu Arg Leu Val Gly Leu Lys 1380 1385 1390 Lys Ser Phe Tyr Gly Ser Thr Leu Phe Leu Cys Arg Arg Pro Thr Pro 1395 1400 1405 Gln Asp Ser Pro Ile Phe Leu Pro Val Asp Asp Thr Ser Phe Arg Trp 1410 1415 1420 Val Glu Ser Leu Lys Gly Ile Leu Ala Asp Glu Asp Ser Ser Arg Pro 1425 1430 1435 1440 Val Trp Leu Lys Ala Ile Asn Cys Ala Thr Ser Gly Val Val Gly Leu 1445 1450 1455 Val Asn Cys Leu Arg Arg Glu Pro Gly Gly Asn Arg Leu Arg Cys Val 1460 1465 1470 Leu Leu Ser Asn Leu Ser Ser Thr Ser His Val Pro Glu Val Asp Pro 1475 1480 1485 Gly Ser Ala Glu Leu Gln Lys Val Leu Gln Gly Asp Leu Val Met Asn 1490 1495 1500 Val Tyr Arg Asp Gly Ala Trp Gly Ala Phe Arg His Phe Leu Leu Glu 1505 1510 1515 1520 Glu Asp Lys Pro Glu Glu Pro Thr Ala His Ala Phe Val Ser Thr Leu 1525 1530 1535 Thr Arg Gly Asp Leu Ser Ser Ile Arg Trp Val Cys Ser Ser Leu Arg 1540 1545 1550 His Ala Gln Pro Thr Cys Pro Gly Ala Gln Leu Cys Thr Val Tyr Tyr 1555 1560 1565 Ala Ser Leu Asn Phe Arg Asp Ile Met Leu Ala Thr Gly Lys Leu Ser 1570 1575 1580 Pro Asp Ala Ile Pro Gly Lys Trp Thr Ser Gln Asp Ser Leu Leu Gly 1585 1590 1595 1600 Met Glu Phe Ser Gly Arg Asp Ala Ser Gly Lys Arg Val Met Gly Leu 1605 1610 1615 Val Pro Ala Lys Gly Leu Ala Thr Ser Val Leu Leu Ser Pro Asp Phe 1620 1625 1630 Leu Trp Asp Val Pro Ser Asn Trp Thr Leu Glu Glu Ala Ala Ser Val 1635 1640 1645 Pro Val Val Tyr Ser Thr Ala Tyr Tyr Ala Leu Val Val Arg Gly Arg 1650 1655 1660 Val Arg Pro Gly Glu Thr Leu Leu Ile His Ser Gly Ser Gly Gly Val 1665 1670 1675 1680 Gly Gln Ala Ala Ile Ala Ile Ala Leu Ser Leu Gly Cys Arg Val Phe 1685 1690 1695 Thr Thr Val Gly Ser Ala Glu Lys Arg Ala Tyr Leu Gln Ala Arg Phe 1700 1705 1710 Pro Gln Leu Asp Ser Thr Ser Phe Ala Asn Ser Arg Asp Thr Ser Phe 1715 1720 1725 Glu Gln His Val Leu Trp His Thr Gly Gly Lys Gly Val Asp Leu Val 1730 1735 1740 Leu Asn Ser Leu Ala Glu Glu Lys Leu Gln Ala Ser Val Arg Cys Leu 1745 1750 1755 1760 Ala Thr His Gly Arg Phe Leu Glu Ile Gly Lys Phe Asp Leu Ser Gln 1765 1770 1775 Asn His Pro Leu Gly Met Ala Ile Phe Leu Lys Asn Val Thr Phe His 1780 1785 1790 Gly Val Leu Leu Asp Ala Phe Phe Asn Glu Ser Ser Ala Asp Trp Arg 1795 1800 1805 Glu Val Trp Ala Leu Val Gln Ala Gly Ile Arg Asp Gly Val Val Arg 1810 1815 1820 Pro Leu Lys Cys Thr Val Phe His Gly Ala Gln Val Glu Asp Ala Phe 1825 1830 1835 1840 Arg Tyr Met Ala Gln Gly Lys His Ile Gly Lys Val Val Val Gln Val 1845 1850 1855 Leu Ala Glu Glu Pro Glu Ala Val Leu Lys Gly Ala Lys Pro Lys Leu 1860 1865 1870 Met Ser Ala Ile Ser Lys Thr Phe Cys Pro Ala His Lys Ser Tyr Ile 1875 1880 1885 Ile Ala Gly Gly Leu Gly Gly Gly Phe Gly Leu Glu Leu Ala Gln Trp Leu 1890 1895 1900 Ile Gln Arg Gly Val Gln Lys Leu Val Leu Thr Ser Arg Ser Gly Ile 1905 1910 1915 1920 Arg Thr Gly Tyr Gln Ala Lys Gln Val Arg Arg Trp Arg Arg Gln Gly 1925 1930 1935 Val Gln Val Gln Val Ser Thr Ser Asn Ile Ser Ser Leu Glu Gly Ala 1940 1945 1950 Arg Gly Leu Ile Ala Glu Ala Ala Gln Leu Gly Pro Val Gly Gly Val 1955 1960 1965 Phe Asn Leu Ala Val Val Leu Arg Asp Gly Leu Leu Glu Asn Gln Thr 1970 1975 1980 Pro Glu Phe Phe Gln Asp Val Cys Lys Pro Lys Tyr Ser Gly Thr Leu 1985 1990 1995 2000 Asn Leu Asp Arg Val Thr Arg Glu Ala Cys Pro Glu Leu Asp Tyr Phe 2005 2010 2015 Val Val Phe Ser Ser Val Ser Cys Gly Arg Gly Asn Ala Gly Gln Ser 2020 2025 2030 Asn Tyr Gly Phe Ala Asn Ser Ala Met Glu Arg Ile Cys Glu Lys Arg 2035 2040 2045 Arg His Glu Gly Leu Pro Gly Leu Ala Val Gln Trp Gly Ala Ile Gly 2050 2055 2060 Asp Val Gly Ile Leu Val Glu Thr Met Ser Thr Asn Asp Thr Ile Val 2065 2070 2075 2080 Ser Gly Thr Leu Pro Gln Arg Met Ala Ser Cys Leu Glu Val Leu Asp 2085 2090 2095 Leu Phe Leu Asn Gln Pro His Met Val Leu Ser Ser Phe Val Leu Ala 2100 2105 2110 Glu Lys Ala Ala Ala Tyr Arg Asp Arg Asp Ser Gln Arg Asp Leu Val 2115 2120 2125 Glu Ala Val Ala His Ile Leu Gly Ile Arg Asp Leu Ala Ala Val Asn 2130 2135 2140 Leu Asp Ser Ser Leu Ala Asp Leu Gly Leu Asp Ser Leu Met Ser Val 2145 2150 2155 2160 Glu Val Arg Gln Thr Leu Glu Arg Glu Leu Asn Leu Val Leu Ser Val 2165 2170 2175 Arg Glu Val Arg Gln Leu Thr Leu Arg Lys Leu Gln Glu Leu Ser Ser 2180 2185 2190 Lys Ala Asp Glu Ala Ser Glu Leu Ala Cys Pro Thr Pro Lys Glu Asp 2195 2200 2205 Gly Leu Ala Gln Gln Gln Thr Gln Leu Asn Leu Arg Ser Leu Leu Val 2210 2215 2220 Asn Pro Glu Gly Pro Thr Leu Met Arg Leu Asn Ser Val Gln Ser Ser 2225 2230 2235 2240 Glu Arg Pro Leu Phe Leu Val His Pro Ile Glu Gly Ser Thr Thr Val 2245 2250 2255 Phe His Ser Leu Ala Ser Arg Leu Ser Ile Pro Thr Tyr Gly Leu Gln 2260 2265 2270 Cys Thr Arg Ala Ala Pro Leu Asp Ser Ile His Ser Leu Ala Ala Tyr 2275 2280 2285 Tyr Ile Asp Cys Ile Arg Gln Val Gln Pro Glu Gly Pro Tyr Arg Val 2290 2295 2300 Ala Gly Tyr Ser Tyr Gly Ala Cys Val Ala Phe Glu Met Cys Ser Gln 2305 2310 2315 2320 Leu Gln Ala Gln Gln Ser Pro Ala Pro Thr His Asn Ser Leu Phe Leu 2325 2330 2335 Phe Asp Gly Ser Pro Thr Tyr Val Leu Ala Tyr Thr Gln Ser Tyr Arg 2340 2345 2350 Ala Lys Leu Thr Pro Gly Cys Glu Ala Glu Ala Glu Thr Glu Ala Ile 2355 2360 2365 Cys Phe Phe Val Gln Gln Phe Thr Asp Met Glu His Asn Arg Val Leu 2370 2375 2380 Glu Ala Leu Leu Pro Leu Lys Gly Leu Glu Glu Arg Val Ala Ala Ala 2385 2390 2395 2400 Val Asp Leu Ile Ile Lys Ser His Gln Gly Leu Asp Arg Gln Glu Leu 2405 2410 2415 Ser Phe Ala Ala Arg Ser Phe Tyr Tyr Lys Leu Arg Ala Ala Glu Gln 2420 2425 2430 Tyr Thr Pro Lys Ala Lys Tyr His Gly Asn Val Met Leu Leu Arg Ala 2435 2440 2445 Lys Thr Gly Gly Ala Tyr Gly Glu Asp Leu Gly Ala Asp Tyr Asn Leu 2450 2455 2460 Ser Gln Val Cys Asp Gly Lys Val Ser Val His Val Ile Glu Gly Asp 2465 2470 2475 2480 His Arg Thr Leu Leu Glu Gly Ser Gly Leu Glu Ser Ile Ile Ser Ile 2485 2490 2495 Ile His Ser Ser Leu Ala Glu Pro Arg Val Ser Val Arg Glu Gly 2500 2505 2510 <210> 34 <211> 8481 <212> DNA <213> Artificial Sequence <220> <223> FASN <400> 34 gagagacggc agcggccccg gcctccctct ccgccgcgct tcagcctccc gctccgccgc 60 gctccagcct cgctctccgc cgcccgcacc gccgcccgcg ccctcaccag agcagccatg 120 gaggaggtgg tgattgccgg catgtccggg aagctgccag agtcggagaa cttgcaggag 180 ttctgggaca acctcatcgg cggtgtggac atggtcacgg acgatgaccg tcgctggaag 240 gcggggctct acggcctgcc ccggcggtcc ggcaagctga aggacctgtc taggtttgat 300 gcctccttct tcggagtcca ccccaagcag gcacacacga tggaccctca gctgcggctg 360 ctgctggaag tcacctatga agccatcgtg gacggaggca tcaacccaga ttcactccga 420 ggaacacaca ctggcgtctg ggtgggcgtg agcggctctg agacctcgga ggccctgagc 480 cgagaccccg agacactcgt gggctacagc atggtgggct gccagcgagc gatgatggcc 540 aaccggctct ccttcttctt cgacttcaga gggcccagca tcgcactgga cacagcctgc 600 tcctccagcc tgatggccct gcagaacgcc taccaggcca tccacagcgg gcagtgccct 660 gccgccatcg tggggggcat caatgtcctg ctgaagccca acacctccgt gcagttcttg 720 aggctgggga tgctcagccc cgagggcacc tgcaaggcct tcgacacagc ggggaatggg 780 tactgccgct cggagggtgt ggtggccgtc ctgctgacca agaagtccct ggcccggcgg 840 gtgtacgcca ccatcctgaa cgccggcacc aatacagatg gcttcaagga gcaaggcgtg 900 accttcccct caggggatat ccaggagcag ctcatccgct cgttgtacca gtcggccgga 960 gtggcccctg agtcatttga atacatcgaa gccccacggca caggcaccaa ggtgggcgac 1020 ccccaggagc tgaatggcat cacccgagcc ctgtgcgcca cccgccagga gccgctgctc 1080 atcggctcca ccaagtccaa catggggcac ccggagccag cctcggggct ggcagccctg 1140 gccaaggtgc tgctgtccct ggagcagggg ctctgggccc ccaacctgca cttccatagc 1200 cccaaccctg agatcccagc gctgttggat gggcggctgc aggtggtgga ccagcccctg 1260 cccgtccgtg gcggcaacgt gggcatcaac tcctttggct tcgggggctc caacgtgcac 1320 atcatcctga ggcccaacac gcagccgccc cccgcacccg ccccacatgc caccctgccc 1380 cgtctgctgc gggccagcgg acgcacccct gaggccgtgc agaagctgct ggagcagggc 1440 ctccggcaca gccaggacct ggctttcctg agcatgctga acgacatcgc ggctgtcccc 1500 gccaccgcca tgcccttccg tggctacgct gtgctgggtg gtgagcgcgg tggcccagag 1560 gtgcagcagg tgcccgctgg cgagcgcccg ctctggttca tctgctctgg gatgggcaca 1620 cagtggcgcg ggatggggct gagcctcatg cgcctggacc gcttccgaga ttccatccta 1680 cgctccgatg aggctgtgaa gccattcggc ctgaaggtgt cacagctgct gctgagcaca 1740 gacgagagca cctttgatga catcgtccat tcgtttgtga gcctgactgc catccagata 1800 ggcctcatag acctgctgag ctgcatgggg ctgaggccag atggcatcgt cggccactcc 1860 ctgggggagg tggcctgtgg ctacgccgac ggctgcctgt cccaggagga ggccgtcctc 1920 gctgcctact ggaggggaca gtgcatcaaa gaagcccatc tcccgccggg cgccatggca 1980 gccgtgggct tgtcctggga ggagtgtaaa cagcgctgcc ccccgggcgt ggtgcccgcc 2040 tgccacaact ccaaggacac agtcaccatc tcgggacctc aggccccggt gtttgagttc 2100 gtggagcagc tgaggaagga gggtgtgttt gccaaggagg tgcggaccgg cggtatggcc 2160 ttccactcct acttcatgga ggccatcgca cccccactgc tgcaggagct caagaaggtg 2220 atccgggagc cgaagccacg ttcagcccgc tggctcagca cctctatccc cgaggcccag 2280 tggcacagca gcctggcacg cacgtcctcc gccgagtaca atgtcaacaa cctggtgagc 2340 cctgtgctgt tccaggaggc cctgtggcac gtgcctgagc acgcggtggt gctggagatc 2400 gcgccccacg ccctgctgca ggctgtcctg aagcgtggcc tgaagccgag ctgcaccatc 2460 atccccctga tgaagaagga tcacagggac aacctggagt tcttcctggc cggcatcggc 2520 aggctgcacc tctcaggcat cgacgccaac cccaatgcct tgttcccacc tgtggagttc 2580 ccagctcccc gaggaactcc cctcatctcc ccactcatca agtgggacca cagcctggcc 2640 tgggacgtgc cggccgccga ggacttcccc aacggttcag gttccccctc agccgccatc 2700 tacaacatcg acaccagctc cgagtctcct gaccactacc tggtggacca caccctcgac 2760 ggtcgcgtcc tcttccccgc cactggctac ctgagcatag tgtggaagac gctggcccgc 2820 gccctgggcc tgggcgtcga gcagctgcct gtggtgtttg aggatgtggt gctgcaccag 2880 gccaccatcc tgcccaagac tgggacagtg tccctggagg tacggctcct ggaggcctcc 2940 cgtgccttcg aggtgtcaga gaacggcaac ctggtagtga gtgggaaggt gtaccagtgg 3000 gatgaccctg accccaggct cttcgaccac ccggaaagcc ccacccccaa ccccacggag 3060 cccctcttcc tggcccaggc tgaagtttac aaggagctgc gtctgcgtgg ctacgactac 3120 ggccctcatt tccagggcat cctggaggcc agcctggaag gtgactcggg gaggctgctg 3180 tggaaggata actgggtgag cttcatggac accatgctgc agatgtccat cctgggctcg 3240 gccaagcacg gcctgtacct gcccacccgt gtcaccgcca tccacatcga ccctgccacc 3300 cacaggcaga agctgtacac actgcaggac aaggcccaag tggctgacgt ggtggtgagc 3360 aggtggctga gggtcacagt ggccggaggc gtccacatct ccgggctcca cactgagtcg 3420 gccccgcggc ggcagcagga gcagcaggtg cccatcctgg agaagttttg cttcactccc 3480 cacacggagg aggggtgcct gtctgagcgc gctgccctgc aggaggagct gcaactgtgc 3540 aaggggctgg tgcaggcact gcagaccaag gtgacccagc aggggctgaa gatggtggtg 3600 cccggactgg atggggccca gatcccccgg gacccctcac agcaggaact gccccggctg 3660 ttgtcggctg cctgcaggct tcagctcaac gggaacctgc agctggagct ggcgcaggtg 3720 ctggcccagg agaggcccaa gctgccagag gaccctctgc tcagcggcct cctggactcc 3780 ccggcactca aggcctgcct ggacactgcc gtggagaaca tgcccagcct gaagatgaag 3840 gtggtggagg tgctggctgg ccacggtcac ctgtattccc gcatcccagg cctgctcagc 3900 ccccatcccc tgctgcagct gagctacacg gccaccgacc gccaccccca ggccctggag 3960 gctgcccagg ccgagctgca gcagcacgac gttgcccagg gccagtggga tcccgcagac 4020 cctgccccca gcgccctggg cagcgccgac ctcctggtgt gcaactgtgc tgtggctgcc 4080 ctcggggacc cggcctcagc tctcagcaac atggtggctg ccctgagaga agggggcttt 4140 ctgctcctgc acacactgct ccgggggcac cccctcgggg acatcgtggc cttcctcacc 4200 tccactgagc cgcagtatgg ccagggcatc ctgagccagg acgcgtggga gagcctcttc 4260 tccagggtgt cgctgcgcct ggtgggcctg aagaagtcct tctacggctc cacgctcttc 4320 ctgtgccgcc ggcccacccc gcaggacagc cccatcttcc tgccggtgga cgataccagc 4380 ttccgctggg tggagtctct gaagggcatc ctggctgacg aagactcttc ccggcctgtg 4440 tggctgaagg ccatcaactg tgccacctcg ggcgtggtgg gcttggtgaa ctgtctccgc 4500 cgagagcccg gcgggaaccg cctccggtgt gtgctgctct ccaacctcag cagcacctcc 4560 cacgtcccgg aggtggaccc gggctccgca gaactgcaga aggtgttgca gggagacctg 4620 gtgatgaacg tctaccgcga cggggcctgg ggggctttcc gccacttcct gctggaggag 4680 gacaagcctg aggagccgac ggcacatgcc tttgtgagca ccctcacccg gggggacctg 4740 tcctccatcc gctgggtctg ctcctcgctg cgccatgccc agcccacctg ccctggcgcc 4800 cagctctgca cggtctacta cgcctccctc aacttccgcg acatcatgct ggccactggc 4860 aagctgtccc ctgatgccat cccagggaag tggacctccc aggacagcct gctaggtatg 4920 gagttctcgg gccgagacgc cagcggcaag cgtgtgatgg gactggtgcc tgccaagggc 4980 ctggccacct ctgtcctgct gtcaccggac ttcctctggg atgtgccttc caactggacg 5040 ctggaggagg cggcctcggt gcctgtcgtc tacagcacgg cctactacgc gctggtggtg 5100 cgtgggcggg tgcgccccgg ggagacgctg ctcatccact cgggctcggg cggcgtgggc 5160 caggccgcca tcgccatcgc cctcagtctg ggctgccgcg tcttcaccac cgtggggtcg 5220 gctgagaagc gggcgtacct ccaggccagg ttcccccagc tcgacagcac cagcttcgcc 5280 aactcccggg acacatcctt cgagcagcat gtgctgtggc acacgggcgg gaagggcgtt 5340 gacctggtct tgaactcctt ggcggaagag aagctgcagg ccagcgtgag gtgcttggct 5400 acgcacggtc gcttcctgga aattggcaaa ttcgaccttt ctcagaacca cccgctcggc 5460 atggctatct tcctgaagaa cgtgacattc cacggggtcc tactggatgc gttcttcaac 5520 gagagcagtg ctgactggcg ggaggtgtgg gcgcttgtgc aggccggcat ccgggatggg 5580 gtggtacggc ccctcaagtg cacggtgttc catggggccc aggtggagga cgccttccgc 5640 tacatggccc aagggaagca cattggcaaa gtcgtcgtgc aggtgcttgc ggaggagccg 5700 gaggcagtgc tgaagggggc caaacccaag ctgatgtcgg ccatctccaa gaccttctgc 5760 ccggcccaca agagctacat catcgctggt ggtctgggtg gcttcggcct ggagttggcg 5820 cagtggctga tacagcgtgg ggtgcagaag ctcgtgttga cttctcgctc cgggatccgg 5880 acaggctacc aggccaagca ggtccgccgg tggaggcgcc agggcgtaca ggtgcaggtg 5940 tccaccagca acatcagctc actggagggg gcccggggcc tcattgccga ggcggcgcag 6000 cttgggcccg tgggcggcgt cttcaacctg gccgtggtct tgagagatgg cttgctggag 6060 aaccagaccc cagagttctt ccaggacgtc tgcaagccca agtacagcgg caccctgaac 6120 ctggacaggg tgacccgaga ggcgtgccct gagctggact actttgtggt cttctcctct 6180 gtgagctgcg ggcgtggcaa tgcgggacag agcaactacg gctttgccaa ttccgccatg 6240 gagcgtatct gtgagaaacg ccggcacgaa ggcctcccag gcctggccgt gcagtggggc 6300 gccatcggcg acgtgggcat tttggtggag acgatgagca ccaacgacac gatcgtcagt 6360 ggcacgctgc cccagcgcat ggcgtcctgc ctggaggtgc tggacctctt cctgaaccag 6420 ccccacatgg tcctgagcag ctttgtgctg gctgagaagg ctgcggccta tagggacagg 6480 gacagccagc gggacctggt ggaggccgtg gcacacatcc tgggcatccg cgacttggct 6540 gctgtcaacc tggacagctc actggcggac ctgggcctgg actcgctcat gagcgtggag 6600 gtgcgccaga cgctggagcg tgagctcaac ctggtgctgt ccgtgcgcga ggtgcggcaa 6660 ctcacgctcc ggaaactgca ggagctgtcc tcaaaggcgg atgaggccag cgagctggca 6720 tgccccacgc ccaaggagga tggtctggcc cagcagcaga ctcagctgaa cctgcgctcc 6780 ctgctggtga acccggaggg ccccaccctg atgcggctca actccgtgca gagctcggag 6840 cggcccctgt tcctggtgca cccaatcgag ggctccacca ccgtgttcca cagcctggcc 6900 tcccggctca gcatccccac ctatggcctg cagtgcaccc gagctgcgcc ccttgacagc 6960 atccacagcc tggctgccta ctacatcgac tgcatcaggc aggtgcagcc cgagggcccc 7020 taccgcgtgg ccggctactc ctacggggcc tgcgtggcct ttgaaatgtg ctcccagctg 7080 caggcccagc agagcccagc ccccacccac aacagcctct tcctgttcga cggctcgccc 7140 acctacgtac tggcctacac ccagagctac cgggcaaagc tgaccccagg ctgtgaggct 7200 gaggctgaga cggaggccat atgcttcttc gtgcagcagt tcacggacat ggagcacaac 7260 agggtgctgg aggcgctgct gccgctgaag ggcctagagg agcgtgtggc agccgccgtg 7320 gacctgatca tcaagagcca ccagggcctg gaccgccagg agctgagctt tgcggcccgg 7380 tccttctact acaagctgcg tgccgctgag cagtacacac ccaaggccaa gtaccatggc 7440 aacgtgatgc tactgcgcgc caagacgggt ggcgcctacg gcgaggacct gggcgcggac 7500 tacaacctct cccaggtatg cgacgggaaa gtatccgtcc acgtcatcga gggtgaccac 7560 cgcacgctgc tggagggcag cggcctggag tccatcatca gcatcatcca cagctccctg 7620 gctgagccac gcgtgagcgt gcgggagggc taggcccgtg cccccgcctg ccaccggagg 7680 tcactccacc atccccaccc caccccaccc cacccccgcc atgcaacggg attgaagggt 7740 cctgccggtg ggaccctgtc cggcccagtg ccactgcccc ccgaggctgc tagatgtagg 7800 tgttaggcat gtcccaccca cccgccgcct cccacggcac ctcggggaca ccagagctgc 7860 cgacttggag actcctggtc tgtgaagagc cggtggtgcc cgtgcccgca ggaactgggc 7920 tgggcctcgt gcgcccgtgg ggtctgcgct tggtctttct gtgcttggat ttgcatattt 7980 attgcattgc tggtagagac ccccaggcct gtccaccctg ccaagactcc tcaggcagcg 8040 tgtgggtccc gcactctgcc cccatttccc cgatgtcccc tgcgggcgcg ggcagccacc 8100 caagcctgct ggctgcggcc ccctctcggc caggcattgg ctcagcccgc tgagtggggg 8160 gtcgtgggcc agtccccgag gagctgggcc cctgcacagg cacacagggc ccggccacac 8220 ccagcggccc cccgcacagc cacccgtggg gtgctgccct tatgcccggc gccgggcacc 8280 aactccatgt ttggtgtttg tctgtgtttg tttttcaaga aatgattcaa attgctgctt 8340 ggattttgaa atttactgta actgtcagtg tacacgtctg gaccccgttt catttttaca 8400 ccaatttggt aaaaatgctg ctctcagcct cccacaatta aaccgcatgt gatctccaaa 8460 aaaaaaaaaa aaaaaaaaaa a 8481 <210> 35 <211> 135 <212> PRT <213> Artificial Sequence <220> <223> LGALS1 <400> 35 Met Ala Cys Gly Leu Val Ala Ser Asn Leu Asn Leu Lys Pro Gly Glu 1 5 10 15 Cys Leu Arg Val Arg Gly Glu Val Ala Pro Asp Ala Lys Ser Phe Val 20 25 30 Leu Asn Leu Gly Lys Asp Ser Asn Asn Leu Cys Leu His Phe Asn Pro 35 40 45 Arg Phe Asn Ala His Gly Asp Ala Asn Thr Ile Val Cys Asn Ser Lys 50 55 60 Asp Gly Gly Ala Trp Gly Thr Glu Gln Arg Glu Ala Val Phe Pro Phe 65 70 75 80 Gln Pro Gly Ser Val Ala Glu Val Cys Ile Thr Phe Asp Gln Ala Asn 85 90 95 Leu Thr Val Lys Leu Pro Asp Gly Tyr Glu Phe Lys Phe Pro Asn Arg 100 105 110 Leu Asn Leu Glu Ala Ile Asn Tyr Met Ala Ala Asp Gly Asp Phe Lys 115 120 125 Ile Lys Cys Val Ala Phe Asp 130 135 <210> 36 <211> 586 <212> DNA <213> Artificial Sequence <220> <223> LGALS1 <400> 36 agttaaaagg gtgggagcgt ccgggggccc atctctctcg ggtggagtct tctgacagct 60 ggtgcgcctg cccgggaaca tcctcctgga ctcaatcatg gcttgtggtc tggtcgccag 120 caacctgaat ctcaaacctg gagagtgcct tcgagtgcga ggcgaggtgg ctcctgacgc 180 taagagcttc gtgctgaacc tgggcaaaga cagcaacaac ctgtgcctgc acttcaaccc 240 tcgcttcaac gcccacggcg acgccaacac catcgtgtgc aacagcaagg acggcggggc 300 ctgggggacc gagcagcggg aggctgtctt tcccttccag cctggaagtg ttgcagaggt 360 gtgcatcacc ttcgaccagg ccaacctgac cgtcaagctg ccagatggat acgaattcaa 420 gttccccaac cgcctcaacc tggaggccat caactacatg gcagctgacg gtgacttcaa 480 gatcaaatgt gtggcctttg actgaaatca gccagcccat ggcccccaat aaaggcagct 540 gcctctgctc cctctgaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 586 <210> 37 <211> 258 <212> PRT <213> Artificial Sequence <220> <223> IGFBP4 <400> 37 Met Leu Pro Leu Cys Leu Val Ala Ala Leu Leu Leu Ala Ala Gly Pro 1 5 10 15 Gly Pro Ser Leu Gly Asp Glu Ala Ile His Cys Pro Pro Cys Ser Glu 20 25 30 Glu Lys Leu Ala Arg Cys Arg Pro Pro Val Gly Cys Glu Glu Leu Val 35 40 45 Arg Glu Pro Gly Cys Gly Cys Cys Ala Thr Cys Ala Leu Gly Leu Gly 50 55 60 Met Pro Cys Gly Val Tyr Thr Pro Arg Cys Gly Ser Gly Leu Arg Cys 65 70 75 80 Tyr Pro Pro Arg Gly Val Glu Lys Pro Leu His Thr Leu Met His Gly 85 90 95 Gln Gly Val Cys Met Glu Leu Ala Glu Ile Glu Ala Ile Gln Glu Ser 100 105 110 Leu Gln Pro Ser Asp Lys Asp Glu Gly Asp His Pro Asn Asn Ser Phe 115 120 125 Ser Pro Cys Ser Ala His Asp Arg Arg Cys Leu Gln Lys His Phe Ala 130 135 140 Lys Ile Arg Asp Arg Ser Thr Ser Gly Gly Lys Met Lys Val Asn Gly 145 150 155 160 Ala Pro Arg Glu Asp Ala Arg Pro Val Pro Gln Gly Ser Cys Gln Ser 165 170 175 Glu Leu His Arg Ala Leu Glu Arg Leu Ala Ala Ser Gln Ser Arg Thr 180 185 190 His Glu Asp Leu Tyr Ile Ile Pro Ile Pro Asn Cys Asp Arg Asn Gly 195 200 205 Asn Phe His Pro Lys Gln Cys His Pro Ala Leu Asp Gly Gln Arg Gly 210 215 220 Lys Cys Trp Cys Val Asp Arg Lys Thr Gly Val Lys Leu Pro Gly Gly 225 230 235 240 Leu Glu Pro Lys Gly Glu Leu Asp Cys His Gln Leu Ala Asp Ser Phe 245 250 255 Arg Glu <210> 38 <211> 2246 <212> DNA <213> Artificial Sequence <220> <223> IGFBP4 <400> 38 aaagtccggg ggagccggtc ccgggcagcc gctcagcccc ctgcccctcg ccgcccgccg 60 cctgcctggg ccgggccgag gatgcggcgc agcgcctcgg cggccaggct tgctcccctc 120 cggcacgcct gctaacttcc cccgctacgt ccccgttcgc ccgccgggcc gccccgtctc 180 cccgcgccct ccgggtcggg tcctccagga gcgccaggcg ctgccgccgt gtgccctccg 240 ccgctcgccc gcgcgcccgc gctccccgcc tgcgcccagc gccccgcgcc cgcgcccagt 300 cctcgggcgg tcatgctgcc cctctgcctc gtggccgccc tgctgctggc cgccgggccc 360 gggccgagcc tgggcgacga agccatccac tgcccgccct gctccgagga gaagctggcg 420 cgctgccgcc cccccgtggg ctgcgaggag ctggtgcgag agccgggctg cggctgttgc 480 gccacttgcg ccctgggctt ggggatgccc tgcggggtgt acaccccccg ttgcggctcg 540 ggcctgcgct gctacccgcc ccgaggggtg gagaagcccc tgcacacact gatgcagggg 600 caaggcgtgt gcatggagct ggcggagatc gaggccatcc aggaaagcct gcagccctct 660 gacaaggacg agggtgacca ccccaacaac agcttcagcc cctgtagcgc ccatgaccgc 720 aggtgcctgc agaagcactt cgccaaaatt cgagaccgga gcaccagtgg gggcaagatg 780 aaggtcaatg gggcgccccg ggaggatgcc cggcctgtgc cccagggctc ctgccagagc 840 gagctgcacc gggcgctgga gcggctggcc gcttcacaga gccgcaccca cgaggacctc 900 tacatcatcc ccatccccaa ctgcgaccgc aacggcaact tccaccccaa gcagtgtcac 960 ccagctctgg atgggcagcg tggcaagtgc tggtgtgtgg accggaagac gggggtgaag 1020 cttccggggg gcctggagcc aaagggggag ctggactgcc accagctggc tgacagcttt 1080 cgagagtgag gcctgccagc aggccaggga ctcagcgtcc cctgctactc ctgtgctctg 1140 gaggctgcag agctgaccca gagtggagtc tgagtctgag tcctgtctct gcctgcggcc 1200 cagaagtttc cctcaaatgc gcgtgtgcac gtgtgcgtgt gcgtgcgtgt gtgtgtgttt 1260 gtgagcatgg gtgtgccctt ggggtaagcc agagcctggg gtgttctctt tggtgttaca 1320 cagcccaaga ggactgagac tggcacttag cccaagaggt ctgagccctg gtgtgtttcc 1380 agatcgatcc tggattcact cactcactca ttccttcact catccagcca cctaaaaaca 1440 tttactgacc atgtactacg tgccagctct agttttcagc cttgggaggt tttattctga 1500 cttcctctga ttttggcatg tggagacact cctataagga gagttcaagc ctgtgggagt 1560 agaaaaatct cattcccaga gtcagaggag aagagacatg taccttgacc atcgtccttc 1620 ctctcaagct agccagaggg tgggagccta aggaagcgtg gggtagcaga tggagtaatg 1680 gtcacgaggt ccagacccac tcccaaagct cagacttgcc aggctccctt tctcttcttc 1740 cccaggtcct tcctttaggt ctggttgttg caccatctgc ttggttggct ggcagctgag 1800 agccctgctg tgggagagcg aagggggtca aaggaagact tgaagcacag agggctaggg 1860 aggtggggta catttctctg agcagtcagg gtgggaagaa agaatgcaag agtggactga 1920 atgtgcctaa tggagaagac ccacgtgcta ggggatgagg ggcttcctgg gtcctgttcc 1980 ctaccccatt tgtggtcaca gccatgaagt caccgggatg aacctatcct tccagtggct 2040 cgctccctgt agctctgcct ccctctccat atctccttcc cctacacctc cctccccaca 2100 cctccctact cccctgggca tcttctggct tgactggatg gaaggagact taggaaccta 2160 ccagttggcc atgatgtctt ttcttctttt tctttttttt aacaaaacag aacaaaacca 2220 aaaaatgtcc agatgaaaaa aaaaaa 2246

Claims (6)

A biomarker composition for diagnosing massive perivillous fibrin deposition (MPFD), comprising the protein of PSMA2 as an active ingredient. According to claim 1,
Wherein the PSMA2 is a polypeptide having the amino acid sequence of SEQ ID NO: 5, MPFD diagnostic biomarker composition. measuring the amount of PSMA2 protein detected in blood collected from the mother; and
A method for providing information necessary for diagnosing MPFD, comprising determining the mother as MPFD when the detection amount of the protein is higher than the detection amount of the protein present in the normal maternal blood. 4. The method of claim 3,
The protein detection amount measurement is performed by liquid chromatography-mass spectrometry (LC-MS) technique or enzyme-linked immunosorbent assay (ELISA) technique, a method of providing information necessary for diagnosing MPFD. A kit for diagnosis of MPFD, comprising an antibody or fragment thereof binding to PSMA2 protein as an active ingredient. 6. The method of claim 5,
The kit is a rapid kit, MPFD diagnostic kit.

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